Antibacterial sequential growth factor delivery from alginate/gelatin methacryloyl microspheres for bone regeneration.

Autologous or allogeneic bone tissue grafts remain the mainstay of treatment for clinical bone defects. However, the risk of infection and donor scarcity in bone grafting pose challenges to the process. Therefore, the development of excellent biomaterial grafts is of great clinical importance for the repair of bone defects. In this study, we used gas-assisted microfluidics to construct double-cross-linked hydrogel microspheres with good biological function based on the ionic cross-linking of Cu2+ with alginate and photo-cross-linking of gelatin methacryloylamide (GelMA) by loading vascular endothelial growth factor (VEGF) and His-tagged bone morphogenetic protein-2 (BMP2) (AGMP@VEGF&BMP2). The Cu2+ component in the microspheres showed good antibacterial and drug-release behavior, whereas VEGF and BMP2 effectively promoted angiogenesis and bone tissue repair. In in vitro and in vivo experiments, the dual cross-linked hydrogel microspheres showed good biological function and biocompatibility. These results demonstrate that AGMP@VEGF&BMP2 microspheres could be used as a bone defect graft substitute to promote effective healing of bone defects and may be applied to other tissue engineering studies.

Current state and influencing factors in airbag management among emergency department nurses: A multicenter study.

BACKGROUND: The emergency department (ED) plays a critical role in establishing artificial airways and implementing mechanical ventilation. Managing airbags in the ED presents a prime opportunity to mitigate the risk of ventilator-associated pneumonia. Nonetheless, existing research has largely overlooked the understanding, beliefs, and practical dimensions of airway airbag management among ED nurses, with a predominant focus on intensive care unit nurses. AIM: To investigate the current status of ED nurses' knowledge, beliefs, and practical behaviors in airway airbag management and their influencing factors. METHODS: A survey was conducted from July 10th to August 10th, 2023, using convenience sampling on 520 ED nurses from 15 tertiary hospitals and 5 sary hospitals in Shanghai. Pathway analysis was utilized to analyze the influencing factors. RESULTS: The scores for ED nurses' airway airbag management knowledge were 60.26 ± 23.00, belief was 88.65 ± 13.36, and behavior was 75.10 ± 19.84. The main influencing factors of airbag management knowledge included participation in specialized nurse or mechanical ventilation training, department, and work experience in the department. Influencing factors of airbag management belief comprised knowledge, department, and participation in specialized nurse or mechanical ventilation training. Primary influencing factors of airbag management behavior included knowledge, belief, department, participation in specialized nurse or mechanical ventilation training, and professional title. The belief in airbag management among ED nurses acted as a partial mediator between knowledge and behavior, with a total effect value of 0.513, and an indirect effect of 0.085, constituting 16.6% of the total effect. CONCLUSION: ED nurses exhibit a positive attitude toward airbag management with relatively standardized practices, yet there remains room for improvement in their knowledge levels. Nursing managers should implement interventions tailored to the characteristics of ED nurses' airbag management knowledge, beliefs, and practices to enhance their airbag management proficiency.

Qualitative exploration of home life experiences and care needs among elderly patients with temporary intestinal stomas.

BACKGROUND: This study employed a phenomenological research approach within qualitative research to explore the challenges encountered by elderly individuals with temporary colostomies in managing their daily lives and care needs. Protecting the anus surgery combined with temporary colostomy has emerged as a prevalent treatment modality for low rectal cancer. However, the ileostomy is susceptible to peri-stoma skin complications, as well as fluid, electrolyte, and nutritional imbalances, posing challenges to effective management. The successful self-management of patients is intricately linked to their adjustment to temporary colostomy; nonetheless, there remains a dearth of research examining the factors influencing self-care among temporary colostomy patients and the obstacles they confront. AIM: To investigate the lived experiences, perceptions, and care requirements of temporary colostomy patients within their home environment, with the ultimate goal of formulating a standardized management protocol. METHODS: Over the period of June to August 2023, a purposive sampling technique was utilized to select 12 patients with temporary intestinal stomas from a tertiary hospital in Shanghai, China. Employing a phenomenological research approach, a semi-structured interview guide was developed, and qualitative interviews were conducted using in-depth interview techniques. The acquired data underwent coding, analysis, organization, and summarization following Colaizzi's seven-step method. RESULTS: The findings of this study revealed that the experiences and needs of patients with temporary intestinal stomas can be delineated into four principal themes: Firstly, Temporary colostomy patients bear various burdens and concerns about the uncertainty of disease progression; secondly, patients exhibit limited self-care capabilities and face information deficits, resulting in heightened reliance on healthcare professionals; thirdly, patients demonstrate the potential for internal motivation through proactive self-adjustment; and finally, patients express a significant need for emotional and social support. CONCLUSION: Home-living patients with temporary intestinal stomas confront multifaceted challenges encompassing burdens, inadequate self-care abilities, informational deficits, and emotional needs. Identifying factors influencing patients' self-care at home and proposing strategies to mitigate barriers can serve as a foundational framework for developing and implementing nursing interventions tailored to the needs of patients with temporary intestinal stomas.

