Search Results (1,057)

The objective of this trial was to evaluate the impact of an α-tocopherol injection on pre-weaning calf performance including markers of growth and behavior. Sixty-one days prior to weaning, both nursing Angus and Hereford steer calves (SC; n = 16) and Angus and Hereford heifer calves (HC; n = 28) were randomly assigned to one of two treatments: (1) no injectable α-tocopherol (CON; n = 23) or (2) 1500 IU of injectable α-tocopherol administered subcutaneously (VitE; n = 21). Average daily gain (ADG), exit velocity (EV), serum urea nitrogen, serum cortisol, and serum α-tocopherol concentrations were evaluated on d 0, 28, and 61 of the trial. Steer calves increased (p = 0.01) ADG compared to HC, with SC gaining about 13% more than HC. There was no impact (p ≥ 0.20) of injectable vitamin E on calf ADG. As the trial progressed, EV slowed (p = 0.0005) in both HC and SC regardless of treatment. Serum α-tocopherol concentrations were influenced (p = 0.04) by an interaction of treatment, sex, and time, with CON-SC being the only group that did not have serum α-tocopherol concentrations decrease throughout the trial. Overall, this trial found that a pre-weaning vitamin E injectable did not improve pre-weaning calf performance, but calf sex did. Full article

Background/Objectives: Advanced technologies in type 1 diabetes mellitus (T1DM) management have reshaped the strategies used to achieve optimal glucose control. Continuous subcutaneous insulin infusion (CSII) and automated insulin delivery (AID) systems are effective alternatives to multiple daily injections (MDI). This study aims to evaluate glycemic regulation in children and adolescents transitioning from MDI to insulin pumps and to raise awareness among patients and their families regarding the benefits of these systems. Methods: 50 pediatric patients with T1DM (24 males, 26 females; mean age 10.76 ± 3.2 years) were evaluated. Cycle 1 established MDI metrics 3 months pre-transition. In cycle 2, patients transitioned either to an AID system (Medtronic MiniMed 780G, (Northridge, CA, USA), 78%), or a non-automated system (Omnipod DASH, 22%). Data were assessed at 3 and 6 months post-initiation. Parameters assessed were glycosylated hemoglobin (HbA1c), time in range (TIR), time above range (TAR), time below range (TBR), glucose management indicator (GMI) and coefficient of variation (CV). Results: The cohort exhibited a statistically significant increase in TIR (p = 0.0038) with mean values of 70.9% at 3 months and 73.2% at 6 months. TAR significantly reduced (p = 0.033) to 26.5% and 24.3% at 3 and 6 months, respectively. Sub-analysis in the AID group revealed a marked increase in TIR (p = 0.0001) alongside significant reductions in TAR (p = 0.0009) and GMI (p = 0.03). Conclusions: Transitioning from MDI to insulin pump therapy, particularly AID systems, leads to modest but significant improvements in specific sensor metrics (TIR, TAR) in real-world clinical practice. The consistency of these results across age groups indicates that AID systems can successfully overcome pediatric and adolescent diabetes management challenges. Full article

Background: In rodent models of intracranial tumor development, evaluating the actual burden experienced by animals beyond procedural severity is essential for ethical and legal compliance. This study examined whether voluntary wheel running (VWR) could serve as a sensitive indicator of post-surgical burden following subcutaneous transmitter implantation, tumor cell injection, and tumor resection. It also assessed whether VWR supports the detection of humane endpoints. VWR outcomes were compared with body weight, clinical scores, heart rate, and activity levels recorded via telemetry. Methods: Fourteen male BDIX rats were housed individually in cages equipped with a running wheel. Under general anesthesia, telemetric devices to monitor heart rate and activity were subcutaneously implanted. After recovery, glioblastoma BT4Ca cells were stereotaxically injected into the right frontal cortex. Eight days later, the resulting tumors were microsurgically resected. Body weight, VWR, heart rate, and general activity were continuously monitored until the animals reached humane endpoint criteria, indicated by sudden weight loss and clinical deterioration. Results: On average, body weight and VWR declined significantly after all surgical procedures, with tumor resection causing the most pronounced effect. As animals approached the endpoint, a marked drop in these parameters was observed, along with an increased clinical score (p < 0.05). Activity measures supported these findings, though less consistently than weight and VWR. Conclusions: Monitoring body weight and VWR enables an effective assessment of the actual postoperative burden experienced by rats undergoing surgeries of different procedural complexity. Moreover, VWR is a valuable supplementary tool for identifying humane endpoints alongside body weight and clinical scoring. Full article

