Search Results (1,348)

Nanotechnology offers innovative methodologies for enhancing the diagnosis and treatment of ovarian cancer by utilizing specialized nanoparticles. The utilization of nanoparticles offers distinct advantages, specifically that these entities enhance the bioavailability of therapeutic agents and facilitate the targeted delivery of pharmacological agents to neoplastic cells. A diverse array of nanoparticles, including but not limited to liposomes, dendrimers, and gold nanoparticles, function as proficient carriers for drug delivery. Nevertheless, notwithstanding the auspicious potential of these applications, challenges pertaining to toxicity, biocompatibility, and the necessity for comprehensive clinical evaluations pose considerable barriers to the widespread implementation of these technologies. The incorporation of nanotechnology into clinical practice holds the promise of significantly transforming the management of ovarian cancer, offering novel diagnostic tools and therapeutic strategies that enhance patient outcomes and prognoses. In summary, the deployment of nanotechnology in the context of ovarian cancer epitomizes a revolutionary paradigm in medical science, amalgamating sophisticated materials and methodologies to enhance both diagnostic and therapeutic outcomes. Continued research and development endeavors are essential to fully realize the extensive potential of these innovative solutions and address the existing challenges associated with their application in clinical settings. Full article

Background: Bipolar disorder (BD) is a chronic and disabling psychiatric condition characterized by recurring episodes of mania, hypomania, and depression. Despite the availability of mood stabilizers, antipsychotics, and antidepressants, long-term management remains challenging due to incomplete symptom control, adverse effects, and high relapse rates. Methods: This paper is a narrative review aimed at synthesizing emerging trends and future directions in the pharmacological treatment of BD. Results: Future pharmacotherapy for BD is likely to shift toward precision medicine, leveraging advances in genetics, biomarkers, and neuroimaging to guide personalized treatment strategies. Novel drug development will also target previously underexplored mechanisms, such as inflammation, mitochondrial dysfunction, circadian rhythm disturbances, and glutamatergic dysregulation. Physiological endophenotypes, such as immune-metabolic profiles, circadian rhythms, and stress reactivity, are emerging as promising translational tools for tailoring treatment and reducing associated somatic comorbidity and mortality. Recognition of the heterogeneous longitudinal trajectories of BD, including chronic mixed states, long depressive episodes, or intermittent manic phases, has underscored the value of clinical staging models to inform both pharmacological strategies and biomarker research. Disrupted circadian rhythms and associated chronotypes further support the development of individualized chronotherapeutic interventions. Emerging chronotherapeutic approaches based on individual biological rhythms, along with innovative monitoring strategies such as saliva-based lithium sensors, are reshaping the future landscape. Anti-inflammatory agents, neurosteroids, and compounds modulating oxidative stress are emerging as promising candidates. Additionally, medications targeting specific biological pathways implicated in bipolar pathophysiology, such as N-methyl-D-aspartate (NMDA) receptor modulators, phosphodiesterase inhibitors, and neuropeptides, are under investigation. Conclusions: Advances in pharmacogenomics will enable clinicians to predict individual responses and tolerability, minimizing trial-and-error prescribing. The future landscape may also incorporate digital therapeutics, combining pharmacotherapy with remote monitoring and data-driven adjustments. Ultimately, integrating innovative drug therapies with personalized approaches has the potential to enhance efficacy, reduce adverse effects, and improve long-term outcomes for individuals with bipolar disorder, ushering in a new era of precision psychiatry. Full article

Alopecia, a prevalent dermatological disorder affecting over half of the global population, is strongly associated with psychological distress. Extracts from Periplaneta americana (L. PA), a medicinal insect resource, exhibit pharmacological activities (e.g., antioxidant, anti-inflammatory, microcirculation improvement) that align with core therapeutic targets for alopecia. This study aimed to systematically investigate the efficacy and mechanisms of PA extracts in promoting hair regeneration. A strategy combining network pharmacology prediction and in vivo experiments was adopted. The efficacy of a Periplaneta americana extract was validated by evaluating hair regrowth status and skin pathological staining in C57BL/6J mice. Transcriptomics, metabolomics, RT-qPCR, and 16s rRNA techniques were integrated to dissect the underlying mechanisms of its hair-growth-promoting effects. PA-011 significantly promoted hair regeneration in depilated mice via multiple mechanisms: enhanced skin superoxide dismutase activity and upregulated vascular endothelial growth factor expression; modulated FOXO/PI3K/AKT signaling pathway and restored skin microbiota homeostasis; and accelerated transition of hair follicles from the telogen to anagen phase. PA-011 exerts hair-promoting effects through synergistic modulation of FOXO/PI3K/AKT signaling and the skin microbiome. As a novel therapeutic candidate, it warrants further systematic investigation for clinical translation. Full article

