Search Results (3,612)

Background: To investigate the effect of angiotensin-(1-7) [Ang-(1-7)] on serum metabolomics in obese type 2 diabetic (T2DM) mice. Methods: Four-week-old male C57BL/6 mice were fed a high-fat diet and intraperitoneally injected with streptozotocin (35 mg/kg) to establish an obese T2DM model. Mice were randomized into control, T2DM and T2DM+Ang-(1-7) groups (n = 6). Body weight and blood glucose were recorded weekly. At 10 weeks, blood glucose, serum inflammatory factors, lipid profiles, and pancreatic β-cell insulin secretion were detected; serum metabolite alterations were analyzed via untargeted metabolomics. Results: 1. Ang-(1-7) intervention decreased blood glucose (p < 0.05) and CRP levels (p < 0.01), and alleviated dyslipidemia (p < 0.05 or p < 0.01), as well as β-cell morphology and insulin expression in obese T2DM mice. 2. Non-targeted metabolomics analysis suggested that Ang-(1-7) may alleviate abnormal amino acid metabolic pathways by regulating levels of metabolites such as L-valine, L-proline, L-histidine, and glutamic acid. This intervention also tended to reduce multiple lipid metabolites, including Omega-3 Arachidonic Acid Ethyl Ester, phosphatidylcholine, and glycerophosphocholine, thereby participating in the modulation of lipid metabolism balance. KEGG enrichment analysis further indicated that Ang-(1-7) was involved in the regulation of protein digestion and the absorption pathway, as well as the HIF-1 signaling pathway related to oxidative stress, bile acid metabolism pathway, and other signaling pathways, and improving the insulin secretion pathway, pyrimidine metabolism, and TCA cycle energy metabolism pathway. Conclusions: Ang-(1-7) may partially improve metabolic disturbances in obese T2DM mice, which is potentially associated with the modulation of multiple metabolic processes, including amino acid metabolism, lipid metabolism, insulin secretion, and TCA cycle energy metabolism. Full article

Beyond gas transport, red blood cells (RBCs) have emerging roles regarding innate immunity, regulating blood flow, and participating in nutrient transport, which can be engineered as drug delivery systems since they contribute to maintaining water homeostasis. Following extensive thermoanalytical studies of human blood plasma, our working group investigated the properties of RBCs, examining their role in healthy and in different disease states by using differential scanning calorimetry (DSC) and the deconvolution of the resulting thermal curve. In the first study, guinea pigs were treated with intraperitoneal chemotherapy. Cyclophosphamide treatment showed a dose-dependent difference between the thermal parameters of control and treated samples, indicating that DSC can be used in this area. Following deconvolution of the DSC studies, the changes can be attributed to the damaged compounds. In the second part of our study, a method for the thermal analysis and deconvolution of RBCs in patients with lower limb ischemia during a three-month cilostazol treatment was developed. The control DSC curve showed 5-6 distinct thermal domains, and in contrast to other drug treatments, this remained stable throughout the entire study period. No effects of stiffness or compact were caused by the anticancer drug cyclophosphamide were observed in the structure of RBCs. These preliminary results highlight the uniqueness of thermodynamic studies of RBCs and provide a fingerprint-like identification of a given individual or disease state. Full article

Antibody–drug conjugates (ADCs) are a promising therapeutic modality for treating cancer. TM4SF1 is an integral membrane protein that internalizes from the cell surface along microtubules to the nucleus and is highly expressed on the surface of both tumor endothelium and tumor cells. We previously reported that in human tumor xenografts in mice, an ADC directed to mouse TM4SF1 (2A7A-LP2) effectively regressed tumors through an anti-vascular mechanism, and an ADC directed to human TM4SF1 (v1.10-LP2) effectively regressed tumors through an anti-tumor cell mechanism. In this study, we investigated the actions of the mouse TM4SF1-directed ADC on VEGF-A-provoked angiogenic vessels. We employed an adenovirus expressing mouse VEGF-A¹⁶⁴ (Ad-VEGF-A) to induce surrogate tumor blood vessels in the ears of nude mice. We showed that an immune effector function-ablated ADC, 3m2A7A-LP2, was better tolerated than its parent 2A7A-LP2. Homing of 3m2A7A to Ad-VEGF-A-induced new blood vessels became evident within six hours after intraperitoneal injection. A single dose of 3m2A7A-LP2 at 3 mg/kg disrupted evolving Ad-VEGF-A-provoked blood vessels within forty-eight hours, and three doses of 3m2A7A-LP2 at 48 h intervals caused striking local ear necrosis; in each case, there was no apparent harm to vessels in the corresponding control virus-injected ears and the surrounding tissues of the same mice. Our studies demonstrate that an ADC-directed against mouse TM4SF1 specifically targeted the newly formed blood vessels induced by Ad-VEGF-A at multiple stages of their development. Thus, TM4SF1-directed ADCs, through their ability to target angiogenic vessels, represent an alternative anti-angiogenic approach for treating solid tumors. Full article

