Abstract: ISGylation has traditionally been examined in the context of antiviral immunity, where it is widely recognized as a protective interferon-stimulated response. This protective dimension may be considered the “yang” of ISGylation, reflecting its role in viral restriction, immune defense, and maintenance of cellular homeostasis. Numerous reviews have emphasized this antiviral and beneficial function while contrasting it with emerging evidence implicating ISGylation in cancer-associated pathways, where its effects remain less clearly defined, often context-dependent, and potentially pathogenic. This disease-promoting dimension may represent the “yin” of ISGylation, in which the same regulatory system may contribute to oncogenic signaling, immune evasion, tumor–stromal interactions, or cancer cell cooperation. However, existing literature has largely treated these opposing roles as parallel but separate phenomena. This review proposes a unifying perspective by examining ISGylation as a dynamic regulatory system whose functional outcome is shaped by cellular context, disease state, and intercellular communication. Recent findings are synthesized on the dual activities of ISG15, both as an intracellular ubiquitin-like modifier and as a free, secreted molecule with cytokine-like properties. While intracellular ISGylation affects viral restriction, immune signaling, and oncogenic pathways, increasing evidence suggests that unconjugated ISG15 can be released from cells and participate in immune modulation beyond the cell of origin. Notably, this review highlights the underexplored role of exosome-mediated ISG15 trafficking as a potential mechanism of cell-to-cell communication. This mode of signaling may be particularly relevant in the tumor microenvironment, where ISGylation could influence immune evasion, tumor–stromal crosstalk, and cooperative cancer cell behavior in ways that are not yet fully appreciated. By integrating intracellular and extracellular dimensions, this review reframes the “protective versus pathogenic” dilemma as a yin–yang regulatory balance and suggests that ISGylation’s therapeutic potential may be embedded in its intertwined intracellular and intercellular communication networks in viral infection and cancer.
Introduction: Monoclonal antibodies (mAbs) that target receptor-mediated oncogenic pathways have revolutionized oncology research. Better therapeutic indices are possible with these mAbs for targeted tumor treatment. This review covers receptor-targeted monoclonal antibodies targeting the EGFR, HER2, and VEGF pathways in solid tumors, as well as their therapeutic use and development. Methods: The study searched the scientific literature to identify key FDA-authorized studies on the EGFR, HER2, and VEGF/VEGFR pathways, as well as translational research and mechanistic investigations of these pathways. The focus was on developing next-generation antibody engineering platforms, understanding resistance mechanisms, and using biomarkers to select patients. Results: Therapeutic monoclonal antibodies (mAbs) inhibited carcinogenic signaling pathways, such as RAS/MAPK and PI3K/AKT. When mAbs engage with the immune system, they activate the complement system and induce antibody-dependent cellular cytotoxicity. Clinical trials have shown that biomarker-selected cohorts of patients with colorectal, breast, lung, gastric, and other cancers have improved survival rates without disease recurrence. Mutations, activation of alternative pathways, and changes in the tumor microenvironment may generate intrinsic and acquired resistance, reducing long-term efficacy. Discussion: Resistance patterns highlight the need for adaptable strategies that account for the biology of multiple target organisms. Cell-penetrating platforms, glycoengineering, antibody-drug conjugates, and bispecific antibodies have been developed to improve therapeutic efficacy, decrease escape mechanisms, and increase drug accessibility. Conclusion: Receptor-targeting monoclonal antibodies are crucial in precision oncology. Future advances must include molecular profiling, smart combination approaches, and nextgeneration antibody engineering to improve response durability and patient outcomes.