Osteoarthritis (OA) is a chronic progressive joint disease characterized by cartilage degradation, subchondral bone remodeling, and synovial inflammation. This complex disorder arises from the interplay between mechanical stress and inflammatory processes, which is mediated by interconnected molecular signaling pathways. This review explores the dual roles of inflammatory and mechanical signaling in OA pathogenesis, focusing on crucial pathways such as NF-kB, JAK/STAT, and MAPK in inflammation, as well as Wnt/β-catenin, Integrin-FAK, and Hippo-YAP/TAZ in mechanotransduction. The interplay between these pathways highlights a vicious cycle wherein mechanical stress exacerbates inflammation, and inflammation weakens cartilage, increasing its vulnerability to mechanical damage. Additionally, we discuss emerging therapeutic strategies targeting these pathways, including inhibitors of cartilage-degrading enzymes, anti-inflammatory biologics, cell-based regenerative approaches, and non-pharmacological mechanical interventions. By dissecting the molecular mechanisms underlying OA, this review aims to provide insights into novel interventions that address both inflammatory and mechanical components of the disease, paving the way for precision medicine in OA management. Full article

Nonalcoholic fatty liver disease (NAFLD) is a clinicopathological syndrome characterised by hepatic steatosis in the absence of significant alcohol consumption or other specific causes of liver injury. It has become one of the leading causes of liver dysfunction worldwide. However, the precise pathophysiological mechanisms underlying NAFLD remain unclear, and effective therapeutic strategies are still under investigation. Autophagy, a vital intracellular process in eukaryotic cells, enables the degradation and recycling of cytoplasmic components through a membrane trafficking pathway. Recent studies have demonstrated a strong association between impaired or deficient autophagy and the development and progression of NAFLD. Restoring autophagic function may represent a key approach to mitigating hepatocellular injury. Nevertheless, due to the complexity of autophagy regulation and its context-dependent effects on cellular function, therapeutic strategies targeting autophagy in NAFLD remain limited. This review aims to summarise the relationship between autophagy and NAFLD, focusing on autophagy as a central mechanism. We discuss the latest research advances regarding interventions such as diet and exercise, pharmacological therapies (including modern pharmacological therapy and plant-derived compounds), and other approaches (such as hormones, nanoparticles, gut microbiota, and vitamins). Furthermore, we briefly highlight potential autophagy-related molecular targets that may offer novel therapeutic insights for NAFLD management. Full article

Cardiovascular disease (CVD) remains the leading cause of mortality worldwide, with hypercholesterolemia identified as a major, but modifiable risk factor. This review serves as the second part of a comprehensive analysis of dyslipidemia management. The first installment laid the groundwork by detailing the key pathophysiological mechanisms of lipid metabolism, the development of atherosclerosis, major complications of hyperlipidemia, and the importance of cardiovascular risk assessment in therapeutic decision-making. It also examined non-pharmacological interventions and conventional therapies, with a detailed focus on statins and ezetimibe. Building upon that foundation, the present article focuses exclusively on emerging pharmacological therapies designed to overcome limitations of standard treatment. It explores the mechanisms, clinical applications, safety profiles, and pharmacogenetic aspects of novel agents such as proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors (alirocumab, evolocumab), small interfering RNA (siRNA) therapy (inclisiran), adenosine triphosphate–citrate lyase (ACL) inhibitor (bempedoic acid), microsomal triglyceride transfer protein (MTP) inhibitor (lomitapide), and angiopoietin-like protein 3 (ANGPTL3) inhibitor (evinacumab). These agents offer targeted strategies for patients with high residual cardiovascular risk, familial hypercholesterolemia (FH), or statin intolerance. By integrating the latest advances in precision medicine, this review underscores the expanding therapeutic landscape in dyslipidemia management and the evolving potential for individualized care. Full article

