
Background: Hemoglobinopathies are among the most common inherited monogenic disorders worldwide, with significant prevalence in India, particularly in tribal and rural populations. Gujarat reports a high burden of both β-thalassemia and sickle cell disorders. Aim: To evaluate the spectrum and clinico-hematological profile of hemoglobinopathies in a tertiary care hospital. Methods: A retrospective and prospective descriptive study was conducted over four years (Jan 2021 to Dec 2024) at a tertiary hospital in Gujarat. A total of 100 confirmed cases of hemoglobinopathies were analyzed. Complete blood count and peripheral smear were performed in a NABL accredited laboratory, and data were analyzed. Results: The most common hemoglobinopathy was β-thalassemia trait (44), followed by sickle cell disorders (27) and sickle cell trait (24). Rare variants included HbES (1) and HbD-Punjab trait (1 ). Two cases of homozygous β-thalassemia were identified in children under 10 years. Clinical features included pallor, fever, and jaundice, particularly in sickle disorders and thalassemia major. Most cases belonged to OBC, SC, and ST communities. Conclusion: Hemoglobinopathies remain a significant public health challenge in Gujarat, with β-thalassemia trait being the most prevalent. Hemoglobin electrophoresis is a cost-effective screening tool that should be integrated into antenatal, premarital, and adolescent health programs. Genetic counselling and molecular follow-up are essential for long-term disease reduction.
Carbonate apatite (CO₃Ap) has evolved as a promising alloplastic bone graft material in periodontal and implant therapies due to its superior biological properties. Unlike hydroxyapatite (HA) and β-tricalcium phosphate (β-TCP), CO₃Ap mimics the mineral composition of natural bone, with carbonate substitution improving its resorption by osteoclasts and promoting bone turnover. Fabricated via a dissolutionprecipitation reaction using calcium carbonate (CaCO₃) precursors, CO₃Ap maintains structural integrity while avoiding thermal decomposition that occurs with other manufacturing processes. The low crystallinity, high specific surface area, and dense microstructure contribute to the enhanced osteoblast differentiation and bone matrix formation. Histological studies have demonstrated CO₃Aps superior bone regeneration capacity compared to HA and β-TCP, with faster healing and greater bone volume observed in animal models. Its honeycomb architecture further supports osteoconductivity by facilitating cellular activity and nutrient flow. CO₃Aps versatility extends to applications in ridge augmentation, sinus lifts, and guided tissue regeneration. Coating titanium implants with CO₃Ap improves osseointegration and mechanical stability, while its mesoporous microspheres offer potential as drug carriers for antibiotics and bioactive molecules. Despite its advantages, CO₃Ap faces limitations such as brittleness and high solubility. Future research aims to optimize its physicochemical properties and develop cost-effective fabrication methods. Composite materials incorporating CO₃Ap with polymers, collagen, or platelet concentrates may further enhance its clinical utility. Overall, CO₃Ap represents a significant advancement in bone grafting materials, with potential for widespread application in regenerative dentistry and tissue engineering.
Introduction Aim: Systemic inflammation is implicated in Parkinson's disease (PD) pathogenesis, but evidence regarding peripheral cytokine levels remains inconsistent. This meta-analysis aimed to summarize the available data on peripheral blood cytokine concentrations in PD patients compared to healthy controls (HCs), and investigate key moderator variables that may affect cytokine concentrations. Materials Methods: A systematic literature search was conducted across multiple electronic databases from August 06 to August 26, 2025. Eligible studies reporting peripheral blood cytokine levels in PD patients and a matched HC group, were included. Data from 100 studies, comprising 7,369 PD patients and 10,978 HCs, were extracted, and the meta-analysis was performed using a random-effects model, with effect sizes expressed as standardized mean differences (Hedges' g). Results: Concentrations of interleukin-6, tumour necrosis factor, interleukin-1 beta, and C-reactive protein were elevated in PD patients relative to HCs. In contrast, no significant differences were observed for interleukin-2, interleukin-4, interleukin-8, and interleukin-10. Subgroup analyses revealed that the analytical methodology, sample source (serum, plasma, or cerebrospinal fluid), and geographic origin of the study population significantly influenced effect sizes, whereas patient age, motor severity (UPDRS-III), and disease stage (Hoehn Yahr) did not demonstrate a significant moderating effect. Conclusion: This meta-analysis confirms a distinct peripheral inflammatory profile in PD, characterized by elevated levels of specific pro-inflammatory cytokines. The findings underscore the potential role of systemic inflammation in PD pathophysiology and highlight methodological and demographic variables as key sources of heterogeneity in the literature, which must be considered in future biomarker studies.
