Search Results (653)

Background: Dangguibuxue decoction (DD), containing Angelica sinensis (Oliv.) Diels (AS) and Astragalus membranaceus (Fisch.) Bge. (AM) (1:5), is a well-known traditional Chinese medicine (TCM) used for strengthening qi and nourishing the blood. DD has shown therapeutic effects in nephropathy patients. However, the underlying mechanisms based on the traditional efficacy are still not fully elucidated. Methods: The chemical constituents in DD were identified using UPLC-MS/MS. Network pharmacology analysis was applied to predict the potential target genes and associated signaling pathways. A renal fibrosis mouse model was induced by the intraperitoneal injection of aristolochic acid I (AA I) at 3.0 mg/kg. Mice were treated with AM, AS, and DD at two dosages by oral gavage for 30 days. Body weights, serum biochemistry, hematology, and histopathology observations were assessed. The key targets predicted were validated using qRT-PCR and Western blotting. The active constituents were screened by molecular docking, and their anti-fibrotic effects were evaluated through in vitro assays. Results: DD effectively improved renal functions and alleviated AA I-induced renal fibrosis. DD alleviated anemia and upregulated the expression of Erythropoietin (EPO). Network pharmacology analysis indicated the involvement of signaling pathways, including the PI3K/Akt, hypoxia-inducible factor-1α (HIF-1α) and transforming growth factor-β (TGF-β) signaling pathways. Experimental validation further demonstrated that DD reduced the protein expression of HIF-1α, collagen I, and TGF-β, and the ratios of phosphorylated Smad2/3 to total Smad2/3. Molecular docking and in vitro assays suggested that rutin may be a potential bioactive compound in DD. Conclusions: This research indicated that DD ameliorated AA I-induced renal fibrosis in mice, which may be associated with the modulation of HIF-1α and TGF-β/Smad signaling pathways. Rutin may be a potential bioactive compound in DD with anti-fibrotic activity, but further studies are still needed to clarify the content of rutin in DD, the amount of its exposure in the body, and its contribution to the effects of DD. Full article

Objective: The purpose of this study is to study cytokine indicators for the identification of severe fever with thrombocytopenia syndrome (SFTS) severity. Methods: We searched the literature in PubMed, Embase, and Web of Science published before 7 April 2026. The main results are presented as forest plots. Subgroup analyses, sensitivity analyses, and publication bias were also performed. Results: A total of 22 articles were eventually included in our study. Our findings demonstrate that circulating concentrations of Interleukin-6 (IL-6) (SMD = 2.02, 95% CI: 1.53–2.51, I² = 95.2%), Interleukin-10 (IL-10) (SMD = 1.18, 95% CI: 0.92–1.44, I² = 71.3%), Interleukin-8 (IL-8) (SMD = 0.91, 95% CI: 0.61–1.20, I² = 69%), Tumor necrosis factor-alpha (TNF-α) (SMD = 0.70, 95% CI: 0.43–0.96, I² = 64.6%), Interferon-gamma (IFN-γ) (SMD = 1.32, 95% CI: 0.69–1.95, I² = 89.1%), Interleukin-1 beta (IL-1β) (SMD = 1.78, 95% CI: 0.85–2.71, I² = 94.8%), Monocyte chemoattractant protein-1 (MCP-1) (SMD = 1.15, 95% CI: 0.80–1.50, I² = 46.1%), Interferon-alpha (IFN-α) (SMD = 1.53, 95% CI: 0.38–2.68, I² = 89.6%), Granulocyte Colony-Stimulating Factor (G-CSF) (SMD = 1.79, 95% CI: 0.99–2.59, I² = 68.1%) and Inducible protein 10 (IP-10) (SMD = 1.11, 95% CI: 0.60–1.62, I² = 58.3%) are significantly elevated in patients with severe SFTS compared with those with mild disease, whereas Transforming Growth Factor-beta (TGF-β) (SMD = −0.51, 95% CI: −0.78–−0.24, I² = 6.0%) and RANTES (SMD = −0.10, 95% CI: −0.40–0.20, I² = 0.0%) levels are reduced in the severe group. Conclusions: By analyzing the cytokine indicators of SFTS patients, we have found some indicators that are representative of SFTS severity. Our findings provide a clinically actionable basis for early severity prediction and further useful evidence for clinicians to manage severe patients efficiently. Full article

