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The intricate origins and diverse symptoms of Alzheimer's disease (AD) pose significant challenges for both diagnosis and treatment. Exosomes and microvesicles, which carry disease-specific cargo from a variety of central nervous system cell types, have emerged as promising reservoirs of biomarkers for AD. Research on the screening of possible biomarkers in Alzheimer's disease using proteomic profiling of EVs is systematically reviewed in this comprehensive review. We highlight key methodologies employed in EV isolation, characterization, and proteomic analysis, elucidating their advantages and limitations. Furthermore, we summarize the evolving landscape of EV-associated biomarkers implicated in AD pathogenesis, including proteins involved in amyloid-beta metabolism, tau phosphorylation, neuroinflammation, synaptic dysfunction, and neuronal injury. The literature review highlights the necessity for robust validation strategies and standardized protocols to effectively transition EV-based biomarkers into clinical use. In the concluding section, this review delves into potential future avenues and technological advancements pivotal in crafting EV-derived biomarkers applicable to AD diagnostics and prognostics. This review contributes to our comprehension of AD pathology and the advancement of precision medicine in neurodegenerative diseases, hinting at a promising era in AD precision medicine. This graphical abstract synthesizes sources of EVs, proteomics techniques, and identified AD biomarkers. It encapsulates the essence of the comprehensive review, aiding in understanding AD pathogenesis and diagnostic potential. [Display omitted] • AD biomarker quest: Proteomics profiles EVs, unveils potential markers. • Review dissects EVs' role in AD, exploring biomarker prospects. • Proteomic methods scrutinized for EVs, aiding AD diagnosis. • EVs reveal AD clues: amyloid-beta, tau, neuroinflammation. • Future outlook: EVs promise precision in AD diagnostics. [ABSTRACT FROM AUTHOR]

Introduction: Damage Associated Molecular Patterns (DAMPs) can initiate and amplify immune responses and can play an important role in the sustenance and progression of periodontal diseases. S100A8, S100A9 and their heterodimer, S100A8/9, are DAMPs or alarmins currently being evaluated for their potential as biomarkers in periodontal diseases. Aim: To quantify and compare salivary levels of S100A8, S100A9 and S100A8/9 in periodontal health, gingivitis or stage 1 periodontitis and stages 3 or 4 periodontitis. Materials and Methods: A cross-sectional analytical study was carried out in the Department of Periodontics, Saveetha Dental College and Hospital, Chennai, India, from December 2022 to February 2023. Periodontal examination and saliva sample collection were done for sixty-eight consecutively enrolled subjects who met the inclusion and exclusion criteria. Study subjects were categorised as group 1, which comprised participants with clinical periodontal health (n=20), group 2, subjects with gingivitis or stage 1 periodontitis (n=20), and group 3, which included patients with stages 3 or 4 periodontitis (n=28). Detailed clinical examination and periodontal charting were done in all study subjects. Saliva samples were processed and stored at -80°C, and enzyme-linked immunosorbent assay was done to quantify S100A8, S100A9 and S100A8/9. Data were analysed using International Business Machines (IBM) Statistical Package for the Social Sciences (SPSS) software version 25.0. Salivary levels of S100A8, S100A9 and S100A8/9 were expressed as mean and standard deviation values. Mean values of the three salivary proteins were compared using the non parametric Kruskal-Wallis test. Bonferroni adjusted pairwise comparisons were also done. The p-values less than 0.05 were considered statistically significant. Results: The mean age of study participants was 38.97±7.62 years. Salivary levels of S100A8 were 41.34±14.34, 141.95± 185.25 and 901.37±65.60 pg/mL in groups 1, 2 and 3, respectively. A statistically significant difference was present among the three groups for mean salivary levels of S100A8 (p-value<0.001). Pairwise comparisons showed that salivary S100A8 values in group 3 were significantly higher than the values observed in clinical health (group 1) (p-value<0.001) and those seen in the gingivitis or stage 1 periodontitis group (group 2) (p-value<0.001). Mean salivary levels of S100A9 and S100A8/9 did not show any statistically significant differences between the groups. Conclusion: There is an altered expression of S100A8, S100A9 and S100A8/9 in periodontal diseases compared to clinical health. Salivary levels of S100A8 are markedly different in cases of advanced periodontal destruction than in periodontal health and early stages of periodontal disease. Salivary S100A8 merits potential as a biomarker for periodontal diseases. [ABSTRACT FROM AUTHOR]

