Analysis of azithromycin (AZT) by reversed-phase high-performance liquid chromatography (RP-HPLC) is often limited by peak tailing caused by silanol interactions and by reliance on dosage-form-specific Pharmacopeia methods. A unified and column-compatible RP-HPLC-UV method has been developed for the determination of AZT in various pharmaceutical dosage forms. Chromatographic separation was performed on a C18 column using a mobile phase of 0.02% triethylamine (TEA) in 10 mM phosphate buffer (pH 7.0 ± 0.05) and acetonitrile (60:40, v/v) under isocratic conditions with UV detection at 210 nm. Validation according to ICH Q2(R2) demonstrated strong linearity ( R ² = 0.9985) over the range of 0.80–1.20 mg/mL, with %residuals within ±2%. Accuracy ranged from 100.41% to 101.00%, and precision (repeatability and intermediate precision) was confirmed by %RSD < 1%. The method exhibited acceptable robustness under the evaluated conditions; however, retention was sensitive to variations in mobile phase pH, highlighting the importance of maintaining strict pH control during routine analysis. Application to commercial products resulted in assay values of 99.42%–103.65% of label claim, meeting USP and BP specifications. This method provides a streamlined and practical analytical approach for routine quality control of AZT across multiple pharmaceutical dosage forms using a unified chromatographic approach.
Hemorrhoid is a multifactorial condition involving inflammation, venous stasis, degeneration of supporting tissue, and vascular fragility. It requires safer adjunctive therapy options for long-term use. This narrative review seeks to comprehensively examine potential anti-hemorrhoidal medicinal plants by linking bioactive compounds, pharmacological targets, and evidence from in vitro , in vivo , and clinical trials. Literature searches were conducted using PubMed, Scopus, Web of Science, ScienceDirect, and Google Scholar, focusing on original research articles that documented anti-inflammatory, antioxidant, venoprotective-venotonic, hemostatic-astringent, analgesic, and wound healing activities. The articles were further synthesized qualitatively according to the pathophysiology of hemorrhoids. A total of 90 articles met the inclusion criteria and were classified based on the predominant mechanism, namely anti-inflammatory–antioxidant agents (14 plants; 41 articles), vasoprotective–venotonic agents (6 plants; 10 articles), astringent–hemostatic agents (6 plants; 14 articles), and analgesic and wound healing acceleration (7 plants; 25 articles). The findings showed that medicinal plants operate through a multitarget manner by suppressing inflammatory mediators, increasing endogenous antioxidant defenses, improving venous tone and microvascular stability, supporting local hemostasis, and accelerating mucosal regeneration. Nonetheless, the evidence remains predominantly derived from preclinical studies, with variations in extraction methods, formulations, routes of administration, and dosages. Overall, medicinal plants have potential as adjuvant therapy for hemorrhoids; nevertheless, standardization of extracts and controlled clinical trials are necessary to ensure efficacy and safety.
Indonesia remains one of the world’s top coffee producers, with Robusta coffee ( Coffea canephora ) being the variety favored by most consumers. Owing to its prominence, numerous studies have highlighted caffeic acid, a polyphenolic compound in coffee extract that has been shown to demonstrate antidiabetic properties. The primary objective of this research is to measure the caffeic acid levels in Robusta coffee brews. To achieve the optimal conditions, a Box–Behnken Design was used to determine the most suitable setting for the independent variables, including acetonitrile, formic acid, and flow rate. The analytical method validation parameters assessed were linearity and range, selectivity, accuracy, and precision, limit of detection (LOD), and limit of quantification (LOQ). The optimized reversed-phase high-performance liquid chromatography system was methanol:acetonitrile:aqueous formic acid pH 2.9 (10:15:75 v/v/v), flow rate of 1.0 mL/min, column temperature of 27 °C, 10 µL injection volume, and wavelength detection at 326 nm. The method showed good specificity and selectivity (Rs ≥ 1.5), with linearity from 5.39 to 32.36 µg/mL ( R 2 = 0.9987). LOD and LOQ were found to be 0.08032 and 0.2434 µg/mL, respectively. The recovery percentage for the intra-day assay was 92.26%–102.94%, while the inter-day percentage yield achieved 94.89% to 102.96% (90%–107%). All of the intra-day and inter-day assays met the required relative standard deviation (RSD) ≤ 5.3%. The average caffeic acid in Robusta coffee brews was 0.772 ± 0.008 mg/g (RSD = 1.066%, n = 6).
