Background: Neuroinflammation in spinal dorsal horn (SDH) plays an important role in the pathogenesis of interstitial cystitis/bladder pain syndrome (IC/BPS). Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) exert potent anti-inflammatory activities in the treatment of various diseases. This study aimed to determine the therapeutic effects of MSC-EVs on IC and furtherly investigate the potential mechanism to attenuate neuroinflammation. Methods: Female IC rat model was established by intraperitoneal injection of cyclophosphamide (50 mg/kg, every 3 days for 3 doses). Inhibition of NLRP3 inflammasome was performed by intraperitoneal injection of MCC950 (10 mg/kg). MSC-EVs were isolated from the culture supernatants of human umbilical cord derived MSCs using ultracentrifugation, and then injected intrathecally into IC rats (20 μg in 10 μl PBS, every other day for 3 doses). Suprapubic mechanical allodynia was assessed using up-down method with von Frey filaments, and micturition frequency was examined by urodynamics. The expression of NLRP3 inflammasome components (NLRP3 and Caspase-1), glial cell markers (IBA-1 and GFAP), proinflammatory cytokines (TNF-α, IL-1β, IL-6 and IL-18) and TLR4/NF-κB signal pathway (TLR4, p65 NK-κB and phospho-p65 NK-κB) in L6–S1 SDH was measured by Western blot analysis. The cellular localization of NLRP3 in SDH was detected using immunofluorescence co-staining. Results: NLRP3 inflammasome was activated in neurons in SDH of IC rats. NLRP3 inflammasome activation contributed to activation of glial cells and process of spinal neuroinflammation in IC rats, and was related to suprapubic mechanical allodynia and frequent micturition. Intrathecal injection of MSC-EVs alleviated suprapubic mechanical allodynia and frequent micturition in IC rats, restrained activation of glial cells and attenuated neuroinflammation in SDH. In addition, MSC-EV treatment significantly inhibited activation of both NLRP3 inflammasomes and TLR4/NF-κB signal pathway. Conclusions: NLRP3 inflammasome activation is involved in the neuroinflammation of IC. Intrathecal injection of MSC-EVs alleviates neuroinflammation and mechanical allodynia in IC by inhibiting the activation of NLRP3 inflammasome, and TLR4/NF-κB signal pathway may be the potential regulatory target.

Background: Kidney stones are a significant health concern in the United States, and their increasing prevalence is linked to increasing obesity rates. This study aimed to assess the trends in kidney stone prevalence among U.S. adults with obesity from 2007 to 2020 using National Health and Nutrition Examination Survey (NHANES) data. Materials and methods: This cross-sectional analysis used anonymized NHANES data from six cycles (2007–2020). Prevalences were estimated using NHANES sample weights; age-standardized prevalences were determined using 2020 census data. Survey-weighted multivariate logistic regression and linear regression models were used to assess risk factors and trends, respectively. Subgroup analyses were performed according to sex, race/ethnicity, and poverty-income ratio (PIR). Results: The overall age-standardized prevalence of kidney stones increased from 9.4% (2007–2008) to 10.2% (2017–2020). The prevalence among individuals with obesity significantly increased from 11.0% to 12.5% ( P for trend = 0.035). The prevalence of kidney stones in females with obesity significantly increased from 8.8% to 11.5% ( P for trend = 0.042), whereas males with obesity showed a slight increase (13.4% to 14.0%). Racial/ethnic disparities were evident among those with obesity: non-Hispanic Whites showed a modest increase (12.4% to 14.2%), Hispanics exhibited a notable increase (7.5% to 10.9%; P for trend = 0.017), and non-Hispanic Blacks had a stable prevalence that increased slightly (5.9% to 6.8%; P for trend = 0.304). The prevalence increased (10.2% to 12.9%; P for trend = 0.051) among individuals with obesity and high PIRs and decreased (12.8% to 11.4%) among those with low PIRs. Conclusions: This study highlights an upward trend in the prevalence of kidney stones among U.S. adults with obesity, from 2007 to 2020. Our findings emphasize the need for targeted public health strategies to address this issue, especially among populations at higher risk due to obesity and socioeconomic factors.