Search Results (1,614)

Cancer is a major global health issue, with rising incidence rates highlighting the urgent need for more effective treatments. Despite advances in cancer therapy, challenges such as adverse effects and limitations of existing treatments remain. Immunotherapy, which harnesses the body’s immune system to target cancer cells, offers promising solutions. Gamma delta (γδ) T cells are noteworthy due to their potent ability to kill various cancer cells without needing conventional antigen presentation. Recent studies have focused on the role of γδ T cells in α-galactosylceramide (α-GalCer)-mediated immunity, opening new possibilities for cancer immunotherapy. We engineered humanized T cell receptor (HuTCR)-T1 γδ mice by replacing mouse sequences with human counterparts. This study investigates the cytotoxic activity of humanized γδ T cells against several human cancer cell lines (A431, HT-29, K562, and Daudi) in vitro, aiming to elucidate mechanisms underlying their anticancer efficacy. Human cancer cells were co-cultured with humanized γδ T cells, with and without α-GalCer, for 24 h. The humanized γδ T cells showed enhanced cytotoxicity across all tested cancer cell lines compared to wild-type γδ T cells. Additionally, γδ T cells from HuTCR-T1 mice exhibited higher levels of anticancer cytokines (IFN-γ, TNF-α, and IL-17) and Granzyme B, indicating their potential as potent mediators of anticancer immune responses. Blocking γδ T cells’ cytotoxicity confirmed their γδ-mediated function. These findings represent a significant step in preclinical development of γδ T cell-based cancer immunotherapies, providing insights into their mechanisms of action, optimization of therapeutic strategies, and identification of predictive biomarkers for clinical application. Full article

Background/Objectives: The receptor for advanced glycation end products (RAGEs) has been implicated in obesity and metabolic dysfunction. However, its precise role in diet-induced obesity remains unclear. Methods: In this study, we investigated the metabolic consequences of RAGE knockout (RAGE KO) in mice subjected to a Western diet (WD). Results: Our findings demonstrate that RAGE KO mice remained significantly leaner than their wild-type (WT) counterparts when fed a WD, exhibiting reduced body weight gain and smaller adipocyte size. Indirect calorimetry revealed that RAGE KO mice had increased oxygen consumption and locomotor activity compared to WT mice, indicating enhanced energy expenditure. Mitochondrial respiration assays indicated significantly greater oxygen consumption in RAGE KO animals. Additionally, systemic inflammation markers, such as TNF-α, were significantly lower in RAGE KO mice when fed a WD, indicating a reduction in diet-induced inflammatory responses. Conclusions: These findings suggest that RAGE plays a key role in metabolic homeostasis, and its deletion confers resistance to obesity and metabolic disruption induced by a Western diet. Targeting RAGE may provide a novel therapeutic approach for combating obesity and related metabolic disorders. Full article

Introduction: Chronic kidney disease (CKD) increases cardiovascular risk through mechanisms such as oxidative stress and the accumulation of advanced glycation end products (AGEs). Glycated albumin (GA) is associated with cardiovascular risk in CKD patients, but its relationship with AGEs and systemic inflammation remains unclear. This study investigated these associations in old patients with severe CKD, with and without diabetes. Methods: We conducted a cross-sectional analysis in 122 patients aged ≥ 65 years with CKD stages G3a–G5, including 67 diabetics and 55 non-diabetics. Patients with confounding comorbidities were excluded. We measured GA, AGEs, various AGEs receptors (RAGE) isoforms, and inflammatory cytokines (CRP, IL-6, TNFα, and MCP-1) using standardized assays. Statistical analyses included group comparisons, correlation coefficients, and multivariate regression. Results: Of 122 patients (mean age 77.7 ± 11.3 years), diabetics had higher GA percentages than non-diabetics (22.0 ± 7.1% vs. 17.5 ± 5.4%, p = 0.0001), while AGEs (2931 ± 763 vs. 3156 ± 809 AU; p = 0.118) and inflammatory markers (CRP 0.240[0.380] vs. 0.200[0.280] mg/dL; p = 0.142; IL-6 3.4[4.0] vs. 3.0[3.8] pg/mL; p = 0.238) were similar between groups. Overall, GA was inversely correlated with estimated glomerular filtration rate (eGFR) (ρ = −0.189, p = 0.037) and positively with glycated hemoglobin (HbA1c) (ρ = 0.525, p < 0.0001), but showed no significant correlation with AGEs, RAGE isoforms, or inflammatory cytokines. In multivariate analysis, only HbA1c remained independently associated with GA (β = 0.222, p = 0.005). Conclusions: In old patients with severe CKD, GA appears to be a more useful marker of glycemic control than glycation stress, the latter of which is the result of multiple factors, including impaired kidney function and systemic inflammation. Full article