This study aims to evaluate the impact of a pharmacist-led educational intervention on clinical outcomes, medication adherence, and health-related quality of life (HRQoL) of Type 2 diabetes comorbid hypertensive patients. Ninety-two participants were block-randomized into control ( n = 46, usual care) and intervention ( n = 46, pharmacist-led education and counseling) groups. Clinical parameters, medication adherence, and HRQoL were assessed at baseline, 3 months, and 6 months. Repeated measures tests and bivariate statistics were used to analyze within-group and between-group differences of outcomes. Seventy-two patients (37 intervention, 35 control) completed the study. The intervention group demonstrated significant reductions in mean glycated hemoglobin (HbA1c) level, systolic and diastolic blood pressure over 6 months ( p < 0.05), while no significant differences in outcomes were observed among the control group. Altogether, 67.6% of participants in the intervention group attained HbA1c < 7%, and 83.8% achieved optimal blood pressure control and adherence to the prescribed medications. HRQoL health utility score shows marginal but significant improvement in the intervention group. Overall, the pharmacist intervention exhibited small to moderate effects in improving most of these outcomes compared to usual care. The findings revealed that pharmacist-led educational interventions significantly improve clinical outcomes, medication adherence, and HRQoL in diabetic-hypertensive patients. The study recommends routine integration of pharmacists in clinical settings for multidisciplinary care of diabetic-hypertensive patients.
Diabetic foot ulcers (DFUs) remain a major clinical concern due to chronic inflammation, dysfunctional angiogenesis, and increased susceptibility to infection, often resulting in delayed healing and the potential for limb amputation. Smart scaffold technologies have emerged as sophisticated biomaterial systems that recreate the extracellular matrix, thus providing not only cellular mechanical support, but also controlled drug release and dynamic biological response. Recently, polymer science, electrospinning, bioprinting, and injectable hydrogels have been significantly combined to produce multifunctional scaffolds that can not only support cell growth and vascularization but also provide targeted antimicrobial treatment. However, despite the fact that preclinical studies showed great potential, several issues still puzzle the transition to clinical use, such as mechanical compatibility with native skin, control of drug release kinetics, scaling production processes, regulatory issues, and cost-effectiveness. In this article, various scaffold mechanical properties with respect to native skin, biomaterial choice, manufacturing scalability, regulatory issues, and clinical effectiveness are thoroughly compared and discussed, whereas previous reviews mostly focused on biomaterial composition or fabrication techniques. On top of that, the crucial progress in sensor-embedded and smart scaffolds is pointed out as the future potential of personalized DFU treatment. This review briefly discusses the major issues that need to be addressed for smart scaffold technologies to go from the laboratory to the hospital, at the same time recognizing a translation challenge and technological progress.
Philadelphia chromosome-positive leukemias involve signaling systems beyond BCR-ABL1, and treatment response may depend on this wider network biology. Second-generation BCR-ABL1 tyrosine kinase inhibitors such as dasatinib, nilotinib, and bosutinib show variable clinical responses according to diagnosis and disease stage. Dasatinib is effective in this context because it is active against SRC-family kinases as well as receptor-proximal kinases and downstream outputs involving the MAPK/ERK, PI3K/AKT and JAK/STAT pathways. This broader pharmacological profile may impair compensatory signaling, which may partly account for its activity against CML and Philadelphia chromosome-positive ALL, especially if SRC-linked or ERK-mediated persistence underlies treatment escape. However, the same breadth could trigger pleural effusion and immune-related effects, underscoring the need for personalized dosing, toxicity monitoring, and adaptive interpretation of responses. This review combines many forms of evidence, including mechanistic, phosphoproteomic, immunologic and clinical evidence, to show that dasatinib acts as a network-modulating tyrosine kinase inhibitor rather than only as an ABL1-directed agent. Translational biomarkers, host immune responses, and systems-biology strategies may help predict incomplete pathway inhibition, guide treatment selection, and improve the durability of deep molecular remission.