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. Significance statement: This study offers a significant contribution through its comprehensive approach to assess the therapeutic potential of blueberry extract. By integrating biological experiments with bioinformatic functional annotations, the research provides a thorough understanding of the bioactive compounds within blueberries and their potential mechanisms in combating lung cancer progression. Furthermore, the identification of key compounds within the extract, their potent cytotoxic effects on A549 cells and their involvement in crucial signaling pathways associated with lung cancer underscore the promising anticancer properties of blueberry‐derived compounds. This holistic methodology not only validates the traditional use of medicinal plants but also sheds light on their potential as valuable sources of novel pharmaceutical agents for future therapeutic advancements. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Diabetes mellitus is a persistent metabolic condition marked by elevated blood glucose levels due to compromised insulin secretion or functionality. The search for natural antidiabetic agents has gained attention due to their potential effectiveness and safety profiles. Sessuvium portulacastrum, a coastal plant, has been traditionally used for various medicinal purposes. This study investigates the antidiabetic potential of Sessuvium portulacastrum aqueous extract by analyzing its inhibitory effects on key enzymes involved in carbohydrate metabolism and exploring its molecular interactions with critical target proteins. The aqueous extract of Sessuvium portulacastrum was prepared and used for in vitro analysis. The reduced activity of the extract against a-amylase and a-glucosidase enzymes, crucial in glucose absorption and postprandial hyperglycemia, was assessed. Molecular docking techniques were employed to explore the potential interactions between active compounds in the extract and diabetes-related proteins, including BAX, GSK3ß, and CADH. The study revealed significant inhibition of both alpha-amylase and alpha-glucosidase enzymes by Sessuvium portulacastrum aqueous extract, indicating its potential to reduce glucose absorption and postprandial hyperglycemia. Moreover, the molecular docking analysis demonstrated strong binding interactions between active compounds in the extract and key proteins involved in diabetes-related pathways, namely apoptotic pathways, glycogen synthesis, and cell adhesion. The findings of this study highlight the promising antidiabetic potential of Sessuvium portulacastrum aqueous extract. Upcoming research should get an attention on isolating and characterizing the active compounds responsible for these effects on antidiabetic therapies from natural sources. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Spermacoce hispida, a medicinal plant from the Rubiaceae family, has garnered attention for its traditional use and reported therapeutic properties. This study aimed to investigate the phytochemical composition and assess the anti-inflammatory and anti-oxidant activities of the ethanolic extract derived from Spermacoce hispida. Materials and Methods: Phytochemical screening of the ethanolic extract involved qualitative analysis to identify major phytoconstituents such as tannins, phenols, and acids. The anti-inflammatory activity was evaluated through in vitro assays, and anti-oxidant potential was assessed using established methods to measure scavenging activity against free radicals and reactive oxygen species. Results: Phytochemical screening revealed the presence of various bioactive constituents in the Spermacoce hispida ethanolic extract, including acid, tannin, protein, and phenolic compounds. Furthermore, the extract exhibited potent anti-oxidant activity, as evidenced by its ability to scavenge free radicals and attenuate ROS-induced oxidative stress. Conclusion: The findings of this study underscore the potential of Spermacoce hispida ethanolic extract as a source of bioactive compounds with anti-inflammatory and anti-oxidant properties. The presence of phytochemicals and the observed bioactivity support its traditional use and suggest potential therapeutic applications. These results contribute to the growing body of knowledge on natural products with health-promoting effects and provide a basis for further research aimed at developing pharmaceutical and medicinal interventions harnessing the benefits of Spermacoce hispida. [ABSTRACT FROM AUTHOR]

Tinospora cordifolia, commonly known as "Giloy" or "Guduchi," is a medicinal plant with a rich history in traditional medicine systems. The aqueous extract of Tinospora cordifolia stems has garnered attention due to its reported pharmacological activities. This study aimed to investigate the in vitro biological properties of the aqueous extract and complement the findings with in silico studies to gain insights into potential molecular interactions. The Tinospora cordifolia stem aqueous extract was subjected to a battery of in vitro assays to assess its biological properties. Anti-inflammatory activity was evaluated using invitro assay. To complement the in vitro findings, in silico studies involving molecular docking analyses were conducted to predict potential interactions between the extract's constituents and relevant biomolecular targets. The in vitro evaluation revealed significant anti-inflammatory activity of the Tinospora cordifolia stem aqueous extract, as evidenced by its ability to suppress the production of proinflammatory cytokines. In silico studies provided insights into the molecular interactions between the extract's bioactive constituents and key inflammatory and antioxidant targets, further supporting the observed biological properties. The combined in vitro biological assays and in silico studies offer a comprehensive assessment of the Tinospora cordifolia stem aqueous extract's potential therapeutic properties. The demonstrated anti-inflammatory activities align with the traditional use of Tinospora cordifolia and suggest its potential in managing inflammatory and oxidative stress-related disorders. The in silico insights provide a molecular understanding of the extract's mode of action, strengthening the rationale for further investigation and development of natural products derived from Tinospora cordifolia for pharmaceutical and medicinal applications. [ABSTRACT FROM AUTHOR]

Background: Crataeva nurvala, a medicinal plant with potential therapeutic properties, offers a promising avenue for the development of novel anti-inflammatory drugs. This study adopted a combined in silico and in vitro approach to investigate the anti-inflammatory potential of compounds derived from Crataeva nurvala. Materials and Methods: In the in silico phase, virtual screening and molecular docking analyses were conducted to identify bioactive compounds from Crataeva nurvala that could interact with key inflammatory targets. Subsequently, selected compounds were synthesized and subjected to in vitro experimentation. Cellular models were employed to assess the anti-inflammatory effects of Crataeva nurvala-derived compounds, focusing on the modulation of pro-inflammatory cytokine levels and the underlying signaling pathways. Results: Virtual screening and molecular docking led to the identification of several bioactive compounds with favorable interactions with inflammatory targets. In the in vitro experiments, treatment with Crataeva nurvala-derived compounds resulted in a significant reduction in pro-inflammatory cytokine production. Moreover, the compounds exhibited the ability to modulate inflammatory signaling pathways, further substantiating their anti-inflammatory potential. Conclusions: This study not only contributes to the development of effective anti-inflammatory drugs but also underscores the value of harnessing natural sources such as Crataeva nurvala for therapeutic interventions in inflammatory disorders. The dual-phase strategy presented here provides a robust framework for anti-inflammatory drug discovery and validation. [ABSTRACT FROM AUTHOR]