Introduction: Inflammatory bowel disease, encompassing ulcerative colitis and Crohn's disease, represents a growing global health burden, characterised by chronic intestinal inflammation, oxidative stress, and progressive mucosal barrier dysfunction. This study investigated the anti-colitic potential of the whole alkaloid extract of Linum usitatissimum (ALU) in a murine model of dextran sodium sulphate (DSS)-induced colitis, evaluating its antioxidant, anti-inflammatory, and mucosal-protective properties. Methods: Forty male BALB/c mice were divided into five groups (n = 8): vehicle control, DSS-only, and three DSS groups treated orally with ALU at 50, 100, or 200 mg/kg daily. Clinical activity, colon weight-to-length ratio, H&E histological scoring, and biochemical markers (CAT, GSH, NO, MDA) were assessed on Day 7. Results: DSS induced marked colitis, which ALU reversed dose-dependently; at 200 mg/kg, ALU normalised the colon weight-to-length ratio, restored CAT and GSH levels, reduced NO and MDA, and produced near-complete histological recovery. Discussion: The current study demonstrates that ALU has considerable antioxidant and intestinal anti-inflammatory capabilities. The anti-colitic effect was demonstrated through multiple pathways, including maintaining a stable body weight, reducing the colon weightto-length ratio, restoring endogenous antioxidant defenses, and inhibiting pro-oxidant and pro-inflammatory mediators. Conclusion: These findings show that the entire alkaloid extract from Linum usitatissimum seeds significantly reduces inflammation in the DSS-induced colitis model in vivo, showing its potential as an anti-inflammatory drug for the treatment of inflammatory bowel diseases.
Background: Beta-sitosterol, a plant-derived phytosterol with potent anticancer and pro-apoptotic properties, suffers from poor oral bioavailability due to its classification as a BCS Class II compound. To overcome this limitation, a transdermal delivery system was explored using vesicular carriers, transethosomes, and transferosomes. The central hypothesis proposed that transethosomal gels, due to their ethanol content and enhanced membrane fluidity, would demonstrate superior drug entrapment, permeation, and anticancer efficacy compared to transferosomal gels. Methods: Transethosomal and transferosomal formulations containing beta-sitosterol were developed and optimized using a Box–Behnken Design. The optimized vesicles were characterized for particle size, zeta potential, and entrapment efficiency, followed by incorporation into Carbopol 934-based gels. These gels were then evaluated for in vitro release, ex vivo skin permeation, cytotoxicity against MCF-7 breast cancer cells, and antibacterial activity. Results: Among the formulations, transethosomes exhibited the most desirable properties, including a vesicle size of 180 nm, an entrapment efficiency of 80.55%, and a zeta potential of −26 mV, indicating stability and enhanced penetration. The optimized transethosomal gel (ET4G3) showed 84.85% drug release, 75.4% ex vivo skin permeation, significant cytotoxicity toward MCF-7 cells, and notable antibacterial activity. Discussion: The ethanol content in transethosomes improved membrane flexibility and skin permeability, resulting in better performance than transferosomes. The release followed Higuchi kinetics, indicating a diffusion-controlled, sustained delivery. Conclusion: The superior efficacy of ET4G3 highlights its potential as a promising transdermal nanocarrier for targeted and sustained breast cancer therapy, offering an effective alternative to conventional oral delivery systems.
Diabetes mellitus is a chronic metabolic disorder with rising global prevalence. Type 2 diabetes mellitus is increasingly recognized as a major risk factor for cognitive decline, leading to conditions such as mild cognitive impairment and Alzheimer’s disease. The underlying mechanisms involve insulin resistance, oxidative stress, neuroinflammation, and vascular dysfunction, necessitating a multidimensional approach for management and early detection. This review aims to summarize the epidemiological trends of diabetes induced cognitive decline, evaluate current pharmacological treatments, explore the role of bioactive compounds, and highlight emerging biomarkers for early diagnosis and therapeutic monitoring. A comprehensive literature search was conducted using Google Scholar, PubMed, and ScienceDirect to identify studies related to diabetes induced cognitive decline, focusing on epidemiology, pharmacological treatments, bioactive compounds, and novel biomarkers. The epidemiological studies highlight the increasing prevalence of cognitive decline among individuals with diabetes, emphasizing the urgent need for early detection and intervention. Current pharmacological treatments, including antidiabetic and neuroprotective agents, have shown potential in managing cognitive decline, although challenges remain in their efficacy and long-term safety. The potential bioactive compounds, including Flavonoids, polyphenols, and others, exhibit antioxidant, anti-inflammatory, and neuroprotective properties, showing promise in mitigating cognitive decline associated with diabetes. Emerging biomarkers offer potential for early diagnosis and personalized treatment strategies. By integrating insights from epidemiology, pharmacological treatment, bioactive compounds, and biomarker research, this review underscores the need for innovative, multidisciplinary approaches to combat diabetes induced cognitive decline. Hence, future research should focus on clinical trials to validate the therapeutic efficacy of bioactive compounds and biomarkers.