Background/Objectives: Pulmonary fibrosis is a progressive and fatal disease characterized by excessive extracellular matrix deposition and irreversible lung remodeling. Although modified mRNA (modRNA) therapeutics offer a promising strategy for regulating disease-driving pathways, effective pulmonary delivery remains challenging due to the inherent liver tropism of conventional lipid nanoparticles (LNPs). This study aimed to establish an optimized platform for lung-selective modRNA delivery and therapeutic screening for pulmonary fibrosis. Methods: A panel of charge-modified LNP formulations was evaluated in vivo for pulmonary tropism following systemic administration of luciferase (Luc) modRNA. Administration routes, biodistribution in healthy and bleomycin (BLM)-induced fibrotic lungs, and endogenous microRNA (miRNA)-mediated de-targeting strategies were assessed. Candidate antifibrotic modRNAs targeting the transforming growth factor-beta (TGF-β) signaling pathway were subsequently evaluated in normal human lung fibroblasts (NHLFs). Results: Among the formulations tested, 50% DOTAP MC3 LNPs demonstrated the most favorable balance of pulmonary transfection, physicochemical properties, and limited off-target expression. Intravenous (IV) administration achieved robust lung expression with a superior safety profile compared with intratracheal (IT) delivery. Importantly, pulmonary biodistribution was preserved in BLM-induced fibrotic lungs despite extensive tissue remodeling. Incorporation of miR-122 recognition sites further enhanced selectivity, resulting in 94.5% of total transgene expression being localized to the lungs while substantially reducing residual hepatic expression. In vitro screening identified dominant-negative TGF-β receptor II (DNTGFBR2) modRNA as a potent inhibitor of TGF-β-induced fibrotic activation, significantly suppressing α-SMA and CTGF expression. Conclusions: These findings establish a comprehensive platform for pulmonary modRNA therapeutic development by integrating lung-selective LNP engineering, optimal systemic delivery, miRNA-mediated de-targeting, and therapeutic payload screening. This strategy provides a foundation for the development of targeted RNA therapies for pulmonary fibrosis and other organ-specific diseases. Full article

A novel low-molecular-weight water-soluble oligosaccharide fraction (LBPP-1) was prepared from lotus bee pollen via microwave-assisted extraction, followed by Sevag deproteinization and diethylaminoethyl (DEAE)-cellulose-52 chromatography purification. Ion chromatography (IC) indicated a glucose-rich composition (84.6 mol% glucose), with minor amounts of arabinose, glucosamine, and galactose. Fourier transform-infrared spectroscopy (FT-IR), methylation analysis, and ¹H nuclear magnetic resonance (NMR) collectively supported the assignment of LBPP-1 as a glucan-rich, structurally heterogeneous oligosaccharide fraction containing candidate →4)-Glcp-rich domains and minor arabinose/galactose-related linkages. However, the marked difference between the IC composition and the sugar-type distribution estimated from PMAA peak areas limits quantitative interpretation of the residue proportions and branching architecture. Furthermore, in vitro biological assays demonstrated that LBPP-1 significantly attenuated lipopolysaccharide (LPS)-induced inflammatory responses in RAW264.7 macrophages. It effectively reduced the secretion of nitric oxide (NO) and the levels of inducible nitric oxide synthase (iNOS), interleukin (IL)-6, and tumor necrosis factor (TNF)-α in RAW264.7 macrophages. Reverse transcription–quantitative polymerase chain reaction (RT-qPCR) analysis further revealed that LBPP-1 selectively suppressed the mRNA expression of cyclooxygenase-2 (COX-2), IL-1β, IL-6, iNOS, and transforming growth factor (TGF)-β1. These findings collectively suggest that LBPP-1, as a bioactive carbohydrate fraction derived from lotus bee pollen, holds promise as a natural functional food ingredient for managing inflammation-related conditions. Full article