Background: The International Association for the Study of Pain (IASP) defines pain as an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage. The primary goal of analgesia is to eliminate the cause of pain but this is not always possible so analgesics are used to treat pain symptomatically. This study aims to scientifically validate the anti-nociceptive activity of stem of Rubia cordifolia using rodent models. Materials and methods: Ethanolic extract of Rubia cordifolia (EERC) stem was used for evaluating the anti-nociceptive activity in Wistar albino rats. Ethanolic extract of Rubia cordifolia stem was used at a dose of 100 and 200 mgkg. Distilled water 10 mlkg was used as vehicle control. Anti-nociceptive activity was evaluated by performing hot water tail immersion test and Eddys hot plate method comparing with Diclofenac (10mgkg) as the standard drug. The data was analyzed using one way ANOVA (analysis of variance) followed by Tukey Krammer test. P value Results: Ethanolic extract of Rubia cordifolia stem at a dose of 200mgkg showed a significant analgesic efficacy in hot water tail immersion test and Eddys hot plate method. Additionally, the results were closely comparable to the standard drug diclofenac. Conclusion: Ethanolic extract of Rubia cordifolia stem shows promising anti-nociceptive activity in Wistar albino rats, suggesting that it could be a valuable natural alternative for pain relief but further studies are necessary to confirm its safety and effectiveness in broader clinical settings.
Recent advancements in nanotechnology have revolutionized biomedical research, offering innovative solutions for disease management. The synthesis of silver nanoparticles (AgNPs) using phyto-extracts has gotten significant attention due to its environmentally benign and economical approach. Momordica cymbalaria, a well-known therapeutic properties containing plant, was utilized for the biosynthesis of AgNPs. Extensive phytochemical analyses, including qualitative and quantitative assessments, were conducted to determine the presence of bioactive constituents facilitating nanoparticle synthesis. A range of micro spectroscopic methods were utilized to characterize the MCAgNPs. Furthermore, their potential anti-inflammatory and anti-oxidant properties were evaluated through in vitro assays. The results suggest that Momordica cymbalaria mediated AgNPs exhibit promising biological activity, making them potential candidates for therapeutic applications in inflammation-related diseases.
Introduction and Aim: Diabetes mellitus requires lifelong pharmacotherapy, yet drug utilization studies rarely capture how patients experience and manage prescribed medicines in daily life. This study aimed to examine drug utilization practices in outpatient diabetes care by integrating drug utilization data with patient perspectives. Materials and Methods: This study was conducted in a tertiary care teaching hospital in India using a sequential explanatory mixed-methods design, which consisted of a quantitative drug utilization study in the first phase followed by qualitative in-depth interviews in the second phase. Drug utilization data from 100 adults with type 2 diabetes mellitus were analyzed descriptively. Inferential associations were examined using chi-square tests. Findings informed purposive sampling for in-depth interviews with 25 patients to explain and expand quantitative findings. Qualitative data were analyzed thematically, and integration occurred at interpretation. Institutional ethics committee approval was obtained, and informed consent was secured from all participants. Results and Conclusion: Oral hypoglycemic agents (OHAs) alone were prescribed to 68 (n68) of patients, while 32 (n32) received OHAs with insulin. Polypharmacy (3 agents) was observed in 46 (n46). Insulin use was significantly associated with longer duration of diabetes (p0.002). Interviews revealed structured routines related to long-term medicine use, organizational strategies for multiple medications, layered self-care practices. Drug utilization in diabetes care reflects both prescribing patterns and patient adaptation. Integrating patient perspectives with drug utilization data provides a more comprehensive understanding of real-world medicine use.