Association between enlarged perivascular spaces in basal ganglia and cerebral perfusion in elderly people.

Background and objective: Enlarged perivascular spaces in basal ganglia (BG-EPVS) are considered an imaging marker of cerebral small vessel disease (CSVD), but its pathogenesis and pathophysiological process remain unclear. While decreased cerebral perfusion is linked to other CSVD markers, the relationship between BG-EPVS and cerebral perfusion remains ambiguous. This study aimed to explore this association. Methods: Elderly individuals with severe BG-EPVS (n = 77) and age/sex-matched controls (n = 89) underwent head CT perfusion imaging. The cerebral perfusion parameters including mean transit time (MTT), time to maximum (TMAX), cerebral blood flow (CBF), and cerebral blood volume (CBV) were quantitatively measured by symmetric regions of interest plotted in the basal ganglia region. Point-biserial correlation and logistics regression analysis were performed to investigate the association between BG-EPVS and cerebral perfusion. Results: There were no significant differences in MTT, TMAX, or CBF between BG-EPVS group and control group. CBV was significantly lower in the BG-EPVS group (p = 0.035). Point-biserial correlation analysis showed a negative correlation between BG-EPVS and CBV (r = -0.198, p = 0.011). BG-EPVS group and control group as the dependent variable, binary logistics regression analysis showed that CBV was not an independent risk factor for severe BG-EPVS (p = 0.448). All enrolled patients were divided into four groups according to the interquartile interval of CBV. The ordered logistic regression analysis showed severe BG-EPVS was an independent risk factor for decreased CBV after adjusting for confounding factors (OR = 2.142, 95%CI: 1.211-3.788, p = 0.009). Conclusion: Severe BG-EPVS is an independent risk factor for decreased CBV in the elderly, however, the formation of BG-EPVS is not solely dependent on changes in CBV in this region. This finding provides information about the pathophysiological consequence caused by severe BG-EPVS.

Assessing professional behaviors: a self-administered scale for medical students during clerkships.

BACKGROUND: Medical professionalism is a core competency for medical students during clerkships for further professional development. Given that the behavior-based framework could provide clear insight and is easy to assess, the study aimed to create a self-administered scale to measure the professional behaviors of medical students during their clerkships. METHODS: A comprehensive literature review on medical professional behaviors in English or Chinese and Delphi interviews were used to develop the initial version of the Self-Administered Scale for Professional Behavior of Medical Students During Clerkships. The reliability and validity analysis based on a survey of medical students from China, Cronbach's α calculations, and Confirmatory Factor Analysis (CFA) specifically were conducted to finalize the scale. The associations of professional behaviors with gender, medical programs, and clerkship duration were examined using Wilcoxon rank-sum tests. RESULTS: We included 121 studies and extracted 57 medical professionalism assessment tools, initially forming a pool of 48 items. To refine these items, eighteen experts participated in two rounds of Delphi interviews, ultimately narrowing down the item pool to 24 items. A total of 492 participants effectively completed the questionnaire. One item was removed due to its correlated item-total correlation (CITC) value, resulting in a final scale containing 23 items with six domains: Respect, Altruism, Communication and Collaboration, Integrity, Duty, and Excellence. The overall Cronbach's alpha value was 0.98, ranging from 0.88 to 0.95 for each domain. The fit indices (χ2/df = 4.07, CFI = 0.96, TLI = 0.95, RMSEA = 0.08, and SRMR = 0.02) signified a good fit for the six-domain model. Medical students' professional behavior was significantly associated with gender (p = 0.03) and clerkship duration (p = 0.001). CONCLUSION: The scale was demonstrated to be reliable and valid in assessing the professional behaviors of Chinese medical students during clerkships.

PD-L2 drives resistance to EGFR-TKIs: dynamic changes of the tumor immune environment and targeted therapy.