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder and the leading cause of dementia in older adults, characterized by memory decline, cognitive impairment, and behavioral disturbances. Pathologically, AD is defined by extracellular accumulation of amyloid-beta (Aβ) plaques and intracellular neurofibrillary tangles composed of hyperphosphorylated tau protein. Although aging remains the predominant risk factor, the disease arises from a multifactorial interaction of genetic predisposition, oxidative stress, environmental influences, and lifestyle factors. Dysregulation of the Wnt signaling pathway, which regulates synaptic function and neuronal plasticity, has been increasingly associated with AD pathogenesis. This pathway’s impairment contributes to synaptic loss, neuroinflammation, and cognitive decline. Conventional therapies for AD primarily alleviate symptoms without halting neurodegeneration, prompting growing interest in natural and bioactive compounds as alternative therapeutic agents. Plant- and marine-derived metabolites exhibit potent antioxidant, anti-inflammatory, and acetylcholines-terase-inhibitory activities that may counteract multiple pathogenic mechanisms in AD. Several studies have demonstrated that these natural compounds can suppress Aβ aggregation, downregulate BACE1 expression, and protect neurons against oxidative and inflammatory damage. Moreover, peptide- and protein-based molecules, particularly those from natural sources, are gaining attention due to their biocompatibility and ability to target specific molecular pathways involved in neurodegeneration. However, challenges such as difficult purification processes, variable bioavailability, and inconsistent clinical outcomes limit their translation into approved therapies. Despite these obstacles, natural compounds provide a promising, multitargeted, and relatively safer approach compared with synthetic drugs. Overall, AD development reflects a complex interplay of genetic, environmental, and lifestyle factors. Exploring natural products and peptide-based therapeutics may therefore offer new strategies to delay disease progression and enhance neuronal resilience, highlighting their potential as complementary options in the future management of Alzheimer’s disease.
Introduction: Osteoarthritis is the fifth leading cause of disability, affecting 10% of the population globally. Current therapies have many negative effects and do not address the underlying cause of the illness. There is not a single such medicinally potent product accessible to treat the disease and slow its progression. Pueraria tuberosa has shown favourable outcomes in the management of osteoarthritis. Material and Method: The current work uses a central composite design to create and optimize a unique herbal medication delivery system of Pueraria tuberosa. The impact of chi-tosan and polyvinyl acetate (PVA) on elongation and drug release has been evaluated using the central composite layout. Drug release, in vivo drug permeation, and UV were used to evaluate transdermal patches (using egg membrane) and drug release kinetics. The formulation's anti-arthritic properties were investigated using the FCA model. Results: Preparation-related factors significantly impacted the physical and chemical features of compositions. Drug release and elongation values of the formulations increased with higher concentrations of Chitosan and a decrease in the level of PVA. Drug release kinetic study indicated the medication adhered to the Higuchi model. Compared to the disease-control and diclofenac-treated mice, the drug-treated mice show substantially higher locomotor activity. Histological investigations showed that compared to animals with diseases, animals on medication had much fewer inflammatory cells in their synovium. Discussion: The optimized formulation with higher Chitosan and lower PVA concentrations enhanced drug release and therapeutic efficacy following the Higuchi model. Improved locomotor activity and reduced synovial inflammation in treated mice confirmed superior anti-inflammatory potential. Conclusion: The findings showed that to create dependable, secure, and potent formulations that rival synthetic medications, additional herbs and their mixtures should be investigated, and more and more clinical trials must be conducted.
Introduction: Tongmai Jiangzhuo Granules (TMJZ), derived from clinical prac-tice, have the function of lowering uric acid in clinical settings and have the potential to protect the liver. In this study, lipid metabolomics and other technologies were used to reveal the mechanism of TMJZ on the hepatoprotective effect in hyperuricemia-related NAFLD mice. Methods: The efficacy of TMJZ in hepatoprotective effect was evaluated by lipid levels, liver function, and liver pathology in mice. LC-MS lipidomics and PLC-DA analysis were used to explore TMJZ's effects on liver lipid metabolism and to identify affected pathways. Key proteins involved in glycerophospholipid metabolism were verified using ELISA and Western blot. Finally, components of TMJZ were identified by LC-MS. Results: TMJZ significantly reduced uric acid levels and lowered serum TC, TG, LDL-c, ALT, and AST in model mice. Histopathological analysis indicated that TMJZ decreased liver weight and improved liver fatty lesions. Lipid metabolomics showed that TMJZ ad-ministration could change the proportions of the main lipid components, including glycer-ophospholipids, glycerides, sphingolipids, fatty acids, and glycolipids, in the liver. TMJZ could increase LCAT and PLA2 levels and decrease LPCAT3 levels. Meanwhile, 533 com-ponents of TMJZ were detected by LC-MS analysis, including Berberine and Salvianolic acid A. Discussion: LCAT, LP-PLA2, and LPCAT3 played essential roles in lipid components, phospholipid biosynthesis, and catabolism, which might be the promising solution of TMJZA for Hyperuricemia-related NAFLD. Conclusion: TMJZ exhibits a favorable anti-NAFLD effect. Its mechanism may involve increasing LCAT and PLA2, decreasing LPCAT3, and regulating the glycerophospholipid metabolism pathway.
