Tenofovir alafenamide (TAF) has demonstrated comparable efficacy to tenofovir disoproxil fumarate (TDF), with improved renal and bone safety, in Chinese participants with chronic hepatitis B enrolled in two Phase 3 trials. This study aimed to evaluate the long-term virologic efficacy, serological and biochemical responses, resistance, and renal and bone safety of TAF over eight years in this population.

Participants completing the three-year double-blind phase were eligible to receive open-label TAF 25 mg/day for up to an additional five years (totaling eight years). Analyses of viral suppression (HBV DNA < 29 IU/mL), alanine aminotransferase normalization, serological responses, resistance surveillance, and safety outcomes were conducted.

Among 334 enrolled participants, 212 of 227 participants randomized to TAF continued open-label TAF (TAF-TAF), and 99 of 107 participants on TDF switched to open-label TAF (TDF-TAF). At Year 8, 79.3% (180/227) and 78.5% (84/107) of participants in the TAF-TAF and TDF-TAF groups, respectively, achieved viral suppression (missing = failure); rates increased to 95.2% (180/189) and 95.5% (84/88) when excluding missing data. Alanine aminotransferase normalization rates remained high and comparable between groups. Serologic response rates continued to increase over time, with higher rates observed in the TAF-TAF group. Estimated glomerular filtration rate (by Cockcroft-Gault) and hip/spine bone mineral density remained stable in the TAF-TAF group through eight years; the small declines in these renal and bone parameters observed during double-blind TDF treatment improved after switching to open-label TAF. No resistance to TAF was detected.

Long-term TAF treatment demonstrated durable virologic efficacy, sustained biochemical and serological responses, and favorable renal and bone safety over eight years in Chinese participants with chronic hepatitis B.

Breast cancer (BCA) is one of the most common cancers worldwide, with a high rate of incidence and mortality. This review provides global information on BCA therapy using curcumin. Chemotherapy, as an effective treatment for different stages of BCA, and curcumin, generally regarded as safe compound and an alternative to synthetic drugs, have been described for the treatment of BCA. A few parameters, including nano-curcumin versus bulk curcumin and its encapsulated form versus its corresponding free form, have been discussed. Curcumin, a safe and edible compound with antitumor properties, is a promising medicinal compound for the treatment of BCA. Encapsulation of curcumin enhances its stability and anticancer efficiency. Nano-curcumin exhibits superior properties when compared to its bulk counterparts, leading to notable interactions and effects.

Infectious diarrhea is a gastrointestinal illness that results in around 1.7 billion cases and 525,000 deaths annually, particularly among children under five, according to the World Health Organization. While some Cameroonian medicinal plants show promise for treating diarrhea, many plants are used without established scientific evidence of their efficacy. These plants include Tithonia diversifolia (T. diversifolia) and Solanum torvum (S. torvum), which are traditionally used to treat diarrheal symptoms. This study sought to investigate the anti-Shigella activity of leaf extracts from T. diversifolia and S. torvum.

Extracts from T. diversifolia and S. torvum were obtained by successive maceration in solvents of increasing polarity, including hexane, dichloromethane, ethyl acetate, methanol, and water. The as-prepared extracts (10) were evaluated for antibacterial activity against selected Shigella species using an in vitro experiment. The mode of action of the bioactive extracts was determined in Shigella through growth kinetic analysis.

Hexane extract from S. torvum (St-HEX-F) and dichloromethane extract from T. diversifolia (Td-DCM-F) inhibited the growth of Shigella flexneri NR-518 and Shigella boydii NR-521 with minimum inhibitory concentration (MIC) values of 500 and 1,000 µg/mL, respectively. Shigella flexneri and Shigella boydii were the most sensitive strains, whereas Shigella sonnei was the most resistant strain. Bacterial growth kinetics revealed that St-HEX-F and Td-DCM-F are bacteriostatic at MIC and bactericidal at 2×MIC and 4×MIC.