Glaucoma is recognized as a progressive optic neuropathy and a leading cause of irreversible blindness worldwide. While intraocular pressure (IOP) is considered the only modifiable risk factor, current medical treatments are challenged by issues such as inadequate IOP control and ocular side effects. Rho kinase (ROCK) inhibitors have been developed as a novel pharmacologic class targeting the trabecular meshwork to enhance conventional aqueous humor outflow. In this review, the pharmacokinetics and IOP-lowering efficacy of key ROCK inhibitors are summarized. Beyond IOP reduction, ROCK inhibitors exhibit neuroprotective, anti-inflammatory, antifibrotic, and ocular perfusion-enhancing effects. Finally, we analyzed the limitations and future prospects of ROCK inhibitors in the management of glaucoma. Full article

Background: Hepatocellular carcinoma (HCC) is one of the most common and fatal malignancies worldwide, characterized by remarkable molecular heterogeneity and poor clinical outcomes. Despite advancements in diagnosis and treatment, the prognosis for HCC remains dismal, largely due to late-stage diagnosis and limited therapeutic efficacy. Therefore, there is a critical need to identify novel therapeutic targets and explore alternative strategies, such as drug repurposing, to improve patient outcomes. Methods: In this study, we employed network pharmacology, molecular docking, and molecular dynamics (MD) simulations to explore the potential therapeutic targets of Nirmatrelvir in HCC. Results: Nirmatrelvir targets were predicted through SwissTarget (101 targets), SuperPred (1111 targets), and Way2Drug (38 targets). Concurrently, HCC-associated genes (5726) were retrieved from DisGeNet. Cross-referencing the two datasets identified 29 overlapping proteins. A protein–protein interaction (PPI) network constructed from the overlapping proteins was analyzed using CytoHubba, identifying 10 hub genes, with HDAC1, HDAC3, and STAT3 achieving the highest degree scores. Molecular docking revealed a strong binding affinity of Nirmatrelvir to HDAC1 (docking score = −7.319 kcal/mol), HDAC3 (−6.026 kcal/mol), and STAT3 (−6.304 kcal/mol). Moreover, Nirmatrelvir displayed stable dynamic behavior in repeated 200 ns simulation analyses. Binding free energy calculations using MM/GBSA showed values of −23.692 kcal/mol for the HDAC1–Nirmatrelvir complex, −33.360 kcal/mol for HDAC3, and −21.167 kcal/mol for STAT3. MM/PBSA analysis yielded −17.987 kcal/mol for HDAC1, −27.767 kcal/mol for HDAC3, and −16.986 kcal/mol for STAT3. Conclusions: The findings demonstrate Nirmatrelvir’s strong binding affinity towards HDAC3, underscoring its potential for future drug development. Collectively, the data provide computational evidence for repurposing Nirmatrelvir as a multi-target inhibitor in HCC therapy, warranting in vitro and in vivo studies to confirm its clinical efficacy and safety and elucidate its mechanisms of action in HCC. Full article

Idiopathic pulmonary fibrosis (IPF) is characterized by excessive extracellular matrix (ECM) deposition driven by aberrant fibroblast-to-myofibroblast transition (FMT). However, the upstream regulators and downstream effectors of this process remain incompletely understood. Here, we identify acyl-CoA synthetase long-chain family member 4 (ACSL4), a lipid metabolic enzyme, as a critical mediator linking complement component 5a (C5a)/C5a receptor 1 (C5aR1) signaling to FMT via calcium signaling. In bleomycin (BLM)-induced pulmonary fibrosis of C57BL/6JGpt mice, and in C5a-stimulated primary lung fibroblasts, the expression of ACSL4 was markedly upregulated. Pharmacological inhibition of ACSL4 (PRGL493) or C5aR1 (PMX53) attenuated the deposition of ECM and suppressed the expression of fibrotic markers in vivo and in vitro. Mechanistically, the activation of C5a/C5aR1 signaling increased intracellular calcium levels and promoted the expression of ACSL4, while inhibition of calcium signaling (FK506) reversed the upregulation of ACSL4 and FMT-related changes, including the expression of α-smooth muscle actin (αSMA) and the migration of fibroblasts. Notably, inhibition of ACSL4 did not affect the proliferation of fibroblasts, suggesting its specific role in phenotypic transition. These findings demonstrate that ACSL4 functions downstream of C5a/C5aR1-induced calcium signaling to promote FMT and the progression of pulmonary fibrosis. Targeting ACSL4 may therefore offer a novel therapeutic strategy for IPF. Full article