The genus Dendrobium is a rich source of bioactive secondary metabolites, particularly bibenzyl derivatives with substantial pharmacological activities, but Dendrobium stuartii remains an underexplored species. Therefore, this study aimed to investigate the drug discovery potential of D. stuartii through an integrated in silico and experimental method. Four key compounds were prioritized through literature analysis, and the interactions with the epidermal growth factor receptor (EGFR) were evaluated using molecular docking. The chemical profile of the acetone extract was characterized using Liquid Chromatography–High Resolution Mass Spectrometry (LC-HRMS). Additionally, biological activities were assessed through antibacterial, antibiofilm, and anti-inflammatory assays. Batatasin III had the strongest predicted binding affinity toward EGFR, and the LC-HRMS analysis confirmed the presence of bibenzyl derivative 3,4ʹ-dihydroxy-5,5ʹ-dimethoxybibenzyl (gigantol). The extract provided antibacterial activity, specifically against S. aureus and P. acnes , inhibited biofilm formation during the mid-phase, and produced substantial anti-inflammatory activity, as evidenced by significant inhibition of protein denaturation. The results suggested D. stuartii as a promising underexplored source of bioactive compounds with potential applications in anticancer and anti-infective drug development.
Diabetic patients exhibit delayed skin wound healing due to chronic hyperglycemia, which results in prolonged tissue recovery. In this work, a skin dressing was synthesized using three natural composites: chitosan, gelatin, and Zingiber officinale herb, commonly known as ginger (CH+GE+ZO). The dressing was applied to albino Wistar rats, which then received an intraperitoneal injection of Alloxan at a dose of 150 mg/kg. Incision caused skin wounds. The antioxidant markers were quantified. A histological study was conducted to evaluate the effectiveness of the skin healing process. Analysis of the oxidative balance revealed a significant ( p < .001) increase in enzymatic antioxidant activities in the CH+GE+ZO-treated group compared to the diabetic group. A considerable increase in non-enzymatic markers was observed compared to the diabetic group ( p < .001). Histologically, the application of a composite synthesized by CH+GE+ZO dressing showed an improvement in the healing process, compared to controls, and a total recovery of wounds was observed around Day 13. This was characterized by a progressive reepithelialization, a structured organization of the layers of the epidermis, as well as a partial restoration of the cutaneous appendages. Overall, the synthesized biological dressing actively contributes to tissue repair and skin healing.
Dysbiosis primarily causes diabetic liver damage, and studies show that people with type 2 diabetes mellitus (T2DM) exhibit considerable changes in their gut microbiome. Escherichia coli, Clostridium symbiosum, and Clostridium hathewayi are among the harmful microorganisms known to increase in diabetes and adversely affect the liver. Importantly, plasma triglycerides, fasting glucose, and glycosylated haemoglobin (HbA1c) showed a negative correlation with Clostridium species, while fasting glucose, HbA1c, and plasma triglycerides showed a positive correlation with Lactobacillus species. These findings suggest that specific bacterial taxa may contribute to the development of T2DM and, in turn, promote liver-related complications. Fecal microbiota transplantation (FMT) may help restore a healthy gut microbiota, which may enhance insulin sensitivity, reduce hepatic fat accumulation, and alleviate metabolic dysfunction associated with the liver. Furthermore, diabetic liver damage has been linked to dysbiosis-related changes in bile acid metabolism. FMT can restore the diversity and function of bile acid-metabolizing bacteria, leading to a more balanced bile acid profile and enhanced bile acid signalling in the liver. This might reduce liver fibrosis and inflammation. Overall, by focusing on dysbiosis and its related pathways, FMT shows potential as a therapeutic intervention for diabetic liver disease. However, further investigation is required to clarify the ideal procedures, long-term security, and effectiveness of FMT in this particular situation. Furthermore, innovations are shifting FMT toward personalized precision therapies that address the complex relationship between gut bacteria, metabolism, and liver health in Type-2 diabetes. This study highlights a novel mechanistic framework linking dysbiosis, liver injury, and FMT restoration, emphasising donor–host microbiome compatibility, duration of effect, and the promise of precision microbiome and next-generation FMT therapies as future directions.