Osteoclastogenesis—the activation and differentiation of osteoclasts—is one of the pivotal processes of bone remodeling and is regulated by RANKL/RANK signaling, the decoy function of osteoprotegerin (OPG), and a cascade of pro- and anti-inflammatory cytokines. The disruption of this balance leads to pathological bone loss in diseases such as osteoporosis and rheumatoid arthritis. FFAR4 (Free Fatty Acid Receptor 4), a G protein-coupled receptor for long-chain omega-3 fatty acids, has been confirmed as a key mediator of metabolic and anti-inflammatory effects. This review focuses on how FFAR4 acts as the selective receptor for the omega-3 fatty acid docosahexaenoic acid (DHA). It activates two divergent signaling pathways. The Gαq-dependent cascade facilitates intracellular calcium mobilization and ERK1/2 activation. Meanwhile, β-arrestin-2 recruitment inhibits NF-κB. These collective actions reshape the cytokine environment. In macrophages, DHA–FFAR4 signaling lowers the levels of TNF-α, interleukin-6 (IL-6), and IL-1β while increasing IL-10 secretion. Consequently, the activation of NFATc1 and NF-κB p65 is profoundly suppressed under TNF-α or RANKL stimulation. Additionally, DHA modulates the RANKL/OPG axis in osteoblastic cells by suppressing RANKL expression, thereby reducing osteoclast differentiation in an inflammatory mouse model. Full article

Background/Objectives: The incidence and prevalence of ischemic stroke, a leading cause of death and disability worldwide, are significantly higher in older adults than in younger individuals. Senescence induces a variety of biological changes that influence the pathogenesis of diseases such as ischemic stroke, thereby necessitating age-specific medical treatments. However, the molecular mechanisms underlying age-related differences in ischemic stroke progression remain poorly understood. Methods: We compared the histological and molecular features of ischemic stroke in a photothrombotic mouse model, focusing on 9-week-old (young) and 90-week-old (old) mice. Results: We found that microglial accumulation at the infarct region of the cerebral cortex was significantly lower in old mice than in young ones. This reduction in the microglial response was accompanied by a decrease in the morphological robustness of the astrocytes forming the glial scar. Furthermore, the mRNA expression of proinflammatory cytokines CXCL10, CCL2, and TNF-α, which were upregulated in the infarct region, was considerably higher in the old mice than in the young ones. Cytokine expression was well correlated with the mRNA levels of Toll-like receptor 4 (TLR4), a key regulator of neuroinflammation in old mice, but less correlated with them in young mice. Interestingly, Tlr4 mRNA expression in young mice was negatively correlated with the mRNA expression of the epigenetic regulator HDAC7, whereas this correlation was positive in old mice. Conclusions: These findings suggest that age-dependent changes in epigenetic regulation, such as the interaction between HDAC7 and TLR4, may contribute to the distinct pathological progression of ischemic stroke in older individuals. Full article

Background/Objective: Early-onset neonatal sepsis (EOS), defined as infection occurring within the first 72 h after birth, remains a major contributor to neonatal morbidity and mortality worldwide. Although advances in perinatal care have improved overall outcomes, the diagnosis of EOS continues to be challenging. Clinical presentations are often nonspecific, laboratory confirmation is often delayed, and immune responses vary considerably among neonates. Expanding our understanding of the molecular mechanisms underlying EOS is essential in enhancing early detection, refining risk stratification, and guiding therapeutic strategies. This systematic review aims to synthesize the available information on the molecular pathways involved in EOS, focusing on pathogen-induced inflammation, systemic immune responses, sterile inflammatory processes, interactions between infectious and non-infectious pathways, as well as emerging molecular diagnostic approaches. Methods: A comprehensive review of original research articles and reviews published between January 2015 and January 2025 was conducted; studies were included based on their focus on human neonates and their analysis of molecular or immunological mechanisms relevant to EOS pathogenesis, immune dysregulation, or novel diagnostic strategies. Results: Pathogen-driven inflammation typically involves the activation of Toll-like receptors (TLRs), the recruitment of neutrophils, and the release of pro-inflammatory cytokines such as IL-6, IL-1β, and TNF-α, particularly in response to vertical transmission of organisms like Escherichia coli and Streptococcus agalactiae. Systemic inflammatory responses are marked by cytokine dysregulation, contributing to multi-organ dysfunction. Sterile inflammation, often initiated by hypoxia–reperfusion injury or intrauterine stress, amplifies susceptibility to sepsis. Interactions between immune, metabolic, and endothelial pathways further exacerbate tissue injury. Recent advances, including transcriptomic profiling, microRNA-based biomarkers, and immune checkpoint studies, offer promising strategies for earlier diagnosis and individualized therapeutic options. Conclusions: EOS arises from a complex interplay of infectious and sterile inflammatory mechanisms. A deeper molecular understanding holds promise for advancing correct diagnostics and targeted therapies, aiming to improve neonatal outcomes. Full article