There is a lack of effective treatments to overcome resistance to EGFR-TKIs in EGFR mutant tumors. A deeper understanding of resistance mechanisms can provide insights into reducing or eliminating resistance, and can potentially deliver targeted treatment measures to overcome resistance. Here, we identified that the dynamic changes of the tumor immune environment were important extrinsic factors driving tumor resistance to EGFR-TKIs in EGFR mutant cell lines and syngeneic tumor-bearing mice. Our results demonstrate that the acquired resistance to EGFR-TKIs is accompanied by aberrant expression of PD-L2, leading a dynamic shift from an initially favorable tumor immune environment to an immunosuppressive phenotype. PD-L2 expression significantly affected EGFR mutant cell apoptosis that depended on the proportion and function of CD8+ T cells in the tumor immune environment. Combined with single-cell sequencing and experimental results, we demonstrated that PD-L2 specifically inhibited the proliferation of CD8+ T cells and the secretion of granzyme B and perforin, leading to reduced apoptosis mediated by CD8+ T cells and enhanced immune escape of tumor cells, which drives EGFR-TKIs resistance. Importantly, we have identified a potent natural small-molecule inhibitor of PD-L2, zinc undecylenate. In vitro, it selectively and potently blocks the PD-L2/PD-1 interaction. In vivo, it abolishes the suppressive effect of the PD-L2-overexpressing tumor immune microenvironment by blocking PD-L2/PD-1 signaling. Moreover, the combination of zinc undecylenate and EGFR-TKIs can synergistically reverse tumor resistance, which is dependent on CD8+ T cells mediating apoptosis. Our study uncovers the PD-L2/PD-1 signaling pathway as a driving factor to mediate EGFR-TKIs resistance, and identifies a new naturally-derived agent to reverse EGFR-TKIs resistance.

Assessing the role of programmed cell death signatures and related gene TOP2A in progression and prognostic prediction of clear cell renal cell carcinoma.

Kidney Clear Cell Carcinoma (KIRC), the predominant form of kidney cancer, exhibits a diverse therapeutic response to Immune Checkpoint Inhibitors (ICIs), highlighting the need for predictive models of ICI efficacy. Our study has constructed a prognostic model based on 13 types of Programmed Cell Death (PCD), which are intertwined with tumor progression and the immune microenvironment. Validated by analyses of comprehensive datasets, this model identifies seven key PCD genes that delineate two subtypes with distinct immune profiles and sensitivities to anti-PD-1 therapy. The high-PCD group demonstrates a more immune-suppressive environment, while the low-PCD group shows better responses to PD-1 treatment. In particular, TOP2A emerged as crucial, with its inhibition markedly reducing KIRC cell growth and mobility. These findings underscore the relevance of PCDs in predicting KIRC outcomes and immunotherapy response, with implications for enhancing clinical decision-making.

Comprehensive evaluation of digital village development in the context of rural revitalization: A case study from Jiangxi Province of China.

Digital rural construction is a key strategic direction to promote China's rural revitalization and alleviate global climate problems. In order to put forward feasible suggestions for the subsequent development and ensure the smooth development of digital village construction, how to reflect the development level of the digital village through scientific and reasonable comprehensive evaluation has become an urgent problem to be solved. This paper establishes a comprehensive evaluation index system through the Delphi method and principal component analysis method, then assigns weights to the evaluation indicators based on the improved CRITIC-G1 method, and then grades the development level of digital villages according to the extension matter element method. Finally, taking Jiangxi Province in China as an example, the overall development level of digital villages in Jiangxi Province is evaluated from the provincial level according to the proposed method. And put forward the corresponding countermeasures and suggestions. Results: Firstly, the development level of digital villages in Jiangxi Province is good, and there is a trend of excellent development level. Secondly, from different aspects of digital rural development, the digitalization of infrastructure, services, economy, and green production in Jiangxi Province is at a good level, and the digitalization of life has reached an excellent level. Thirdly, from the perspective of development trends, the digitization of infrastructure has a progressive trend towards an excellent level of development, while the digitization of services, economy and green production has signs of development regression. According to the analysis results, the relevant countermeasures and suggestions are put forward from four aspects: talent, capital, governance system and development planning. Other regions can evaluate the development level of the digital village according to the evaluation model proposed in this paper so as to analyze the existing problems and put forward targeted solutions to promote the construction of the digital village.

