Inflammatory Biomarkers as Predictors of Infected Diabetic Foot Ulcer

Dmitriyeva, Mariya; Kozhakhmetova, Zhanar; Urazova, Saltanat; Kozhakhmetov, Saken; Turebayev, Dulat; Toleubayev, Medet

doi:10.2174/1573399817666210928144706

Cited by 9 publications

(6 citation statements)

References 82 publications

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“…Second, we recognize that other epigenetic enzymes may regulate Mφ function in diabetic wounds and that these enzymes do not work in isolation but rather contribute at different phases of wound repair to the cell phenotype [ 63 – 65 ]. Third, we realize that IL-6 is unlikely to be the only driver of JAK1,3/STAT3 signaling in wounds, although IL-6 elevation in diabetic wounds is well documented [ 66 , 67 ], and we show that it is persistently elevated in diabetic wound Mφs. Finally, we have not directly examined the interplay between Mφs and other structural cells, such as smooth muscle cells or fibroblasts, that exist within the wound.…”

Section: Discussionmentioning

confidence: 68%

Macrophage-specific inhibition of the histone demethylase JMJD3 decreases STING and pathologic inflammation in diabetic wound repair

et al. 2022

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Macrophage plasticity is critical for normal tissue repair following injury. In pathologic states such as diabetes, macrophage plasticity is impaired, and macrophages remain in a persistent proinflammatory state; however, the reasons for this are unknown. Here, using single-cell RNA sequencing of human diabetic wounds, we identified increased JMJD3 in diabetic wound macrophages, resulting in increased inflammatory gene expression. Mechanistically, we report that in wound healing, JMJD3 directs early macrophage-mediated inflammation via JAK1,3/STAT3 signaling. However, in the diabetic state, we found that IL-6, a cytokine increased in diabetic wound tissue at later time points post-injury, regulates JMJD3 expression in diabetic wound macrophages via the JAK1,3/STAT3 pathway and that this late increase in JMJD3 induces NFκB-mediated inflammatory gene transcription in wound macrophages via an H3K27me3 mechanism. Interestingly, RNA sequencing of wound macrophages isolated from mice with JMJD3-deficient myeloid cells (Jmjd3f/fLyz2Cre+) identified that the STING gene (Tmem173) is regulated by JMJD3 in wound macrophages. STING limits inflammatory cytokine production by wound macrophages during healing. However, in diabetic mice, its role changes to limit wound repair and enhance inflammation. This finding is important since STING is associated with chronic inflammation, and we found STING to be elevated in human and murine diabetic wound macrophages at late time points. Finally, we demonstrate that macrophage-specific, nanoparticle inhibition of JMJD3 in diabetic wounds significantly improves diabetic wound repair by decreasing inflammatory cytokines and STING. Taken together, this work highlights the central role of JMJD3 in tissue repair and identifies cell-specific targeting as a viable therapeutic strategy for nonhealing diabetic wounds.

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Section: Discussionmentioning

confidence: 68%

Macrophage-specific inhibition of the histone demethylase JMJD3 decreases STING and pathologic inflammation in diabetic wound repair

et al. 2022

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“…It is reported 24 that IL‐6 stimulates the inflammatory and autoimmune processes of many diseases, such as diabetes, atherosclerosis, depression, Alzheimer's disease, systemic lupus erythematosus, multiple myeloma, prostate cancer, Behcet's disease, and rheumatoid arthritis. IL‐6 has certain value in the course monitoring of type 2 diabetes patients with foot infection 25 . Therefore, these above research results suggested that TNF‐ α, PCT, and IL‐6 could be used as diagnostic factors of DFU.…”

Section: Discussionmentioning

confidence: 89%

“…IL-6 has certain value in the course monitoring of type 2 diabetes patients with foot infection. 25 Therefore, these above research results suggested that TNF-α, PCT, and IL-6 could be used as diagnostic factors of DFU. In addition, the results of this study showed that the levels of PCT, TNF-α, and IL-6 in the DFU patients with cardiovascular events group were significantly higher than those in the nonoccurrence group, suggesting that abnormal inflammatory response in DFU patients could promote the occurrence of adverse cardiovascular events.…”

Section: Discussionmentioning

confidence: 91%

Correlation between inflammatory factors, autophagy protein levels, and infection in granulation tissue of diabetic foot ulcer