Extracts from T. diversifolia and S. torvum possess anti-Shigella activity and could be used as a potential source of active ingredients for developing new treatments against diarrhea caused by multidrug-resistant Shigella.

Gliomas remain a major challenge in brain cancer treatment. Although genetic mutations have been widely studied, recent research indicates that epigenetic changes, which alter gene activity without changing the DNA sequence, also contribute significantly to tumor growth and treatment resistance. This review seeks to elucidate the principal drivers and modulators of brain tumor development, emphasizing the complex interaction between tumor metabolism and epigenetic regulation. It highlights how metabolic intermediates influence chromatin structure and transcriptional events driving glioma progression. Metabolic intermediates, such as acetyl-CoA and S-adenosylmethionine, serve as essential epigenetic cofactors, directly impacting chromatin structure and gene expression. Additionally, metabolic disorders like diabetes not only frequently coexist with gliomas but also exacerbate tumor progression through mechanisms such as inflammation, oxidative stress, and epigenetic reprogramming. Tumors located near brain regions controlling heart function may also increase the risk of sudden death, particularly in diabetic patients. The review proposes a comprehensive framework to understand glioma development by linking metabolism, epigenetics, and overall health. This integrated perspective leads to novel personalized treatment approaches, targeting both the tumor and the patient’s broader metabolic health, with the potential to improve survival rates and quality of life for glioma patients.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is an independent risk factor for cardiovascular disease (CVD). While gut bacteria have been linked to CVD, the role of intestinal fungi in subclinical coronary atherosclerosis (SCA) remains unclear. In this study, we aimed to investigate the association between the gut mycobiome and SCA in MASLD.

A cross-sectional study was conducted among 103 MASLD patients without established CVD. Fibrosis and steatosis were assessed using magnetic resonance elastography (MRE) and proton density fat fraction, respectively. SCA was defined by coronary artery calcification (CAC). Fecal fungal composition was analyzed via internal transcribed spacer sequencing.

Mean age was 60.8 ± 11.2 years; 51.5% were men; 20.4% had cirrhosis. CAC correlated with MRE (r = 0.489, p < 0.001), interleukin-6 (r = 0.407, p < 0.001), and tumor necrosis factor-α (r = 0.254, p = 0.018), but not proton density fat fraction. Cirrhosis patients had higher CAC than F0–F3 (456.9 vs. 205.9, p = 0.033). Candida albicans (C. albicans) abundance was greater in cirrhosis and correlated with CAC (r = 0.403, p < 0.001) and MRE (r = 0.212, p = 0.032). In multivariate analysis, older age, diabetes, obesity, cirrhosis, and enriched C. albicans independently predicted CAC ≥ 100 AU in MASLD.

In MASLD, cirrhosis and C. albicans enrichment are independently associated with higher SCA burden, suggesting advanced liver disease and a potential fungal contribution to CVD pathogenesis.

Metabolic dysfunction-associated steatotic liver disease (MASLD) affects approximately 32% of the US adult population. The present study aimed to utilize the All of Us electronic health record-linked large cohort to assess seven metabolic risk factors (MRFs) simultaneously, the impact by ethnicity and age, and clinical presentations of MASLD.

This study included a MASLD group (n = 15,060) and a frequency-matched control group (n = 75,300). Multivariable analyses were performed to compare the frequencies of MRFs and clinical outcomes between the two groups. Type 1 diabetes was not included in the multivariable analysis. Subgroup analyses were conducted according to race and ethnicity, as well as age.