Objectives: This study presents the antioxidant and anti-inflammatory activity of the ethanolic extract of Euphorbia hirta leaf extract. Materials and Methods: The antioxidant and anti-inflammatory activity of the extract was performed by in vitro assay. Our research employs a comprehensive approach combining experimental assays and computational simulations to assess the extract's potential bioactive components and their interactions with key biomolecules. Results: The study's results demonstrated a progressive rise in the percentage of inhibition, which was dependent on the dosage, in both antioxidant and anti-inflammatory activities. This trend was observed for both the extract and the standard, encompassing concentrations ranging from 100 to 500 µg/ml. Conclusion: The results showed that Euphorbia hirta's possesses antioxidant and anti-inflammatory activity, and this may contribute to a traditional medicinal. The discoveries of this study contribute to a deeper understanding of Euphorbia hirta's medicinal properties and its potential as a source of natural therapeutic agents. [ABSTRACT FROM AUTHOR]

Background: Nowadays, diabetes mellitus has become common worldwide due to changes in lifestyle, sedentary life, alterations in food habits, and other genetic and environmental factors. It is necessary to create awareness about the growing pandemic. Aim: To evaluate the antidiabetic potential of Evolvulus alsinoides. Methods: In vitro a-amylase inhibition and a-glucosidase inhibition activity. Molecular docking analysis. Results: The plant is rich in naturally occurring phytocompound. The results of the study showed that E. alsinoides has the potential to inhibit the activity of alpha-amylase and alpha-glucosidase. Moreover, this result was validated using in silico molecular docking studies that showed a good binding affinity of one of the major phytocompound, caffeic acid, with molecules in the insulin signaling cascade. Conclusion: E. alsinoides has a potent antidiabetic activity and can be further employed in animal and human studies. [ABSTRACT FROM AUTHOR]

Introduction: Stress and stress-related diseases have far-reaching consequences in both personal and professional life. Saliva analysis has become very appealing in comparison to other detection methods due to its non-invasive sampling. This study aimed to assess the Correlation between stress, discrimination and salivary stress biomarkers level among Transgender and Gender Non-Conforming (TGNC) population in chennai. Methodology: Snowball Non-Probability sampling technique was used to include the participants (control n=11, TGNC n=11), Unstimulated saliva was collected by Passive drool method and evaluated using competitive sandwich ELISA technique. Results: To find out the statistical significant difference we used Mann Whitney U test. There was a high statistical significance in 8-OHdG levels between control and TGNC. No statistical significant difference in (Total Antioxidant Capacity) TAC levels. Where, p>0.05. Spearman's correlation was used to correlate between the groups. Conclusion: In conclusion, the results of Correlation between stress, discrimination and salivary biomarker level of 8-OHdG showed statistical significant difference with p>0.05. The results of this study will be useful in guiding larger-scale studies to assess & to shape practical interventions to benefit TGNC. [ABSTRACT FROM AUTHOR]

Globally, millions of people suffer from poor wound healing, which is associated with higher mortality rates and higher healthcare costs. There are several factors that can complicate the healing process of wounds, including inadequate conditions for cell migration, proliferation, and angiogenesis, microbial infections, and prolonged inflammatory responses. Current therapeutic methods have not yet been able to resolve several primary problems; therefore, their effectiveness is limited. As a result of their remarkable properties, bio-based materials have been demonstrated to have a significant impact on wound healing in recent years. In the wound microenvironment, bio-based materials can stimulate numerous cellular and molecular processes that may enhance healing by inhibiting the growth of pathogens, preventing inflammation, and stimulating angiogenesis, potentially converting a non-healing environment to an appropriately healing one. The aim of this present review article is to provide an overview of the mechanisms underlying wound healing and its pathophysiology. The development of bio-based nanomaterials for chronic diabetic wounds as well as novel methodologies for stimulating wound healing mechanisms are also discussed. [ABSTRACT FROM AUTHOR]

Starch-based nanofibrous scaffolds exhibit a potential wound healing processes as they are cost-effective, flexible, and biocompatible. Recently, natural polymers have received greater importance in regenerative medicine, mainly in the process of healing wounds and burns due to their unique properties which also include safety, biocompatibility, and biodegradability. In this respect, starch is considered to be one of the reliable natural polymers to promote the process of wound healing at a significantly faster rate. Starch and starch-based electrospun nanofibrous scaffolds have been used for the wound healing process which includes the process of adhesion, proliferation, differentiation, and regeneration of cells. It also possesses significant activity to encapsulate and deliver biomaterials at a specific site which persuades the wound healing process at an increased rate. As the aforementioned scaffolds mimic the native extracellular matrix more closely, may help in the acceleration of wound closure, which in turn may lead to the promotion of tissue reorganization and remodeling. In-depth knowledge in understanding the properties of nanofibrous scaffolds paves a way to unfold novel methods and therapies, also to overcome challenges associated with wound healing. This review is intended to provide comprehensive information and recent advances in starch-based electrospun nanofibrous scaffolds for wound healing. [Display omitted] [ABSTRACT FROM AUTHOR]