Effective diabetes management heavily relies on appropriate insulin administration, which strongly depends on the correct administration strategy. In this sense, insulin administration plays a fundamental role, as its use depends on the patient’s clinical condition and diabetes type. Traditional syringe-based methods require proper training to ensure that insulin is successfully delivered into the subcutaneous tissue, where it can be absorbed and metabolized; however, it is desirable to develop an insulin applicator that does not require training for its appropriate use. Aiming to provide support solutions that help patients to develop a correct administration technique, a biodesign-based methodology, coupled with biomimetic concepts, is employed to design a device that assists the user in creating a stable skin fold and guiding needle orientation during injection without requiring exhaustive training for device usage. A three-step approach is employed for the design, where computational fluid dynamics (CFD) and finite element analysis (FEA) methods are employed to ensure that the device produces a laminar insulin flow and the device strength is tested. It should be pointed out both methods are required since complications produced by sudden flows must be avoided, with CFD allowing assessment of the device mechanical properties in terms of the device strength. Initial functional evaluation indicates that the proposed approach does not require extensive training or complex operational procedures, facilitating its integration into everyday use. The device design is validated from the results obtained for the CFD analysis, as no turbulent flow is produced, whereas the FEA indicates that the geometrical form can handle the stresses produced by the folding generation without generating excessive deformations. Moreover, an infrared thermography analysis is also carried out to find out if the folding force generation is located in the zone of interest, the results of which indicate that the device operates in the desired physical zone. Full article

Residual cardiovascular risk arises from dysregulated expression of genes encoding apolipoprotein(a) (LPA), apolipoprotein C-III (APOC3), angiopoietin-like gene 3 (ANGPTL3), and proprotein convertase subtilisin/kexin type 9 (PCSK9). RNA-based therapies, small interfering RNAs (siRNAs), and antisense oligonucleotides (ASOs) modulate these targets at the post-transcriptional level through RNA interference and RNase H-mediated degradation, respectively. This scoping review maps the molecular mechanisms, target involvement, and pharmacodynamic outcomes of RNA therapies for managing residual cardiovascular risk, with contextual comparison to traditional lipid-lowering agents. A systematic search of PubMed, Embase, Web of Science, and Scopus was performed from 2020 to February 2026. Of the 1088 records identified, 30 studies met the inclusion criteria. RNA therapies have demonstrated potential for engagement, with 80–98% reductions in Lp(a) (pelacarsen, olpasiran, zerlasiran, lepodisiran), 50–80% reductions in triglycerides (olezarsen, plozasiran, volanesorsen), and 36–44% reductions in low-density lipoprotein cholesterol (LDL-C). Mechanistically, siRNAs achieve gene silencing through RISC-mediated mRNA cleavage, with sustained pharmacodynamic effects (3–6 months) because of Argonaute-2 stability, while gapmer ASOs recruit RNase H1 for mRNA degradation. Conjugation with GalNAc allows for hepatocyte-specific delivery with a subcutaneous bioavailability of 70–85%. Safety profiles were favorable, with injection site reactions (4–12%) being the most common adverse event. This analysis maps the emerging molecular landscape of RNA therapies, highlighting their substantial precision for targeting residual cardiovascular risk pathways that cannot be addressed by traditional agents. Full article

Dermal senescence is associated with reduced fibroblast activity, decreased extracellular matrix synthesis, and impaired tissue repair. Commercial injectable formulations containing poly-L-lactic acid (PLLA), hyaluronic acid (HA), and polydeoxyribonucleotide (PDRN)-associated compounds have been proposed for dermal remodeling approaches and modulate tissue-response pathways; however, comparative studies evaluating commercially available formulations under standardized experimental conditions remain limited. This study aimed to characterize the morphology of formulations containing PLLA, HA, and PDRN, used alone or in combination, by environmental scanning electron microscopy (ESEM), and to investigate formulation-associated histological and collagen-related molecular responses in a murine model. Formulations containing PLLA, HA, HA + PDRN, and PLLA, HA and PDRN were administered into the dorsal subcutaneous tissue of 14 Mus musculus mice (Swiss strain). After 30 days, tissue response was assessed by ultrasound, histological analysis with Masson’s trichrome staining, and RT-qPCR quantification of collagen-related gene expression. ESEM analysis revealed distinct morphological characteristics among the biomaterials, and the combined PLLA, HA and PDRN formulation exhibited a more complex and integrated multiphase structure. Histological analysis showed preserved tissue architecture in all groups, with no evidence of marked inflammatory response or structural disruption. RT-qPCR demonstrated significantly higher COL1A1 expression in the PLLA-only and PLLA, HA, and PDRN groups compared with controls (p < 0.05), whereas no significant differences were observed for COL2A1 or COL3A1. These findings indicate that PLLA-containing formulations were associated with selective COL1A1 upregulation under the evaluated conditions, suggesting formulation-associated collagen-related molecular responses in this short-term model. Full article