Vitamin D which is mainly designated as hormone, play numerous significant roles in our human body. They not only fall under bone health but other body systems which strongly get affected due to vitamin D deficiency. Especially In todays society due to faulty life style and improper food habit vitamin deficiencies are seen to manifest various chronic health disorders which are interplayed by their association with other endocrine factors specially hormones. The current review work shows the less elaborated relationship between Vitamin D and cortisol a highly relevant adrenal corticosteroid involved in stress response. This review work highlights the positive and negative correlation between these 2 hormones which may influence both mental and physical health of individual. Many studies have indicated that there may be an imperceptible possibility that these two bio molecules may possess some sort of inter-dependent association. Significant information obtained from this review focuses on generating awareness regarding the impact of vitamin D and Cortisol on combating serious health issues from their early inception
Background: Breast carcinoma remains a serious global health concern, with over 2.3 million women diagnosed annually and significant mortality rates persisting despite improvements in screening and treatment protocols. Aim: This is an observational, case control, hospital-based study which was carried out to find the role of inflammatory markers in patients with breast carcinoma and their correlation with tumour markers. Metrials Methods: The study population consists of (3) three distinct study groups, Group A: patients diagnosed with breast carcinoma (n70), Group B: healthy controls (n70) and Group C: patients with benign breast disease (n70). Patients suffering from any tumor of breast identified for the first time were included in this study population. Recurrent cases were excluded from the study. Serum level of CRP and IL-6 were measured as inflammatory marker whereas CEA and CA 15 - 3 were measured as tumour markers in this study population. Results: There was significant elevation of inflammatory markers in patients with breast carcinoma when compared to healthy control. The inflammatory markers were found to be positively correlated with patients with breast carcinoma but this correlation was not significant. Conclution: Early detection of elevated inflammatory markers could serve as a predictive tool for breast cancer prognosis. Integrating CRP and IL-6 screening in routine diagnostics may help identify high-risk patients earlier.
Background: Cardiac autonomic neuropathy (CAN) is a clinically significant yet frequently underrecognized complication of type 2 diabetes mellitus (T2DM). Heart rate variability (HRV) analysis provides a non-invasive method for evaluating cardiac autonomic function. This study aimed to assess time-domain HRV parameters in asymptomatic patients with T2DM compared to healthy controls. Methods: In this hospital-based case-control study, 50 patients with T2DM and 50 age-matched healthy controls (4060 years) were enrolled following institutional ethics approval. Short-term (5-minute) ECG recordings were obtained under standardized conditions. Time-domain HRV indices - mean RR interval, heart rate, SDNN, RMSSD, pNN50, RRΔ index, and TINN were analyzed. Group comparisons were performed using independent samples t-test. Effect sizes (Cohens d) and 95 confidence intervals (CIs) were calculated, and Bonferroni correction was applied for multiple comparisons. Results: Compared with controls, patients with T2DM exhibited significantly reduced SDNN (mean difference 6.60 ms; 95 CI: 10.4 to 2.8), RMSSD (10.39 ms; 95 CI: 15.6 to 5.1), pNN50 (4.69; 95 CI: 5.6 to 3.7), and TINN (155.1 ms; 95 CI: 210.4 to 99.8) (adjusted p Conclusion: Time-domain HRV parameters were significantly reduced in asymptomatic individuals with T2DM, suggesting early subclinical cardiac autonomic dysfunction. Short-term HRV assessment may serve as a practical screening tool for early detection of CAN.