The overall frequency of MASLD was 6.0%. Compared with the control group, individuals with MASLD had significantly higher independent frequencies of obesity (66.1% vs. 41.3%), type 2 diabetes (39.5% vs. 16.9%), hypertension (64.3% vs. 38.6%), hyperlipidemia (59.8% vs. 37.3%), obstructive sleep apnea (28.9% vs. 13.4%), and hypothyroidism (21.2% vs. 13.4%). Obesity was identified as the strongest independent MRF among Asians, Whites, and Hispanics, particularly in individuals younger than 50 years, whereas hypertension was the strongest independent MRF in Blacks. MASLD was also associated with significantly higher frequencies of cardiac events, including coronary artery disease (17.1% vs. 9.4%) and myocardial infarction (7.1% vs. 4.2%); hepatic events, including cirrhosis (7.5% vs. 1.1%) and hepatocellular carcinoma (0.5% vs. 0.1%); and elevated liver enzymes, including alanine aminotransferase (27.7% vs. 10.1%), aspartate aminotransferase (18.0% vs. 6.4%), and alkaline phosphatase (19.8% vs. 13.1%), compared with the control group.

Our study demonstrated that obesity, hypertension, hyperlipidemia, type 2 diabetes, obstructive sleep apnea, and hypothyroidism were independent MRFs for MASLD overall, but the ranking of these MRFs by odds ratios could vary by ethnicity and age. MASLD presents with significantly higher rates of alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase elevation, as well as cardiac and hepatic events.

Terahertz (THz) radiation is increasingly explored for biomedical applications, however, its non-thermal effects on cellular metabolism and regulatory networks remain insufficiently characterized. This study aimed to investigate how 2.3 THz radiation affects metabolic pathways and membrane-associated signaling in human melanoma cells.

SK-MEL-28 melanoma cells were exposed to 2.3 THz radiation for 45 min using the 1st Novosibirsk free-electron laser. Cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and trypan blue assays. Metabolic alterations were detected by targeted metabolomics using liquid chromatography–tandem mass spectrometry. Gene network analysis was performed using the ANDSystem platform to reconstruct gene and protein interaction networks linking altered metabolites to membrane receptors, lipid raft proteins, and signaling pathways. Overrepresentation analysis of biological processes was applied to identify enriched functional categories.

THz exposure did not affect cell viability but induced significant alterations in purine metabolism, pantothenate/CoA biosynthesis, and the pentose phosphate pathway. Network analysis revealed that these metabolic changes were associated with membrane raft reorganization and receptor-mediated signaling involving epidermal growth factor receptor and G-protein subunits. Additional effects were observed in pathways related to chromatin organization and post-translational regulation.

THz radiation induces coordinated remodeling of metabolic and regulatory networks in melanoma cells without cytotoxicity. These findings highlight the role of membrane-associated signaling in mediating THz-induced cellular responses and provide insight into potential biomedical applications of THz technologies.

Candida species, particularly Candida albicans, are major contributors to denture-induced stomatitis because of their ability to form biofilms on removable dental prostheses. Although chemical cleansers are effective, concerns regarding material degradation and mucosal irritation have spurred interest in non-chemical alternatives. This review aims to systematically compare the efficacy of chemical and non-chemical denture cleansers in reducing Candida spp. on removable dental prostheses.

A systematic review was conducted according to the PRISMA 2020 guidelines. Comprehensive searches of PubMed, Scopus, and Web of Science (2003–2025) yielded 624 records. After duplicate removal and screening, 20 studies (10 randomized controlled trials (RCTs) and 10 in vitro studies) were included. The risk of bias was assessed using the Cochrane Risk of Bias 2.0 for RCTs and QUIN/SYRCLE tools for in vitro studies.

Chemical cleansers such as sodium hypochlorite (0.25–2.5%), chlorhexidine (0.2–2%), and effervescent peroxide tablets achieved 80–100% colony-forming unit reduction in most studies, with some reporting complete biofilm eradication. In contrast, non-chemical agents showed a 40–85% colony-forming unit reduction rate. Chemical cleansers caused increased surface roughness and discoloration in six of the ten studies included. Non-chemical agents preserved material integrity and were preferred by patients for their taste and ease of use. The risk of bias was low to moderate in 80% of the RCTs and low in 10 of the 13 in vitro studies.