The Chromobox (CBX) family comprises key epigenetic regulators involved in transcriptional repression through chromatin modifications. Dysregulation of polycomb CBX proteins has been linked to epigenetic gene silencing and cancer progression. However, the specific roles and prognostic value of CBX family members in colorectal cancer (CC) remain unclear. In this study, we show that CBX genes are significantly dysregulated in CC tissues and cell models compared to normal colorectal tissue. Among them, CBX4 and CBX8 emerged as the most upregulated isoforms in tumors. Functional analyses revealed that CBX4 overexpression enhances CC cell proliferation, while its silencing reduces tumor growth. Similarly, pharmacological inhibition of CBX4 in patient-derived tumor organoids led to decreased proliferation, supporting its pro-tumorigenic role. Immunofluorescence analysis further revealed alterations in NF-κB signaling upon CBX4 inhibition, along with reduced mRNA levels of pathway components including NF-κB, TNF, IL-1, and c-Myc. These findings point to a potential interplay between CBX4 and inflammation-related pathways in CC. Overall, our study highlights the oncogenic role of CBX4 in colorectal cancer and supports its potential as a novel therapeutic target and early biomarker for disease progression. Full article

Hypertrophic cardiomyopathy (HCM) is a prevalent and often underdiagnosed genetic cardiac disorder characterized by left ventricular hypertrophy and, in many cases, dynamic left ventricular outflow tract obstruction (LVOTO). The development of cardiac myosin inhibitors (CMIs) represents an emerging therapeutic approach in the pharmacological management of obstructive HCM (oHCM). This review offers an integrated and up-to-date synthesis of the cardiac myosin inhibitor class, with a focus on mavacamten, aficamten, and the broader landscape of emerging agents. It also highlights recent clinical trial outcomes, pharmacokinetic and pharmacogenetic considerations, and potential future directions in therapy. Furthermore, we incorporate the most recent data up to May 2025, including late-breaking trial results and real-world safety findings, aiming to provide clinicians with a practical and comprehensive perspective on this evolving drug class. A narrative review was conducted by systematically searching PubMed, Scopus, Google Scholar, and ClinicalTrials.gov for English-language articles and trials published between January 2016 and May 2025. Keywords included “cardiac myosin inhibitor”, mavacamten”, “aficamten”, “MYK-224”, and “hypertrophic cardiomyopathy.” Inclusion criteria encompassed clinical trials and comprehensive reviews specifically addressing CMIs in cardiac applications. CMIs such as mavacamten and aficamten have demonstrated significant clinical benefits in reducing LVOT gradients, improving exercise capacity, and alleviating symptoms in patients with oHCM. Mavacamten is currently approved for clinical use, while aficamten is in advanced regulatory review. Comparative data suggest potential advantages of aficamten in the onset of action, pharmacokinetic profile, and tolerability. Emerging evidence supports the exploration of CMIs in pediatric populations, heart failure with preserved ejection fraction (HFpEF), and non-obstructive HCM (nHCM), although results are still preliminary. Cardiac myosin inhibitors offer a novel, pathophysiology-targeted approach to managing oHCM. While mavacamten has established efficacy, next-generation agents like aficamten may offer improved safety and versatility. Further long-term studies are needed to clarify their role across broader patient populations. Full article

Background: The metabolic dysfunction-associated steatotic liver disease (MASLD) represents an escalating global health concern, with effective treatments still lacking. Given its complex pathogenesis, multi-targeted strategies are highly desirable. Methods: This study reports the isolation of four flavone C-glycosides (FCGs) from Dianthus superbus L. and explores their potential in treating MASLD. The bioactivity and underlying mechanisms of FCGs were systematically evaluated by integrating network pharmacology, molecular docking, and zebrafish model validation. Results: Network pharmacology analysis revealed that FCGs may modulate multiple MASLD-related pathways, including lipid metabolism, insulin signaling, inflammation, and apoptosis. Molecular docking further confirmed strong binding affinities between FCGs and key protein targets involved in these pathways. In the zebrafish model of MASLD induced by egg yolk powder, FCGs administration markedly attenuated obesity, hepatic lipid accumulation, and liver tissue damage. Furthermore, FCGs improved lipid metabolism and restored locomotor function. Molecular analyses confirmed that FCGs upregulated PPARγ expression to promote lipid metabolism, restored insulin signaling by enhancing INSR, PI3K, and AKT expression, and suppressed inflammation by downregulating TNF, IL-6 and NF-κB. Additionally, FCGs inhibited hepatocyte apoptosis by elevating the BCL-2/BAX ratio. Conclusions: These findings highlight the multi-pathway regulatory effects of FCGs in MASLD, underscoring its potential as a novel therapeutic candidate for further preclinical development. Full article