• Mathan tailam (MT) and Mahamegarajanga tailam (MMRT) significantly enhanced wound healing in Wistar albino rats, achieving over 90% closure by day 12 compared to day 17 for controls. • Treated wounds showed improved re-epithelialization, collagen deposition, angiogenesis, fibroblast proliferation, and granulation tissue formation. • Immunohistochemistry indicated upregulated α-SMA, VEGF, and IL-10, reflecting active tissue repair. • MT and MMRT promoted healing through IL-10, VEGF, and TNF-α pathways, with increased mRNA expression of IL-10, TGF-β, and TNF-α. • The study underscores the potential of MT and MMRT as affordable and effective wound healing formulations. • Our findings warrant further clinical research to explore their applications in various wound types and skin conditions, potentially benefiting a wider patient population. 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. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a multifaceted neurodegenerative condition marked by gradual cognitive deterioration and the loss of neurons. While conventional bulk RNA sequencing techniques have shed light on AD pathology, they frequently obscure the cellular diversity within brain tissues. The advent of single-cell RNA sequencing (scRNA-seq) has transformed our capability to analyze the cellular composition of AD, allowing for the detection of unique cell populations, rare cell types, and gene expression alterations at an individual cell level. This review examines the use of scRNA-seq in AD research, focusing on its contributions to understanding cellular diversity, disease progression, and potential therapeutic targets. We discuss key technological innovations, data analysis techniques, and challenges associated with scRNA-seq in studying AD. Furthermore, we highlight recent studies that have utilized scRNA-seq to identify novel biomarkers, uncover disease-associated pathways, and elucidate the role of non-neuronal cells, such as microglia and astrocytes, in AD pathogenesis. By providing a comprehensive overview of advancements in scRNA-seq for unraveling cellular heterogeneity in AD, this review highlights the transformative impact of scRNA-seq on our comprehension of disease mechanisms and the creation of targeted treatments. [Display omitted] [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) stands as a formidable challenge in modern medicine, characterized by progressive neurodegeneration, cognitive decline, and memory impairment. Despite extensive research, effective therapeutic strategies remain elusive. The antioxidant, anti-inflammatory, and neuroprotective properties of curcumin, found in turmeric, have demonstrated promise. The poor bioavailability and rapid systemic clearance of this drug limit its clinical application. This comprehensive review explores the potential of curcumin-loaded polymeric nanomaterials as an innovative therapeutic avenue for AD. It delves into the preparation and characteristics of diverse polymeric nanomaterial platforms, including liposomes, micelles, dendrimers, and polymeric nanoparticles. Emphasis is placed on how these platforms enhance curcumin's bioavailability and enable targeted delivery to the brain, addressing critical challenges in AD treatment. Mechanistic insights reveal how these nanomaterials modulate key AD pathological processes, including amyloid-beta aggregation, tau phosphorylation, oxidative stress, and neuroinflammation. The review also highlighted the preclinical studies demonstrate reduced amyloid-beta plaques and neuroinflammation, alongside improved cognitive function, while clinical trials show promise in enhancing curcumin's bioavailability and efficacy in AD. Additionally, it addresses the challenges of clinical translation, such as regulatory issues, large-scale production, and long-term stability. By synthesizing recent advancements, this review underscores the potential of curcumin-loaded polymeric nanomaterials to offer a novel and effective therapeutic approach for AD, aiming to guide future research and development in this field. [Display omitted] • Curcumin-loaded nanomaterials improve bioavailability for Alzheimer's treatment. • Polymeric platforms enable targeted brain delivery of curcumin in AD therapy. • Nanomaterials modulate amyloid-beta aggregation and tau phosphorylation. • Review highlights preclinical and clinical efficacy of curcumin nanomaterials. • Challenges in clinical translation of curcumin-loaded nanomaterials are discussed. [ABSTRACT FROM AUTHOR]

• Septicemia exhibits a higher morbidity and mortality rate compared to infections caused by susceptible Pseudomonas aeruginosa (P. aeruginosa). In the case of ocular infections mediated by multidrug-resistant (MDR) P. aeruginosa, there is a potential for significant vision impairment or blindness. • This research utilized advanced genomics-based techniques to identify potential drug targets within P. aeruginosa , with a specific focus on the bacterial septal ring protein RlpA. • The target protein chosen was Rare Lipo Protein A (RlpA), and its crystal structure underwent geometric optimization using NCBI data collection, excluding human non-homologs, and applying other relevant criteria. • Virtual screening and docking techniques were applied, followed by contacting the manufacturer to acquire the shortlisted small molecules. The purchased compounds were then tested against drug-susceptible, MDR, and pan-drug-resistant P. aeruginosa using Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) tests. • Among the tested compounds, 3-Chlorophthalic acid displayed significant anti-Pseudomonas activity. Subsequent validation included assessing its toxicity levels through the MTT assay and confirming its specificity against the RlpA gene via reverse transcriptase-real-time PCR. The study demonstrated heightened anti-Pseudomonas activity coupled with reduced toxicity to host cells. • These findings hold promise for potential clinical studies, suggesting that 3-Chlorophthalic acid could provide a viable solution to combat infections caused by multidrug-resistant P. aeruginosa , addressing a critical challenge in healthcare. According to the World Health Organization, infectious diseases, particularly those caused by multidrug-resistant bacteria (MDR), are projected to claim the lives of 15 million people by 2050. Septicemia carries a higher morbidity and mortality rate than infections caused by susceptible Pseudomonas aeruginosa , and MDR-mediated ocular infections can lead to impaired vision and blindness. To identify and develop a potential drug against MDR P. aeruginosa , we employed in silico reverse genetics-based target mining, drug prioritization, and evaluation. Rare Lipoprotein A (RlpA) was selected as the target protein, and its crystal structure was geometrically optimized. Molecular docking and virtual screening analyses revealed that RlpA exhibits strong binding affinity with 11 compounds. Among these, 3-chlorophthalic acid was evaluated, and subsequent in vitro assays demonstrated significant anti- Pseudomonas activity with negligible cytotoxicity. The compound was further evaluated against both drug-susceptible and MDR P. aeruginosa strains in vitro , with cytotoxicity assessed using an MTT assay. The study demonstrated that 3-chlorophthalic acid exhibits potent anti- Pseudomonas activity with minimal toxicity to host cells. Consequently, this compound emerges as a promising candidate against MDR P. aeruginosa , warranting further investigation. [ABSTRACT FROM AUTHOR]

