Search Results (3,567)

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterised by cognitive decline, synaptic loss, and multifaceted pathology involving amyloid-β (Aβ) aggregation, tau hyperphosphorylation, neuroinflammation, and impaired proteostasis. In recent years, biologic therapies, such as monoclonal antibodies, vaccines, antisense oligonucleotides (ASOs), and gene therapies, have gained prominence as promising disease-modifying strategies. In this review, we provide a comprehensive synthesis of current biologic approaches under clinical evaluation for AD. Drawing on data curated from ClinicalTrials.gov (as of 2025), we systematically summarise the molecular targets, therapeutic modalities, mechanisms of action, trial phases, and sponsors of over 60 biologic agents. These include Aβ-directed antibodies targeting distinct conformers such as protofibrils, pyroglutamate-modified species, and soluble oligomers; tau-targeted immunotherapies and RNA-based interventions; and emerging platforms focused on neuroimmune modulation, peptide hormones, and microbiota-based strategies. Gene and RNA therapeutics, particularly ASOs and small interfering RNAs (siRNAs) delivered intrathecally or via lipid nanoparticles, are also reviewed for their potential to modulate intracellular targets with high specificity. We also analyse the historical landscape of biologic candidates that failed to reach approval, discussing key reasons for trial discontinuation, including lack of clinical efficacy, safety concerns (e.g., amyloid-related imaging abnormalities), or inadequate biomarker responses. These cases offer crucial insights for refining future drug design. Looking ahead, we highlight major challenges and evolving perspectives in AD biologic therapy: expanding therapeutic targets beyond Aβ and tau, overcoming delivery barriers to the brain, designing prevention-oriented and genetically stratified trials, and navigating regulatory and ethical considerations. Together, these efforts signal a paradigm shift in AD drug development, from symptomatic treatment to mechanism-based precision biologics. By integrating real-time clinical trial data with mechanistic insight, this review aims to inform both translational research and therapeutic innovation in AD. Full article

Starch serves as a crucial storage substance in both cereal crops and root/tuber crops, with its composition and properties determining the quality of storage organs. The Waxy (Wx) gene, encoding a key enzyme in starch biosynthesis, plays a pivotal role in this metabolic pathway. However, existing reviews seldom systematically elaborate on Wx gene regulatory mechanisms from the perspective of intrinsic molecular networks. Focusing on the model crop rice, this article synthesizes research advances in Wx-mediated starch biosynthesis regulation over the past decade. We analyze the structural features of the Wx gene and factors influencing its regulatory function during starch synthesis. In conclusion, future research directions are proposed to provide references for Wx gene studies in other crops, as well as theoretical foundations for rice varietal improvement and molecular design breeding. Full article

The miR156 family, crucial for phase transition and stress responses in plants, remains functionally uncharacterized in the ecologically and commercially important gymnosperm Larix kaempferi. This study systematically investigated L. kaempferi miR156 through phylogenetic analysis, structural prediction, expression profiling during somatic embryogenesis, and heterologous functional validation in Arabidopsis. Four MIR156 family members (LkMIR156s) were identified in Larix kaempferi, each with a characteristic stem-loop structure and highly conserved mature sequences. Computational predictions indicated that these LkMIR156s target four LkSPL family genes (LkSPL1, LkSPL2, LkSPL3, and LkSPL9). qRT-PCR analysis showed that mature LkmiR156s expression remained relatively low during early embryonic development but was significantly upregulated at the cotyledonary stage (21–42 days). Precursor transcript levels peaked earlier (around 28 days) than those of the mature LkmiR156, which remained highly expressed throughout cotyledonary embryo development. This sustained high expression coincided with cotyledon morphogenesis and embryonic dormancy. Functional validation via heterologous overexpression of LkMIR156b1 in Arabidopsis resulted in increased rosette leaf numbers (42.86% ± 6.19%) and individual leaf area (54.90% ± 6.86%), phenotypically consistent with the established role of miR156 in growth regulation. This study reveals the temporal expression dynamics of LkmiR156s during L. kaempferi somatic embryogenesis and its coordinated expression patterns with cotyledon development and embryonic dormancy. The functional conservation of the miR156-SPL module was confirmed in a model plant, providing key molecular insights into the developmental regulatory network of conifers. These findings offer potential strategies for optimizing somatic embryogenesis techniques in conifer species. Full article