Sulfated polysaccharides (SPs) from green seaweed species have been scarcely studied for the development of novel pharmaceutical, cosmetic or nutraceutical products. The present study aimed to investigate the physico-chemical characteristics of the sulfated polysaccharidic fractions isolated from Cladophora vagabunda green seaweed and to evaluate their anti-aging properties in vitro. SPF1 and SPF2 fractions were separated from the purified polysaccharidic extract by size exclusion chromatography. The content of neutral carbohydrates, uronic acids and sulfate was assessed, while Fourier transform infrared spectroscopy (FT-IR) analysis confirmed the presence of a functional group characteristic for sulfated polysaccharides. Capillary zone electrophoresis indicated the monosaccharides profile and the presence of bioactive fucose and uronic acids. The two fractions differed in sulfate content (22.59% and 29.44%). SF2 showed stronger collagenase inhibition (95.69%), whereas SF1 exhibited greater elastase inhibition (84.2%) in comparison with EGCG. Both fractions exhibited antioxidant, anti-collagenase and anti-elastase activities and also a good biocompatibility and capacity to modulate the cell cycle progression in human dermal fibroblast culture. They showed anti-inflammatory potential by inhibition of interleukin-1 beta (IL-1β), tumor necrosis factor-α (TNF-α) and nitric oxide (NO) production in lipopolysaccharide (LPS)-inflamed THP-1-derived macrophages. Also, the level of matrix metalloproteinase-1 (MMP-1) and MMP-9 secretion was reduced after treatment with C. vagabunda fractions with MMP-1 reduced by ~95% in both fractions and MMP-9 reduced by ~79% in SF2 compared with the control. Both fractions stimulated the growth of probiotic cultures Lactobacillus acidophilus and L. rhamnosus. All these results demonstrated, for the first time, the anti-aging potential of sulfated polysaccharides isolated from C. vagabunda green seaweed. Full article

Follistatin (FST) binds to and neutralizes members of the transforming growth factor-beta (TGF-β) superfamily, thereby regulating diverse physiological processes, including regulation of skeletal muscle, adipose, and bone homeostasis. FST also promotes adipose browning and enhances energy metabolism, leading to improved plasma lipid profiles and metabolic health in mice. Given the emerging association between brown adipose tissue (BAT) activation and reduced atherosclerosis, we investigated the anti-atherogenic potential of FST. Transcriptomic and metabolomic analyses of the Hybrid Mouse Diversity Panel (HMDP) revealed that Fst expression was negatively correlated with aortic lesion area and positively correlated with the expression of multiple adipose browning-associated genes. Adeno-associated viral delivery of Fst (AAV1-FST344) in Ldlr^−/− mice significantly reduced aortic lesion area, improved plasma lipid profiles, and decreased expression of adhesion (VCAM1) and inflammatory (iNOS, TNF-α) markers in white adipose tissue (WAT), liver, and heart. Fst gene delivery also markedly increased uncoupling protein 1 (UCP1) expression in WAT, consistent with WAT browning. Integrated correlation analyses of Fst expression with tissue metabolites, together with plasma metabolite–lesion associations identified in the HMDP, implicated the arginase 1 (Arg1)-mediated metabolic pathway as a key regulator of atherogenesis. Consistent with these findings, Arg1 expression was significantly elevated in WAT, liver, and heart of AAV1-FST344-treated mice and in wild-type versus Fst-knockout mouse embryonic fibroblasts (MEFs). Immunostaining localized Arg1 predominantly to CD68⁺ macrophages in heart and liver. Given recent evidence identifying Arg1 as a novel mediator of efferocytosis, these findings suggest that Arg1 may promote macrophage metabolic reprogramming and resolution of inflammation by enhancing the clearance of apoptotic cells. Furthermore, Fst gene delivery increased the expression of fibroblast growth factor 21 (Fgf21) and adiponectin (AdipoQ) in WAT. Collectively, these findings identify Fst as a novel anti-atherogenic regulator that protects against vascular disease by promoting adipose browning, improving lipid metabolism, and activating Arg1-mediated metabolic pathways. Full article

Periodontitis is a chronic inflammatory disease driven largely by dysregulated host responses that lead to destruction of periodontal tissues. Integrins are heterodimeric transmembrane receptors that regulate cell adhesion and bidirectional signaling in epithelial cells, immune cells, periodontal ligament fibroblasts, and osteoclasts. During disease progression, integrin-related responses may shift across overlapping molecular phases. Epithelial integrins such as α3β1 and α6β4 support barrier integrity, whereas α5β1 may facilitate microbial interaction and inflammatory signaling. β2 integrins and α4β1 contribute to leukocyte recruitment and inflammatory amplification, whereas increased α9β1-associated signaling and reduced αvβ6-mediated regulation of transforming growth factor β (TGF-β) may promote inflammatory persistence. Matrix-associated integrins, including α2β1 and α11β1, support extracellular matrix (ECM) organization and mechanotransduction, whereas αvβ3 cooperates with Receptor activator of nuclear factor kappa B ligand (RANKL) to promote osteoclast activity and alveolar bone resorption. Impaired β1 integrin-dependent signaling and potentially reduced αvβ5-associated efferocytosis may contribute to defective resolution and regeneration. Importantly, integrin expression, activation, and downstream signaling are distinct, and the strength of evidence varies among integrin subtypes. This review proposes a conceptual framework in which periodontitis reflects a dynamic imbalance in integrin-mediated processes that link inflammation, bone resorption, and regenerative failure, rather than being a direct equivalent of clinical periodontal stages or grades. Full article

