Search Results (785)

Bacterial cellulose (BC) is an emerging biopolymer for skin tissue regeneration; however, its functionalization with natural antimicrobial agents remains limited. This study reports the preclinical evaluation of a BC-based dressing for diabetic wounds. BC membranes were obtained from mango pulp agro-waste by Komagataeibacter xylinus cultivation (6.32 g/L) and functionalized with grapefruit seed oil (GSO) at three v/v ratios (1:100, 1:200 and 1:500). FTIR spectroscopy confirmed GSO incorporation into the BC matrix through physical interactions, with a dose-dependent loading. Antimicrobial activity of the BC/GSO dressings was screened against Staphylococcus aureus, Escherichia coli and Candida albicans by agar diffusion, showing dose-dependent inhibition zones. Following the minimum effective dose principle, the BC/GSO 1:500 (v/v) formulation was selected for comprehensive biocompatibility evaluation (cytotoxicity, mutagenicity, pyrogenicity and sensitization) and for in vivo wound-healing testing in a streptozotocin-induced diabetic Wistar rat model. Cell viability above 70% was achieved from membrane-extract dilution 1:100,000, while mutagenicity, pyrogenicity and sensitization assays confirmed the absence of adverse biological responses. In vivo, BC/GSO 1:500 (v/v) dressings supported wound closure comparable to nitrofurazone, with no clinical signs of infection. Overall, these results position BC/GSO dressings as a sustainable, biocompatible and antimicrobial candidate for early-stage diabetic wound regeneration and demonstrate the technical feasibility of valorizing mango pulp agro-waste into a high-value biomedical biopolymer. Full article

Pneumocystis is an opportunistic fungal pathogen that causes severe Pneumocystis pneumonia (PCP) in immunocompromised individuals and laboratory animals. Three host-specific species—Pneumocystis murina (P. murina), Pneumocystis carinii (P. carinii), and Pneumocystis jirovecii (P. jirovecii)—are closely associated with infections in humans and laboratory animals. However, the conventional method, microscopic staining, suffers from low sensitivity, operator-dependent subjectivity, and inability to differentiate species, highlighting the urgent need for a multiplex qPCR assay. In this study, we established a multiplex qPCR method targeting the mtLSUrRNA gene of P. murina, the TS gene of P. carinii, and the mtSSUrRNA gene of P. jirovecii. Primers and probes were designed and optimized using a matrix approach. The method was systematically evaluated for sensitivity, specificity, and reproducibility using recombinant plasmid standards and laboratory animal samples. Validation was performed on 260 mouse lung samples, 30 P. murina-positive samples, 25 rat lung samples, 6 rat bronchoalveolar lavage fluid (BALF) samples, and 8 P. carinii-positive samples. Results were compared with single-plex qPCR and staining microscopy (performed on 68 mouse lung samples, 38 Pneumocystis-positive samples). The limits of detection (LOD) were 5 copies/μL for P. murina, 6 copies/μL for P. carinii, and 8 copies/μL for P. jirovecii. Standard curves showed excellent linearity (R² ≥ 0.999) with amplification efficiencies of 90–110%. No non-specific reactions were observed with 22 common pathogens, and intra-/inter-group coefficients of variation (CV%) were below 1%. Moreover, interference testing revealed minimal matrix effects on the amplification system and no mutual interference among the primers and probes. The multiplex qPCR detected all 38 positive samples (100%), showing 100% concordance with single-plex qPCR, whereas Giemsa staining detected none (0%) and toluidine blue staining only 60% (3/5) of the tested positives, suggesting that the multiplex qPCR achieved higher detection rates than staining microscopy. In conclusion, this novel multiplex qPCR method offers high sensitivity, specificity, and reproducibility, providing a sensitive and specific tool for laboratory animal health monitoring and epidemiological surveillance. Its clinical application for human PCP diagnosis requires further validation with authentic human specimens. Full article