Germplasm resources embody the genetic diversity of plants and form the foundation for breeding and the ongoing improvement of elite cultivars. The establishment of germplasm banks, along with their systematic evaluation, constitutes a critical step toward the conservation, sustainable use, and innovative utilization of these resources. Liriodendron, a rare and endangered tree genus with species distributed in both East Asia and North America, holds considerable ecological, ornamental, and economic significance. However, a standardized evaluation system for Liriodendron germplasm remains unavailable. In this study, 297 Liriodendron germplasm accessions were comprehensively evaluated using 34 phenotypic traits and whole-genome resequencing data. Substantial variation was observed in most phenotypic traits, with significant correlations identified among several characteristics. Cluster analysis based on phenotypic data grouped the accessions into three distinct clusters, each exhibiting unique distribution patterns. This classification was further supported by principal component analysis (PCA), which effectively captured the underlying variation among accessions. These phenotypic groupings demonstrated high consistency with subsequent population structure analysis based on SNP markers (K = 3). Notably, several key traits exhibited significant divergence (p < 0.05) among distinct genetic clusters, thereby validating the coordinated association between phenotypic variation and molecular markers. Genetic diversity and population structure were assessed using 4204 high-quality single-nucleotide polymorphism (SNP) markers obtained through stringent filtering. The results indicated that the Liriodendron sino-americanum displayed the highest genetic diversity, with an expected heterozygosity (He) of 0.18 and a polymorphic information content (PIC) of 0.14. In addition, both hierarchical clustering and PCA revealed clear population differentiation among the accessions. Association analysis between three phenotypic traits (DBH, annual height increment, and branch number) and SNPs identified 25 highly significant SNP loci (p < 0.01). Of particular interest, the branch number-associated locus SNP_17_69375264 (p = 1.03 × 10⁻⁵) demonstrated the strongest association, highlighting distinct genetic regulation patterns among different growth traits. A minimal set of 13 core SNP markers was subsequently used to construct unique DNA fingerprints for all 297 accessions. In conclusion, this study systematically characterized phenotypic traits in Liriodendron, identified high-quality and core SNPs, and established correlations between key phenotypic and molecular markers. These achievements enabled differential analysis and genetic diversity assessment of Liriodendron germplasm, along with the construction of DNA fingerprint profiles. The results provide crucial theoretical basis and technical support for germplasm conservation, accurate identification, and utilization of Liriodendron resources, while offering significant practical value for variety selection, reproduction and commercial applications of this species. Full article

Paratuberculosis is a chronic zoonotic bacterial infection, primarily affecting ruminants. This review examines the disease in the Arabian Peninsula, focusing on distribution, molecular diversity, prevalence, and associated risk factors. Following PRISMA guidelines, a systematic search was conducted in PubMed, Scopus, and Web of Science. After duplicate removal and eligibility screening, data extraction, analysis, and quality assessment were performed. Pathogen sequences were retrieved from NCBI GenBank for phylogenetic analysis. The review included a total of 31 published articles from 1997 to 2025, of which 23 were used in the meta-analysis. Most studies (n = 12) were published between 2011 and 2015, predominantly from Saudi Arabia (n = 22), with no reports from Qatar, Bahrain, or Yemen. The majority of the studies involved camels and sheep (n = 16 on each species), followed by cattle (n = 9), goats (n = 7), humans (n = 2), and buffalo (n = 1). Phylogenetic analysis delineates two major clades—Type S and Type C—suggesting greater genetic diversity in Type S. The estimated pooled seroprevalence and pathogen prevalence in livestock ruminants were 8.1% and 22.4%, respectively. Herd-level estimated pooled seroprevalence was 26.9%. Small ruminants (19.3%) were more sero-prevalent than large ruminants (7.4%), with goats (28.7%) significantly (p < 0.01) more affected than sheep (21.5%), camel (9.8%), and cattle (6.6%). Clinical signs in ruminants included chronic diarrhea, emaciation, anorexia, alopecia, wry neck, and dehydration. The reviewed study patterns and findings suggest high pathogen diversity and a significant risk of transboundary transmission at the human–animal interface in this region. A One Health surveillance approach is crucial, particularly on farms with diarrheic and emaciated animals. Establishing a national surveillance plan and phased (short-, intermediate-, and long-term) control programs is essential to mitigate economic losses, limit transmission, overcome the cultural barrier, and protect public health. Full article