Background: Postmenopausal women are at high risk of Alzheimer’s disease (AD) incidence and progression. Irisin, an exercise-induced myokine, has neuroprotective and antiaging effects against AD, especially in menopausal women suffering from insulin resistance (IR). For the first time, the novel role of irisin induced by melatonin (MTN) or/and physical exercise (PHE) was investigated in the current ovariectomized (OVX)/AD rat model by modulating brain neuroinflammation and IR-related markers. Methods: Fifty female Wistar rats were divided into five groups, with one representing a sham group. AD was induced in the other four bilateral OVX rat groups by daily intraperitoneal injection of D-galactose/AlCl₃ (60 and 10 mg/kg, respectively) for 42 days. Group III–V: Animals were exposed to MTN (10 mg/kg/day; i.p.), PHE, and a combination of these, respectively, in the final 14 days of the experiment. Results: The OVX/AD rats showed significant deterioration in learning, memory, neurochemical, and histopathological examinations, while the MTN or/and PHE treatments significantly increased serum and brain irisin, improving memory in a Y-maze assessment. Thus, hippocampal histopathological alterations and IR-related markers decreased. In addition, suppressed hippocampal amyloid-beta protein expression and neuroinflammatory content of tumor necrosis factor-alpha (TNF-α), p38 mitogen-activated protein kinase (p38 MAPK), and NOD-like receptor protein-3 (NLRP3) were associated with an increase in peroxisome proliferator-activated receptor-gamma (PPAR-γ) protein expression and insulin-like growth factor-1 content in hippocampal tissues, collectively suppressing glial fibrillary acidic protein (GFAP) content, leading to an increase in brain-derived neurotrophic factor expression. Conclusions: Irisin induction may serve as a novel avenue in AD/menopause treatment and prevention via modulating the TNF-α/p38 MAPK/PPAR-γ/NLRP3/GFAP pathway. Full article

Toxoplasma gondii is an obligate intracellular parasite that infects virtually all warm-blooded animals, progressing through acute and chronic stages. The Akt/mTOR signaling axis plays critical roles in cell survival, proliferation, and metabolism, making it a key target for intracellular pathogens. This study investigated how T. gondii infection modulates this pathway during both infections. Outbred CD-1 mice were infected intraperitoneally with the virulent GT1 strain of T. gondii. Mice for acute studies were sacrificed five days post-infection, while those for chronic studies were treated with sulfadiazine and sacrificed five months post-infection. Phosphoprotein expression of eight Akt/mTOR pathway components was measured in liver tissues using a multiplexed bead-based immunoassay. Acute T. gondii infection caused broad suppression of Akt/mTOR signaling, with 6 of 8 markers significantly downregulated, including pS6RP^Ser235/236, pAKT^S473, pBAD^Ser136, pIRS1^S636/639, pPTEN^Ser380, and pGSK-3α/β^Ser21/9. In contrast, chronic infection related to cyst burden selectively activates specific nodes of the pathway, including pBAD^Ser136, pmTOR^Ser2448, and pGSK-3α/β^Ser21/9. Infection induced strong correlations between inter-components, which reflect coherent and coordinated pathway-level reprogramming rather than random perturbation. These findings show that acute and chronic T. gondii infections have opposing effects on host Akt/mTOR signaling for their own benefit, which may present new therapeutic targets. Full article