Introduction: Immediate dental implant placement in fresh extraction sockets has become a widely accepted treatment modality, yet marginal bone loss remains a significant clinical concern. Advanced Platelet-Rich Fibrin Plus (A-PRF+) represents a novel autolo-gous biomaterial with enhanced regenerative properties. This prospective clinical study aimed to evaluate the effect of A-PRF+ on Marginal Bone Level (MBL) preservation in immediate dental implant placement. Materials and Methods: Sixteen patients (3 males, 13 females; mean age 44.25 years) re-quiring immediate implant placement in fresh extraction sockets were enrolled. Fifty dental implants (Dentium, USA) were randomly allocated into two groups: study group (n = 26) receiving A-PRF+ as graft material for jumping distance augmentation, and control group (n = 24) without augmentation material. Randomization was performed using computer-generated random sequences with allocation concealment via sealed opaque envelopes. Im-plants were placed 1mm subcrestal following atraumatic extraction. A-PRF+ was prepared using a standardized centrifugation protocol (1300 rpm, 8 minutes). Marginal bone levels were measured using calibrated periodontal probes at baseline and 24 weeks post-surgery, with implant length serving as the reference for calibration. Results: At baseline, mean MBL was 14.11mm (study group) and 14.25mm (control group). After 24 weeks, the study group demonstrated superior bone preservation with a mean MBL of 12.36mm compared to 11.50mm in the control group (p < 0.05). The overall survival rate was 96% with 4% failure rate. Maxillary sites showed significantly better outcomes in the study group compared to controls (p < 0.01), while mandibular sites showed no significant difference between groups. Discussion: The superior marginal bone preservation observed in the A-PRF+ group high-lights its potential as a valuable adjunct in immediate implant therapy. The statistically sig-nificant difference, particularly in maxillary sites, suggests that A-PRF+ may effectively counteract the physiological bone remodeling that typically follows tooth extraction. This autologous biomaterial likely enhances healing by concentrating growth factors and provid-ing a stable fibrin scaffold, both of which are critical for bone regeneration in the jumping distance. Conclusion: A-PRF+ application significantly enhances marginal bone level preservation in immediate dental implant placement. The autologous biomaterial demonstrates particular efficacy in maxillary sites, supporting its clinical application as an adjunctive treatment for immediate implant protocols.
Introduction: Curcuma xanthorrhiza Roxb, a medicinal plant endemic to Indonesia, is widely utilized in traditional medicine for its immunomodulatory effects. Objectives: This study investigates the potential of enhancing the growth and secondary metabolite production of C. xanthorrhiza through tissue culture methods, with a specific focus on the role of coconut water as a natural growth stimulant. Methods: Using a systematic experimental design, we applied varying concentrations of coconut water (0%, 10%, and 20%) in Murashige and Skoog (MS) media containing 2,4-Dichlorophenoxyacetic acid (2,4-D) and Indole-3-Butyric Acid (IBA) at 0.4 ppm each. The shoot explants were cultured for eight weeks, during which qualitative analyses were conducted using Thin Layer Chromatography (TLC) to identify the secondary metabolite profiles. A bioinformatics approach was conducted to predict the activity of curcuminoids against target receptors Cytotoxic T-Lymphocyte-Associated Protein 4 (CTLA-4) and Programmed Cell Death Protein 1 (PD-1). Results: Addition of 20% coconut water significantly optimized callus induction and overall growth, resulting in consistent curcuminoid production across all treatments. Bioinformatics analyses suggest that curcumin has a dual modulatory effect on the CTLA-4 and PD-1 pathways, highlighting its potential utility in immunomodulatory cancer therapies. However, further validation through in vitro and in vivo studies is warranted. Discussions: This research contributes to the scientific validation of traditional uses of C. xanthorrhiza in plant medicine and enhances understanding of its bioactive compounds, supporting efforts to preserve indigenous medicinal plant knowledge and its application in modern healthcare solutions. Conclusions: This research highlights the effectiveness of incorporating natural coconut water into tissue culture practices, thereby facilitating the cultivation and yield of C. xanthorrhiza and contributing to the preservation of its traditional medicinal applications while addressing the growing demand for herbal medicines.