Background/Objectives: Recurrent meningiomas remain difficult to manage due to the absence of effective systemic therapies and comparatively high treatment failure rates, particularly in high-grade tumors. Stereotactic radiosurgery (SRS) offers a minimally-invasive and precise option, particularly for tumors in surgically complex locations. However, the risks associated with re-irradiation, and recent changes in the WHO classification of CNS tumors highlight the need for more personalized and strategic treatment approaches. This systematic review evaluates the safety, efficacy, and clinical considerations for use of SRS for recurrent meningiomas. Methods: In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic literature search was conducted using the PubMed, Scopus, and Web of Science databases for studies reporting outcomes of SRS in recurrent, pathologically confirmed intracranial meningiomas. Studies were excluded if they were commentaries, reviews, case reports with fewer than three cases, or had inaccessible full text. The quality and risk of bias of the included studies were assessed using the modified Newcastle-Ottawa Scale. Data on patient and tumor characteristics, SRS treatment parameters, clinical outcomes, adverse effects, and statistical analysis results were extracted. Results: Sixteen studies were included. For WHO Grade I tumors, 3- to 5-year progression-free survival (PFS) ranged from 85% to 100%. Grade II meningiomas demonstrated more variable outcomes, with 3-year PFS ranging from 23% to 100%. Grade III tumors had consistently poorer outcomes, with reported 1-year and 2-year PFS rates as low as 0% and 46%, respectively. SRS performed after surgery alone was associated with superior outcomes, with local control rates of 79% to 100% and 5-year PFS ranging from 40.4% to 91%. In contrast, tumors previously treated with radiotherapy, with or without surgery, showed substantially poorer outcomes, with 3- to 5-year PFS ranging from 26% to 41% and local control rates as low as 31%. Among patients with prior radiotherapy, outcomes were particularly poor in Grade II and III recurrent tumors. Toxicity rates ranged from 3.7% to 37%, and were generally higher for patients with prior radiation. Predictors of worse PFS included prior radiation, older age, and Grade III histology. Conclusions: SRS may represent a reasonable salvage option for carefully selected patients with recurrent meningioma, particularly following surgery alone. Outcomes were notably worse in high-grade recurrent meningiomas following prior radiotherapy, emphasizing the prognostic significance of both histological grade and treatment history. Notably, the lack of molecular and genetic data in most existing studies represents a key limitation in the current literature. Future prospective studies incorporating molecular profiling may improve risk stratification and support more personalized treatment strategies. Full article

Chronic pain is a significant and complex health condition characterized by persistent or recurrent pain lasting more than three months. Exercise-based rehabilitation is an effective non-pharmacological intervention, yet its underlying mechanisms have not been fully elucidated. This review systematically maps the molecular pathways of exercise-induced analgesia onto the pathophysiological cascades of chronic pain, aiming to fill a key gap in the current literature. It explores the molecular and cellular mechanisms underpinning the pathophysiology of chronic pain, indicating that the persistence of chronic pain stems from peripheral sensitization driven by inflammatory mediators and central sensitization involving glial cell activation and N-methyl-D-aspartate (NMDA) receptor-mediated neuroplasticity. Exercise can interrupt these pathological cascades through multi-system adaptations, including activation of the endogenous opioid and serotonergic systems activation and anti-inflammation. However, a significant gap remains in translating this mechanistic understanding of chronic pain into optimized, personalized exercise prescriptions, requiring future research into different exercise modalities, sex-specific responses, and the impact of comorbidities. Full article

Alkanolamine additives play a critical role in enhancing the early process performance of cement slurries, thereby improving construction efficiency and structural durability. This study systematically evaluates the effects of ethanolamine (EA), diethanolamine (DEA), and triethanolamine (TEA) on cement slurry properties, including the thickening time, rheology, density, shrinkage, and hydration kinetics. Clear structure–activity relationships are established based on the findings. The experimental analysis demonstrated that increasing the hydroxyl group count in the alkanolamines significantly accelerated cement hydration. At a dosage of 1.0%, the thickening time of the cement slurry was significantly shortened to 125 min (EA), 15 min (DEA), and 12 min (TEA), respectively. Concomitantly, a reduction in fluidity was observed, with flow diameters measuring 15.8 cm (EA), 14.6 cm (DEA), and 14.1 cm (TEA). The rheological analysis revealed that the alkanolamine additives significantly increased the consistency coefficient (K) and decreased the flowability index (n) of the slurry, with TEA exhibiting the most pronounced effect. The density measurements confirmed the enhanced settlement stability, as the density differences diminished to 0.1 g/cm³ at the optimal dosages (0.6% TEA and 0.8% DEA). The hydration degree analysis indicated a hydration rate acceleration of up to 32% relative to plain slurry, attributed to the hydroxyl-facilitated promotion of Ca(OH)₂ formation and C₃S dissolution. The XRD analysis confirmed that the alkanolamines modified the reaction kinetics without inducing phase transformation in the hydration products. Crucially, the hydroxyl group count governed the performance: a higher hydroxyl density intensified Ca²⁺/Al³⁺ complexation, thereby reducing ion mobility and accelerating setting. These findings establish a molecular design framework for alkanolamine-based additives that balances early process performance development with practical workability. The study advances sustainable cement technology by enabling targeted optimization of rheological and mechanical properties in high-demand engineering applications. Full article