Multidrug-resistant tuberculosis (MDR-TB) remains a global health challenge. Short-term regimens using second-line anti-tuberculosis drugs (SLDs) show promise for improved outcomes, but real-world data from high-burden countries are limited. This study aimed to evaluate the effectiveness and safety of short-term SLD regimens in MDR-TB patients at a national referral center in Indonesia. A retrospective observational cohort study was conducted among MDR-TB patients aged >14 years who received short-term therapy (≥6 months) at the Dr. Hasan Sadikin General Hospital outpatient clinic from July 2023 to December 2024. Data were extracted from medical records and the Tuberculosis Information System. The primary outcomes were treatment success (cured or treatment completed) according to World Health Organization definitions, and adverse events (AEs) were documented and graded. Statistical analyses included descriptive statistics, multinomial logistic regression, Spearman correlation, and non-parametric tests. Among 72 patients screened, 54 met the inclusion criteria. Treatment success was achieved in 74.08% (40/54) of patients: 40 were cured, 7 died, and 7 failed due to diagnostic changes. The median time to sputum culture conversion was 6 months (interquartile range 2–6). Gastrointestinal AEs were most common (56.38%), primarily nausea (36.17%). Musculoskeletal/neurological events occurred in 12.76%, and cardiac events occurred in 5.31%. No significant associations were found between demographic characteristics and treatment outcomes or total AEs. Short-term SLD regimens demonstrated good effectiveness (74.08% success) with manageable AEs, supporting their use in resource-limited settings with active drug safety monitoring.
Skin aging induced by ultraviolet (UV) B (UV-B) radiation is marked by decreased glutathione (GSH) levels, increased tyrosinase activity, and elevated melanin synthesis, leading to hyperpigmentation. Although 4% hydroquinone (HQ) is widely used as the standard treatment due to its high efficacy, it poses significant risks of side effects. This study aimed to evaluate the potential of Passiflora edulis fruit extract cream as a natural alternative with minimal adverse effects. We employed a comprehensive approach combining in vitro assays, a UV-B–induced hyperpigmentation model in C57BL/6 mice, and computational analyses to evaluate the efficacy of the P. edulis fruit extract. The results showed that the extract exhibited weak anti-tyrosinase activity, moderate antioxidant capacity, and low SPF protection in vitro. In vivo, the P. edulis cream significantly increased GSH levels and reduced melanin content (p < 0.05) more effectively than HQ, and similarly decreased tyrosinase activity (p < 0.05). Computational predictions indicated that major bioactive compounds were safe and exhibited comparable or superior binding affinities to tyrosinase compared to HQ. In summary, P. edulis fruit extract cream showed promising anti-photoaging effects and may offer a complementary mechanism of action compared to HQ.
Fusarium proliferatum has been widely reported as a promising producer of bioactive secondary metabolites. In this study, we conducted genome mining to investigate the putative biosynthetic gene clusters (BGCs) from the fungal strain F. proliferatum ZO-L2-4 isolated from the leaves of Zingiber officinale Roscoe (ginger). First, the fungal gDNA was extracted and then subjected to library preparation. Next, it was sequenced using Illumina NextSeq 2000. The contigs were assembled, then the genes were predicted using AUGUSTUS and GeneMark and annotated using Kyoto Encyclopedia of Genes and Genomes. The BGCs analysis was conducted using Antibiotics and Secondary Metabolites Analysis Shell (AntiSMASH) Fungal Version. From sequencing and assembly, we obtained a genome sequence in a size of 43.6 Mb consisting of 12 nuclear and one mitochondrial contigs, N50 of 4,304,280 bp, L50 of 5, and GC content of 48.14%. Genome annotation suggested that the predicted genes mainly functioned in global maps, followed by carbohydrate metabolism and amino acid metabolism. The AntiSMASH analysis identified 43 BGCs, dominated by terpene biosynthetic genes, nonribosomal peptide synthase (NRPS), NRPS-like, polyketide synthases, and hybrids. Among these, only six BGCs showed the highest homology with the gene clusters that are responsible for the biosynthesis of oxyjavanicin, choline, bikaverin, Alternaria citri toxin (ACT)-toxin II, koraiol, and gibepyrone-A. Most of the remaining were unknown by far. Putative identification employing high-resolution mass spectrometry suggested the presence of beauvericin as the predominant metabolite, along with tryptophol, terpestacin, ergosterol peroxide, indole, and terpendole E in the methanolic extract of F. proliferatum. These findings enhance our understanding of the molecular biology of the Fusarium genus and may pave the way for discovering novel bioactive secondary metabolites from this fungal strain through gene knockout and heterologous expression.