Objective: Linezolid (LZD), an oxazolidinone antibiotic widely used against Gram-positive infections, has been associated with mitochondrial dysfunction and hepatotoxicity, particularly during prolonged use. This study aimed to investigate the protective effects of adenosine triphosphate (ATP) and Liv-52 against LZD-induced liver injury, with a focus on oxidative stress, inflammation, and necroptosis pathways. Methods: Twenty-four male Wistar rats were randomly assigned to four groups: healthy control (HG), LZD-treated (LZDG), Liv-52 + LZD (LVLZ), and ATP + LZD (ATLZ). Liv-52 (50 mg/kg, orally) and ATP (5 mg/kg, intraperitoneally) were administered prior to LZD (125 mg/kg, orally) for 14 days. Results: Following LZD administration, malondialdehyde (MDA) levels markedly increased, indicating oxidative stress, while total glutathione (tGSH), superoxide dismutase (SOD), and catalase (CAT) activities significantly decreased. Histopathological examination revealed pronounced hepatocellular damage accompanied by increased NF-κB, NLRP3, RIPK3, and MLKL expression, indicating activation of inflammatory and necroptotic pathways. Treatment with ATP and Liv-52 significantly ameliorated these biochemical, histopathological, and molecular alterations. Conclusions: Treatment with ATP and Liv-52 significantly attenuated oxidative stress, improved histopathological alterations, and suppressed the expression of inflammatory and necroptotic markers. Notably, ATP exhibited a more pronounced protective effect compared to Liv-52. In conclusion, LZD induces hepatotoxicity through oxidative stress-mediated inflammatory and necroptotic mechanisms, while ATP and Liv-52 confer hepatoprotection, with ATP showing superior efficacy. Full article

Background/Objectives: AIDS is a serious threat to human health and remains incurable; however, EK-16A, an ingenol derivative, shows promise as a functional cure. In this study, we aimed to extract EK-16A from Euphorbia kansui, used in traditional Chinese medicine, to develop an oral self-nanoemulsifying drug delivery system (SNEDDS) for EK-16A and evaluate it in vivo. Methods: EK-16A was purified by SFC combined with conventional extraction. The optimal SNEDDS formulation was selected by emulsification and stability testing. Pharmacokinetics, metabolomics, and proteomics were used for in vivo evaluation. Results: 1. The extraction yield of EK-16A was four times higher than that of the conventional process; the extraction scale was increased by 25 times, and the purity of EK-16A reached 98.0%. 2. EK-16A is a BCS Class IV compound with low solubility and permeability. The compound’s content degraded to 49.8% after 3 months at 25 °C/60% RH. The EK-16A SNEDDS formulation A#1 showed no degradation after 3 months at 40 °C/75% RH. The absolute bioavailability after oral administration of formulation A#1 in rats was 0.445%. 3. The proteomics results showed that EK-16A significantly downregulated the PI3K-AKT signaling pathway in SHIV-infected rhesus macaques. Specifically, all 11 identified differential proteins were significantly downregulated. Conclusions: 1. The extraction process for EK-16A features high yield, purity and large scale. 2. The SNEDDS formulation enhances the stability of EK-16A and successfully delivers this low-solubility and permeability compound into the systemic circulation. 3. Proteomics analysis revealed that EK-16A significantly downregulates the PI3K-AKT signaling pathway in SHIV-infected rhesus macaques. However, further experiments, such as measuring plasma viremia and cell-associated SHIV RNA, are needed to confirm this mechanism. Full article

Diabetes is a chronic disease that severely impairs wound healing, slowing wound closure; thus, the risk of infection and increases the occurrence of other complications. The development of a suitable material that can accelerate the process of chronic wound regeneration, particularly in diabetic wounds, remains a significant challenge. In the present study, Sepigel 305^® paraffin-based oil-in-water cream containing spherical gold nanoparticles–bioactive glass was used in rats with induced diabetes mellitus. After wound closure, the stage of regeneration was evaluated histopathologically. It was shown that the wounds treated with the experimental product were closed macroscopically after 14 days, but the histological images still indicated an inflammatory process, suggesting incomplete deep dermal healing. Macroscopic closure of wounds treated with the studied cream after 14 days, which is a normal time for skin healing, represents a successful outcome in diabetic patients because the risk of bacterial infection is reduced, and thus the chance of complete healing increases. Full article