Three-dimensional (3D) surface-enhanced Raman scattering (SERS) substrates have demonstrated remarkable abilities of ultrasensitive and reproducible molecular detection. The combination of both electromagnetic and chemical enhancement processes, light trapping, and multiple scattering effects of 3D structures are what enhance their performance. The principles of underlying enhancements are summarized systematically, and the main types of 3D substrates—vertically aligned nanowires, dendritic and fractal nanostructures, porous frameworks and aerogels, core–shell and hollow nanospheres, and hierarchical hybrid structures—are categorized in this review. Advances in fabrication techniques, such as template-assisted growth, electrochemical and galvanic deposition, dealloying and freeze-drying, self-assembly, and hybrid integration, are critically evaluated in terms of structural tunability and scalability. Novel developments in the field of biosensing are also highlighted, including non-enzymatic glucose sensing, tumor biomarker sensing, and drug delivery. The remaining limitations, such as low reproducibility, mechanical stability, and substrate standardization, are also noted, and future directions, such as stimuli-responsive designs, multifunctional hybrid platforms, and data-driven optimization strategies of SERS technologies, are also included. Full article

This study examined a novel ethoxy-segment-regulated hydrophobic associative amphiphilic copolymer, P(AA-AAEO_n), and systematically evaluated its solution self-assembly behavior and enhanced oil recovery (EOR) performance. The influence of ethylene oxide (EO) chain length and polymer concentration on particle size distribution and aggregation morphology was analyzed using dynamic light scattering (DLS). The results revealed a concentration-dependent transition from intramolecular to intermolecular association, accompanied by a characteristic decrease followed by an increase in hydrodynamic diameter. At a fixed AA:AAEO_n molar ratio (400:1), increasing EO segment length increased aggregate size and improved colloidal stability. Viscometric analysis showed that longer EO chains markedly increased molecular chain flexibility and solution viscosity. Interfacial tension measurements demonstrated superior interfacial activity of P(AA-AAEO_n) compared to polyacrylic acid (PAA), and longer EO chains further reduced oil–water interfacial tension. Emulsification tests verified its strong ability to emulsify crude oil. Sandpack flooding experiments and micromodel studies demonstrated effective conformance control and high displacement efficiency, achieving up to 30.65% incremental oil recovery. These findings offered essential insights for designing hydrophobic associative polymers with tunable interfacial properties for EOR applications. Full article

Echinostomatidae is a taxonomically complex group with substantial species diversity and richness. The vast majority of species in this family parasitize birds and mammals, including humans, causing significant economic losses and medical costs. In this study, Echinostoma miyagawai (Digenea, Echinostomatidae) and Patagifer bilobus (Digenea, Echinostomatidae) were isolated from domestic duck and Grus japonensis, respectively. The nearly complete ribosomal transcription unit (rTU) sequences of two echinostomes were obtained, with the rTU for P. bilobus being obtained for the first time. The nearly complete rTU sequence of P. bilobus (6790 bp) and E. miyagawai (6893 bp) encompass the small-subunit (18S) ribosomal DNA (rDNA), internal transcribed spacer 1 (ITS1), 5.8S rDNA, internal transcribed spacer 2 (ITS2), and large-subunit (28S) rDNA. The complete lengths of 18S, ITS1, 5.8S, ITS2, and 28S sequences for E. miyagawai are 1989 bp, 444 bp, 162 bp, 431 bp, and 3858 bp, respectively. For P. bilobus, complete or nearly complete lengths of these sequences are 1929 bp (nearly complete), 419 bp, 162 bp, 432 bp, and 3848 bp (nearly complete), respectively. The 18S, ITS, and 28S sequences of E. miyagawai show the highest sequence similarity with other E. miyagawai. The ITS and 28S sequences of P. bilobus show the highest sequence similarity with other P. bilobus, while 18S sequence shows the highest similarity with E. miyagawai. This is likely due to the unavailability of the 18S sequence of P. bilobus in GenBank. Repeat sequences were identified in 18S, ITS1, ITS2, and 28S sequences, with the 28S sequence containing the most repeats and the 5.8S sequence having none. The results of phylogenetic reconstruction indicated that E. miyagawai clusters with other Echinostoma spp., while P. bilobus clusters with other Patagifer spp., forming sister taxa. This study not only provides the first rTU sequence for P. bilobus but also reinforces the sister group status of Patagifer to Echinostoma through phylogenetic evidence. Finally, this study represents the first record of the G. japonensis as a new host for P. bilobus and the first report of a bird from the crane family (Gruidae) as a host for any echinostome species. These findings are significant as they expand our understanding of the host range and ecological interactions of Echinostomatidae. The data obtained provide a valuable resource of molecular markers for studying the taxonomy, population genetics, and systematics of the family Echinostomatoidea. This research contributes to a more comprehensive understanding of the evolutionary relationships and biodiversity within this complex group of parasites, which is crucial for developing effective strategies to mitigate their impact on both wildlife and human health. Full article