Background and Objectives: The aim of this study is to evaluate the effects of oridonin on a cisplatin-induced ovarian injury rat model. Materials and Methods: Thirty female rats were divided into three groups. Group 1: control; group 2: cisplatin; group 3: cisplatin plus oridonin group. In groups 2 and 3, the rats were injected with 2.5 mg/kg (twice weekly) cisplatin intraperitoneally (i.p.) for 4 weeks. In Group 3, rats received oridonin (10 mg/kg/day, i.p.). At the end of the study, the ovaries were removed in all groups. Histopathologic analysis and follicle counting were performed. Plasma anti-Müllerian hormone (AMH), malondialdehyde (MDA), and tumor necrosis factor-alpha (TNF-α) levels were measured, while ovarian transforming growth factor-beta 1 (TGF-β1), SMAD family member 3 (SMAD3), and tissue inhibitor of metalloproteinases-1 (TIMP-1) levels were evaluated. Results: Oridonin alleviated cisplatin-induced histopathological changes in the ovarian tissue. The numbers of primordial, primary, secondary, and tertiary follicles were significantly decreased, while ovarian fibrosis was significantly increased in Group 2 compared with Group 1 (p < 0.05). Co-treatment with oridonin statistically significantly increased follicle counts at all developmental stages and markedly reduced ovarian fibrosis in group 2 compared with group 3. Compared with Group 1, AMH decreased, whereas MDA, TNF-α, TGF-β1, SMAD3, and TIMP-1 increased in Group 2 (p < 0.001); these alterations were markedly attenuated in Group 3. Conclusions: These findings suggest that oridonin may exert protective effects against cisplatin-induced ovarian injury. Full article

Major depressive disorder (MDD) is a complex and heterogeneous psychiatric disorder with a high prevalence. Neuroinflammation may define biologically distinct patient subgroups with different mechanisms, clinical phenotypes, and treatment responses. This narrative review integrates current evidence around three linked questions: how neuroinflammatory processes contribute to depression, how biomarkers can identify clinically relevant inflammatory phenotypes, and how these findings can inform anti-inflammatory treatment strategies. The major mechanisms discussed include microglial activation and neuroimmune signaling, hypothalamic–pituitary–adrenal axis dysregulation and glucocorticoid receptor resistance, kynurenine pathway alterations, and cytokine-driven impairment of neurogenesis and synaptic plasticity. These pathways interact with stress responses, neurotransmitter systems, and neuronal function, while their expression may vary according to sex, age, hormonal status, disease stage, and treatment exposure. These interconnected pathways may contribute to depressive symptoms by disrupting neurotransmitter systems and impairing neural plasticity. In addition, this review discusses several candidate biomarkers, including C-reactive protein (CRP), interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), brain-derived neurotrophic factor (BDNF) and transforming growth factor-β1 (TGF-β), which may support patient stratification, treatment prediction, and assessment of target engagement. Clinical trials of anti-inflammatory agents have shown inconsistent and generally modest effects in unselected MDD populations. By integrating mechanistic evidence with biomarker-guided therapeutic implications, this review aims to clarify how neuroinflammatory research may inform more precise and individualized treatment strategies for depression. Full article

Background: GDF15 (growth/differentiation factor-15) is part of the transforming growth factor-beta family and represents a cellular stress-induced gene. It might have a role in metaflammation and adipoflammation. We aimed to investigate the effects of Toll-like receptor (TLR) activation and hypoxia-related pathways together with metabolic factors on GDF15 regulation in adipocytes and adipose tissue (AT). Methods: GDF15 mRNA quantities in the human adipocyte cell line SGBS, in visceral (VAT) and subcutaneous adipose tissue (SAT) (resected from n = 96 obese and characterized patients), and in murine 3T3-L1 adipocytes were measured by real-time RT-PCR. GDF15 protein concentrations in cell supernatants and serum were quantified by ELISA. The following stimuli/pathways were investigated: insulin, glucose, TLR ligands (TLR2/6, TLR3, TLR4, TLR7, TLR9), bile acids, synthetic FXR/TGR5 activators, and HIF1α activators. Results: Basal GDF15 expression is low and only marginally induced in SGBS cells. In contrast, GDF15 is expressed in human SAT and VAT and correlates positively with the corresponding GDF15 protein concentration in peripheral blood serum of obese patients. Among metabolic factors, insulin and bile acids such as ursodeoxycholic acid upregulate GDF15 expression in 3T3-L1 adipocytes, the latter via FXR but not via TGR5. Among innate immune regulators, only TLR7 activation and hypoxic mediators upregulate whereas STAT3 signaling downregulates GDF15. Conclusion: GDF15 expression in human SAT and VAT is correlated to peripheral blood GDF15 concentrations and is regulated by metabolic and innate immune response pathways involved in AT inflammation and metaflammation. Full article