Background: Detecting cancer at an early stage before clinical manifestation could be an effective strategy to decrease cancer mortality. Thus, identifying liquid biopsy biomarkers with high efficacy could be a promising approach for non-invasive diagnosis of cancer. Main text: Liquid biopsies are increasingly used as a supplement to biopsy, as it enables disease progression to be detected months before clinical and radiographic confirmation. Many bodily fluids contain exosomal microRNAs (miRNAs) which could provide a new class of biomarkers for early and minimally invasive cancer diagnosis due to the stability of miRNAs in exosomes. In this review, we mainly focused on the exosomal miRNAs (liquid biopsy) as biomarkers in the diagnosis and prognosis of various cancers. Conclusion: Exosomal miRNAs can be used as diagnostic and prognosis biomarkers that provide unique insights and a more dynamic perspective of the progression and therapeutic responses in various malignancies. Therefore, the development of novel and more sensitive technologies that exploit exosomal miRNAs should be a priority for cancer management. [ABSTRACT FROM AUTHOR]

Aim: The study was aimed at assessing the effect of β-sitosterol on carbohydrate metabolic enzymes in high-fat diet and sucrose-induced type-2 diabetic rats. Experimental design: Adult male Wistar rats were used and divided into four groups: Group I: Control; Group II: Type-2 diabetic rats; Group III: Type-2 diabetic rats treated with β-sitosterol (20 mg/kg b.wt/day, orally for 30 days); and Group IV: Type-2 diabetic rats treated with metformin (50 mg/kg b.wt/day, orally for 30 days). After 30 days of treatment, animals were anesthetized; liver tissues were dissected out and used for the assessment of glucokinase, glucose-6-phosphatase, glycogen synthase, glycogen phosphorylase, and phosphoenolpyruvate carboxykinase (PEPCK) enzyme activities which were studied by spectrophotometric analysis. Results: The activity of glucose-6-phosphatase, glycogen phosphorylase, and PEPCK was significantly raised (P < 0.05) in type-2 diabetic rats. Conversely, glucokinase and glycogen synthase activities were significantly reduced (P < 0.05) in type-2 diabetic rats. Oral administration of the plant sterol (β-sitosterol) could effectively normalize the detrimental changes caused by high diet induction to that of the control and standard drug metformin. Conclusion: The present study shows that β-sitosterol regulates carbohydrate metabolic enzymes in the liver, thereby β-sitosterol may have therapeutic potential candidate for the management of type-2 diabetes. [ABSTRACT FROM AUTHOR]

Background: Changes in lifestyle, such as high-calorie diet intake and lack of exercise, have increased the global prevalence of obesity and diabetes. The major pathophysiological event contributing to the development of type 2 diabetes mellitus is the target tissues to insulin action. β-sitosterol (24-ethyl cholestene-3-ol), a naturally occurring plant sterol, ubiquitously found in many plants such as wheat germ, rice bran, flax seeds, peanuts, soybean, and pumpkin seeds. It has been reported to elicit multitude of bioactivities including antihyperlipidemic and antihyperglycemic activity. Aim: The study was aimed at assessing the effect of β-sitosterol on antioxidant enzymes in high-fat diet-induced type-2 diabetic rats. Experimental Design: Adult male Wistar rats were used and divided as Group I: Control; Group II: Type-2 diabetic rats; Group III: Type-2 diabetic rats treated with β-sitosterol (20 mg/kg body weight [b.wt]/day, orally for 30 days); and Group IV: Type-2 diabetic rats treated with metformin (50 mg/kg b.wt/day, orally for 30 days). After 30 days of treatment, animals were anesthetized; liver tissues were dissected out and used for the assessment of antioxidant enzymes (superoxide dismutase [SOD], catalase [CAT], glutathione peroxidase [GPx], glutathione-S-transferase [GST], and glutathione reductase [GR]). Results: SOD, CAT, GPx, GST, and GR enzyme activity was found to be significantly reduced (P < 0.05) in type-2 diabetic rats when compared with control animals. Oral administration of the plant sterol could effectively improve the activity of these enzymes (P < 0.05) to that of the control and standard drug metformin. Conclusion: The present study shows that β-sitosterol exhibits antidiabetic activity by facilitating antioxidant enzymes in the liver. [ABSTRACT FROM AUTHOR]