Cancer immunotherapy has emerged as a transformative approach in oncology with the discovery of therapeutic cancer vaccines as a promising strategy. These vaccines, either standalone or in conjunction with adoptive cell therapy or immune checkpoint blockade therapy, show promise. However, the clinical success of conventional cancer vaccines remains limited due to poor immunogenicity, suboptimal antigen presentation, and inadequate delivery at the site of action. Application of nanotechnology for developing nanovaccines may address these challenges and offer solutions to these limitations. Nano-vaccines mimic the physicochemical and structural properties of the antigen system and may activate both humoral and cellular immune responses. These systems can be used to fine-tune intracellular delivery and antigen cross-presentation. Furthermore, it offers prolonged blood circulation stability, improved immune system engagement, without the need for supplemental doses and the need to maintain the cold chain, as well as the potential to develop large-scale production. This review explores the vaccine delivery via artificial or naturally derived nanoparticles in cancer immunotherapy, focusing on their ability to deliver/co-deliver inert ingredients and multiepitope antigens into lymphoid organs and monoclonal antibodies. Furthermore, immunogenic mRNA for cancer immunotherapy delivered via nano-vaccine will also be examined. Overall, nanovaccines represent a promising frontier in precision immunotherapy with significant implications for cancer treatment.
Oxidative stress accelerates aging and contributes to various degenerative diseases. Amaranthus tricolor (red spinach) is known for its strong antioxidant properties. However, its cellular mechanisms in modulating aging remain unclear. This study utilized the fission yeast Schizosaccharomyces pombe as a model to evaluate the protective and pro-longevity effects of ethanol-derived A. tricolor leaf extract. Treatment with 49 μg/ml extract enhanced yeast survival under H2O2-induced oxidative stress and extended chronological lifespan compared to untreated and calorie-restriction controls. The extract also increased mitochondrial membrane potential (ΔΨm), as assessed by Rhodamine staining. Flow cytometry revealed an elevated proportion of cells in the G0/G1 phase, indicating delayed cell cycle progression. Gene expression analysis showed upregulation of aging-related (sir2+) and oxidative stress-response genes (sod2+, ctt1+). Liquid chromatography-high resolution mass spectrometry profiling identified major metabolites, including (2E)-3-(3,4-dimethoxyphenyl)acrylic acid, 2-O-caffeoylglucaric acid, and (10E,15Z)-9,12,13-trihydroxy-10,15- octadecadienoic acid. Overall, the findings demonstrate that A. tricolor extract enhances oxidative stress resistance and promotes cellular longevity in yeast, supporting its potential as a natural source for nutraceutical development.
There is growing evidence demonstrating the use of computer modeling in biomedicine as new technologies emerge in every discipline. Computational, translational, experimental, and clinical methods are all combined in current drug development to find possible novel potential medications. However, limited attention has been given to summarizing global publication trends in this field. The aim of the current study is to describe and assess global trends in applying the bibliometric approach to drug development and discovery regarding the importance of molecular modeling. A literature search was conducted to extract all relevant papers on molecular modeling in drug discovery and development using the Scopus database. The data were gathered for the year 2005–2024. Insights are classified based on authors, title of publication sources, countries, type of documents, research domains, and so on. A total of 3,489 papers were retrieved, demonstrating a surge of interest in molecular modeling within drug discovery and development, with a significant rise in recent years. The top countries contributing were the United States, India, and China. Journal articles constituted the highest percentage of papers, and the most productive source was the Journal of Chemical Information and Modeling. The study highlights the tools and software used in modern drug development and discovery-related analysis that were developed using machine learning techniques. There has been an upsurge of interest in molecular modeling in drug discovery and development, as shown by a growing trend in research publications in recent years. This study is the first extensive bibliometric evaluation between 2005 and 2024 with specific emphasis on molecular modeling in drug development and discovery. The results serve as a useful guide for academicians, researchers, and policy-makers to identify global trends and future research directions in this new field.