Nephrolithiasis, predominantly driven by calcium oxalate (CaOx) crystal deposition, poses a significant global health burden due to its high prevalence and recurrence rates and limited preventive/therapeutic options. Recent research has underscored a pivotal role for macrophage polarization in nephrolithiasis pathogenesis. Pro-inflammatory phenotype macrophages exacerbate crystal-induced injury and foster stone formation by amplifying crystal adhesion via an NF-κB–IL-1β positive-feedback axis that sustains ROS generation and NLRP3 inflammasome activation, whereas anti-inflammatory phenotype macrophages facilitate crystal clearance and tissue repair. We have summarized the research on treating nephrolithiasis and related renal injury by targeting macrophage polarization in recent years, including therapeutic approaches through pharmacological methods, epigenetic regulation, and advanced biomaterials. At the same time, we have critically evaluated the novel therapeutic strategies for macrophage reprogramming and explored the future development directions of targeting macrophage reprogramming for nephrolithiasis treatment, such as using single-cell/spatial omics to reveal the heterogeneity of macrophages in the stone microenvironment, chimeric antigen receptor macrophages (CAR-Ms) as a potential therapy for specific crystal phagocytosis in certain areas, and multi-omics integration to address inter-patient immune differences. This review highlights that macrophage reprogramming is a transformative frontier in nephrolithiasis management and underscores the need for further research to translate these molecular insights into effective clinical applications. Full article

The serotonergic system, originating in the raphe nuclei, differentially modulates the dorsal and ventral hippocampus, which are implicated in cognition and emotion, respectively. Emerging evidence from rodent models (e.g., neonatal ventral hippocampal lesion, pharmacological NMDA receptor antagonist exposure) and human postmortem studies indicates dorsoventral serotonergic alterations in schizophrenia. These data include elevated 5-HT1A receptor expression in the dorsal hippocampus, linking serotonergic hypofunction to cognitive deficits, and hyperactive 5-HT2A/3 receptor signaling and denser serotonergic innervation in the ventral hippocampus driving local hyperexcitability associated with psychosis and stress responsivity. These dorsoventral serotonergic alterations are shown to disrupt the excitation–inhibition balance, impair synaptic plasticity, and disturb network oscillations, as established by in vivo electrophysiology and functional imaging. Synthesizing these multi-level findings, we propose a novel “dorsoventral serotonin imbalance” model of schizophrenia, in which ventral hyperactivation predominantly contributes to psychotic symptoms and dorsal hypoactivity underlies cognitive deficits. We further highlight promising preclinical evidence that selective targeting of region- and receptor-specific targeting, using both pharmacological agents and emerging delivery technologies, may offer novel therapeutic opportunities enabling symptom-specific strategies in schizophrenia. Full article

Benzothiazole derivatives have emerged as being highly significant in drug discovery due to their versatile biological activities and structural adaptability. Incorporating nitrogen and sulfur, this fused heterocyclic scaffold exhibits wide-ranging pharmacological properties, including anticancer, antimicrobial, anti-inflammatory, antidiabetic, neuroprotective, and diagnostic applications. A diverse set of clinically approved and investigational compounds, such as flutemetamol for Alzheimer’s diagnosis, riluzole for ALS, and quizartinib for AML, illustrates the scaffold’s therapeutic potential in varied applications. These agents act via mechanisms such as enzyme inhibition, receptor modulation, and amyloid imaging, demonstrating the scaffold’s high binding affinity and target specificity. Advances in synthetic strategies and our understanding of structure–activity relationships (SARs) continue to drive the development of novel benzothiazole-based therapeutics with improved potency, selectivity, and safety profiles. We also emphasize recent in vitro and in vivo studies, including drug candidates in clinical trials, to provide a comprehensive perspective on the therapeutic potential of benzothiazole-based compounds in modern drug discovery. This review brings together recent progress to help guide the development of new benzothiazole-based compounds for future therapeutic applications. Full article