Background/Objectives: Betanin (BET), a prominent phytochemical mainly derived from Beta vulgaris, exhibits strong anti-inflammatory and antioxidant activities owing to its distinctive chemical structure. Nevertheless, its potential analgesic effect in the context of inflammatory pain remains insufficiently explored. Accordingly, this study investigated the analgesic effects of BET in a complete Freund’s adjuvant (CFA)-induced rat model of inflammatory pain. Methods: Rats received a single subcutaneous injection of 100 µL CFA to induce inflammatory pain, followed by oral administration of BET at doses of 40 or 80 mg/kg/day for 14 days. Results: BET treatment significantly reduced paw edema and improved HPL (hot plate latency) in CFA-injected rats. Biochemically, in the ipsilateral spinal cord of rats, BET at both 40 and 80 mg/kg significantly increased IL-4, and only the 80 mg/kg dose significantly reduced oxidative stress (MDA) and IL-1β. TNF-α levels were slightly reduced at both doses and did not reach statistical significance versus CFA. At the molecular level, miR-107 was significantly downregulated by BET at 80 mg/kg (but not 40 mg/kg), while miR-145 was significantly upregulated by both 40 mg/kg and 80 mg/kg compared to CFA. Pearson’s correlation indicated that miR-107 was positively correlated with MDA, IL-1β and TNF-α but negatively with IL-4, whereas miR-145 was positively correlated with IL-4 but negatively with IL-1β. PCA biplot analysis corroborated these findings, showing simultaneous presence of MDA, IL-1β, TNF-α, and miR-107 with CFA, and IL-4 and miR-145 were only related to control and CFA+BET80 groups. In addition, using transmission electron microscopy imaging, we found that BET alleviated neuronal damage in CFA-treated rats. Furthermore, molecular docking analysis predicted that BET may exhibit stable binding interactions with several inflammation- and apoptosis-related targets, including AKT1, mTOR, IKKβ, TNF-α, IL-1β, COX-2, caspase-3, caspase-7, and caspase-8, supporting its multi-target anti-inflammatory and antiapoptotic effects. Conclusions: Overall, our data suggest that BET can possibly exert analgesic effects in CFA-induced inflammatory pain by modulating oxidative stress and favoring a shift toward an anti-inflammatory status. These effects coincided with downregulation of miR-107, overexpression of miR-145, and improvements in inflammatory pain behaviors. Further investigations are required to validate the involvement of specific miRNA- and pathway-mediated effects. Nevertheless, our findings highlight BET as a promising natural candidate for future development of anti-inflammatory and analgesic strategies. Full article

The neurotoxin botulinum toxin type A (BoNT/A), produced by the bacteria Clostridium botulinum, is commonly injected intramuscularly (IM) for the management of chronic muscle hyperactivity, such as post-stroke spasticity. New indications such as peripheral neuropathic pain require alternative routes of BoNT/A administration, such as subcutaneous (SC) or intradermal (ID). While IM BoNT/A injections may elicit anti-drug-antibodies (ADAs), their occurrence following SC or ID administration is unknown. Therefore, we investigated whether repeated SC or ID injections of 150 kDa BoNT/A can elicit ADAs in a dose-dependent manner, and whether these differ depending upon the route of administration. Mice were injected 5 times ID or SC with 150 kDa BoNT/A or, for higher doses, inactive mutant BoNT/A (DRBoNT/A) or inactivated toxoid (IA-BoNT/A). Total ADAs were analyzed by an immunoassay and the subgroup of neutralizing ADAs by an in vivo digit abduction score (DAS) assay following a challenge of 0.6 U BoNT/A IM. DRBoNT/A and IA-BoNT/A injections elicit ADAs (22.7 U/mL vs. 460.5 U/mL for ID; 4.7 U/mL vs. 339.4 U/mL for SC), while therapeutic doses of 150 kDa BoNT/A do not. Whereas mice with repeated 150 kDa BoNT/A injections at therapeutic dose show an unrestricted DAS of 3.7 (ID) or 3.4 (SC), mice injected repeatedly with 1.8 µg/kg DRBoNT/A or 500 µg/kg IA-BoNT/A show only a minimal DAS of ≤0.7, indicating a high titer of neutralizing ADAs. No differences were observed between administration routes. Accordingly, repeated ID or SC injections of pure 150 kDa BoNT/A at therapeutic doses fail to induce ADA formation in mice. On the other hand, DRBoNT/A ID injections induce higher ADA concentrations than SC, but generate similar amounts of neutralizing ADAs. IA-BoNT/A injections induce ADAs and neutralizing ADAs similarly after ID and SC injections. ADA development at intermediate BoNT/A doses can be higher after ID injection, but does not lead to differences in neutralizing ADAs. Our data demonstrate that the antibody response to botulinum toxin depends predominantly on the protein load, and less on the administration route. Full article