Optic pathway glioma (OPG) is a rare pediatric low-grade glioma, frequently associated with neurofibromatosis type 1 (NF–1), that presents unique therapeutic challenges due to its anatomical location and its potential to impair vision, endocrine function, and developmental trajectories. Current clinical management prioritizes a multidisciplinary, patient-specific approach aimed at tumor control while preserving long-term quality of life. Strategies vary based on clinical presentation, ranging from observation in asymptomatic cases to chemotherapy for progressive or symptomatic tumors. Surgical and radiation options are limited due to potential risks and complications. In recent years, advances in molecular characterization have guided the development of targeted therapies, particularly MEK inhibitors, which demonstrate encouraging efficacy and reduced toxicity profiles. In parallel, investigational therapies including immunotherapy and precision medicine-based approaches are under clinical evaluation. This review provides a synthesis of current standard practices, emerging targeted treatments, and ongoing clinical trials, drawing on relevant literature and expert consensus to inform clinicians and families about available therapeutic options. Literature discussed in this review was identified through a non-systematic search of published articles, clinical trial registries, and authoritative guidelines, with selection based on relevance, clinical significance, and contribution to understanding current and emerging management strategies for OPG. Full article

Background: Melanoma, the deadliest human skin cancer, frequently harbors activating BRAF mutations, with V600E being the most prevalent. These alterations drive constitutive activation of the MAPK pathway, promoting uncontrolled cell proliferation, survival, and dissemination. The advent of BRAFi and MEKi has significantly improved outcomes in BRAF V600-mutant melanoma. However, therapeutic resistance remains a major clinical barrier. Methods: This review integrates recent findings from preclinical and clinical studies to delineate resistance mechanisms to BRAF-targeted therapy. It categorizes resistance into primary (intrinsic), adaptive, and acquired forms, and analyzes their molecular underpinnings, including genetic and epigenetic alterations, pathway reactivation, and microenvironmental interactions. Results: Primary resistance is linked to pre-existing genetic and epigenetic changes that activate alternative signaling pathways, such as PI3K-AKT. Adaptive and acquired resistance includes secondary BRAF mutations, pathway redundancy, phenotype switching, and immune and stromal interactions. High-throughput sequencing has revealed novel mutations, including NRAS, NF1, and PTEN alterations, that contribute to resistance. Discussion: Understanding the multifaceted nature of resistance is critical to improving outcomes in advanced melanoma. This review highlights emerging strategies to overcome resistance, including combinatorial therapies, metabolic targeting, and biomarker-driven approaches, aiming to inform future therapeutic development and precision oncology strategies. Full article