Chemical denture cleansers are more potent antifungal agents, but they may damage prosthetic materials. Non-chemical cleansers offer safe and moderately effective alternatives to chemical cleansers. A personalized, evidence-based oral hygiene regimen is recommended for patients.

In the past decade, immune checkpoint inhibitors (ICIs) have dramatically changed cancer treatment, significantly improving outcomes for patients with various malignancies. Nonetheless, their widespread application has resulted in a rise in immune-related adverse events due to excessive immune activation, including immune-mediated hepatotoxicity (IMH). IMH can cause serious complications and even death, underscoring the need for early prediction and intervention. This review outlines the current understanding of risk factors and predictive biomarkers for IMH in cancer patients undergoing ICI therapy, with risk factors divided into patient-associated, tumor-associated, and agent-associated categories. Higher IMH risk is related to female sex, younger age, extreme BMI, Asian ethnicity, and chronic liver disease. Cancer type, prior ICI treatment, dual ICI combination therapy, and the concurrent use of chemotherapy, targeted agents, or other hepatotoxic drugs (e.g., acetaminophen, statins) also increase the risk of IMH. Potential predictive biomarkers encompass circulating blood cells, serum proteins, autoantibodies, cytokines, gene profiles, and the gut microbiome. Despite promising findings, the predictive value of these biomarkers remains inconsistent, and no definitive biomarker has been established for routine clinical use. Large-scale prospective studies are essential to verify the predictive value of these biomarkers and facilitate their integration into clinical practice, thereby providing deeper insights into the early identification and individualized management of IMH during ICI therapy.

Cholelithiasis and gallstone-related complications remain one of the most prevalent gastrointestinal diseases globally. Age, gender, body mass index, physical activity, dietary factors, and genetics play a role in the development of gallstones. More than 20% of patients with gallstones will develop symptomatic disease during their lifetime, which can often lead to complications and significant morbidity. Laparoscopic cholecystectomy is considered the standard of care for symptomatic gallstone disease. Still, in select patient populations and in those who are non-surgical candidates, medical management, with bile acid therapy such as ursodeoxycholic acid (UDCA) or mechanical therapy such as extracorporeal shock wave lithotripsy, is preferred. UDCA is a hydrophilic bile acid that lowers biliary cholesterol saturation and aids in dissolving small, cholesterol-rich gallstones. UDCA appears to be well tolerated in the populations studied. While serious adverse events were uncommon in the available literature, UDCA’s efficacy is limited by a high recurrence rate. The aim of this review is to summarize the current evidence and developments regarding the role of UDCA therapy in the management of cholelithiasis and choledocholithiasis.

This review presents the Oncodarwinian Hypothesis, which proposes a new medical paradigm: that of cancer as a potential macro-immunoadaptive response (susceptible to fine-tuning or reprogramming/management via artificial intelligence-based 3D printed p53 superproteins). A traditional hypothesis-generation method was adopted; it entails observing a biophenomenon longitudinally (tumor-precursor out-of-control cell division), formulating and refining targeted research questions, and then, rooted in a prior interdisciplinary theoretical framework, outlining (per deductive reasoning) a testable answer or statement apt to predict outcomes. Two main theoretical findings emerge from this review: the plausibility of a wireless p53 superprotein molecular biochip (3D printed) and cancer cells’ dual-focus immunological nature. It will be necessary to approach the key issue and prognosis of (supposedly meaningless) uncontrolled cell division in a different light. Basically, the same diseasing cancer also constitutes a self-replicating immunoadaptive algorithm that needs to be deciphered. An interdisciplinary quest to unravel its “source code” involves genomic palaeontology and learning the natural selection programming language — for developing (personalized) artificial intelligence-assisted p53 superproteins.