Background/Objectives: Sepsis is a life-threatening syndrome arising from a dysregulated host response to infection, frequently leading to multiple organ dysfunction, with the lungs being among the most severely affected organs. Oxidative stress, inflammation, apoptosis, and DNA damage play key roles in the pathogenesis of sepsis-induced acute lung injury (ALI). Beyond its lipid-lowering effects, rosuvastatin possesses anti-inflammatory and antioxidant properties that may confer protective effects in sepsis. This study was designed to investigate the dose-dependent prophylactic efficacy of rosuvastatin in mitigating pulmonary damage in rats with cecal ligation and puncture (CLP)-induced sepsis. Methods: Sprague–Dawley rats were randomly divided into six groups: Sham, Sham + rosuvastatin (10 mg/kg), Sham + rosuvastatin (20 mg/kg), CLP, CLP + rosuvastatin (10 mg/kg), and CLP + rosuvastatin (20 mg/kg). Rosuvastatin was administered via oral gavage 4 h before the surgical procedures in the experimental groups. All animals were sacrificed 16 h following surgical procedures. Lung tissues were analyzed for biochemical markers, including malondialdehyde (MDA) and reduced glutathione (GSH), as well as histopathological changes and immunohistochemical expression of NF-κB/p65, caspase-3, and 8-OHdG. Results: CLP-induced sepsis significantly increased MDA levels while decreasing GSH levels, indicating enhanced oxidative stress. Rosuvastatin treatment significantly reversed these changes. Histopathological analysis revealed marked lung injury in the CLP group, including alveolar inflammation, interstitial inflammation, vascular congestion, and increased alveolar septal thickness, all of which were significantly reduced following rosuvastatin administration. Immunohistochemical findings demonstrated increased expression of NF-κB/p65, caspase-3, and 8-OHdG in the CLP group, whereas rosuvastatin significantly attenuated these expressions. No significant difference in prophylactic efficacy was observed between the 10 mg/kg and 20 mg/kg doses of rosuvastatin. Conclusions: Rosuvastatin demonstrated a protective effect against sepsis-induced pulmonary damage by reducing oxidative stress, inflammation, apoptosis, and DNA damage. These findings suggest that rosuvastatin may have prophylactic potential in sepsis; however, further support is needed from investigations of cellular pathways in different mechanistic directions. Full article

Rotavirus A (RVA) G3P[3] genotype is widely reported in dogs and less frequently in cats, with only sporadic human cases worldwide. All reported human infections have occurred in children, suggesting increased susceptibility likely linked to close contact with pets and age-related hygiene practices. The identification of a novel genotype constellation in Brazilian canine G3P[3] strains in 2017 prompted full-genotype characterization of the historical RVA/Human-wt/BRA/IAL-R451/2011/G3P[3] strain, previously sequenced only for VP7 and VP4, to define its genomic constellation and relatedness to canine strains. All 11 segments were analyzed by RT-PCR, sequencing and phylogenetics. The rare genotype–lineage constellation G3.III-P[3]-I2.XX-R3.II-C2.V-M3.II-A9-N2.XXIV-T3.II-E3.II-H6.I, shared with Brazilian canine strains, was identified, supporting a potential common origin. RVA/Human-wt/BRA/IAL-R451/2011/G3P[3] strain showed high genetic similarity (93.2–99%) with canine, feline and canine/feline-like human strains worldwide, with six genes (VP1, VP6 and NSP2–NSP5) closely related to Brazilian dog isolates (97.6–99%), indicating its canine origin. NSP2 clustered with strains from domestic (bovine), synanthropic (rat) and human hosts, while VP7 and VP4 were associated with wildlife (bat; raccoon dog) and environmental (sewage; river water) strains, supporting interhost reassortment and highlighting aquatic environments as reservoirs for interspecies transmission. Identification of new lineages (VP1, VP3 and NSP2) within the AU-1-like backbone reflects its underexplored diversity. This novel constellation likely circulated in dogs and may spill over to humans via close contact, reinforcing a One Health approach to understand RVA zoonotic risk, especially in hotspot regions like Brazil. Full article