Background: Bai-Zhu (Atractylodes macrocephala Koidz. [Asteraceae]) is classified in traditional Chinese medicine (TCM) as an herb that targets the gastric and pancreatic meridians to support normal nutrient uptake. As such, Bai-Zhu is commonly included in herbal formulations for treating gastrointestinal dysfunction and alleviating pain and swelling. Formulae containing Bai-Zhu are also frequently used as complementary or alternative therapies to mitigate the side effects of tumor treatments. However, their direct effects on cancer cells remain inadequately understood in modern biomedical science. This study aims to characterize the impact of Bai-Zhu-containing formulae on breast cancer cells using contemporary molecular and cellular biology approaches. Methods: A tetrazolium-based semiautomated colorimetric (MTT) assay was used to assess cell viability. Western blotting was performed to evaluate protein expression. Quantitative RT-PCR was employed to measure the relative expression levels of selected genes. A Matrigel invasion assay was used to assess the invasive capacity of cancer cells. Results: Water extracts of Bai-Zhu or formulae containing Bai-Zhu increased the expression of metastasis-related proteins Zeb1 and Slug in breast cancer cells. Moreover, these formulae further enhanced Zeb1 and Slug expression when combined with the chemotherapeutic drug doxorubicin. Matrigel invasion assays confirmed that these treatments promoted the invasive activity of breast cancer cells. Conclusions: The use of Bai-Zhu-containing formulae should be carefully evaluated, particularly in cancer patients who use them as complementary or alternative treatments, due to their potential to promote tumor metastasis.
Background: The prevalence of myopia is increasing worldwide and is projected to affect nearly half of the global population by 2050. Although genetic susceptibility plays an important role, early-life environmental exposures are increasingly recognized as modifiable contributors to myopia development. Antibiotics are frequently prescribed during infancy and early childhood and can alter gut microbiota composition, which has been implicated in ocular disorders. Methods: We conducted a retrospective cohort study using data from a national health insurance database. Children aged three years or younger who received systemic antibiotics were included, while those with pre-existing myopia or retinopathy were excluded. Antibiotic-exposed children were matched with non-exposed controls by age, sex, and relevant comorbidities. Cox proportional hazards regression models were used to estimate adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for incident myopia. Results: Early-life antibiotic exposure was associated with a significantly increased risk of myopia compared with non-exposed controls (aHR = 1.03; 95% CI: 1.02-1.04), accompanied by a higher cumulative incidence of myopia (log-rank test, p < 0.001). The elevated risk was observed in both females (incidence rate [IR] = 66.98 vs. 64.10; aHR =1.05; 95% CI: 1.04-1.07) and males (IR = 61.53 vs. 59.66; aHR = 1.04; 95% CI: 1.02-1.05). Urbanization level, parental monthly income, and comorbidities were independently associated with antibiotic exposure. The increased risk of myopia persisted irrespective of antibiotic treatment duration (<11 days; aHR = 1.19; 95% CI: 1.15-1.23) or cumulative dose (defined daily dose <2833; aHR = 1.31; 95% CI: 1.28-1.33). Conclusions: Early-life exposure to antibiotics is associated with a higher incidence of myopia in children. These findings underscore the importance of cautious and judicious antibiotics prescribing during early childhood to mitigate potential long-term ocular health risks.
Background:Emodin exhibits various pharmacological activities, including hepatoprotective effects. However, its clinical application is limited by poor absorption and low oral bioavailability. This study aimed to optimize emodin through benzoylation and to assess the hepatoprotective potential of the resulting derivatives integrating bioinformatics and in vitro methods. Methods:We conducted network pharmacology, molecular docking and molecular dynamics (MD) simulations to predict potential targets and interactions of benzoylated emodin derivatives. The derivatives were synthesized and evaluated for cytotoxicity using the MTT assay. The hepatoprotective effects were assessed in vitro using a paracetamol-induced HepG2 cell injury model. Results:Network pharmacology analysis and gene expression profiling identified four major targets-HSP90AA1, MAPK14, RELA, and PRKACA-as key liver disease-related targets of emodin and its derivatives. Molecular docking study revealed that the benzoylated emodin derivatives exhibited generally lower (more negative) binding energies compared to emodin across all four targets. MD simulations confirmed that the complex RELA with these derivatives is more stable than with emodin. These findings were consistent with in vitro assays, emodin and its derivatives increased cell viability or protected the cells up to 60-70%. Conclusion:This study provides a comprehensive evaluation of benzoylated emodin derivatives as potential hepatoprotective agents. The findings suggest that these derivatives exhibit binding affinity toward important targets related to cirrhosis, reduced toxicity to cells, and enhanced the efficacy in protecting the liver in vitro liver injury model.