Secondary hyperparathyroidism (SHPT) is a major component of chronic kidney disease–mineral and bone disorder (CKD-MBD), reflecting progressive disturbances in mineral metabolism, endocrine signaling, skeletal remodeling, and parathyroid-gland biology. Traditionally, preoperative parathyroid hormone (PTH) has been used primarily as a biochemical threshold for surgical referral. However, persistent PTH elevation in advanced CKD-related SHPT may reflect more than isolated endocrine activity; available evidence suggests it integrates parathyroid-gland remodeling, receptor resistance, skeletal turnover, treatment refractoriness, and systemic CKD-MBD severity. This review summarizes key molecular and cellular mechanisms of progressive SHPT, including diffuse-to-nodular hyperplastic transition, downregulation of calcium-sensing receptor (CaSR) and vitamin D receptor (VDR) signaling, disruption of the fibroblast growth factor 23 (FGF23)–Klotho axis, and activation of transforming growth factor-α (TGF-α)/epidermal growth factor receptor (EGFR) proliferative pathways. Building on this mechanistic framework, we discuss how persistent PTH elevation has been linked to glandular remodeling, resistance to calcimimetic and vitamin D therapy, high-turnover renal osteodystrophy, hungry bone syndrome, altered intraoperative PTH kinetics, postoperative endocrine–skeletal remodeling, and long-term recurrence. Severe SHPT is also increasingly recognized as a systemic CKD-MBD phenotype associated with vascular calcification, cardiovascular risk, metabolic instability, and impaired quality of life. Within this framework, preoperative PTH is best interpreted as an integrated biomarker within a broader assessment of glandular remodeling, skeletal metabolic activity, endocrine resistance, and systemic CKD-MBD biology, rather than as an isolated biochemical threshold. Full article

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a multifactorial inflammatory disease characterized by heterogeneous phenotypes and endotypes, necessitating personalized therapeutic strategies. Precision medicine approaches integrating molecular biomarkers may improve treatment selection and disease stratification. In this prospective controlled study, we investigated the tissue-level immunohistochemical effects of oral corticosteroids (OCSs) and topical steroids on the expression of periostin, eotaxin, interleukin-4 (IL-4), transforming growth factor-β (TGF-β), and tumor necrosis factor-α (TNF-α) in nasal polyp tissue. Sixty-five patients eligible for endoscopic sinus surgery (ESS) were enrolled and divided into two groups: Group 1 (n = 42) received topical steroids combined with oral prednisone (40 mg/day for 7 days preoperatively), whereas Group 2 (n = 23) received topical steroids alone. Immunohistochemical analysis demonstrated a significant reduction in periostin and eotaxin expression in both epithelial and stromal compartments following OCS therapy, accompanied by increased TGF-β expression. No significant differences were observed in IL-4 or TNF-α expression. These findings indicate that short-term OCSs selectively modulate molecular pathways associated with eosinophilic inflammation and tissue remodeling in CRSwNP, supporting biomarker-driven precision medicine strategies. Full article

Mesenchymal stromal cells (MSCs) are multipotent cells characterized by their regenerative capacity and strong immunomodulatory properties. In recent years, MSC-based therapy has attracted significant attention as a potential treatment for a wide range of immune-mediated and degenerative diseases. The therapeutic effects of MSCs are primarily mediated through paracrine signaling and secretion of cytokines that regulate immune responses and promote tissue repair. This review focuses on five key cytokines involved in MSC immunomodulation: interleukin-6 (IL-6), interleukin-10 (IL-10), transforming growth factor-beta (TGF-β), tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1β). These cytokines interact within a complex signaling network that allows MSCs to suppress excessive inflammation and restore immune balance. The role of MSC therapy is examined in several clinically relevant conditions, including systemic lupus erythematosus, systemic sclerosis, ischemic stroke, spinal cord injury, diabetes mellitus, and female infertility. Across these diseases, MSCs demonstrate the ability to inhibit pro-inflammatory immune cell activity, promote regulatory immune phenotypes, reduce oxidative stress, and stimulate regeneration through the secretion of growth factors and extracellular vesicles. Despite promising experimental and early clinical findings, several limitations remain, including variability in MSC sources, limited cell survival after transplantation, and the need for optimized dosing strategies. Overall, MSC therapy represents a multifunctional therapeutic approach combining immunomodulation, anti-inflammatory activity, and regenerative support. Further research is required to better understand cytokine interactions, improve standardization of MSC-based treatments, and enhance clinical efficacy across diverse pathological conditions. Full article