Subcutaneous thrombotic vasculopathy (STV) is a rare, non-inflammatory occlusive disorder of the cutaneous microvasculature that predominantly involves the subcutaneous tissue and may closely mimic inflammatory vasculitis. We describe a case of STV with overlapping features of leukocytoclastic vasculitis (LCV) in a 23-year-old woman presenting with rapidly progressive, painful purpuric skin lesions. The patient had a history of polysubstance use disorder and reported intravenous injection of crushed oral oxycodone and methylphenidate tablets. Histopathological examination of a deep skin biopsy revealed fibrin-rich thrombi occluding small vessels of the dermis and subcutaneous tissue. Fine granular IgA deposits in the walls of numerous superficial dermal blood vessels shown using direct immunofluorescence suggested LCV. Overall, the findings supported a mixed thrombotic-inflammatory vasculopathy with predominant features of STV. This case highlights the diagnostic complexity of STV and may suggest intravenous injection of crushed oral medications as a potential trigger through particle-induced microvascular obstruction and secondary thrombosis. In addition, we conducted a literature review indicating that STV remains a rare and likely underrecognized entity, with only a limited number of reported cases. Full article

Background/Objectives: Trigeminal neuralgia (TN) is a debilitating neurological condition characterized by recurrent, severe pain linked to peripheral and central sensitization within trigeminal pathways. Current pharmacologic treatments are limited by inadequate efficacy or dose-limiting side effects, and botulinum neurotoxin type A (BoNT/A) has emerged as a viable option. However, its potential use in the management of TN is hampered by methodological limitations in existing studies and a lack of pivotal clinical trials. This study investigated the efficacy, optimal treatment site, preventive utility, and duration of effect of incobotulinumtoxinA (Inco/A), a BoNT/A, in a model of TN. Methods: An infraorbital nerve chronic constriction injury model was used to induce mechanical allodynia in male Sprague–Dawley rats, reproducing the trigeminal sensitization seen in TN. The effects of subcutaneous Inco/A (1, 2, and 4 U) were measured using the mechanical sensitivity (von Frey) test to evaluate the dose response, effect of injection location, potential preventive nature of treatment, and duration of benefit. Results: Inco/A produced a robust, dose-dependent reduction in mechanical allodynia, predominantly via a local mechanism of action. Both preventive and therapeutic administration of Inco/A was efficacious, with significant reduction in allodynia even when administered up to 28 days before nerve injury. The anti-allodynic effect persisted up to 56 days post-injection. Conclusions: Inco/A is highly effective in alleviating mechanical allodynia in a validated rat model of TN. The findings highlight Inco/A as a promising candidate for clinical translation in TN and related neuropathic pain syndromes and support systematic investigation in well-controlled human trials. Full article