Introduction: Genetic polymorphisms in DNA repair pathways can modulate DNA repair capacity and influence susceptibility to aging-related disorders, including Parkinson's disease (PD). This study evaluated the association between the DNA ligase I rs20579 polymorphism and PD risk. Materials and methods: Genotyping of DNA ligase I rs20579 was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 123 PD patients and 492 age-and sex-matched controls of Taiwanese Han ethnicity. Associations between rs20579 genotypes and PD risk were analyzed. Results: Among controls, the genotype distribution of rs20579 was 78.7 % GG, 19.3 % AG, and 2.0 % AA, compared with 75.6 %, 21.1 %, and 3.3 % among PD cases, respectively (p for trend = 0.6290). No significant differences were observed in the prevalence of AG (p = 0.6939) or AA (p = 0.4908) genotypes between cases and controls. Allelic analysis showed a non-significant increase in PD risk for A allele carriers (OR = 1.21, 95 % CI = 0.80-1.83, p = 0.4189). Stratified analysis revealed no significant genotype differences among males. In females, the AA genotype was associated with a borderline increased risk of PD (OR = 1.86, 95 % CI = 1.00-3.47, p = 0.0526). Conclusion: In this Taiwanese Han cohort, the DNA ligase I rs20579 A allele may be a genetic marker of increased PD susceptibility in females. Further studies in larger, independent populations are warranted to confirm its clinical relevance.
Background: Due to unique dietary culture, Asian patients with endometriosis usually seek assistance through traditional Chinese herbal medicine (TCHM), making combined treatments of Western and Chinese medicine quite common in Asia. However, limited molecular evidence has been provided to demonstrate the therapeutic benefits of TCHM in treating endometriosis. Aims: To investigate the functional impacts of TCHM treatment in their traditional formulae on peritoneal immunity, lesion growth, and adhesion formation, we performed studies by using a disease mouse model that exhibits the features of blood stasis and stagnation. Methods: Four well-known TCHM formulae, frequently used for treating symptoms similar to endometriosis, were applied to a mouse model with human endometriosis features. Lesion growth, modulation of peritoneal immune responses, pain-associated behaviors, and endometriosis adhesion were analyzed after TCHM treatment. Results: Among the formulae, Danggui Buxue Tang (DBT) and Shaofu Zhuyu Tang (SZT) can promote blood circulation into the peritoneal cavity, resulting in increased large (LpMs) and small (SpMs) peritoneal macrophages with M1 phenotype polarization. Macrophage activation restrained lesion formation, chronic inflammation, and nerve fiber growth in the treated mice. Behavioral studies further confirmed pain-relief effects that enhanced spontaneous loco-motor activity and reduced evoked mechanical hyperalgesia. Interestingly, DBT and SZT treatments can also down-regulate the expression of key adhesion molecules, such as ICAM-1 and AKAP12, in the lesions, leading to reduced endometriosis adhesion in treated mice. Conclusion: These findings reveal the functional effects of TCHM formulae, especially DBT and SZT, on macrophage-mediated immune responses in the peritoneal cavity, which may benefit patients with endometriosis.