Chronic exposure to fine particulate matter (${\mathrm{PM}}_{2.5}$) derived from residential wood combustion is a major environmental health concern in southern Chile and other cold-climate regions. Although ${\mathrm{PM}}_{2.5}$ has been linked to adverse reproductive outcomes, it remains unclear whether sustained exposure induces pregestational uterine alterations that compromise reproductive competence before the first pregnancy. This study evaluated the effects of chronic wood smoke-derived ${\mathrm{PM}}_{2.5}$ exposure on uterine morphology and molecular markers in nulliparous rats. A two-generation exposure model was used to assess cumulative effects. Second-generation (G2) female Sprague Dawley rats continuously exposed from conception were housed in filtered air (FA, control; $n=12$) or ${\mathrm{PM}}_{2.5}$-containing ambient air (NFA; $n=12$) until reproductive maturity (82 days). Uterine horns were analyzed by histology, planimetry, immunohistochemistry, immunofluorescence, and second harmonic generation microscopy. Markers of hypoxia, inflammation, extracellular matrix remodeling, angiogenesis, proliferation, apoptosis, and DNA repair were quantified. Chronic ${\mathrm{PM}}_{2.5}$ exposure increased hypoxia-inducible factor 1$\alpha$, tumor necrosis factor-$\alpha$, vascular endothelial growth factor A, and collagen types I, III, and IV, while transforming growth factor-$\beta$ expression and Ki-67-positive proliferating cells were reduced. Exposed rats showed increased apoptosis and decreased nuclear expression of ${\mathrm{O}}^6$-methylguanine-DNA methyltransferase, indicating impaired DNA repair capacity. Second harmonic generation imaging demonstrated increased collagen deposition with marked fibrillar disorganization. These findings indicate that chronic wood smoke-derived ${\mathrm{PM}}_{2.5}$ exposure induces hypoxia-driven structural and molecular alterations in the uterus of nulliparous rats before first pregnancy, including extracellular matrix remodeling, inflammatory imbalance, angiogenic dysregulation, reduced proliferation, and compromised DNA repair, suggesting early disruption of uterine homeostasis and increased susceptibility to adverse reproductive outcomes. Full article

Platelet-rich gel supernatants (PRGS) are increasingly used in veterinary medicine due to their regenerative and immunomodulatory properties; however, most studies focus on individual mediators and provide limited insight into their coordinated biological behavior. This study aimed to characterize the integrated inflammatory–regenerative signatures of bovine PRGS stored under different temperature conditions using a multivariate approach. Concentrations of transforming growth factor beta-1 (TGF-β1), tumor necrosis factor alpha (TNF-α), interleukin-2 (IL-2), and interleukin-6 (IL-6) were evaluated in PRGS samples from six clinically healthy cows stored at −80, −20, 4, 21, and 37 °C for up to 326 h. Data were standardized and explored using hierarchical clustering and heatmaps, and principal component analysis (PCA) based on area under the concentration–time curve (AUC) was used to integrate temporal behavior. Temperature-dependent multivariate signatures were identified, with frozen PRGS clustering separately from samples stored at moderate temperatures. The first two principal components explained 43.0% and 28.9% of the variance and defined an inflammatory–regenerative gradient contrasting TGF-β1/IL-2 versus TNF-α/IL-6 profiles. Linear mixed-effects modeling showed that PC1 was significantly affected by temperature and time (p < 0.001), whereas PC2 was influenced by temperature, time, and their interaction (p ≤ 0.048). Differences among temperatures were minimal at early time points but became more pronounced from 48 to 96 h onward, following a temperature gradient with higher values at moderate temperatures and lower values under frozen conditions. These findings indicate that storage temperature reshapes the integrated biological profile of PRGS, rather than merely preserving mediator composition. Full article