Background: Cerebral aneurysm (CA) is a focal or diffuse pathological dilation of the cerebral arterial wall that arises due to various etiological factors. It represents a serious vascular condition, particularly affecting the elderly, and carries a high risk of rupture and neurological morbidity. Clonidine (CL), an α2-adrenergic receptor agonist, has been reported to suppress aneurysm progression; however, its underlying molecular mechanisms, especially in relation to cerebral endothelial dysfunction, remain unclear. This study aimed to investigate the potential of CL to mitigate CA development by modulating apoptosis, inflammation, and oxidative stress in an Angiotensin II (Ang II)-induced endothelial injury model. Methods: Human brain microvascular endothelial cells (HBMECs) were used to establish an in vitro model of endothelial dysfunction by treating cells with 1 µM Ang II for 48 h. CL was administered 2 h prior to Ang II exposure at concentrations of 0.1, 1, and 10 µM. Cell viability was assessed using the MTT assay. Oxidative stress markers, including reactive oxygen species (ROS) and Nitric Oxide (NO), were measured using 2′,7′–dichlorofluorescin diacetate (DCFDA). Gene expression levels of vascular endothelial growth factor (VEGF), matrix metalloproteinases (MMP-2 and MMP-9), high mobility group box 1 (HMGB1), and nuclear factor kappa B (NF-κB) were quantified using RT-qPCR. Levels of proinflammatory cytokines; tumor necrosis factor-alpha (TNF-α), Interleukin-6 (IL-6), and interferon-gamma (IFN-γ); were measured using commercial ELISA kits. Results: Ang II significantly increased ROS production and reduced NO levels, accompanied by heightened proinflammatory cytokine release and endothelial dysfunction. MTT assay revealed a marked decrease in cell viability following Ang II treatment (34.18%), whereas CL preserved cell viability in a concentration-dependent manner: 44.24% at 0.1 µM, 66.56% at 1 µM, and 81.74% at 10 µM. CL treatment also significantly attenuated ROS generation and inflammatory cytokine levels (p < 0.05). Furthermore, the expression of VEGF, HMGB1, NF-κB, MMP-2, and MMP-9 was significantly downregulated in response to CL. Conclusions: CL exerts a protective effect on endothelial cells by reducing oxidative stress and suppressing proinflammatory signaling pathways in Ang II-induced injury. These results support the potential of CL to mitigate endothelial injury in vitro, though further in vivo studies are required to confirm its translational relevance. Full article

Background/Objectives: Sepsis-induced cardiomyopathy (SIC) is a serious clinical disorder with a high death rate. Qifu decoction (QFD) is a renowned traditional Chinese medicine with documented pharmacological actions, such as anti-inflammatory, anti-oxidant and anti-apoptosis activities, and it has good therapeutic effects on cardiovascular diseases. This study aimed to reveal the cardioprotective effects and underlying mechanisms of QFD against SIC. Methods: Electrocardiography, histopathological examination, and biochemical indicator determination were carried out to investigate the cardioprotective effects of QFD in the treatment of LPS-induced SIC mice. Metabolomics and network pharmacology strategies were employed to preliminarily analyze and predict the mechanisms of QFD against SIC. Molecular docking and Western blot were further applied to validate the core targets and potential pathways for the treatment of SIC in in vitro and in vivo models. Results: It was found that QFD considerably enhanced cardiac function; attenuated myocardial injury; and reduced the serum levels of LDH, CK-MB, IL-1β, and TNF-α by 28.7%, 32.3%, 38.6%, and 36.7%, respectively. Metabolomic analysis showed that QFD could regulate seven metabolic pathways, namely, glutathione metabolism; alanine, aspartate, and glutamate metabolism; arachidonic acid metabolism; glycerophospholipid metabolism; purine metabolism; sphingolipid metabolism; and fatty acid metabolism. Network pharmacology suggested that the anti-SIC effect of QFD may be mediated through the TNF, toll-like receptor, NOD-like receptor, NF-κB, and PPAR signaling pathways. Additionally, 26 core targets were obtained. Molecular docking revealed that active ingredients such as formononetin, kaempferol, quercetin, and (R)-norcoclaurine in QFD had a high affinity for binding to PPARα and TLR4. Further Western blot validation indicated that QFD could regulate the protein levels of NLRP3, TLR4, NF-κB, IL-6, TNF-α, COX2, sPLA2, PPARα, CPT1B, and CPT2. Conclusions: This study demonstrates that QFD can alleviate SIC by suppressing the TLR4/NF-κB/NLRP3 inflammatory pathway and modulating impaired FAO through the activation of the PPARα/CPT pathway, highlighting QFD as a promising candidate drug for SIC treatment. Full article