Decreased Treg cells induced by bisphenol A is associated with up-regulation of PI3K/Akt/mTOR signaling pathway and Foxp3 DNA methylation in spleen of adolescent mice.

The current study aimed to explore whether bisphenol A (BPA) exposure aggravated the decrease in Tregs induced by ovalbumin (OVA) in adolescent female mouse models of asthma, and whether the process was associated with mTOR-mediated signaling pathways and DNA methylation levels. A total of 40 female C57BL/6 mice at the age of four weeks were used and divided into five groups after 1 week of domestication. Each group consisted of eight mice: the control group, OVA group, OVA + BPA (0.1 µg mL-1) group, OVA + BPA (0.2 µg mL-1) group, and OVA + BPA (0.4 µg mL-1) group. Results revealed that Foxp3 protein levels decreased in the spleens of mice exposed to BPA compared to those in the OVA group. After an elevation in BPA dose, the mRNAs of methyltransferases (Dnmt1, Dnmt3a, and Dnmt3b) were gradually upregulated. The mechanism was related to the activity of TLR4/NF-κB and PI3K/Akt/mTOR signaling pathways and the enhancement of Foxp3 DNA methylation. Our results, collectively, provided a new view for studying the mechanisms underlying BPA exposure-induced immune dysfunction. Investigation of the regulatory mechanisms of DNA methylation in the abnormal Th immune response caused by BPA exposure could help reveal the causes and molecular mechanisms underlying the high incidence of allergic diseases in children in recent years.

Cerebral Small Vessel Disease Burden in Patients with Transient Global Amnesia and its Relationship with Recurrence.

OBJECTIVE: Cerebral Small Vessel Disease (CSVD) has not been systematically studied in patients with Transient Global Amnesia (TGA). We aimed to investigate the CSVD burden in patients with TGA and its relationship with TGA recurrence. METHODS: We retrospectively examined 69 patients diagnosed with TGA in a single center between January 2015 and November 2023. The overall CSVD burden and single CSVD imaging markers, including enlarged perivascular spaces in the hippocampus (H-EPVS), were measured in each patient and compared with those in 69 age- and sex-matched healthy controls. Multivariate logistic regression was performed to determine independent predictors of recurrence. RESULTS: Of the 69 included patients, 40 (58%) were female, and the median age was 67 years (range 42-83 years). Twenty-one patients (30.4%) showed dot-like hippocampal hyperintensities on diffusion-weighted imaging (DWI). The mean follow-up was 51 months. Sixteen patients (23.2%) experienced TGA recurrence. The burden of overall CSVD, lacunes, WMH, EPVS, and extensive H-EPVS was higher in TGA patients than in controls. TGA patients who experienced recurrence had a heavier overall CSVD burden, lower frequency of hippocampal DWI hyperintensities, and longer follow-up duration than those who had with single episode. In the multivariate analysis, only follow-up duration was an independent predictor of TGA recurrence. CONCLUSION: The overall CSVD burden and extensive H-EPVS burden were higher in patients with TGA than healthy controls. Follow-up duration but not overall CSVD burden may predict TGA recurrence.

Antimicrobial sensitisers: Gatekeepers to avoid the development of multidrug-resistant bacteria.

The resistance of multidrug-resistant bacteria to existing antibiotics forces the continued development of new antibiotics and antibacterial agents, but the high costs and long timeframe involved in the development of new agents renders the hope that existing antibiotics may again play a part. The "antibiotic adjuvant" is an indirect antibacterial strategy, but its vague concept has, in the past, limited the development speed of related drugs. In this review article, we put forward an accurate concept of a "non-self-antimicrobial sensitisers (NSAS)", to distinguish it from an "antibiotic adjuvant", and then discuss several scientific methods to restore bacterial sensitivity to antibiotics, and the sources and action mechanism of existing NSAS, in order to guide the development and further research of NSAS.

The regulatory relationship between NAMPT and PD-L1 in cancer and identification of a dual-targeting inhibitor.