Diabetic nephropathy (DN), a severe microvascular complication of diabetes mellitus, is a leading cause of end-stage renal disease. Current therapies that focus on glycemic and blood pressure control are insufficient, prompting the need for novel interventions. While the systemic metabolic effects of ethanolic extract of Strychnos potatorum seeds (EESP), including changes in body weight, blood glucose, and insulin levels, and its role in upregulation of fibroblast-specific protein-1, have been previously reported, this study investigated the renoprotective potential of the EESP in a streptozotocin-induced rat model of DN. The study focused on the modulation of the tight junction protein Zonula occludens-1 (ZO-1), which maintains the integrity of the glomerular filtration barrier. Thirty male Wistar albino rats were divided into five groups and treated with EESP (500 mg/kg) or metformin (50 mg/kg) for 30 days. Urine analysis, renal histopathology, electron microscopy study, ZO-1 immunohistochemistry, gene expression, and protein expression were analyzed. EESP administration significantly improved renal function by reducing the urinary albumin (p = 0.03), protein (p = 0.01), urea, and creatinine levels. It alleviated oxidative stress markers such as lipid peroxidation, hydrogen peroxide, and protein carbonyls, while restoring antioxidant enzyme (glutathione peroxidase, glutathione S-transferase, superoxide dismutase, and catalase) activity (p = 0.001). Histological and ultrastructural analyses revealed reduced glomerular basement membrane thickening, tubular atrophy, and podocyte damage. Notably, EESP upregulated ZO-1 expression at both the gene (2.25-fold) and protein (3.6-fold) levels, suggesting improved slit diaphragm integrity and reduced proteinuria. These findings suggest that EESP offers a multifaceted renoprotective effect in DN through the mitigation of oxidative stress, structural preservation, and enhancement of ZO-1 expression. Further mechanistic and clinical studies are warranted to validate S. potatorum as a potential therapeutic candidate for DN.
Oral clarithromycin therapy for Helicobacter pylori is limited by short gastric residence and variable intragastric exposure. Formulating clarithromycin in mucoadhesive gastroretentive granules (MGG) may extend the gastric residence time, increase the concentration, and control drug release at the site of action for a longer time, and improving bioavailability and therapeutic efficacy in eradicating H. pylori. Polymers with certain swelling ability and mucoadhesive properties are critical to produce MGG. Therefore, this study aims to explore various polymers for their potential as carriers for mucoadhesive gastroretentive dosage forms. Clarithromycin was mixed in a ratio of 1:1 with HPMC K15M, HPC MF, HEC 250 HHX, Carbomer (Carbopol 971p), or Polymethacrylates (Eudragit RS PO), and MGG were prepared using the wet granulation method. The yield of obtained dry granules was measured, then the size, moisture content, and flow properties were characterized. Muco-/bio-adhesive properties were analyzed based on adhesion strength and MGG retained during the ex-vivo study. The swelling index and drug release profile of MGG in HCl 0.1 N (pH 1.2) were analyzed. The results showed that all polymers produced free-flowing granules with effective hydration and gastric tissue adhesion. Among them, the Carbopol-based granules (F4) offered the best overall balance of rapid gel formation for early attachment, good ex-vivo retention to 8 hours, and prolonged release maintained to 12 hours. Release profiles were best described by the Higuchi kinetic model, consistent with diffusion and dissolution-controlled drug release mechanisms from a hydrated matrix with polymer swelling. This work provides the first direct, granule-form comparison of multiple polymers for mucoadhesive gastro-retentive delivery of clarithromycin. The Carbopol 971p matrix (F4) emerges as a promising carriers to prolong gastric residence and sustain local drug availability, supporting reduced dosing frequency and improved patient convenience. Future studies will optimize polymer ratios and evaluate in-vivo pharmacokinetics and antibacterial performance.