Rationale: Oral squamous cell carcinoma (OSCC) carries a poor prognosis despite advances in multimodal therapy. Nanomedicine represents a compelling strategy to enhance targeted drug delivery and improve therapeutic outcomes. Here, we investigated sEV-mediated delivery of curcumin as a novel therapeutic approach for OSCC. Methods: Small extracellular vesicles (sEVs) were isolated from Jurkat cells by size-exclusion chromatography and loaded with curcumin via sonication to generate JCsEV. Functional effects were assessed in vitro using wound healing, transwell invasion, and metabolic activity assays across multiple cancer cell lines. Therapeutic efficacy in vivo was evaluated in the 4-nitroquinoline 1-oxide (4-NQO) immunocompetent murine model of oral carcinogenesis. Female C57BL/6J mice received intraperitoneal treatment for four weeks with PBS, free curcumin, unloaded JsEV, or JCsEV. Tumor number, tumor burden, and body weight changes were assessed at the experimental endpoint. Results: In vitro, JCsEV significantly inhibited tumor cell migration, invasion, and metabolic activity compared with controls (p < 0.05). In vivo, treatment with JCsEV significantly reduced tumor number and tumor burden in the 4-NQO model (p < 0.01). In addition, body weight loss was reduced in JCsEV-treated mice compared with controls. Conclusion: sEV-mediated delivery of curcumin effectively suppresses tumor progression in experimental OSCC. These findings establish proof-of-concept for sEV-based nanomedicine as a therapeutic strategy for OSCC and provide a compelling rationale for further translational investigation of sEVs as drug delivery platforms. Full article

Objectives: This study aimed to investigate the therapeutic efficacy of a hydrogel loaded with Wharton’s Jelly mesenchymal stem cells (WJ-MSCs) and melatonin, administered to the liver either via mesh–hydrogel implantation or intraperitoneal hydrogel injection, in a thioacetamide (TAA)-induced liver fibrosis animal model. Methods: A collagen-based hydrogel containing WJ-MSCs and melatonin was prepared for injection as well as combined with electrospun mesh for implantation. Hydrogel and mesh were characterized with respect to morphology, degradation, and mechanical properties. In in vivo studies, liver fibrosis was induced in rats by intraperitoneal injection of TAA for 6 weeks. After fibrosis induction, animals received either hydrogel injection or implantation of the combined construct. After 21 days, serum and liver tissues were collected, and biochemical, histopathological, and ultrastructural analyses were performed through comparative evaluation of experimental groups. Results: SEM results demonstrated that hydrogel, with appropriate porosity, was well integrated with the mesh without any detachment. The mesh, composed of submicron-scale fibers, exhibited a Young’s modulus of 10.37 ± 2.33 MPa. The hydrogel presented a degradation profile with a 40% mass loss in 24 h, reaching approximately 50% by day 30. Biochemical results indicated significant improvement in liver regeneration with both treatment strategies, particularly with the implanted construct. Histopathological analysis revealed decreased inflammation and hepatocyte vacuolization following both treatments; however, collagen accumulation was significantly reduced in the implant group. Ultrastructural analysis showed preserved nuclear integrity and reduced endoplasmic reticulum dilation and degenerative changes in implant group. Conclusions: The combination of WJ-MSCs and melatonin-loaded hydrogel with supportive mesh particularly enhanced tissue regeneration in liver fibrosis. Full article

This study explored the regulatory role of nuclear factor E2-related factor 2 (Nrf2) in aerobic exercise improving oxidative stress and inflammatory responses in mice with insulin resistance (IR) induced by a high-fat diet. We established an IR mouse model through a high-fat diet, then subjected the IR mice to aerobic exercise, intraperitoneal injection of luteolin, or a combined intervention. After 6 weeks of intervention, we measured serum lipid and glucose profiles; evaluated skeletal muscle morphology by H&E staining; quantified mRNA expression levels of Nrf2 and its downstream targets in the skeletal muscle by RT-qPCR; and determined protein abundance, localization, and expression patterns of Nrf2 and NOD-like receptor protein 3 (NLRP3) inflammasome by Western blotting and immunohistochemistry, respectively. In the skeletal muscle of IR mice, Nrf2 and its downstream targets were significantly down-regulated, whereas NLRP3 inflammasome was markedly up-regulated (p < 0.05 or p < 0.01). IR mice subjected to aerobic exercise exhibited reduced serum glucose and lipid levels together with a lower insulin-resistance index (p < 0.05 or p < 0.01); morphologically, inter-myofibrillar spaces were narrowed, intrafiber vacuoles diminished, and cellular integrity restored. Concomitantly, Nrf2 and its downstream targets were up-regulated, whereas NLRP3 inflammasome components were down-regulated in the skeletal muscle (p < 0.05 or p < 0.01). Intraperitoneal administration of luteolin during exercise, however, partially attenuated or reversed these exercise-induced improvements by inhibiting the activation of Nrf2 (p < 0.05 or p < 0.01). These results indicate that aerobic exercise confers protective effects against IR by activating the Nrf2 signaling pathway, thereby attenuating oxidative stress and inflammation; these benefits are markedly attenuated when Nrf2 activity is pharmacologically inhibited. Full article