Introduction: Clozapine remains the gold-standard antipsychotic for treatment-resistant schizophrenia, but its use is hindered by rare but serious adverse effects, such as hematologic abnormalities and myocarditis. Purpose: This study investigated the adverse impacts of clozapine on blood markers and electrocardiographic (ECG) findings among patients with schizophrenia, emphasizing in early detection of life-threatening complications. Methods: All patients initiated on clozapine at a psychiatric hospital in Athens, Greece, between January 2022 and June 2024 were considered for inclusion. Thirty-one patients with complete clinical and laboratory data were monitored for hematological, biochemical, and ECG changes at baseline, days 5-10, and after 1-2 months. Parameters evaluated included white blood cell (WBC) counts, differential counts, C-reactive protein (CRP), hepatic enzymes, creatine phosphokinase (CPK), troponin, and ECG changes. Results: Of the 31 patients, two (6.5%) developed clozapine-induced myocarditis within the first three weeks, confirmed by clinical symptoms, ECG abnormalities, and elevated troponin levels, necessitating immediate clozapine discontinuation. Four patients exhibited prolonged QTc, two overlapping with myocarditis cases. Eleven experienced elevated CRP, while eosinophilia and transient hepatic or muscular enzyme elevations were also common, especially during rapid titration phases; indicating inflammatory responses or mild organ involvement. No cases of agranulocytosis or severe eosinophilic complications occurred. Conclusions: Clozapine can induce significant hematologic, inflammatory, hepatic, muscular, and cardiac adverse effects, particularly during rapid titration. Systematic monitoring of blood markers and ECGs was vital in early detection and management of these complications, especially myocarditis. The findings underscore the importance of cautious titration protocols and tailored surveillance strategies to enhance clozapine safety in clinical practice.
Background: Triple-negative breast cancer (TNBC) is an aggressive subtype with limited treatment options and poor prognosis. Understanding the underlying molecular mechanisms, particularly immune-related gene networks, is critical for identifying novel therapeutic targets. Aim: This study aimed to identify immune-related hub genes involved in TNBC progression by integrating micro-array and RNA sequencing data. Methods: We integrated microarray and RNA sequencing datasets from five Gene Expression Omnibus (GEO) studies (GSE36295, GSE37751, GSE61724, GSE38959, and GSE58135) to identify differentially expressed genes (DEGs). Protein-protein interaction (PPI) networks were constructed using the STRING database. Key modules and hub genes were identified through network analysis. Functional enrichment was performed to elucidate biological pathways, while immune infiltration analysis assessed associations with the tumor microenvironment. Drug-gene interaction databases were queried for FDA-approved compounds targeting hub genes. Results: The PPI network revealed 179 nodes and 781 edges, indicating high connectivity. Module analysis highlighted a significant cluster with the identified key genes such as CDK1, BUB1B, CCNA2, BUB1, CCNB1, KIF20A, CENPF, TOP2A, KIF11 and MELK validated at both mRNA and protein levels. Functional enrichment revealed pathways related to cell cycle control, chromosome segregation, and kinase activity. Immune infiltration analysis indicated involvement of B cells, macrophages, and neutrophils in the TNBC microenvironment. Drug-gene mapping revealed a lack of FDA-approved drugs targeting certain key hub genes. Conclusion: This integrative study identified key immune-related hub genes driving TNBC progression, with KIF20A emerging as a promising yet underexplored target. Drug repurposing strategies focusing on KIF20A and other identified hub genes may accelerate the development of effective treatments, offering valuable insights for future therapeutic and prognostic evaluations in TNBC.
Background:Telomere length (TL) is a biomarker of biological aging and a predictor of age-related diseases. Dietary patterns, including dairy consumption, may influence telomere dynamics, but the evidence remains limited, particularly in Asian populations. This study investigates the association between dairy consumption and relative telomere length (RTL) in Taiwanese adults, with results analyzed by hypertension status. Methods:A cross-sectional survey was conducted among 259 adults in Taipei, Taiwan. RTL was measured using quantitative PCR from buccal cells. Dietary intake was assessed through self-reported questionnaires, with a focus on dairy frequency and fat content. Multiple linear regression models were used to examine the association between dairy intake and TL, adjusting for demographic and lifestyle factors. Results:Among normotensive individuals, higher frequency of dairy consumption was significantly associated with shorter RTL (β = -0.082, p < 0.01), particularly with low-fat and fat-free dairy products (β = -0.106, p < 0.01). No significant associations were observed in the hypertensive group. Conclusion:Dairy intake, particularly of low-fat products, may contribute to telomere shortening in normotensive adults. This association was not evident in hypertensive individuals, possibly due to a ceiling effect of chronic inflammation. These findings highlight the need for individualized nutritional guidance in public health strategies targeting healthy aging.