In familial Alzheimer’s disease (FAD), presenilin 1 (PSEN1) E280A cholinergic-like neurons (ChLNs) induce aberrant secretion of extracellular amyloid beta (eAβ). How PSEN1 E280A ChLNs-eAβ affects microglial activity is still unknown. We obtained induced microglia-like cells (iMG) from human peripheral blood cells (hPBCs) in a 15-day differentiation process to investigate the effect of bolus addition of Aβ42, PSEN1 E280A cholinergic-like neuron (ChLN)-derived culture supernatants, and PSEN1 E280A ChLNs on wild type (WT) iMG, PSEN1 E280A iMG, and sporadic Alzheimer’s disease (SAD) iMG. We found that WT iMG cells, when challenged with non-cellular (e.g., lipopolysaccharide, LPS) or cellular (e.g., Aβ42, PSEN1 E280A ChLN-derived culture supernatants) microenvironments, closely resemble primary human microglia in terms of morphology (resembling an “amoeboid-like phenotype”), expression of surface markers (Ionized calcium-binding adapter molecule 1, IBA-1; transmembrane protein 119, TMEM119), phagocytic ability (high pHrodo™ Red E. coli BioParticles™ phagocytic activity), immune metabolism (i.e., high generation of reactive oxygen species, ROS), increase in mitochondrial membrane potential (ΔΨm), response to ATP-induced transient intracellular Ca²⁺ influx, cell polarization (cluster of differentiation 68 (CD68)/CD206 ratio: M1 phenotype), cell migration activity according to the scratch wound assay, and especially in their inflammatory response (secretion of cytokine interleukin-6, IL-6; Tumor necrosis factor alpha, TNF-α). We also found that PSEN1 E280A and SAD iMG are physiologically unresponsive to ATP-induced Ca²⁺ influx, have reduced phagocytic activity, and diminished expression of Triggering Receptor Expressed on Myeloid Cells 2 (TREM2) protein, but when co-cultured with PSEN1 E280A ChLNs, iMG shows an increase in pro-inflammatory phenotype (M1) and secretes high levels of cytokines IL-6 and TNF-α. As a result, PSEN1 E280A and SAD iMG induce apoptosis in PSEN1 E280A ChLNs as evidenced by abnormal phosphorylation of protein TAU at residue T205 and cleaved caspase 3 (CC3). Taken together, these results suggest that PSEN1 E280A ChLNs initiate a vicious cycle between damaged neurons and M1 phenotype microglia, resulting in excessive ChLN death. Our findings provide a suitable platform for the exploration of novel therapeutic approaches for the fight against FAD. Full article

Lifileucel, a tumor-infiltrating lymphocyte (TIL) cell therapy approved for advanced melanoma, demonstrates promise for treating other solid tumors, including endometrial cancer (EC). The current study evaluates the feasibility of manufacturing TILs from EC tumors using Iovance’s proprietary 22-day Gen2 manufacturing process. Key parameters, including TIL yield, viability, immune phenotype, T-cell receptor clonality, and cytotoxic activity, were assessed. Of the 11 EC tumor samples processed at research scale, 10 (91%) successfully generated >1 × 10⁹ viable TIL cells, with a median yield of 1.1 × 10¹⁰ cells and a median viability of 82.8%. Of the four EC tumor samples processed at full scale, all achieved the pre-specified TVC and viability targets. Putative tumor-reactive T-cell clones were maintained throughout the manufacturing process. Functional reactivity was evidenced by the upregulation of 4-1BB in CD8+ T cells, OX40 in CD4+ T cells, and increased production of IFN-γ and TNF-α upon autologous tumor stimulation. Furthermore, antitumor activity was confirmed using an in vitro autologous tumor organoid killing assay. These findings demonstrate the feasibility of ex vivo TIL expansion from EC tumors. This study provides a rationale for the initiation of the phase II clinical trial IOV-END-201 (NCT06481592) to evaluate lifileucel in patients with advanced EC. Full article