Major depressive disorder (MDD) affects over 280 million people worldwide and is associated with functional disability, reduced productivity, and impaired quality of life. Despite extensive research, its etiology and management remain complex and multi-factorial. This review critically examines contemporary etiological hypotheses, emerging biomarkers, and recent therapeutic advancements in MDD. A systematic search of PubMed, Embase, Scopus, and PsycINFO databases identified English-language studies relevant to pathophysiology and treatment. Stress-related mechanisms, including hyperactivity of the hypothalamic–pituitary–adrenal (HPA) axis, elevated cortisol, and dysregulated inflammatory cytokines (e.g., IL-6, TNF-α), are consistently implicated. Neuroimaging and proteomic studies reveal structural and functional alterations in the prefrontal cortex, hippocampus, and amygdala, while genetic polymorphisms (e.g., BDNF Val66Met) are associated with susceptibility. Therapeutically, rapid-acting antidepressants such as ketamine achieve 50-70% response rates within 24 hours, compared with 30-40% for conventional SSRIs over 4-6 weeks. Non-pharmacological approaches, including cognitive-behavioral therapy and mindfulness-based interventions, show remission rates of 30-50% in moderate-to-severe depression. The integration of biomarker research with innovative treatments highlights the potential for personalized, patient-centered care. Future studies should focus on large-scale biomarker validation and the development of tailored therapeutic algorithms to optimize outcomes in MDD.
Background: Guipi Tang has been used as a therapeutic agent in many diseases because of its function of balancing the immune state; however, there are no reports concerning the effects of Guipi Tang on unexplained Recurrent Spontaneous Abortion (RSA). Objective: The present experiment was designed to investigate the effects of Guipi Tang on the pregnancy outcomes of the RSA mouse as well as explore its underlying mechanism. results: In the RSA group, the rate of absorbed embryo was statistically higher than control group. Whereas, Guipi Tang administration showed a protective effect on spontaneous abortion in RSA mice. The morphology of maternal-fetal interface was improved by Guipi Tang. The RSA + Guipi Tang group demonstrated remarkably augmented expression levels of Arginase-1, CD206+ and IL-10, as well as diminished level of IL-1β compared with RSA group. Methods: Thirty female CBA/J mice aging 8-10 weeks were randomly categorized into 3 groups and copulated with BALB/c mice aging 8-10 weeks (BALB/c×CBA/J) as control group (n=10), or copulated with DBA/2 mice aging 8-10 weeks (DBA/2×CBA/J) as RSA model (n=10), or DBA/2×CBA/J mice aging 8-10 weeks with Guipi Tang administration as RSA + Guipi Tang group (n=10). The number of resorbed embryos was counted on 13.5 days after gestation. Furthermore, histological analysis of placental and decidual tissues was performed. Immunohistochemistry and western blotting were also employed to detect protein expressions of Arginase-1, CD206+(M2-phenotype macrophage), IL-1β, and IL10 in the placental and decidual tissues. Results: In the RSA group, the rate of absorbed embryos was statistically higher than that of the control group. At the same time, the Guipi Tang administration showed protective effects against embryo loss in RSA mice. The morphology of the maternal-fetal interface was improved by Guipi Tang. The RSA + Guipi Tang group demonstrated remarkably augmented expression of Arginase-1, CD206+, and IL-10, as well as the diminished expression of IL-1β, compared with the RSA group. Discussion: Immune cell metabolic reprogramming could be one of the vital targets for improving the pregnancy outcomes of RSA. Besides, the Guipi Tang administration is beneficial for maintaining immune tolerance at the maternal-fetal interface. These data provide a new perspective for RSA treatment. Conclusion: Guipi Tang administration demonstrates protective effects on pregnancy outcomes in the RSA mouse, at least partly via regulating glutamine metabolism, thereby balancing macrophage polarization at the maternal-fetal interface.