Background/Objectives: Combination of antiparasitic drugs with different mechanisms of action has been suggested as an effective strategy to delay the development of parasite resistance. Considering the need to understand the pharmacological basis of drug combinations, the current study evaluated the potential pharmacokinetic (PK) interactions and the clinical efficacy (pharmacodynamic response) occurring after the subcutaneous administration of ivermectin (IVM) and levamisole (LEV), administered either as single treatments or concurrently to different groups of parasitized calves on three commercial farms (A, B and C). Methods: Forty-five (45) male calves naturally infected with gastrointestinal nematodes were randomly allocated into three groups (n = 15): IVM, treated with IVM by subcutaneous injection (0.2 mg/kg); LEV, treated subcutaneously with LEV (8 mg/kg); IVM + LEV, simultaneously treated with IVM and LEV (two subcutaneous injections at the same dose rates). Seven animals from each treated group (farm C) were randomly selected to perform the PK study. Drug concentrations were measured by HPLC. The therapeutic response (efficacy) was determined at 14 days after treatment by the fecal egg reduction test. Results: The mean area under the concentration vs time curve (AUC) for IVM obtained after administration of IVM alone (274 ± 65.1 ng.d/mL) was similar to that obtained when IVM was co-administered with LEV (295 ± 111 ng.d/mL). Likewise, mean LEV AUC values were similar after LEV administration alone (8.90 ± 2.69 µg.h/mL) or combined with IVM (9.11 ± 1.82 µg.h/mL). No adverse PK interactions were observed after the combined treatment, with similar PK parameters (p > 0.05) obtained between the single-drug and the combination-based strategies. On farm A, the overall fecal egg reductions were 38% (IVM), 99% (LEV) and 100% (IVM + LEV). While Cooperia spp. and Haemonchus spp. showed reduced susceptibility to IVM treatment, LEV demonstrated high efficacy against both genera, with only a minimal proportion of Haemonchus spp. remaining after treatment. Similarly, total fecal egg reductions were 42% (IVM), 99% (LEV) and 100% (IVM + LEV) on farm B, and 54% (IVM), 99% (LEV) and 100% (IVM + LEV) on farm C. On those farms, IVM was ineffective against Cooperia spp. and/or Haemonchus spp., while LEV failed to control Ostertagia spp. Remarkably, the combination of both molecules was the only treatment that achieved 100% efficacy against all nematode genera (Cooperia, Ostertagia, Haemonchus and Oesophagostomum spp.). Conclusions: Based on the described PK and pharmacodynamic (PD) assessments, the IVM + LEV combination appears to be a promising pharmacological option for controlling resistant gastrointestinal nematodes in cattle, with the additional potential to delay the progression of nematode anthelmintic resistance. Overall, the study provides original and robust pharmacokinetic and efficacy data that contribute to the optimization of parasite control strategies in cattle. This drug combination strategy may enhance treatment efficacy and contribute to improved parasite control in cattle production systems. Full article

Background and Aims: Automated insulin delivery (AID) systems are standard of care for type 1 diabetes mellitus (T1DM). Tubeless AID systems may improve treatment acceptance, but real-world European data in patients transitioning from multiple daily injections (MDI) or open-loop patch pump therapy are limited. This study evaluated real-world glycemic, safety, and quality-of-life (QoL) outcomes after transition to a tubeless automated closed-loop system (Omnipod 5^®, OP5^®). Research Design and Methods: In this prospective, multicenter observational study, adults with T1DM transitioned from MDI or open-loop continuous subcutaneous insulin infusion to OP5^® and were followed for 180 days. Continuous glucose monitoring-derived metrics and validated patient-reported outcome measures were assessed. Subgroup analyses were performed by prior therapy. Results: Of the 94 enrolled participants, 88 completed the study. At 180 days, HbA1c decreased from 7.5% to 7.1% (p < 0.001), and time in range increased from 59.0% to 68.0% (p < 0.001) without increased hypoglycemia. The proportion achieving TIR_70–180 ≥ 70% rose from 12.5% to 43.2%. Improvements were greater among prior MDI users. Treatment satisfaction and diabetes-related QoL improved significantly. The mean time in automated mode was 90.9%. Conclusions. Transition to tubeless AID significantly improved glycemic and psychosocial outcomes, supporting its effectiveness in routine clinical practice. Full article