The developmental processes of microglia follow a general pattern, from immature amoeboid (activated) cells to fully ramified (inactivated) surveilling microglia. However, little is known about the mechanisms controlling the transition of microglia from an activated to an inactivated state during brain development. Due to the complexity of microenvironmentally dynamic changes during neuronal differentiation, interactions between developing nerve cells and microglia might be involved in this process. Extracellular vesicles (EVs) are cell-released particles that serve as mediators of cellular crosstalk and regulation. Using neural progenitor cells (NPCs) and a long-term neuron culture system, we found that EVs derived from NPCs or developing neurons possessed differential capacity on the induction of microglial activation. The exposure of microglia to NPC- or immature neuron (DIV7)-derived EVs resulted in the higher expression of protein and mRNA of multiple inflammatory cytokines (e.g., TNF-α, IL-1β, and IL-6), when compared with mature neuron-derived EVs. Exploration of the intracellular signaling pathways revealed that MAPK signaling, IκBα phosphorylation/degradation, and NF-κB p65 nuclear translocation were strongly induced in microglia treated with NPC- or immature neuron-derived EVs. Using a pharmacological approach, we further demonstrate that Toll-like receptor (TLR) 7-mediated activation of NF-κB and MAPK signaling cascades contribute to EV-elicited microglial activation. Additionally, the application of conditioned media derived from microglia treated with NPC- or immature neuron-derived EVs is found to promote the survival of late-developing dopaminergic neurons. Thus, our results highlight a novel mechanism used by NPCs and developing neurons to modulate the developmental phases and functions of microglia through EV secretion. Full article

Background/Objectives: Ulcerative colitis (UC) is characterized by the interplay between immune responses and dysbiosis in disease development. Aiming to provide additional insights into disease development and potential treatment strategies, the present study investigates the local effect of oral treatment with polysaccharides obtained from Auricularia auricula’s submerged culture in an experimental model of DSS-induced colitis and its impact on lesion resolution. Methods: The structure and monosaccharide composition of Auricularia polysaccharides were characterized through Nuclear Magnetic Resonance (NMR). To evaluate the effect of this polysaccharide on the murine model, wild-type and Dectin-1 knockout mice were treated or not with the exopolysaccharide (EPS) while under DSS consumption. During the experimental period, feces samples were collected to evaluate microbial shifts during disease development, and, finally, the colonic tissue was analyzed to assess the inflammatory process and cytokine production. Results: The EPS composition showed a polymeric mixture of glucans and fucogalactomannans. The treatment of the wild-type DSS-induced colitis group improved the inflammatory response by increasing gut–homeostatic cytokines, such as interleukin-10 (IL-10) and tumor necrosis factor-alpha (TNF-α). The Dectin-1 KO mice group did not show the same enhancement after EPS treatment. The microbiome analysis revealed a difference in the genotype, and the treatment modified the DSS microbiome modulation, with nine and four ASVs in WT and Dectin-1 KO mice, respectively. Conclusions: The EPS treatment demonstrated therapeutic potential in treating inflammatory intestinal diseases by modulating cytokine secretion and microbiota composition, which is dependent on the Dectin-1 receptor’s carbohydrate recognition. Full article

Human cytomegalovirus (HCMV) establishes lifelong latency in the host, with the bone marrow (BM) CD34+ cells serving as a key reservoir. To investigate tissue-specific immune responses to CMV, we analysed paired peripheral blood mononuclear cells (PBMCs) and bone marrow mononuclear cells (BMMNCs) from HCMV-seropositive donors using multiparametric flow cytometry and cytokine FluroSpot assays. We assessed immune cell composition, memory T cell subsets, cytokine production, cytotoxic potential, activation marker expression, and checkpoint inhibitory receptor (CIR) profiles, both ex vivo and following stimulation with lytic and latent HCMV antigens. BMMNCs were enriched in CD34+ progenitor cells and exhibited distinct T cell memory subset distributions. HCMV-specific responses were compartmentalised: IFN-γ responses predominated in PBMCs following lytic antigen stimulation, while IL-10 and TNF-α responses were more prominent in BMMNCs, particularly in response to latent antigens. US28-specific T cells in the BM showed elevated expression of CD39, PD-1, BTLA, CTLA-4, ICOS, and LAG-3 on CD4+ T cells and increased expression of PD-1, CD39, BTLA, TIGIT, LAG-3, and ICOS on CD8+ T cell populations, suggesting a more immunoregulatory phenotype. These findings highlight functional and phenotypic differences in HCMV-specific T cell responses between blood and bone marrow, underscoring the role of the BM niche in shaping antiviral immunity and maintaining viral latency. Full article