Deng,

Wang,

2024

Immunity Inflam & Disease

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ObjectiveTo observe the expression of inflammatory factors and autophagy‐related proteins in granulation tissue of diabetic foot ulcer (DFU) patients and analyze their relationship with infection.MethodsThis is a retrospective cohort study. One hundred and fifty‐two patients with DFU in our hospital from July 2020 to March 2022 were selected as the DFU group, including 98 cases in infection stage group and 54 cases in infection control group. The patients were further graded as the mild (51 cases), the moderate (65 cases), and the severe infection group (36 cases) according to the Wagner grading criteria. Sixty‐seven patients with foot burns during the same period were selected as the control group. The distribution of pathogenic bacteria on the ulcer surface was examined using fully automated bacterial analyzer. The expression of inflammatory factors (procalcitonin [PCT], tumor necrosis factor‐α [TNF‐α], and interleukin‐6 [IL‐6]) was valued by real‐time fluorescence quantitative PCR (qRT‐PCR). Protein expression was measured by immunohistochemistry (IHC). The correlation was analyzed by Pearson.ResultsThe surface infection of DFU patients was mostly induced by gram‐negative and gram‐positive bacteria, with Pseudomonas aeruginosa predominating among the Gram‐negative bacteria and Staphylococcus aureus among the gram‐positive bacteria. The infection stage group had higher content of PCT, TNF‐α, and IL‐6 and lower content of Beclin‐1 and LC3 than the infection control group (p < .001). The levels of PCT, TNF‐α, and IL‐6 in the DFU patients with cardiovascular events were higher than those in the nonoccurrence group (p < .001). Glycated hemoglobin in patients with DFU was positively correlated with PCT, TNF‐α, and IL‐6 levels (p < .05), and negatively correlated with Beclin‐1 and LC3 levels (p < .001).ConclusionP. aeruginosa and S. aureus were predominant bacterial in DFU infections. Inflammatory factor and autophagy protein expression were closely correlated with the degree of infection.

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“…Researchers have been interested in finding the differences between IDFUs and DFUs, and these markers may be suitable for prognostic purposes [31]. Our objective was to identify the differences between above-and below-the-ankle limb amputation, and we found that only WBCs and HbA1c showed significant differences.…”

Section: Discussionmentioning

confidence: 90%

Pentraxin-3 and Other Inflammatory Markers for an Infected Diabetic Foot Ulcer Diagnosis: A Prospective Study

Ardelean,

Balta,

Neamtu

et al. 2023

Diagnostics

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Strategies have been researched and implemented to reduce the number of people with diabetic foot ulcers (DFUs). One problem is the accurate assessment of DFU severity, which is the main factor in resource allocation and treatment choice. The primary objective of this study was to assess pentraxin-3 as a biomarker of an infected DFU (IDFU), the limb amputation level prognosis, and patient survival. The secondary objectives were to evaluate and compare other markers, including white blood cells (WBCs), C-reactive protein (CRP), the erythrocyte sedimentation rate (ESR), and procalcitonin (PCT), for identifying IDFUs. Over a period of two years, 145 patients were followed; 131 of these were analyzed for this study. Pentraxin-3 was found to be a good predictor of death (p = 0.047). A comparison between IDFUs and DFUs revealed the following differences: PCT had the highest AUROC of 0.91, sensitivity of 93.7, and specificity of 83.3%. CRP had a cutoff value of 226 mg/L, an AUROC of 0.89, a sensitivity of 95.5%, and a specificity of 83.3%. Fibrinogen had an AUROC of 0.87 at a cutoff value of 5.29 g/L, with a good sensitivity and specificity of 85% and 87%, respectively. ESR had a cutoff value of 46 mm/h, an AUROC of 85%, a sensitivity of 83.7%, and a specificity of 83.3%. Pentraxin-3 showed promising results in predicting IDFUs and DFUs, and it served as a marker for the risk of death in IDFU patients during the 6 month follow-up. Other markers, including CRP, PCT, ESR, and fibrinogen, were more effective in differentiating between IDFUs and DFUs.

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Inflammatory Biomarkers as Predictors of Infected Diabetic Foot Ulcer

Cited by 9 publications

References 82 publications

Macrophage-specific inhibition of the histone demethylase JMJD3 decreases STING and pathologic inflammation in diabetic wound repair

Macrophage-specific inhibition of the histone demethylase JMJD3 decreases STING and pathologic inflammation in diabetic wound repair

Correlation between inflammatory factors, autophagy protein levels, and infection in granulation tissue of diabetic foot ulcer

Pentraxin-3 and Other Inflammatory Markers for an Infected Diabetic Foot Ulcer Diagnosis: A Prospective Study

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