Cirrhotic ascites develops when portal hypertension and arterial under-filling chronically activate neuro-hormonal pathways that drive renal sodium-water retention. Augmented proximal tubular sodium reabsorption, predominantly mediated by the apical sodium/hydrogen exchanger 3 (NHE3), plays a fundamental role in this process. Given the spatial coupling of NHE3 and the sodium-glucose cotransporter 2 (SGLT2), selective SGLT2 inhibition reduces NHE3 activity via functional suppression within the apical microdomain. The increased sodium chloride delivery to the macula densa augments tubuloglomerular feedback and modulates the renin–angiotensin–aldosterone system. Early clinical investigations, ranging from case reports and retrospective analyses to pilot randomized trials, indicated potential benefits in controlling ascites and reducing decompensation events. However, their limited sample size, heterogeneous endpoints, and predominantly observational design constrain the generalizability of the findings. This review concentrates on the molecular mechanisms and emerging clinical evidence supporting the therapeutic potential of SGLT2 inhibitors in the management of cirrhotic ascites.

Liver fibrosis is characterized by the excessive deposition of extracellular matrix, a process primarily driven by activated hepatic stellate cells (HSCs), and currently lacks effective therapy. Cathepsin K (CTSK) exhibits context-dependent roles across organ systems in fibrosis, but its function in liver fibrosis is unclear. This study aimed to investigate the role and underlying mechanisms of CTSK during liver fibrosis.

CTSK expression was analyzed in human fibrotic liver samples via transcriptomic analysis and confirmed in murine fibrosis models. The function of CTSK was investigated in both primary HSCs and LX-2 cells by assessing its effects on cell activation, proliferation, apoptosis, and the underlying signaling pathways following CTSK overexpression. The therapeutic potential was evaluated using an adeno-associated virus serotype 8 to overexpress CTSK in two etiologically distinct murine fibrosis models.

CTSK was upregulated in activated HSCs and fibrotic livers. Furthermore, we discovered that it mediates a negative feedback loop to inhibit the TGF-β/Smad pathway via Smad7/Smurf2-dependent TGF-β receptor-I degradation, thereby suppressing HSC activation and proliferation. CTSK also induced mitochondrial apoptosis through Bax/Bcl-2 imbalance and caspase-3 activation. Together, these actions contribute to the anti-fibrotic effect of CTSK. Notably, adeno-associated virus serotype 8-mediated CTSK overexpression attenuated liver fibrosis across multiple murine models.

Our study demonstrates that elevated CTSK functions as an endogenous protective factor that attenuates liver fibrosis. CTSK mediates negative feedback inhibition of the TGF-β pathway while concurrently promoting the mitochondrial apoptosis pathway. The dual anti-fibrotic mechanisms identify CTSK as a promising therapeutic target for liver fibrosis.

Primary hepatocellular carcinoma (HCC) remains one of the leading causes of cancer-related mortality worldwide, with curative options still limited for patients with advanced disease. As an emerging modality of cancer immunotherapy, tumor vaccines represent a promising approach that activates the host immune system to recognize and eliminate malignant cells. Multiple vaccine platforms, including peptide vaccines, dendritic-cell vaccines, nucleic-acid vaccines, and viral-vector vaccines, have been explored for HCC. Among these, peptide- and dendritic-cell-based vaccines are supported by the most extensive clinical data, demonstrating favorable safety and immunogenicity profiles. The advent of personalized therapeutic cancer vaccines based on tumor-specific antigens has further refined the precision of vaccine design. Nevertheless, several major challenges persist, including immune suppression within the tumor immune microenvironment, marked tumor heterogeneity, immune-escape mechanisms, and limited vaccine immunogenicity, all of which hinder clinical efficacy. In addition, issues related to standardization, large-scale production, and regulatory oversight remain unresolved. Recent advances in sequencing technology, nanotechnology, and artificial intelligence have opened new avenues for optimizing vaccine platforms and delivery strategies. Combination therapies that integrate cancer vaccines with immune checkpoint inhibitors, chemotherapy, or locoregional treatments are also being actively investigated to improve patient outcomes. In summary, although vaccine-based immunotherapy for HCC is still at an early stage, its integration with personalized medicine and multimodal therapeutic strategies holds great potential for improving the long-term prognosis of patients with HCC. Therefore, this review aims to systematically summarize current advances in tumor vaccine–based immunotherapy for hepatocellular carcinoma, with a particular focus on vaccine platforms, target antigens, clinical trial outcomes, and future challenges for clinical translation.