Introduction: Lidocaine (lignocaine) is a widely used local anesthetic and an anti-arrhythmic drug. However, conventional synthetic routes involve toxic reagents and environmentally hazardous conditions. This study aims to develop a cost-effective, eco-friendly, and scalable synthetic methodology for lidocaine and its process- and product-related impurities. Methods: An environmentally benign synthetic route was developed using palladium on carbon (Pd/C) as a reducing agent, methanol as a safer solvent, and potassium carbonate and potassium iodide as mild bases. Thirteen lidocaine analogs and impurities were synthesized under optimized conditions. The compounds were purified by column chromatography and characterized using TLC, IR, ^1H NMR, and mass spectrometry. Reaction parameters, such as yield, temperature, and stoichiometry, were systematically optimized. In silico solubility prediction of lidocaine hydrochloride was performed using a machine learning-based model. Results: The method achieved high yields (80–97%) across most analogs, demonstrating improved efficiency compared to conventional approaches. Spectroscopic characterization confirmed the structures of the synthesized compounds. The process reduced the use of hazardous reagents while maintaining reproducibility and scalability. The synthesized impurities were suitable as reference standards for pharmaceutical quality control. Solubility prediction indicated favorable aqueous solubility at physiological pH. Discussion: The developed approach addresses limitations of traditional methods by improving environmental safety, process efficiency, and product purity. The integration of computational solubility prediction enhances the applicability in formulation development, although reliance on predictive models remains a limitation. Conclusion: This study presents a sustainable and efficient synthetic protocol (3336+) for lidocaine and its impurities, offering significant advantages for large-scale pharmaceutical manufacturing and impurity profiling.
Disintegrating tablets incorporated into Multi-Unit Pellet Systems (MUPS) is an innovative method of delivering drugs that combines the benefits of multiple-unit formulations with the ease of a single-dose administration. This review article explores the difficulties and advancements in creating and using disintegrating tablets for multiple-unit pellet systems (MUPS). Key challenges include formulation complexities like manufacturing process limitations, stability concerns, and regulatory compliance barriers. Solutions to these issues involve creating advanced dosage forms like disintegrating TMUPS. The review examines case studies that illustrate the effective adoption and market expansion of MUPS, resulting in enhanced patient adherence and improved treatment results. In addition, the review emphasizes the advantages, formulation, and process-related challenges in developing disintegrating tablets of MUPS, i.e., conversion of MUPS to a single-unit system (SUS). Additionally, the discussion encompasses future and sustainable materials that can be adopted to advance the formulation development of disintegrating TMUPS. It emphasizes the continual efforts to overcome current obstacles and take advantage of new opportunities to improve drug delivery.
Introduction: Cancer ranks among the leading causes of death globally. Dysregulation of growth factor receptors like EGFR, through oncogene activation or tumor suppressor loss, underlies aggressive, therapy-resistant malignancies, making EGFR a prime therapeutic target. Method: Computational methods such as molecular docking, molecular dynamics simulations, Density Functional Theory (DFT) calculations, and in silico pharmacokinetic profiling to investigate ligand-target binding interactions were utilized in this study. Drug-like-ness properties were also evaluated based on Lipinski's rule of five. Results: All designed quinazoline derivatives were subjected to in-silico evaluation involving molecular docking, molecular dynamics, DFT, and the (absorption, distribution, metabolism, excretion, and toxicity) ADMET study as EGFR inhibitors. In addition, drug-likeness was determined using the Lipinski rule of five. Among all proposed 4-amino quinazoline derivatives, it was found that all ligands showed binding energy scores in the range of -7.5 to -7.8 kcal/mol. Lower water solubility (logS), which ranged from -3.652 log mol/L to -3.463 log mol/L Discussion: The current study focuses on the in-silico evaluation and molecular prediction of some quinazoline derivatives as EGFR inhibitors. Ligands A1, A3, A4, and A5 showed relatively favorable bioactivity, likeness with one violation as compared to standard drugs included in this computational study, which indicated that A1, A3, A4, and A5 ligands were excellent EGFR inhibitors. Conclusion: These parameters enable the selection of the most promising candidates for synthesis to address EGFR-TK gene mutations and resistance.