Objective: The existing work was designed to appraise whether Secukinumab diminishes acute kidney injury in a Cisplatin- induced rat model and to explore the potential underlying mechanisms for this protective effect. Methods: In vivo study, rats were distributed haphazardly into five sets (six animals in each group): control, Secukinumab control, Cisplatin (8 mg/kg, a single dose, intraperitoneally (IP)), and two pretreated groups; Secukinumab (10 and 20 mg/kg single subcutaneous (SC) injection) + Cisplatin. Blood samples and kidney tissues were gathered and analyzed histopathologically and biochemically. In vitro investigation, MCF-7 human breast cancer cells were treated with Cisplatin alone with Secukinumab, and cell viability (MTT assay), combination index, and apoptosis-related markers were analyzed. Results: Secukinumab administration lowered serum levels of BUN, creatinine and LDH with marked elevation in renal TAC and a significant reduction in MDA, iNOS, KIM-1 and NGAL compared to Cisplatin. Additionally, Secukinumab pre-treatment markedly suppressed the inflammatory process and enhanced autophagy, reflected by elevated AMPKα1, SIRT1, and Beclin-1, accompanied by reduced P38 MAPK and NF-κB p65 (Phospho-Ser536) levels and expression levels of IL-6 and P62/SQSTM1 in kidney tissues, contrasted with the Cisplatin group. Secukinumab administration effectively protected against kidney injury, and histopathological examinations of the kidneys confirmed these results. On the other hand, in vitro study results revealed that the combination of Cisplatin and Secukinumab had a synergistic cytotoxic effect and an enhancing effect on the apoptotic pathway (increased P53 and BAX and decreased BCL-2). Secukinumab effectively protects against Cisplatin- induced acute kidney injury by decreasing oxidative stress, inflammation, and enhancing autophagy. Additionally, it synergizes with Cisplatin in vitro to promote cancer cell apoptosis, highlighting its dual reno-protective and anticancer potential. Full article

Objective: Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is an aggressive locoregional treatment for selected patients with peritoneal surface malignancies. Although its oncological role has been widely discussed, longitudinal data focusing on postoperative quality-of-life (QoL) trajectories remain limited. This study aimed to describe longitudinal QoL trajectories during the first two years after CRS/HIPEC and to provide exploratory descriptive comparisons according to selected clinical characteristics. Methods: This retrospective single-center cohort study included 144 consecutive adult patients who underwent CRS/HIPEC between January 2018 and July 2022. Patients were evaluated preoperatively and postoperatively at day 14 and at 1, 3, 6, 12, 18, and 24 months. QoL was assessed during routine follow-up primarily using the EORTC QLQ-C30 questionnaire; the EORTC QLQ-CR29 was also administered in institutional practice as a supplementary instrument in selected settings. Repeated QLQ-C30 measurements were analyzed descriptively using the Friedman test with post hoc Nemenyi comparisons. Results: Questionnaire completion rates were 100% at baseline, postoperative day 14, and month 1; 96.5% at months 3 and 6; 91.0% at month 12; 81.9% at month 18; and 75.7% at month 24. Longitudinal analyses demonstrated significant time effects across multiple QoL domains, including global health status, physical functioning, emotional functioning, role functioning, cognitive functioning, social functioning, pain, fatigue, and diarrhea. The most pronounced deterioration was observed in the early postoperative period, particularly at postoperative day 14. Thereafter, several domains improved gradually; however, recovery was domain-specific and did not consistently return to preoperative levels during follow-up. In exploratory descriptive analyses, patients with major postoperative complications showed more pronounced early impairment in global health status, physical functioning, and social functioning, together with greater pain and fatigue burden, particularly at postoperative day 14 and month 1. Exploratory subgroup comparisons also suggested heterogeneity in recovery patterns according to primary tumor origin. Later follow-up findings should be interpreted cautiously in view of attrition over time and the absence of adjusted longitudinal modeling. Conclusions: Quality of life declines substantially during the early postoperative period after CRS/HIPEC, followed by gradual but incomplete recovery over time. This recovery pattern is non-linear and varies across domains. Exploratory descriptive findings suggested that early postoperative QoL impairment may be greater in patients with major complications, but these subgroup patterns require confirmation in prospectively designed studies using adjusted longitudinal models. Longitudinal QoL assessment may provide clinically meaningful insight into postoperative recovery after CRS/HIPEC. Full article