Uncontrolled bleeding, coagulation disorders, and infection-related complications still present substantial challenges in emergency medicine and trauma care. Developing multifunctional hemostatic materials represent an effective strategy for addressing clinical hemostasis problems. In this study, Galla chinensis polyphenols, the effective extract of Galla chinensis, were loaded onto calcium alginate-mesoporous silica granules (CMS-GC). The CMS granules were prepared by in situ liquid-phase technology and GC was loaded by impregnation methods. In vitro and in vivo studies showed that CMS-GC not only activate the endogenous coagulation pathway via GC, but also the multi-level interconnected pores of CMS granules can promote the cross-linking of GC with plasma proteins and formation of a three-dimensional network structure, which further enhances the coagulation effect and shortens the blood clotting time to less than 80 s. In rat liver and femoral artery hemorrhage models, CMS-GC significantly shortened hemostasis time and reduced blood loss, demonstrating superior hemostatic performance. Moreover, within the moist environment sustained by alginate, GC mitigates inflammatory responses via its antibacterial and free-radical clearance properties, and synergistically facilitates wound healing. This CMS-GC multifunctional granule provides an efficient new strategy for traumatic bleeding and subsequent repair. Full article

Background: The impact of climate change on birds’ migration and ticks’ reservoir habits is contributing to the spread of Crimean–Congo hemorrhagic fever (CCHF), caused by CCHF virus (CCHFV), to new continents and countries. CCHF is endemic to the Eastern Mediterranean Region, including Iraq, and is witnessing a substantial surge in confirmed cases with considerable disparity and gaps in managing CCHF cases. The increasing CCHF spread across Asia, Africa, and Europe, including Spain and Turkey, highlights the danger of its expansion. Developing high-confidence diagnostic criteria, identifying risk factors, and accurate predictors of CCHF outcomes are critical to managing suspected and confirmed cases of CCHF and to reducing the current case fatality rate of CCHF, which is the goal of this study. Methods: We completed a retrospective evaluation of 61 confirmed cases of CCHF in Basrah (Iraq). The cases were screened according to the clinical presentation, and CCHF cases were identified by ELISA and validated by PCR. Data was analyzed using SPSS version 22. T-tests, chi-square/Fisher exact tests, and Pearson’s correlation were used, with significance set at p < 0.05 and high significance at p < 0.01. Results: We found that repeated exposure to animals during animal slaughtering was a significant risk factor. In addition, 5% of the patients with confirmed CCHF, mainly from rural areas, reported exposure to rats. Clinical presentations included fever, headache, gastrointestinal problems, eye and orbital symptoms, and hemorrhagic complications. Predictors of death included advanced age, decreased platelet counts, and neuropsychiatric symptoms such as delusions and confusion. Conclusions: Our findings identify clinical and laboratory features of CCHF cases in Iraq, which will help to implement the most effective interventions to manage CCHF cases and protect the public in all Iraqi governorates. In summary, this study highlights a recent and significant rise in CCHF cases in Basrah Governorate, Iraq. Notably, 5% of confirmed cases reported contact with rats. The paper also proposes diagnostic criteria and identifies key predictors of mortality to support improved clinical management of CCHF. These findings underscore the urgent need for strengthened public health interventions, including enhanced infection prevention and control measures, increased awareness, and improved surveillance systems. The findings have important implications for improving control procedures, guiding therapeutic development, informing vaccine strategies, and supporting evidence-based policy alongside future research efforts. Full article