Aim: The present study was designed to evaluate the effect of chebulinic acid on Bcl-2 family protein and p53 expression in A431 human skin cancer cells in vitro. Cell Culture and Treatment: The skin cancer cell line, A431 was purchased from the National Centre for Cell Sciences, Pune, India, and cultured in Dulbecco’s Modified Eagle’s Medium supplemented with fetal bovine serum, penicillin G, and streptomycin. The cells were placed in 5% CO2 incubator and the further experiments were started after the confluency stage was attained. The cells were incubated at 37°C with the various doses of chebulinic acid (10, 25, 50, and 100 μg/ml) in a CO2 incubator to find out the inhibitory concentration of IC50. Results: A431 skin cancer cell line showed a significant increase in the levels of Bcl-2, p-Bcl2, and Bcl-xL whereas decreased in the levels of p53 at the doses of 50 and 100 μg. However, an effective dose of chebulinic acid (100 μg/ml) altered the levels bring back to the normalcy. Conclusion: The anticancer potential of the chebulinic acid is mediated through the controlling of apoptotic signaling molecules such as Bcl-2, Bcl-xL, and tumor suppressor proteins p53. Hence, this study concludes that chebulinic acid can be used as one of the potential therapeutic herbal drugs for the treatment of skin cancer. Further studies on the molecular mechanisms of the action of chebulinic acid are warranted to ascertain its potential. [ABSTRACT FROM AUTHOR]

Ovarian cancer is a frequent malignancy that affects a large percentage of women. Endometriosis is a chronic condition, where there is a production of benign lesions were observed in the uterine environment. PCOS is a metabolic disorder characterized by the presence of numerous cysts in the ovaries. The relation between ovarian malignancies and PCOS, by an increased ratio of ovarian stromal tissues in PCOS patients. The direct correlation is not yet confirmed among the three disorders, but it is often noted that they share risk factors, such as obesity, hormonal imbalances. Epigenetic factors have shown to be an important reason for cancer progression. Our findings at the epigenetic level includes a comparative analysis, point mutations in genes, overactivation of signaling pathways. This review paper, highlight the possible correlation between the three disorders in terms of genetic and epigenetic factors and how it could together trigger the cancer progression and metastasis. [Display omitted] • Epigenetic regulation of ovarian cancer, endometriosis and PCOS. • Biomarkers in ovarian and endometrial cancer. • Genetic mutations that cause ovarian cancer and endometrial cancer. • Potential risk factors for PCOS, endometrial cancer and ovarian cancer. • Role of non-coding RNA in PCOS, endometrial cancer and ovarian cancer. [ABSTRACT FROM AUTHOR]

Modern lifestyle, genetics, nutritional overload through high-fat diet attributed prevalence and diabetes outcomes with various complications primarily due to obesity in which energy-dense diets frequently affect metabolic health. One possible issue usually associated with elevated chronic fat intake is insulin resistance, and hyperglycemia constitutes an important function in altering the carbohydrates and lipids metabolism. Similarly, in assessing human susceptibility to weight gain and obesity, genetic variations play a central role, contributing to keen interest in identifying the possible role of epigenetics as a mediator of gene-environmental interactions influencing the production of type 2 diabetes mellitus and its related concerns. Epigenetic modifications associated with the acceptance of a sedentary lifestyle and environmental stress factors in response to energy intake and expenditure imbalances complement genetic alterations and lead to the production and advancement of metabolic disorders such as diabetes and obesity. Methylation of DNA, histone modifications, and increases in the expression of non-coding RNAs can result in reduced transcriptional activity of key β-cell genes thus creating insulin resistance. Epigenetics contribute to changes in the expression of the underlying insulin resistance and insufficiency gene networks, along with low-grade obesity-related inflammation, increased ROS generation, and DNA damage in multiorgans. This review focused on epigenetic mechanisms and metabolic regulations associated with high-fat diet (HFD)-induced diabetes mellitus. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) remains a major global health challenge, with its underlying molecular mechanisms, particularly the role of FOXM1, not yet fully understood. This study employed an integrated approach combining bioinformatics along with experimental validation to explore the role of FOXM1 in CRC. Using advanced computational tools and experimental techniques, we aimed to clarify the biological significance of FOXM1 and its potential impact on CRC progression and treatment. Bioinformatic analyses, including pan-cancer views, mRNA expression analysis, immune infiltrations, pathway enrichment, and functional annotations, highlighted the oncogenic potential of FOXM1 in CRC. Protein and gene expression analyses (western blot and qPCR) were conducted in HCT-116 and HT-29 cells. Platforms like GEPIA and UALCAN confirmed the diagnostic relevance of FOXM1, showing upregulated mRNA expression across various stages and metastasis. The influence of FOXM1 on immune cells, particularly CD4+, CD8+, and B cells, was significant, as revealed by immunohistochemistry. Protein-protein interaction analysis through STRING and CYTOSCAPE identified genes closely linked to FOXM1 in CRC. KEGG pathway enrichment suggested FOXM1's involvement in the p53 pathway, reinforcing its role in oncogenesis. Experimental validation confirmed elevated FOXM1 expression in HCT-116 and HT-29 cells. In summary, this study indicates that targeting FOXM1 could be a promising therapeutic strategy in CRC, emphasizing its importance in the molecular landscape of cancer progression., Competing Interests: Declaration of competing interest The authors state that they do not have any known competing financial interests or personal relationships that could have influenced the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

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., (© 2024. The Author(s), under exclusive licence to The Society of The Nippon Dental University.)