Cancer is a heterogeneous disease. Although both tumor metabolism and tumor immune microenvironment are recognized as driving factors in tumorigenesis, the relationship between them is still not well-known, and potential combined targeting approaches remain to be identified. Here, we demonstrated a negative correlation between the expression of NAMPT, an NAD+ metabolism enzyme, and PD-L1 expression in various cancer cell lines. A clinical study showed that a NAMPTHigh PD-L1Low expression pattern predicts poor prognosis in patients with various cancers. In addition, pharmacological inhibition of NAMPT results in the transcription upregulation of PD-L1 by SIRT-mediated acetylation change of NF-κB p65, and blocking PD-L1 would induce NAMPT expression through a HIF-1-dependent glycolysis pathway. Based on these findings, we designed and synthesized a dual NAMPT/PD-L1 targeting compound, LZFPN-90, which inhibits cell growth in a NAMPT-dependent manner and blocks the cell cycle, subsequently inducing apoptosis. Under co-culture conditions, LZFPN-90 treatment contributes to the proliferation and activation of T cells and blocks the growth of cancer cells. Using mice bearing genetically manipulated tumors, we confirmed that LZFPN-90 exerted target-dependent antitumor activities, affecting metabolic processes and the immune system. In conclusion, our results demonstrate the relevance of NAD+-related metabolic processes in antitumor immunity and suggest that co-targeting NAD+ metabolism and PD-L1 represents a promising therapeutic approach.

Combination of click chemistry and Schiff base reaction: Post-synthesis of covalent organic frameworks as an immobilized metal ion affinity chromatography platform for efficient capture of global phosphopeptides in serum with chronic obstructive pulmonary disease.

Reasonable design and construction of functionalized materials are of great importance for the enrichment of global phosphopeptides. In this work, Ti4+ functionalized hydrophilic covalent organic frameworks by introducing glutathione (GSH) and 2,3,4-trihydroxy benzaldehyde (THBA) via click chemistry and Schiff base reaction (COF-V@GSH-THBA-Ti4+ ) was constructed and applied for selective enrichment of phosphopeptides in serum. Benefit from the high surface area, excellent hydrophilicity as well as regular mesoporous structure, COF-V@GSH-THBA-Ti4+ displayed high selectivity (molar ratio of 2000:1), low limit of detection (0.5 fmol), high load capacity (100.0 mg/g) and excellent size-exclusion effect (1:10000) for enrichment of phosphopeptides. For actual bio-sample analysis, 15 phosphopeptides assigned to 10 phosphoproteins with 16 phosphorylated sites and 33 phosphopeptides assigned to 25 phosphoproteins with 34 phosphorylated sites were detected from the serum of patients with chronic obstructive pulmonary disease (COPD), and normal controls. Biological processes and molecular functions analysis further disclosed the difference of serums with phosphoproteomics between COPD and normal controls.

DGAT2 inhibition blocks SREBP-1 cleavage and improves hepatic steatosis by increasing phosphatidylethanolamine in the ER.

Diacylglycerol acyltransferase 2 (DGAT2) catalyzes the final step of triglyceride (TG) synthesis. DGAT2 deletion in mice lowers liver TGs, and DGAT2 inhibitors are under investigation for the treatment of fatty liver disease. Here, we show that DGAT2 inhibition also suppressed SREBP-1 cleavage, reduced fatty acid synthesis, and lowered TG accumulation and secretion from liver. DGAT2 inhibition increased phosphatidylethanolamine (PE) levels in the endoplasmic reticulum (ER) and inhibited SREBP-1 cleavage, while DGAT2 overexpression lowered ER PE concentrations and increased SREBP-1 cleavage in vivo. ER enrichment with PE blocked SREBP-1 cleavage independent of Insigs, which are ER proteins that normally retain SREBPs in the ER. Thus, inhibition of DGAT2 shunted diacylglycerol into phospholipid synthesis, increasing the PE content of the ER, resulting in reduced SREBP-1 cleavage and less hepatic steatosis. This study reveals a new mechanism that regulates SREBP-1 activation and lipogenesis that is independent of sterols and SREBP-2 in liver.

Dapagliflozin improves podocytes injury in diabetic nephropathy via regulating cholesterol balance through KLF5 targeting the ABCA1 signalling pathway.

Diabetic nephropathy (DN), one of the more prevalent microvascular complications in patients diagnosed with diabetes mellitus, is attributed as the main cause of end-stage renal disease (ESRD). Lipotoxicity in podocytes caused by hyperglycemia has been recognised as a significant pathology change, resulting in the deterioration of the glomerular filtration barrier. Research has demonstrated how dapagliflozin, a kind of SGLT2i, exhibits a multifaceted and powerful protective effect in DN, entirely independent of the hypoglycemic effect, with the specific mechanism verified. In this present study, we found that dapagliflozin has the potential to alleviate apoptosis and restore cytoskeleton triggered by high glucose (HG) in vivo and in vitro. We also discovered that dapagliflozin could mitigate podocyte cholesterol accumulation by restoring the expression of ABCA1, which is the key pathway for cholesterol outflows. This research also mechanistically demonstrates that the protective effect of dapagliflozin can be mediated by KLF-5, which is the upstream transcription factor of ABCA1. Taken together, our data suggest that dapagliflozin offers significant potential in alleviating podocyte injury and cholesterol accumulation triggered by high glucose. In terms of the mechanism, we herein reveal that dapagliflozin could accelerate cholesterol efflux by restoring the expression of ABCA1, which is directly regulated by KLF-5.