Introduction: Qi-Ju-Di-Huang-Wan (QJDHW), a traditional herbal remedy frequently utilized, has been used in managing Sjögren’s syndrome (SS) in China. However, the pharmacological mechanism remains unclear. Here, we aimed to investigate the therapeutic mechanisms of QJDHW in the treatment of SS through performing a network pharmacology analysis. Materials and Methods: The bioactive components and corresponding targets of QJDHW were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP), while SS-related genes were obtained from the DisGeNET and GeneCards platforms. Overlapping targets between QJDHW and SS were used to construct a Protein-Protein Interaction (PPI) network with the help of Cytoscape and the BisoGenet plugin. To further elucidate the underlying mechanisms, functional enrichment was conducted using Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Finally, molecular docking was performed to evaluate the binding affinity between selected active ingredients and target proteins. Results: QJDHW comprises eight medicinal herbs containing 82 bioactive compounds and 142 predicted targets. Among these, 29 targets overlapped with SS-associated genes and were considered potential therapeutic targets. Protein–Protein Interaction (PPI) network analysis identified 221 core genes. Functional enrichment analysis yielded 2,036 Gene Ontology (GO) terms and 121 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, with significant enrichment (adjusted p < 0.05) in pathways including MAPK signaling, apoptosis, and viral infection–related pathways. Molecular docking revealed strong binding affinities between representative compounds (e.g., luteolin, quercetin) and core targets (e.g., ESR1, NTRK1), with binding energies all ≤ –7.0 kcal/mol, confirming potential molecular interactions underlying QJDHW’s therapeutic effects. Discussion: The therapeutic action of QJDHW may involve modulation of pathways related to immune responses, antiviral defenses, and apoptosis regulation. Notably enriched path-ways included MAPK signaling, apoptosis, and those associated with viral infections such as human T-cell leukemia virus type 1, hepatitis C, and Epstein-Barr virus. Molecular dock-ing supported the interaction between key compounds and selected targets. Conclusion: This network pharmacology study indicates that QJDHW may exert therapeu-tic effects in SS by targeting multiple bioactive compounds, genes, and biological pathways, particularly those involved in antiviral activity, immune modulation, and inhibition of apop-tosis.
Introduction: Curcumin, due to its large molecular weight, is poorly absorbed by the body, resulting in low blood concentrations. To address this challenge, researchers have developed a variety of nanoformulations to enhance its bioavailability. This review article examines the potential of these curcumin nano-formulations in the management of Inflam-matory Bowel Disease (IBD). While curcumin is known for its anti-inflammatory properties, its limited bioavailability restricts its therapeutic effectiveness. The current systematic re-view seeks to investigate the mechanisms and bioavailability of each curcumin nano-formu-lation to gain a comprehensive understanding of their potential to ameliorate IBD symptoms. Methods: A comprehensive search of scientific databases, including PubMed, Scopus, Google Scholar, and Web of Science, was conducted using the keywords "nano," "curcu-min," "inflammatory bowel diseases," and "colitis." This search encompassed the period from the inception date to July 2024. For analysis, only original articles published in English were included. Non-English articles, reviewed literature, conference proceedings, book chapters, or irrelevant material were systematically excluded from consideration. Results: From a total of 559 articles, only 69 were included. Based on the collected data, the different nano-formulations often divide into one of the following categories: Nanosuspen-sions, Microemulsions, Lipid-Based Systems, Polymeric Nanoparticles, Polymeric Mi-celles, Niosomes, Nanodispersions, Dendrimers, Phytosomes, Inorganic Nanocarriers, and Hybrid Nanocarriers. Discussion: Nano-curcumin is effective in reducing inflammatory factors such as TNF-α, IL-1β, and IL-6, and in enhancing anti-inflammatory factors such as IL-4 and IL-10. While research on nano-curcumin for IBD is promising, more clinical studies are needed to estab-lish appropriate dosages and assess potential side effects. Conclusion: This systematic review highlights the main inflammatory pathways that can be suppressed by various curcumin nano-formulations and the need to explore the cost-effec-tiveness and safety of nano-curcumin in human trials.