Lung cancer is a leading cause of death worldwide and is often accompanied by declines in musculoskeletal health (i.e., cachexia). Despite affecting a majority of lung cancer patients, cachexia remains understudied and currently has no cure. We have previously demonstrated that liver metastases (LMs) exacerbate cachexia in murine models of colorectal cancer, and, while the liver represents a common site of metastases and is associated with poor prognosis in patients with lung cancer, whether LMs heighten musculoskeletal wasting in mice bearing lung cancer is unknown. Here, we aimed to characterize the impact of LMs on musculoskeletal health in a mouse model of lung cancer cachexia. C57BL/6J male mice were injected with LLC tumor cells either subcutaneously or intrasplenically (LMs) to mimic hepatic metastases (n = 6–9/group). Upon sacrifice, skeletal muscle, bone, and plasma were collected for morphological and molecular analyses. Consistently, compared to healthy controls, metastatic tumor hosts displayed greater reductions in muscle weights (~17%), in line with decreased muscle torque (~23%) and reduced muscle cross-sectional area (~10%). On a molecular level, skeletal muscle from mice bearing LMs had elevated levels of pStat3, Murf1, and Atrogin-1, suggesting enhanced protein catabolism. Similar to skeletal muscle, metastatic tumor hosts displayed greater losses in trabecular bone and increased skeletal fragility. Plasma proteomics identified 211 and 131 differentially expressed proteins in metastatic hosts compared to control animals and subcutaneous LLC hosts, respectively. Top regulated pathways in mice bearing LMs included neutrophil degranulation, BAG2 signaling, and cachexia signaling. Overall, our findings demonstrate that LMs are accompanied by accelerated musculoskeletal wasting and weakness in a mouse model of lung cancer cachexia. This work highlights the need for animal models that mimic advanced cancer, thus providing a better understanding of the mechanisms that mediate cachexia. Full article

Background: TV-44749 is a subcutaneous (sc) long-acting injectable (LAI) formulation of olanzapine that recently demonstrated efficacy and safety as a treatment for schizophrenia in adults without the occurrence of post-injection delirium/sedation syndrome (PDSS) in the phase 3 SOLARIS trial (NCT05693935). TV-44749’s sc route of administration and formulation were designed to provide prolonged olanzapine release over a monthly dosing interval and to avoid the risk of post-injection delirium/sedation syndrome (PDSS). It was designed as a copolymer in situ-forming depot technology to provide a LAI formulation that could withstand physiological and environmental factors that could affect controlled-release kinetics. Methods: To evaluate the robustness of the TV-44749 formulation, an in vitro release (IVR) study in human plasma was conducted, comparing TV-44749 to the commercially available intramuscular (im) long-acting injection formulation of olanzapine pamoate monohydrate. In addition, in vivo studies in rats were conducted to assess the effect of injection site manipulation following TV-44749 sc injection on olanzapine release from the depot. Results: The IVR study showed that upon contact with human plasma, copolymers comprising TV-44749 formulation instantly precipitate and form a solid matrix that entraps olanzapine particles. This prevents an uncontrolled release of olanzapine. Additionally, in vivo rat studies found that manipulation of the injection site after TV-44749 administration, by either heating or rubbing at different time-points, resulted in no meaningful effect on overall olanzapine exposure. Conclusions: The presented findings support the robustness of the TV-44749 formulation in maintaining controlled-release properties, even under conditions that could otherwise compromise release performance. Full article

Background/Objective: Myocardial fibrosis (MF) is a prevalent pathological endpoint in various heart diseases, characterized by extracellular matrix (ECM) dysregulation and oxidative stress. Hyperoside (Hyp) plays a role in regulating cardiac oxidative stress and fibrosis. This study aimed to elucidate whether Hyp regulates isoproterenol (ISO)-induced MF in mice by modulating the GATA4/HIF-1α signaling pathway and reducing oxidative stress. Methods: The binding affinity of Hyp to GATA4 and HIF-1α was assessed through molecular docking and dynamics simulation. The MF model of mice was established by subcutaneous injection of ISO. Cardiac function was measured by echocardiography. Myocardial injury and collagen deposition were examined using H&E and Sirius red staining. Levels of fibrosis markers, oxidative stress indicators, and GATA4/HIF-1α pathway indicators in serum and heart tissue were quantified by ELISA, Western blot, RT-qPCR and flow cytometry. The distribution of myocardial marker proteins was visualized by immunofluorescence and immunohistochemistry. Results: Molecular docking revealed high binding affinity of Hyp to GATA4 and HIF-1α (binding energies < −5.0 kcal·mol⁻¹), and dynamics simulation showed that the complex’s structure remained stable over 100 nanoseconds (RMSD < 0.1 nm). High-dose Hyp (36 mg/kg) significantly improved cardiac function, myocardial injury, collagen deposition, and inflammatory infiltration in MF mice. Molecularly, Hyp effectively reduces oxidative stress and fibrosis through upregulating GATA4 and downregulating HIF-1α. Conclusions: Hyp suppresses oxidative stress by activating the GATA4/HIF-1α pathway, presenting a promising therapeutic target for the treatment of MF. Full article