Estrogen-related receptor γ (ERRγ) has been reported to regulate various inflammation-related diseases. Herein, we attempted to evaluate the effects of DN200434 as a modulator for ERRγ in mice with atopic dermatitis (AD). Levels of mRNA and protein expression for ERRγ were evaluated in normal and DNCB-induced AD-diagnosed skin. The effects of DN200434 on the chemokines, inflammatory cytokines, and AKT/MAPK/NFκB pathway signaling were investigated in TNF-α/IFN-γ-treated HaCaT cells. DNCB-induced AD mice received DN200434 intraperitoneally for 10 days. Epidermal thickness at the dorsal aspect of the inflamed skin, spleen index, serum IgE levels, and proinflammatory cytokine levels in the skin lesions were measured. Histopathological evaluations, including assessments of epidermal hyperplasia, dermal inflammation, hyperkeratosis, folliculitis, and mast cell counts, were performed to confirm diagnostic features. Significant elevations in ERRγ expression at the RNA and protein levels were observed in DNCB-induced AD lesions. DN200434 suppressed chemokine and inflammatory cytokine expression and inhibited the elevated phosphorylation levels of AKT, ERK, p38, and NFκB in TNF-α/IFN-γ-treated HaCaT cells. Treatment with DN200434 alleviated DNCB-induced AD symptoms. The histopathological score and levels of infiltrated mast cells were also markedly lower in DN200434-treated AD mice than in vehicle-treated AD mice. Consistently, DN200434 reduced the serum IgE level and mRNA expression of TNFα and IL-6 in AD-diagnosed lesions. Collectively, our findings indicated the feasibility of ERRγ as a therapeutic target for the regulation of AD and that DN200434 can be a useful therapeutic agent in treating AD. Full article

Background: Ginger contains gingerols, shagaols, paradols, gingerdiones, and terpenes, which have been shown to display anti-inflammatory properties and inhibit pain receptors. For this reason, ginger has been marketed as a natural analgesic. This study examined whether a specialized ginger extract obtained through supercritical CO₂ extraction and subsequent fermentation affects pain perception, functional capacity, and markers of inflammation. Methods: Thirty men and women (56.0 ± 9.0 years, 164.4 ± 14 cm, 86.5 ± 20.9 kg, 31.0 ± 7.5 kg/m²) with a history of mild to severe joint and muscle pain as well as inflammation participated in a placebo-controlled, randomized, parallel-arm study. Participants donated fasting blood, completed questionnaires, rated pain in the thighs to standardized pressure, and then completed squats/deep knee bends, while holding 30% of body mass, for 3 sets of 10 repetitions on days 0, 30, and 56 of supplementation. Participants repeated tests after 2 days of recovery following each testing session. Participants were matched by demographics and randomized to ingest 125 mg/d of a placebo or ginger (standardized to contain 10% total gingerols and no more than 3% total shogaols) for 58 days. Data were analyzed by a general linear model (GLM) analysis of variance with repeated measures, mean changes from the baseline with 95% confidence intervals, and chi-squared analysis. Results: There was evidence that ginger supplementation attenuated perceptions of muscle pain in the vastus medialis; improved ratings of pain, stiffness, and functional capacity; and affected several inflammatory markers (e.g., IL-6, INF-ϒ, TNF-α, and C-Reactive Protein concentrations), particularly following two days of recovery from resistance exercise. There was also evidence that ginger supplementation increased eosinophils and was associated with less frequent but not significantly different use of over-the-counter analgesics. Conclusions: Ginger supplementation (125 mg/d, providing 12.5 mg/d of gingerols) appears to have some favorable effects on perceptions of pain, functional capacity, and inflammatory markers in men and women experiencing mild to moderate muscle and joint pain. Registered clinical trial #ISRCTN74292348. Full article