Introduction: Primary dysmenorrhea is manifested as uterine cramps before and/or during menstruation without pelvic disease, which causes painful menstruation. Many patients with primary dysmenorrhea expressed the presence of emotional depression, anxi-ety, and stress. Vitamin E has been demonstrated to reduce menstrual pain, but its impact on primary dysmenorrhea-related mood responses remains unexplored. Methods: The present report examined the ameliorative effects of α-tocopherol (α-T) and tocotrienol-rich palm oil extract (TRPO) on a mouse model of primary dysmenorrhea, in-duced by oxytocin injection in estrogen-primed female mice. The depressive- and anxiety-like responses were tested via the open field. Social interaction and tail suspension test. The serum corticosterone and hippocampal pro-inflammatory cytokine levels were measured via an ELISA test. Results: Our study revealed that mice induced with primary dysmenorrhea, via estradiol and oxytocin injections, exhibited depressive- and anxiety-like behaviors. Treatment with α-T (50 and 100 mg/kg) and TRPO (100 and 200 mg/kg) via the oral route significantly modu-lated these behavioral changes. Interestingly, treatment with TRPO, but not α-T, signifi-cantly modulated the increased serum corticosterone level. An ELISA study on the hippo-campal tissue showed that α-T and TRPO significantly suppressed elevated IL-1β and IL-6, but only TRPO inhibited the elevated TNF-α. Discussion: The results suggested that TRPO relieved primary dysmenorrhea-related mood disorders, at least in part, by modulating the stress-related and pro-neuroinflammatory path-ways, with a slightly different mechanism than α-T. Conclusion: This study's findings may establish a new basis for utilizing vitamin E or its isomers in treating depressive and anxiety-like responses associated with primary dysmen-orrhea, thereby enhancing women's health.
Introduction: One of the most significant public health issues facing all countries is Diabetes mellitus, whose prevalence has more than doubled over the last three decades. The prevalence of prediabetes and Type 2 Diabetes Mellitus (T2DM) has increased markedly among children, adolescents, and young adults over the past two decades. Effective management typically involves lifestyle changes and pharmacological intervention, particularly oral antidiabetic agents for Type 2 diabetes. However, current therapies face limitations, including adverse effects and issues with patient adherence. Due to its significant influence on insulin resistance and type 2 diabetes, adiponectin has been identified as a key protective factor against the harmful metabolic and cardiovascular effects of obesity. In order to improve ATP synthesis, adiponectin primarily acts by decreasing hepatic gluconeogenesis and increasing muscular glucose transport. Methods: A comprehensive review of recent literature (2010-2025) was conducted using databases such as PubMed, ScienceDirect, and Nature. The selected studies included in vitro experiments, in vivo models, and in silico simulations that investigated adiponectin’s molecular mechanisms, receptor interactions, therapeutic implications, and translational challenges. Results: Evidence demonstrates that adiponectin improves insulin sensitivity, stimulates fatty acid oxidation, reduces hepatic lipid accumulation, and exerts anti-inflammatory and antioxidant effects. In silico studies, including molecular docking, molecular dynamics, and structural modeling, have accelerated the discovery of potential AdipoR agonists. Discussion: Adiponectin is a multifunctional regulator that bridges the gap between metabolic regulation and innovative therapeutics, offering great potential for the management of diabetes. In order to overcome translational obstacles, future advancements will depend on integrating computational predictions with experimental validation and developing customized treatment techniques. Conclusion: ADIPOQ or its signaling pathway could be targeted as a promising strategy for developing novel antidiabetic interventions.
Background: Acute Peripheral neuropathy is a significant complication of both Diabetes Mellitus and fluoroquinolone antibiotics. Only a few articles in the literature summarise the findings of acute peripheral neuropathy in the context of diabetic patients taking fluoroquinolone antibiotics. Case Presentation: A 38-year-old female with diabetes was administered Inj. Ciprofloxacin 0.5 mg IV as a test dose to manage the right foot diabetic ulcer, and she developed a sudden burning sensation all over her body. This case report tried to explain the various scientific perspectives on the pathogenesis of acute peripheral neuropathy in a diabetic patient taking fluoroquinolone. The case report discussed is based on findings from the Indian Pharmacopoeia Commission (IPC)-sponsored Pharmacovigilance Programme of India (PvPI) Adverse Drug Reaction (ADR) reporting form. Conclusion: There are multifactorial causes that may synergistically aggravate the acute peripheral neuropathy condition in diabetic patients taking fluoroquinolone antibiotics. There is a need to be very careful while giving fluoroquinolone to a diabetic patient.