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., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Scientific Review Board, Saveetha Dental College and Hospitals issued approval SRB/SDC/UG-2105/24/OPATH/191. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Esakki et al.)

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., Competing Interests: Human subjects: All authors have confirmed that this study did not involve human participants or tissue. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, M et al.)

Introduction: Diabetes mellitus (DM) poses a significant global health challenge, with its prevalence steadily increasing. Natural compounds derived from plants have garnered attention for their potential therapeutic effects in managing this metabolic disorder. Camellia sinensis , commonly known as tea, is rich in bioactive compounds exhibiting various pharmacological properties. This study investigates the potential anti-diabetic activity of C. sinensis leaf extract through in vitro analysis., Materials and Methods: Camella sinensis  leaf extract was prepared by grinding the plant's leaf into a powder, mixing it with distilled water, and heating. The antidiabetic activity was assessed through α-Amylase and α-Glucosidase inhibitory assays, employing varying concentrations of the plant extract. Molecular docking analysis utilized Autodock 1.5.6 software (The Scripps Research Institute, California, US) to predict ligand-receptor interactions, guiding subsequent experimental validation., Result: Camella sinensis  leaf extract exhibited high phenolic content, suggesting potential in managing hyperglycemia. Tannins may aid glucose absorption and inhibit adipogenesis, making them promising for non-insulin-dependent DM (NIDDM). Terpenoids, with antioxidant activity, inhibit advanced glycation. Saponins and steroids were absent. Molecular docking revealed residues like IR, IRS1, and AS160 with significant impact on α-Amylase and α-Glucosidase, comparable to metformin., Conclusion: The findings of this study highlight the promising potential of C. sinensis leaf extract in managing hyperglycemia associated with DM. The high phenolic content aids in glucose regulation. Specifically, the presence of tannins suggests a potential role in modulating glucose absorption and inhibiting adipogenesis, which could be particularly beneficial for individuals with NIDDM. These findings provide valuable insights into the molecular mechanisms underlying the potential therapeutic efficacy of C. sinensis leaf extract against DM, paving the way for further research and development of novel therapeutic interventions in diabetes management., Competing Interests: Human subjects: All authors have confirmed that this study did not involve human participants or tissue. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, B et al.)

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-1β, 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., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

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., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

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 (GSK3β), wingless-related integration site 2 (Wnt2), and β-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 GSK3β 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 GSK3β, Wnt2, and β-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., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, R et al.)

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., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Zuvairiya et al.)

Background: Crataeva nurvala , a medicinal plant with potential therapeutic properties, offers a promising avenue for the development of novel anti-inflammatory drugs. This study adopted a combined in silico and in vitro approach to investigate the anti-inflammatory potential of compounds derived from Crataeva nurvala ., Materials and Methods: In the in silico phase, virtual screening and molecular docking analyses were conducted to identify bioactive compounds from Crataeva nurvala that could interact with key inflammatory targets. Subsequently, selected compounds were synthesized and subjected to in vitro experimentation. Cellular models were employed to assess the anti-inflammatory effects of Crataeva nurvala -derived compounds, focusing on the modulation of pro-inflammatory cytokine levels and the underlying signaling pathways., Results: Virtual screening and molecular docking led to the identification of several bioactive compounds with favorable interactions with inflammatory targets. In the in vitro experiments, treatment with Crataeva nurvala -derived compounds resulted in a significant reduction in pro-inflammatory cytokine production. Moreover, the compounds exhibited the ability to modulate inflammatory signaling pathways, further substantiating their anti-inflammatory potential., Conclusions: This study not only contributes to the development of effective anti-inflammatory drugs but also underscores the value of harnessing natural sources such as Crataeva nurvala for therapeutic interventions in inflammatory disorders. The dual-phase strategy presented here provides a robust framework for anti-inflammatory drug discovery and validation., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Pharmacy and Bioallied Sciences.)

Background: Spermacoce hispida , a medicinal plant from the Rubiaceae family, has garnered attention for its traditional use and reported therapeutic properties. This study aimed to investigate the phytochemical composition and assess the anti-inflammatory and anti-oxidant activities of the ethanolic extract derived from Spermacoce hispida ., Materials and Methods: Phytochemical screening of the ethanolic extract involved qualitative analysis to identify major phytoconstituents such as tannins, phenols, and acids. The anti-inflammatory activity was evaluated through in vitro assays, and anti-oxidant potential was assessed using established methods to measure scavenging activity against free radicals and reactive oxygen species., Results: Phytochemical screening revealed the presence of various bioactive constituents in the Spermacoce hispida ethanolic extract, including acid, tannin, protein, and phenolic compounds. Furthermore, the extract exhibited potent anti-oxidant activity, as evidenced by its ability to scavenge free radicals and attenuate ROS-induced oxidative stress., Conclusion: The findings of this study underscore the potential of Spermacoce hispida ethanolic extract as a source of bioactive compounds with anti-inflammatory and anti-oxidant properties. The presence of phytochemicals and the observed bioactivity support its traditional use and suggest potential therapeutic applications. These results contribute to the growing body of knowledge on natural products with health-promoting effects and provide a basis for further research aimed at developing pharmaceutical and medicinal interventions harnessing the benefits of Spermacoce hispida ., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Pharmacy and Bioallied Sciences.)