Juniperus phoenicea L. is a popular plant in alternative medicine, particularly in the steppe and highland regions of western Algeria. The present study focuses on characterizing the essential oil of Juniperus phoenicea growing spontaneously in the Ain El Orak region of El Bayadh province, where it is a valuable resource. The essential oil yield obtained by hydrodistillation was 0.98%, and its characterization by GC-MS revealed 46 compounds, predominantly α-Terpinolene at 21.29%, Limonene at 14.68%, Terpinene 4-ol at 12.04%, β-Myrcene at 9.93%, and β-Pinene at 7.31%. The study of the anti-radical activity against DPPH showed an IC50 value of approximately 0.23 mg/mL. The evaluation of the anti-ulcer property on experimentally induced ulcers in mice through oral administration of ethanol demonstrated excellent protection of the gastric mucosa, with 48.07%, 54.87%, and 81.92% protection for doses of 50, 100, and 200 mg/kg, respectively, comparable to omeprazole at 72.40%. The hepatoprotective activity against toxicity induced by intraperitoneal injection of a 250 mg/kg dose of paracetamol in mice showed a protective effect expressed by the decrease in serum levels of AST (260.33 ± 9.69 IU/L) and ALT (56.22 ± 9.63 IU/L) to values comparable to the those of the physiological group, especially for the 300 mg/kg dose of the essential oil of J. phoenicea. Full article

The liver is a critical organ in drug metabolism and detoxification. Ganoderma lingzhi triterpenoids, a major class of bioactive compounds in G. lingzhi extracts, exhibit liver protective effects with pharmaceutical potential. In this study, we established an acute liver injury model in mice via intraperitoneal injection of 0.25% Carbon tetrachloride(CCl₄) olive oil. Prophylactic and therapeutic administration of G. lingzhi triterpenoid extracts were evaluated using alanine aminotransferase (ALT), aspartate aminotransferase (AST), superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and hepatic histopathology. Western blot analysis assessed protein expression of anti-inflammatory and antioxidant stress-related pathways (Nrf2/Keap1 and MyD88/NF-κB-p65). Intervention effects on acute liver injury were determined by measuring protein molecular weight following triterpenoid treatment. In summary, G. lingzhi triterpenoids significantly alleviate oxidative stress and inflammatory responses in mice with acute liver injury by activating the KEAP1-Nrf2 antioxidant pathway and inhibiting the NF-κB-p65 and MyD88-mediated inflammatory pathways. These triterpenoids reduced serum transaminase levels, improved hepatic histopathological damage, and exerted effective protective effect on liver tissue. This study provides experimental support for the comprehensive evaluation of G. lingzhi’s anti-inflammatory and antioxidant effects. Full article

Copper is a common pollutant in aquatic environments. Excess copper in water can enter aquatic organisms through respiration, feeding, and adsorption, thereby exerting serious adverse effects on their health. In this study, NEW Genetically Improved Farmed (GIFT) Nile tilapia (Oreochromis niloticus L.) was used to explore the effect of copper on the hepatopancreas and post-exposure recovery. Acute exposure was simulated via an intraperitoneal injection of 3.75 mg Cu²⁺/kg body mass, while physiological saline injections served as the control. Samples were collected on days 1, 7, 14, and 21 post-exposure to evaluate growth performance, histopathological changes, antioxidant enzyme activities, and the expression of oxidative stress-related genes in the hepatopancreas. The results show that body length and mass increased within 21 days of the injection and copper exposure did not significantly affect fish growth. On day 1 after copper injection, numerous vacuoles appeared in hepatopancreatic tissues. On day 14, congestion and obvious hepatic sinusoids were observed. However, on day 21, the tissue structure showed gradually recovery. Compared to the control group, superoxide dismutase (SOD) activity was significantly higher in the exposed group on days 1, 14, and 21, and SOD gene expression was significantly elevated on day 21. Catalase (CAT) activity was significantly higher on day 7, and the expression of the CAT gene increased significantly on days 1 and 21. Glutathione peroxidase (GSH-Px) activity decreased significantly on day 7, whereas GPX gene expression increased significantly at the same time point. No significant difference in acetylcholinesterase (AChE) activity was observed during the experiment. In conclusion, copper administered via intraperitoneal injections induced significant activation of the antioxidant defense system and histopathological damage in the hepatopancreas of tilapia. Although tissue damage gradually recovered over time, the activation of the antioxidant defense system partially persisted. Ultimately, copper exposure did not significantly affect growth indicators such as body length and mass. These results advance our understanding of copper toxicity in farmed fish and provide a scientific reference for safe aquaculture production. Full article