Polygonum capitatum (PC) is an ethnomedicine with reported antibacterial and anti-inflammatory activities and has been clinically used in urinary tract infection (UTI)-related disorders. However, its in vivo exposure characteristics and metabolically associated therapeutic mechanisms in acute pyelonephritis (AP) remain insufficiently understood. To address this issue, this study aimed to evaluate the therapeutic effects of PC in an Escherichia coli (E. coli)-induced rat model of AP and to explore constituents and metabolic pathways associated with its activity. Different PC extracts were screened for antibacterial and anti-inflammatory activities, and the 70% ethanol extract was selected for further study. Seven major compounds were quantified by HPLC. In AP rats, the pharmacokinetic profiles of these compounds in plasma and the renal cortex were analyzed by microdialysis-coupled HPLC-MS/MS. Pharmacodynamic evaluation included urinary bacterial load, urinalysis, renal function, inflammatory cytokines, and renal histopathology. Exploratory PK–PD analysis, untargeted renal metabolomics, and targeted metabolomics of the tryptophan–kynurenine (Trp–Kyn) pathway were also performed. The 70% ethanol extract of PC exhibited the strongest antibacterial and anti-inflammatory activities. The total content of seven active compounds was 3.85%, with gallic acid being the predominant compound (3.42%). Pharmacokinetic analysis revealed that gallic acid, protocatechuic acid, methyl gallate, and quercitrin achieved relatively high systemic exposure and renal distribution. In AP rats, the pharmacokinetic profiles of several compounds were altered, with increased plasma exposure of protocatechuic acid, vanillic acid, ethyl gallate, and syringic acid, while protocatechuic acid also showed higher exposure in the renal cortex. PC treatment reduced urinary bacterial load, improved renal function and urinalysis parameters, alleviated histopathological injury, and decreased inflammatory mediator levels, particularly in renal tissue. Exploratory PK–PD correlations were observed between several compounds and selected pharmacodynamic indicators. Metabolomic analysis suggested disturbances in glycerophospholipid metabolism and the Trp–Kyn pathway in AP rats, some of which were partially reversed after PC treatment. PC showed antibacterial and anti-inflammatory effects in AP rats. Gallic acid, protocatechuic acid, methyl gallate, and quercitrin may be candidate constituents associated with the therapeutic effects of PC, while modulation of glycerophospholipid metabolism and the Trp–Kyn pathway may be involved in its action against AP. These findings provide preclinical pharmacological evidence supporting the therapeutic potential of PC in AP. Full article