Intelligence detection of oil absorption in French fries by surface profiles.

Surface profiles are important evaluation indices for oil absorption behavior of fried foods. This research established two intelligent models of partial least-squares regression (PLSR) and back propagation artificial neural network (BP-ANN) for monitoring the oil absorption behavior of French fries based on the surface characteristics. Surface morphology and texture of French fries by rapeseed oil (RO) and high-oleic peanut oil (HOPO) at different temperatures were investigated. Results showed that oil content of samples increased with frying temperature, accounting for 37.7% and 41.4% of samples fried by RO and HOPO respectively. The increase of crust ratio, roughness and texture parameters (Fm, Nwr, fwr, Wc) and the decrease of uniformity were observed with the frying temperature. Coefficients of prediction set of PLSR and BP-ANN models were more than 0.93, which indicated that surface features combined with chemometrics were rapid and precise methods for determining the oil content of French fries.

Human dental pulp stem cell-derived exosomes decorated titanium scaffolds for promoting bone regeneration.

Exosomes, nanoscale extracellular vesicles crucial for intercellular communication, hold great promise as a therapeutic avenue in cell-free tissue regeneration. In this study, we identified and utilized exosomes to adorn anodized titanium scaffolds, inducing osteogenic differentiation in human dental pulp stem cells (hDPSCs). The osteogenesis of hDPSCs was stimulated by exosomes derived from hDPSCs that underwent various periods of osteogenic differentiation. After purification, these exosomes were loaded onto anodized titanium scaffolds. Notably, the scaffolds loaded with exosomes deriving from osteogenic differentiated hDPSCs demonstrated superior bone tissue regeneration compared to those loaded with exosomes deriving from hDPSCs within 10-week. RNA-sequencing analysis shed light on the underlying mechanism, revealing that the osteogenic exosomes carried specific cargo, which is due to upregulated miRNAs (Hsa-miR-29c-5p, Hsa-miR-378a-5p, Hsa-miR-10b-5p and Hsa-miR-9-3p) associated with osteogenesis. And down-regulated anti-osteogenic miRNA (Hsa-miR-31-3p, Hsa-miR-221-3p, Hsa-miR-183-5p and Hsa-miR-503-5p). In conclusion, the identification and utilization of exosomes derived from osteogenic differentiated stem cells offer a novel and promising strategy for achieving cell-free bone regeneration.

GDF-15 alleviates diabetic nephropathy via inhibiting NEDD4L-mediated IKK/NF-κB signalling pathways.

Podocyte inflammatory injury has been indicated to play a pivotal role in the occurrence and development of diabetic nephropathy (DN). However, the pathogenesis of inflammation remains unclear. Recent researches have shown that GDF-15, a member of the transforming growth factor-ß superfamily, were elevated under pathological conditions, such as myocardial ischemia, cancer, as well as inflammation. Here, we demonstrated that GDF-15 could alleviate podocyte inflammatory injury by modulating the NF-κB pathway. GDF-15 and other pro-inflammatory factors, such as TNF-α, IL-1ß, and IL-6 were upregulated in the serum of HFD/STZ rat models. GDF-15 was also elevated in diabetic glomeruli and hyperglycemic stimuli treated-podocytes. The silence of GDF-15 in HG-stimulated podocytes further augmented inflammation and podocyte injury, while overexpression of GDF-15 significantly reduced the inflammatory response in podocytes. Mechanistically, we demonstrated that GDF-15 could inhibit the nuclear translocation of NF-κB through IKK and IκBα by interaction with ubiquitin ligase NEDD4L. Taken together, our data suggested a protective mechanism of elevated GDF-15 in DN through obstruction of ubiquitin degradation of IKK by inhibiting NEDD4L expression, thus decreasing the activation of NF-κB and relieving the inflammation. GDF-15 could serve as a potential therapeutic target for DN.