Background: Integrating artificial intelligence-based large language models (AI-LLMs) into medical and other scientific domains is increasingly recognized as a tool to support complex tasks, such as interpreting histopathology slides and scientific figures. AI-LLMs can simplify these processes by providing clearer explanations. By improving accessibility and comprehension, AI-LLMs can significantly assist healthcare professionals in diagnosing and therapy determination. Students and the public also find it easier to understand complex scientific concepts and images. Objectives: This study explores the capability of AI-LLMs in interpreting histopathological slides and scientific images. This study aims to evaluate the performance of AI-LLMs in supporting diagnostics and improving comprehension in biomolecular sciences. Methods: The study was divided into two parts: interpreting histopathology slides and scientific figures. Twelve histopathology images and twelve scientific figures were tested on each of the three most frequently used chatbots (ChatGPT-4, Gemini Advanced, and Copilot). Responses from the chatbots were coded and blindly examined by expert raters using five parameters-relevance, clarity, depth, focus, and coherence-on a 5-point Likert scale. Statistical analysis included one-way ANOVA and multiple linear regression. Results: ChatGPT-4 outperformed Gemini Advanced and Copilot in histopathology and scientific image interpretation (P < 0.001) with significantly higher scores across all parameters (relevance, clarity, depth, focus, and coherence). ChatGPT-4's superior performance may be due to its advanced algorithms, extensive training data, specialized modules, and user feedback. Conclusions: ChatGPT-4 excels in interpreting histopathology and scientific images, which may lead to improving diagnostic accuracy, clinical decision-making, and reducing pathologists' workload. It also benefits education by enhancing students' understanding of complex images and promoting interactive learning. ChatGPT-4 shows a significant potential to improve patient care and enrich student learning
Background:Over recent decades, considerable attention has been directed toward the discovery of novel compounds capable of targeting survival-related signaling networks as therapeutic candidates for triple-negative breast cancer (TNBC). Central to TNBC pathobiology are the Akt/mTOR and MAPK/ERK signaling axes, both contribute to tumor progression and therapeutic resistance. Caffeic acid (CA), a naturally derived phenolic compound with anti-inflammatory activity, has previously been investigated for its anti-cancer potential. Purpose:In the present study, we explored the therapeutic value of newly synthesized CA derivatives in TNBC models using both cellular and animal based systems. Methods:The anti-tumor efficacy of these CA derivatives was examined through a series of functional assays, including cell proliferation, clonogenicity, cell cycle profiling, apoptosis quantification, ELISA, western blotting, and histopathological analysis. Results:Among the tested derivatives, decyl caffeate (DC) demonstrated the most pronounced inhibitory effects on TNBC cell growth, significantly decreasing viability, colony formation, and enhancing cisplatin responsiveness (P < 0.05). DC induced G2/M phase arrest in MDA-MB-468 cells, accompanied by suppression of cyclin B1 and CDK1 expression. In addition, DC downregulated both total and phosphorylated c-Myc and reduced secretion of TGF-α, a key ligand for EGFR. Apoptotic responses were evident through upregulation of Bax, cleaved caspase3, and cleaved-PARP. Mechanistic analysis revealed that these effects were mediated via concurrent inactivation of the Akt/mTOR and MAPK/ERK signaling pathways. Oral administration of DC in a murine TNBC xenograft model significantly suppressed tumor growth in vivo. Conclusion:Altogether, these results highlight DC as a promising bioactive compound that targets essential oncogenic pathways in TNBC and support its potential for further preclinical development.