Intervertebral disc degeneration (IDD) is a fundamental pathological basis of low back pain, yet its pathogenic mechanisms remain incompletely understood. Infection by low-virulence anaerobic bacteria has recently been recognized as a potential etiological factor. In this study, Cutibacterium acnes (C. acnes) was detected in 13.7% of degenerated intervertebral disc (IVD) tissues, and its presence was significantly associated with younger patients and Modic changes. In vitro experiments demonstrated that C. acnes supernatant induces oxidative stress, apoptosis, and extracellular matrix (ECM) degradation in nucleus pulposus (NP) cells in a dose-dependent manner. RNA sequencing and functional validation further indicated that these pathological effects are mediated through activation of the p38 MAPK signaling pathway. Pharmacological inhibition of p38 with the specific inhibitor BIRB-796 effectively reversed the observed cellular damage. Wogonin exhibited negligible cytotoxicity toward NP cells and significantly attenuated C. acnes supernatant-induced oxidative stress, apoptosis, and ECM metabolic imbalance by inhibiting the phosphorylation of p38, JNK, and ERK1/2 within the MAPK pathway. Furthermore, in vivo experiments confirmed that Wogonin alleviated disc height loss, reduced T2-weighted signal attenuation, and mitigated histological damage induced by C. acnes in rat models, thereby restoring the balance between ECM synthesis and degradation. Collectively, this study demonstrates for the first time that C. acnes supernatant exacerbates IDD through activation of the p38 MAPK signaling pathway. It further shows that Wogonin can specifically inhibit this pathway and effectively ameliorate C. acnes-mediated IDD damage in both in vitro and in vivo models. These findings expand the theoretical framework of infection-related mechanisms underlying IDD and identify potential therapeutic targets and candidate agents for the treatment of IDD associated with C. acnes infection. Low back pain is a common health issue affecting populations worldwide, with intervertebral disc degeneration as its core etiology. However, the pathogenic causes in some patients, especially young individuals, remain incompletely understood. This study found that Cutibacterium acnes, a low-virulence bacterium commonly colonizing human skin and mucous membranes, produces metabolic products that can induce damage to the core cells of the intervertebral disc, exacerbate disc degeneration, and this process is associated with the abnormal activation of specific cellular signaling pathways. Through clinical sample detection, cell experiments, and animal model validation, we confirmed that infection with this bacterium is closely related to young patients and specific spinal imaging changes. Meanwhile, we identified Wogonin, a natural compound extracted from Scutellaria baicalensis, which can effectively inhibit the aforementioned abnormal signaling pathways, alleviate cell damage caused by bacterial metabolic products, and improve the pathological state of intervertebral disc degeneration. This study not only reveals the role of low-virulence bacterial infection in intervertebral disc degeneration and provides a new explanation for the pathogenic mechanism in young patients but also offers a natural antibiotic-free candidate for addressing bacterial resistance. It holds significant reference value for the clinical diagnosis and treatment of spinal diseases as well as the development of related drugs. Full article

The incidence of Leptospira spp. infections in cats did not seem to be of major importance until the early 21st century. The relatively rare occurrence of individuals presenting antibodies against Leptospira spp. and the almost unheard of clinical cases appeared to suggest that felids are poorly prone to Leptospira infections. Considering the close contact of cats with rodents (mice, rats, etc.), which are the main reservoir of leptospires, the above observations may, on the one hand, be surprising, but on the other hand, may reflect species-specific biological or ecological factors influencing susceptibility, although the underlying mechanisms remain poorly understood. The suspicions indicating cats as incidental hosts or asymptomatic carriers of Leptospira spp., their proximity to humans, and the “One Health” approach—particularly relevant recently in control of zoonoses—contributed in recent decades to greater research interest in feline leptospiral infections. Recent increasingly frequent data on the occurrence of antileptospiral antibodies in cats, cases of isolation of leptospiral DNA or viable spirochetes from blood or urine samples, and finally cases of clinical disease may support these hypotheses, although the available evidence remains limited and warrants further investigation. This review presents the current data on the incidence and pathogenesis of infections caused by Leptospira spp. in cats and their potential epidemiological role, including their possible contribution to environmental contamination and zoonotic transmission. Full article

The Ca_v1.3 L-type calcium (Ca²⁺) channel plays a critical role in cardiac excitation-contraction coupling, regulating heart rate, contractility, and gene expression. The C-terminus of Ca_v1.3 has recently been shown to translocate to the nucleus and act as a transcriptional factor to modulate the function of Ca²⁺-activated K⁺ channels in atrial cardiomyocytes. However, the role of the Ca_v1.3-C-terminus in the regulation of transcription of its own Ca_v1.3 gene remains unknown. We evaluated the impact of the nuclear translocation of the Ca_v1.3-C-terminus on the transcription of the Ca_v1.3 gene and Ca_v1.3 promoter activity in vitro using cultured neonate rat ventricular myocytes (NRVMs), and mouse atrial cardiomyocytes (HL-1). Lentiviral infection of NRVMs demonstrated that the cleaved Ca_v1.3-C-terminus translocates to the nucleus where it acts as a trans-regulator. The C-terminus of Ca_v1.3 increased transcription of Ca_v1.3 in vitro in NRVMs and in vivo in mice ventricles. Additionally, MEF2 transcription factor binding sites within the Ca_v1.3 promoter may contribute to the regulatory effect of the Ca_v1.3-C-terminus. These data are the first to demonstrate unique upregulation of Ca_v1.3 transcription by its own mobile Ca_v1.3-C-terminus both in vitro and in vivo. These findings suggest that the Ca_v1.3-C-terminus has intrinsic properties as a trans-regulator of gene expression and may contribute to the modulation of cardiac function. Full article