Tinospora cordifolia , commonly known as "Giloy" or "Guduchi," is a medicinal plant with a rich history in traditional medicine systems. The aqueous extract of Tinospora cordifolia stems has garnered attention due to its reported pharmacological activities. This study aimed to investigate the in vitro biological properties of the aqueous extract and complement the findings with in silico studies to gain insights into potential molecular interactions. The Tinospora cordifolia stem aqueous extract was subjected to a battery of in vitro assays to assess its biological properties. Anti-inflammatory activity was evaluated using invitro assay. To complement the in vitro findings, in silico studies involving molecular docking analyses were conducted to predict potential interactions between the extract's constituents and relevant biomolecular targets. The in vitro evaluation revealed significant anti-inflammatory activity of the Tinospora cordifolia stem aqueous extract, as evidenced by its ability to suppress the production of pro-inflammatory cytokines. In silico studies provided insights into the molecular interactions between the extract's bioactive constituents and key inflammatory and antioxidant targets, further supporting the observed biological properties. The combined in vitro biological assays and in silico studies offer a comprehensive assessment of the Tinospora cordifolia stem aqueous extract's potential therapeutic properties. The demonstrated anti-inflammatory activities align with the traditional use of Tinospora cordifolia and suggest its potential in managing inflammatory and oxidative stress-related disorders. The in silico insights provide a molecular understanding of the extract's mode of action, strengthening the rationale for further investigation and development of natural products derived from Tinospora cordifolia for pharmaceutical and medicinal applications., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Pharmacy and Bioallied Sciences.)

Background: Nowadays, diabetes mellitus has become common worldwide due to changes in lifestyle, sedentary life, alterations in food habits, and other genetic and environmental factors. It is necessary to create awareness about the growing pandemic., Aim: To evaluate the antidiabetic potential of Evolvulus alsinoides ., Methods: In vitro α-amylase inhibition and α-glucosidase inhibition activity. Molecular docking analysis., Results: The plant is rich in naturally occurring phytocompound. The results of the study showed that E. alsinoides has the potential to inhibit the activity of alpha-amylase and alpha-glucosidase. Moreover, this result was validated using in silico molecular docking studies that showed a good binding affinity of one of the major phytocompound, caffeic acid, with molecules in the insulin signaling cascade., Conclusion: E. alsinoides has a potent antidiabetic activity and can be further employed in animal and human studies., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Pharmacy and Bioallied Sciences.)

Diabetes mellitus is a persistent metabolic condition marked by elevated blood glucose levels due to compromised insulin secretion or functionality. The search for natural antidiabetic agents has gained attention due to their potential effectiveness and safety profiles. Sessuvium portulacastrum , a coastal plant, has been traditionally used for various medicinal purposes. This study investigates the antidiabetic potential of Sessuvium portulacastrum aqueous extract by analyzing its inhibitory effects on key enzymes involved in carbohydrate metabolism and exploring its molecular interactions with critical target proteins. The aqueous extract of Sessuvium portulacastrum was prepared and used for in vitro analysis. The reduced activity of the extract against α-amylase and α-glucosidase enzymes, crucial in glucose absorption and postprandial hyperglycemia, was assessed. Molecular docking techniques were employed to explore the potential interactions between active compounds in the extract and diabetes-related proteins, including BAX, GSK3β, and CADH. The study revealed significant inhibition of both alpha-amylase and alpha-glucosidase enzymes by Sessuvium portulacastrum aqueous extract, indicating its potential to reduce glucose absorption and postprandial hyperglycemia. Moreover, the molecular docking analysis demonstrated strong binding interactions between active compounds in the extract and key proteins involved in diabetes-related pathways, namely apoptotic pathways, glycogen synthesis, and cell adhesion. The findings of this study highlight the promising antidiabetic potential of Sessuvium portulacastrum aqueous extract. Upcoming research should get an attention on isolating and characterizing the active compounds responsible for these effects on antidiabetic therapies from natural sources., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Pharmacy and Bioallied Sciences.)

Objectives: This study presents the antioxidant and anti-inflammatory activity of the ethanolic extract of Euphorbia hirta leaf extract., Materials and Methods: The antioxidant and anti-inflammatory activity of the extract was performed by in vitro assay. Our research employs a comprehensive approach combining experimental assays and computational simulations to assess the extract's potential bioactive components and their interactions with key biomolecules., Results: The study's results demonstrated a progressive rise in the percentage of inhibition, which was dependent on the dosage, in both antioxidant and anti-inflammatory activities. This trend was observed for both the extract and the standard, encompassing concentrations ranging from 100 to 500 μg/ml., Conclusion: The results showed that Euphorbia hirta 's possesses antioxidant and anti-inflammatory activity, and this may contribute to a traditional medicinal. The discoveries of this study contribute to a deeper understanding of Euphorbia hirta 's medicinal properties and its potential as a source of natural therapeutic agents., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Pharmacy and Bioallied Sciences.)

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., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Pharmacy and Bioallied Sciences.)

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., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2024 The Author(s). Published with license by Taylor & Francis Group, LLC.)

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., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Benedict et al.)