Type 2 diabetes (T2D) is a complex metabolic disease characterized by chronic hyperglycemia due to insulin resistance and inadequate insulin secretion. Beyond the classically implicated organs, emerging evidence highlights the gut as a central player in T2D pathophysiology through its interactions with metabolic organs. The gut hosts trillions of microbes and enteroendocrine cells that influence inflammation, energy homeostasis, and hormone regulation. Disruptions in gut homeostasis (dysbiosis and increased permeability) have been linked to obesity, insulin resistance, and β-cell dysfunction, suggesting multifaceted “Gut-X axes” contribute to T2D development. We aimed to comprehensively review the evidence for gut-mediated crosstalk with the pancreas, endocrine system, liver, and kidneys in T2D. Key molecular mechanisms (incretins, bile acids, short-chain fatty acids, endotoxins, etc.) were examined to construct an integrated model of how gut-derived signals modulate metabolic and inflammatory pathways across organs. We also discuss clinical implications of targeting Gut-X axes and identify knowledge gaps and future research directions. A literature search (2015–2025) was conducted in PubMed, Scopus, and Web of Science, following PRISMA guidelines (Preferred Reporting Items for Systematic Reviews). Over 150 high-impact publications (original research and review articles from Nature, Cell, Gut, Diabetologia, Lancet Diabetes & Endocrinology, etc.) were screened. Data on gut microbiota, enteroendocrine hormones, inflammatory mediators, and organ-specific outcomes in T2D were extracted. The GRADE framework was used informally to prioritize high-quality evidence (e.g., human trials and meta-analyses) in formulating conclusions. T2D involves perturbations in multiple Gut-X axes. This review first outlines gut homeostasis and T2D pathogenesis, then dissects each axis: (1) Gut–Pancreas Axis: how incretin hormones (GLP-1 and GIP) and microbial metabolites affect insulin/glucagon secretion and β-cell health; (2) Gut–Endocrine Axis: enteroendocrine signals (e.g., PYY and ghrelin) and neural pathways that link the gut with appetite regulation, adipose tissue, and systemic metabolism; (3) Gut–Liver Axis: the role of microbiota-modified bile acids (FXR/TGR5 pathways) and bacterial endotoxins in non-alcoholic fatty liver disease (NAFLD) and hepatic insulin resistance; (4) Gut–Kidney Axis: how gut-derived toxins and nutrient handling intersect with diabetic kidney disease and how incretin-based and SGLT2 inhibitor therapies leverage gut–kidney communication. Shared mechanisms (microbial SCFAs improving insulin sensitivity, LPS driving inflammation via TLR4, and aryl hydrocarbon receptor ligands modulating immunity) are synthesized into a unified model. An integrated understanding of Gut-X axes reveals new opportunities for treating and preventing T2D. Modulating the gut microbiome and its metabolites (through diet, pharmaceuticals, or microbiota therapies) can improve glycemic control and ameliorate complications by simultaneously influencing pancreatic islet function, hepatic metabolism, and systemic inflammation. However, translating these insights into clinical practice requires addressing gaps with robust human studies. This review provides a state-of-the-art synthesis for researchers and clinicians, underlining the gut as a nexus for multi-organ metabolic regulation in T2D and a fertile target for next-generation therapies. Full article

(1) Objective: This study aimed to systematically elucidate the molecular mechanisms by which gypenosides (GP), a major active component of Gynostemma pentaphyllum, ameliorate hypercholesterolemia by modulating the hepatic steroidogenesis pathway, and to identify key therapeutic targets. (2) Methods: We established a high-fat diet (HFD)-induced hypercholesterolemia (HC) mouse model and performed GP intervention. An integrated multi-omics approach, combining transcriptomics and proteomics, was utilized to comprehensively analyze GP’s effects on the expression of genes and proteins associated with hepatic cholesterol synthesis, transport, and steroid hormone metabolism. (3) Results: HFD induced significant dysregulation, with 48 steroidogenesis pathway-related genes and 35 corresponding proteins exhibiting altered expression in HC mouse livers. GP treatment remarkably reversed these HFD-induced abnormalities, significantly restoring the expression levels of 42 genes and 14 proteins. Multi-omics integration identified seven critical genes/proteins—Cyp3a25, Fdft1, Tm7sf2, Hmgcs1, Fdps, Mvd, and Pmvk—that were consistently and significantly regulated by GP at both transcriptional and translational levels. Furthermore, correlation analyses demonstrated that Cyp3a25 was significantly negatively correlated with serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C), whereas Fdft1, Tm7sf2, Hmgcs1, Fdps, Mvd, and Pmvk showed significant positive correlations. (4) Conclusions: GP effectively ameliorates cholesterol dyshomeostasis through a multi-targeted mechanism in the liver. It inhibits endogenous cholesterol synthesis by downregulating key enzymes (Hmgcs1, Fdft1, Pmvk, Mvd, Fdps, Tm7sf2), promotes cholesterol efflux and transport (upregulating Abca1, ApoB), and accelerates steroid hormone metabolism (upregulating Cyp3a11, Cyp3a25). These findings provide robust scientific evidence for the development of GP as a safe and effective novel therapeutic agent for hypercholesterolemia. Full article