Objectives: Seawater-immersed burn wounds are highly susceptible to contamination, persistent inflammation, oxidative stress, and delayed healing, while current irrigation solutions remain suboptimal for such acute injuries. This study aimed to evaluate the therapeutic efficacy and underlying mechanisms of plasma-activated water (PAW) as a novel irrigation strategy for these complex wounds. Methods: The antibacterial efficacy of PAW against marine pathogens was first evaluated in vitro. Subsequently, a rat model of seawater-immersed burn injury was established in male Sprague-Dawley (SD) rats to assess the therapeutic effects of PAW irrigation on wound healing, infection control, and underlying biological mechanisms. Results: In vitro, PAW significantly eradicated two major marine pathogens, Vibrio vulnificus and Vibrio parahaemolyticus (p < 0.001). In vivo, PAW markedly accelerated wound closure, achieving complete healing in 23.60 ± 6.50 days vs. 38.67 ± 2.08 days (Normal saline group) and 58.33 ± 10.97 days (Model group) (p < 0.05). PAW significantly reduced bacterial burden, modulated inflammation by decreasing interleukin-6 and increasing interleukin-10, and alleviated oxidative stress, as evidenced by reduced malondialdehyde levels and enhanced superoxide dismutase activity. Histological evaluation demonstrated enhanced re-epithelialization, collagen deposition, and increased expression of vascular endothelial growth factor and platelet endothelial cell adhesion molecule-1. No adverse effects on serum biochemistry or major organ histopathology were observed. Conclusions: PAW may be a safe, promising, and multifunctional irrigation strategy that promotes seawater-immersed burn healing through coordinated antibacterial, anti-inflammatory, antioxidant, and pro-angiogenic effects, highlighting its strong potential for clinical translation. Full article

Maternal infection (MI) can increase the risk of neurodevelopmental and behavioural changes. This study examined MI-induced changes in motor coordination through the inflammatory-pathway-mediated epigenetic status of Reln. On gestational day (GD) 10, rats were assigned as (i) Control (Ctrl); (ii) Cronobacter sakazakii (CS) infection on GD-10 through recto-vaginal colonization; (iii) Negative Control (NC) [infected with C. sakazakii and treated with dimethyl sulfoxide (DMSO) 1 h before and 24 h after infection]; and (iv) C. sakazakii-infected rats treated with matrix metalloproteinase inhibitor (MMPI), 1 h before and 24 h after infection (CS + MMPI). Offspring were subjected to footprint analysis and the ladder rung walking test, which revealed that MI caused significant deficits in motor coordination. In addition, MI activated complement components—a disintegrin and metalloproteinase with thrombospondin motifs-1 (ADAMTS-1, C5a)—as well as proinflammatory cytokines such as interleukin-6 (IL-6) and matrix metalloproteinases (MMP-2, MMP-3, and MMP-9). Furthermore, the levels of DNA methyltransferase 3 alpha (DNMT3A), methyl-CpG-binding protein 2 (MeCP2), and histone H3 lysine 4 trimethylation (H3K4me3) were elevated in the CS and NC groups. Concurrently, the level of Reln promoter methylation increased; as a result, mRNA and protein, as well as postsynaptic density protein-95 (PSD-95), levels were decreased. Overall, the findings suggest that MI altered MMP-2/3/9 activity, H3K4me3, and the methylation of Reln, thereby affecting reelin, synaptic protein expression, and motor coordination in an experimental meningitis rat model. Full article