Background and Objectives: Doxorubicin is an antineoplastic drug used to treat cancer. However, side effects limit its use. Edaravone (EDO) is a recently discovered, powerful drug with antioxidant properties. The aim of the present study was to show the negative effects of doxorubicin and the protective effect of EDO on the thyroid gland using scintigraphic and biochemical methods. Materials and Methods: Thirty-five male Wistar rats were randomly divided into five groups (n = 7) to establish the following study groups: control, doxorubicin, and 1, 10, or 30 mg/kg EDO. DOX (18 mg/kg cumulative intraperitoneal injection (i.p.) was performed on the 19th, 20th, and 21st days of the experiment. EDO (1, 10, and 30 mg/kg) was administered on the first day of the trial and continued for 21 days. These groups also received i.p. injections of DOX (18 mg/kg) on the 19th, 20th, and 21st days of the experiment. On the 22nd day of the experiment, scintigraphic imaging of the thyroid glands of rats was performed using ^99mTc pertechnetate as the radiopharmaceutical. Serum levels of T3, T4, TSH, NLRP3, IL-1β, and IL-18, as well as thyroid tissue levels of MDA, TNF-α, and IL-6, were determined using the ELISA method. Results: DOX significantly reduced ^99mTc pertechnetate uptake in the thyroid gland compared to the control group (p < 0.001). It reduced plasma levels of thyroid hormones T3 (p < 0.001) and T4 (p < 0.001) while increasing TSH levels (p < 0.01). Additionally, NLRP3, IL-1β, IL-18, MDA, TNF-α, and IL-6 levels were significantly increased in the DOX group compared with the control group (all p < 0.001). Pretreatment with EDO significantly attenuated doxorubicin-induced abnormalities in the thyroid gland (p < 0.001). Conclusions: The data from scintigraphic and biochemical analyses revealed the development of hypothyroidism after doxorubicin administration in rats. It was shown that pretreatment with EDO could partially prevent hypothyroidism caused by doxorubicin. Full article

Substances released by cardiomyocytes after myocardial infarction (MI) lead to inflammasome assembly. Heart failure (HF) is associated with skeletal muscle inflammation. Methotrexate (MTX) reduces cardiovascular outcomes in chronic inflammation patients. Lipid core nanoparticle-associated MTX (MTX-LDE) attenuated cardiac remodeling in MI rats. We investigated the effects of early MTX-LDE administration on cardiac remodeling and inflammasomes in soleus muscle of MI rats. Wistar rats were separated into Sham, MI, and MI-MTX groups. MTX was initiated 24 h after MI at 1 mg/kg/week intraperitoneally for 10 weeks. Soleus protein expression of NLRP1, NLRP3, NLRC4, ASC, procaspase-1, Caspase-1, pro-IL-1β, and IL-1β was quantified by Western blotting; Nlrp1a, Nlrp3, Nlrc4, Pycard (Asc), Casp1, and Il1b gene expression was assessed by qPCR; and statistical analysis used Student’s t test and ANOVA. Rats with infarction size > 35% total left ventricle (LV) area were included in the study; infarction size did not differ between groups. Echocardiogram showed infarcted groups with LV dilation and dysfunction. Diastolic function was worse in MI-MTX than MI. NLRP1 and NLRC4 protein expression was lower in MI-MTX than Sham. Expression of other proteins and gene expression did not differ between groups. Early MTX-LDE administration reduces NLRP1 and NLRC4 protein expression in soleus muscle without improving cardiac remodeling in rats. Full article