Lung cancer remains the leading cause of cancer-related mortality worldwide. Early detection of pulmonary nodules is crucial for timely diagnosis and effective treatment. Conventional computer-aided detection systems have shown limitations, including high false-positive rates and low sensitivity. Recent advances in deep learning, particularly convolutional neural networks (CNNs), have shown great potential in improving the accuracy and reliability of nodule detection and classification. This study aimed to develop and evaluate an automatic method for lung nodule detection and classification using a CNN-based architecture applied to computed tomography images from the publicly available LIDC-IDRI database.

This retrospective study was conducted on 82 patients (10,496 computed tomography slices) selected from the LIDC-IDRI database. The proposed method consists of five main steps: image preprocessing, lung parenchyma segmentation using Otsu’s thresholding and morphological operations, detection of nodule candidates, feature extraction, and classification using a CNN model. The CNN architecture includes two convolutional layers (20 and 30 filters, 3×3 kernel), ReLU activation, max-pooling layers, and a Softmax output layer. The network was trained with a mini-batch size of 32 for 50 epochs using the Stochastic Gradient Descent with Momentum optimizer (learning rate = 0.001, momentum = 0.9). Model performance was evaluated in terms of sensitivity, specificity, precision, and accuracy.

The proposed CNN model successfully detected pulmonary nodules and achieved accurate classification between benign and malignant nodules. On the LIDC-IDRI dataset, the model achieved a sensitivity of 98.7%, specificity of 97.5%, precision of 97.9%, and accuracy of 98.4%. Comparative analysis with recent studies, including hybrid CNN-long short-term memory and ResNet-based models, demonstrated that the proposed method provides competitive performance while maintaining lower computational complexity. The classification of nodule subtypes (solid, partially frosted, totally frosted) showed satisfactory discrimination results.

The proposed CNN-based system demonstrates the feasibility and robustness of deep learning for automatic lung nodule detection and classification. Despite strong results, the study acknowledges limitations such as single-database validation and a relatively small training size. Future work will focus on validating the model across other datasets (e.g., ELCAP, NELSON) and optimizing multi-class classification performance to enhance generalizability and clinical applicability.

Autoimmune hepatitis (AIH) frequently coexists with extrahepatic autoimmune diseases (EADs), but their prevalence, characteristics, progression, and treatment effect in the Han Chinese population remain unclear. This study aimed to evaluate the prevalence and spectrum of EADs and to assess their clinical features, disease course, and treatment outcomes in Han Chinese patients with AIH.

Medical records of 371 Han Chinese patients with AIH (diagnosed from March 2016 to October 2023) were retrospectively analyzed.

Among the 371 AIH patients, 304 (81.94%) were female, with a median age of 52.5 years (interquartile range, 46.0–61.0). A total of 23.98% (89/371) had at least one EAD, including 27.06% (82/303) in type 1 AIH, 11.11% (7/63) in antibody-negative AIH, and none in type 2. A single EAD was the most common (20.21%, 75/371). The most frequent EADs were Sjogren’s syndrome (8.63%) and autoimmune thyroid disease (8.36%). Compared with patients without EADs, those with EADs had lower alanine aminotransferase, red blood cell, and hemoglobin levels, but higher aspartate aminotransferase/alanine aminotransferase ratio and antinuclear antibody (ANA) positivity (all P < 0.05). ANA positivity was independently associated with EADs (odds ratio = 2.209, 95% confidence interval = 1.242–3.927, P = 0.007). After three months of treatment, the complete biochemical response rate was lower in the EADs group than in the non-EADs group (40.0% vs. 55.3%, P = 0.024), whereas no significant differences were observed at 6, 12, 24, or 36 months (all P > 0.05).