β-Thalassemia and sickle cell disease (SCD) are inherited hemoglobinopathies that pose substantial global health challenges. Gene therapy has emerged as a transformative, potentially curative approach by directly targeting the underlying genetic defects responsible for these disorders. This systematic review and meta-analysis critically assessed the clinical efficacy and safety of contemporary gene therapy modalities, including lentiviral-based platforms (e.g., Zynteglo) and Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas9–based approaches (e.g., Casgevy), in patients with β-thalassemia and SCD. A comprehensive literature search spanning January 2013 to March 2025 was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. Pooled analyses demonstrated a significant increase in transfusion independence among treated patients (Z = 5.89, p < 0.001), with moderate heterogeneity across studies. Lentiviral gene therapies consistently achieved haemoglobin normalisation and sustained transfusion freedom, whereas early-phase CRISPR trials highlighted favourable safety profiles and high gene-editing precision. Despite these promising outcomes, challenges such as insertional mutagenesis, off-target editing, high therapeutic costs, and limited availability in resource-constrained regions persist. In summary, gene therapy represents a clinically effective and potentially curative intervention for β-thalassemia and SCD. Nonetheless, rigorous long-term safety monitoring and strategies to enhance global accessibility are essential to ensure equitable implementation and sustainable patient outcomes.
Etlingera rubroloba is a traditional medicinal plant in Southeast Sulawesi, Indonesia. To date, no studies have been reported on the chemical and pharmacological aspects of E. rubroloba rhizomes. The total secondary metabolites of the methanol extract of E. rubroloba rhizome was analysed, by using the UPLC-High-Resolution Mass Spectrometry (HRMS) technique. It involves the isolation and structural elucidation of major compounds through chromatographic and spectroscopic methods, as well as an evaluation of the biological activities of the extracts and compounds, including antioxidant, anti-inflammatory, and antidepressant effects (the latter tested in silico). Six major compounds were identified for the first time from this species: Stigmasterol (ER1), Stigmast-4-en-6β-ol-3-one (ER2), Yakuchinone A (ER3), 1-(3’-methoxy-4’-hydroxyphenyl)-7-(4’’-hydroxyphenyl)-3-heptanone (ER4), 3,5-dimethoxy-4-acetoxy cinnamic alcohol (ER5), and p-Coumaric acid (ER6). The diarylheptanoids (ER3 and ER4) exhibited superior antioxidant activity, while the steroids (ER1 and ER2) demonstrated strong anti-inflammatory effects. Additionally, docking simulations suggested that ER1 and ER2 exhibited low binding energies towards monoamine oxidase, dopamine transporter, and serotonin transporter, indicating a possible relevance to neurotransmission pathways associated with depression. These findings highlight the chemical composition and pharmacological potential of E. rubroloba rhizomes, marking the first report of their antioxidant, anti-inflammatory, as well as their potential to interact with targets associated with depression, which represents a promising avenue for further confirmation through in vitro studies.
Solid oral modified-release dosage forms (SOMRDFs) are pharmaceutical technologies that alter the rate and/or onset of drug release compared with immediate-release (IR) formulations. This has been a significant advance, as many IR formulations fail to reach or maintain therapeutic plasma concentrations for the required duration to treat diseases, primarily due to the problematic biopharmaceutical and pharmacokinetic characteristics of many active ingredients. Types of SOMRDFs are described by regulatory entities in the USA as extended-release and delayed release. However, research in the literature and other regulatory entities does not apply consistent criteria regarding the terms used to name these types of formulations. This review shows that the terminology used for SOMRDFs is frequently not associated with specific characteristics of dissolution profiles. The use of confusing terms in the brand names of products with SOMRDFs in Colombia was also identified. This significant conceptual misunderstanding could lead to errors in the prescribing and use of these technologies and could mislead future researchers investigating this field. The purpose of this review is to minimise future misinterpretations when referring to or researching any type of modified release technology by proposing harmonised terms for describing SOMRDFs.