In the Han Chinese population, 23.98% of AIH patients had EADs, with Sjogren’s syndrome and autoimmune thyroid disease being the most common. ANA positivity was a significant risk factor for EADs. EAD patients had a poorer initial treatment response at three months, but comparable long-term biochemical response from six months.

Nutrition plays a pivotal role in the prevention and management of gastrointestinal and hepatic diseases, yet dietary guidance remains generic, limiting its effectiveness. Conditions such as inflammatory bowel disease, irritable bowel syndrome, metabolic dysfunction-associated steatotic liver disease, celiac disease, and gastroesophageal reflux disease are significantly influenced by dietary factors. Personalized nutrition has emerged as a promising strategy to tailor interventions, but conventional approaches fail to account for individual metabolic, genetic, and microbiome variability, limiting their clinical impact. The rapid rise of artificial intelligence (AI) has transformed precision nutrition by integrating genomics, microbiome profiles, metabolic markers, and real-time dietary tracking to generate individualized recommendations. AI-driven systems are advancing dietary assessment, condition-specific nutrition optimization, and continuous monitoring through tools such as wearable devices and natural language processing-based diet analysis. These innovations hold transformative potential in gastroenterology and hepatology, offering dynamic, patient-specific strategies that may enhance clinical outcomes. However, challenges remain, including the lack of standardized AI-driven protocols, ethical concerns such as bias and data privacy, limited clinical validation, and the underrepresentation of nutrition in many current AI applications. Opportunities for progress include developing federated learning models, expanding real-world validation studies, and designing regulatory and ethical frameworks for safe implementation. This narrative review synthesizes literature published between 2015 and 2025 across five databases, highlighting key applications, limitations, and future directions of AI-driven personalized nutrition in gastroenterology and hepatology. It provides insights into how AI could reshape patient-centered care through more individualized, effective, and scalable dietary strategies.

Thalassemia is a group of anemias that result from inherited defects in the production of the beta chain of hemoglobin. It is stabilized by gamma globin, which combines to form fetal hemoglobin. One therapeutic approach is to target histone deacetylase (HDAC), which plays an important role in controlling beta thalassemia. This study sought to identify a natural inducer for treating this disease.

Twenty-five Andrographis paniculata compounds were screened using Schrödinger Suite 2020 (Maestro 12.3) for ligand preparation, grid generation, glide extra precision docking and molecular mechanics/generalized born surface area scoring. The HDAC2 crystal structure (Protein Data Bank ID: 4LXZ) was prepared by removing crystallographic water molecules and performing restrained minimization. Top-scoring complexes were subjected to 5-ns molecular dynamics simulations in GROMACS 2019 using the optimized potentials for liquid simulations force field, three interaction site point charge solvation, and standard neutralization and equilibration protocols. Absorption, distribution, metabolism, and excretion properties were predicted using QikProp.

Among the twenty five screened compounds, SRJ09 derivative of andrographolide, ranked among the top candidates based on glide extra precision docking and molecular mechanics/generalized born surface area scores and was therefore selected for further analysis. SRJ09 showed favorable binding to the HDAC2 active site, with interactions comparable to the reference inhibitor 20Y. Absorption, distribution, metabolism, and excretion predictions indicated acceptable drug-likeness, and molecular dynamics simulations demonstrated stable SRJ09–HDAC2 complex behavior over 5 ns.

We concluded that beta thalassemia may benefit from the use of andrographolide, and SRJ 09 as prospective HDAC2 inhibitor drugs that are favourable and efficacious and that generate fetal hemoglobin. Therefore, this bioactive compound is worth further investigation using in vitro and in vivo studies.