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Objective: This retrospective study aimed to investigate the association between TNs and the systemic immune-inflammation index (SII) and the aggregate index of systemic inflammation (AISI) in patients with T2DM. Methods: A total of 370 T2DM patients, who were admitted to Dongzhimen Hospital between January 2020 and March 2023, were included in this retrospective study. Binary logistic regression models with multivariable adjustment were employed to assess the relationship between SII, AISI quartiles, and TNs. Furthermore, receiver operating characteristic (ROC) curve analysis was performed to assess the diagnostic accuracy of SII and AISI in identifying T2DM patients with TNs. Results: Age, diabetes duration, diabetic nephropathy (DN), SII, and AISI demonstrated significant positive associations with TNs. Compared to the first quartile of SII, the second, third, and fourth quartiles showed increased risks of TNs with hazard ratios (HRs) of 1.578 (0.883–2.820), 2.279 (1.257–4.131), and 3.626 (1.931–6.810), respectively (P < 0.001). Similar results were observed for AISI and TNs. ROC curve analysis revealed that SII and AISI exhibited a high discriminatory capability for identifying TNs in the overall and male participant group, whereas the significance among females was not discernible. Conclusions: This study provides evidence that SII and AISI are independent risk factors for TNs, suggesting that elevated SII and AISI levels may contribute to the development of TNs in patients with T2DM particularly among male individuals. [ABSTRACT FROM AUTHOR]

[Display omitted] • Novel 25 dehydroabietic acid derivatives. • D1 shows the strongest relaxation effect in vitro and in vivo. • D1 has multi-targets effect. Using dehydroabietic acid as the lead compound for structural modification, 25 dehydroabietic acid derivatives were synthesized. Among them, compound D1 not only showed the strongest relaxation effect on the aortic vascular ring in vitro (Emax = 99.5 ± 2.1%, EC 50 = 3.03 ± 0.96 µM), but also significantly reduced systolic and diastolic blood pressure in rats at a dose of 2.0 mg/kg in vivo. Next, the vascular protective effect of the best active D1 and its molecular mechanism were further investigated by HUVECs. The results showed that D1 induced endothelium-dependent diastole in the rat thoracic aorta in a concentration-dependent manner. Endothelium removal or aortic ring pretreatment with NG-nitro- l -arginine methylester (l -NAME), 1 H -[1,2,4]-oxadiazolo-[4,3-a]-quinoxalin-1-one (ODQ), and tetraethylammonium (TEA) significantly inhibited D1 -induced relaxation. In addition, wortmannin, KT5823, triciribine, diltiazem, BaCl 2 , 4-aminopyridine, indomethacin, propranolol, and atropine attenuated D1 -induced vasorelaxation. D1 increased the phosphorylation of eNOS in HUVECs Furthermore, D1 attenuated the expression of TNF-α-induced cell adhesion molecules such as ICAM-1 and VCAM-1. However, this effect was attenuated by the eNOS inhibitors l -NAME and asymmetric dimethylarginine (ADMA). The findings suggest that D1 -induced vasorelaxation through the PI3K/Akt/eNOS/NO/cGMP/PKG pathway by activating the K Ca , K ir and K V channels or muscarinic and β-adrenergic receptors, and inhibiting the l -type Ca2+ channels, which is closely related to the hypotensive action of the agent. Furthermore, D1 exhibits an inhibitory effect on vascular inflammation, which is associated with the observed vascular protective effects. [ABSTRACT FROM AUTHOR]

[Display omitted] • MgIG mitigated LPS-induced liver damage by inhibiting apoptosis and inflammation. • MgIG increased the expression of IL-22 in LPS-induced mice. • MgIG inhibited TLR4/NF-κB pathways and induced autophagy in LPS-treated mice. • MgIG has hepatoprotective effects partially by IL-22-activated autophagy. Liver disease has become a major cause of premature mortality worldwide. It is well known that dysregulated inflammation response plays a crucial role in most liver diseases. As a Chinese medicinal herb, Magnesium isoglycyrrhizinate (MgIG) has been proven to have good hepatoprotective activity and has been used in clinic to treat liver disease. However, the mechanisms by which MgIG regulates LPS-induced liver injury and inflammation in vivo remain elusive. In our study, MgIG pretreatment mitigated LPS-induced liver damage by suppressing apoptosis and inflammation via regulating macrophage/neutrophil infiltration. MgIG ameliorated the effects of LPS on pro-oxidant enzymes (NOX1/2/4) and anti-oxidant enzymes (SOD1/2). Interestingly, we found that the level of the hepatoprotective cytokine interleukin (IL)–22 was significantly upregulated in MgIG-treated liver tissues, which might be a potential mechanism of MgIG against liver injury. Moreover, we found that MgIG treatment not only inhibited TLR4/MyD88/NF-κB signaling pathway, but also activated autophagy. Furthermore, IL-22 treatment activated autophagy and inhibited TLR4/NF-κB signaling pathway in vitro , suggesting that IL-22-activated autophagy and -inhibited inflammation also participated in the protective effects of MgIG. Altogether, our results uncovered the potential mechanisms of the hepatoprotective effects of MgIG, which provided critical evidence to support the use of MgIG to prevent and treat liver diseases. [ABSTRACT FROM AUTHOR]

Although oral probiotics can improve breast microecology and alleviate the inflammatory response, there are no data regarding cases with existing abscesses. We aimed to investigate the effect of Lactobacillus fermentum CECT5716 during needle aspiration in patients with lactational breast abscesses. Patients (aged 20–41 years) with lactational single-cavity breast abscesses (diameter 3–6 cm) from 12 hospitals were randomly assigned to the experimental (n = 51) and control groups (n = 50). Outcome measures included the abscess cure rate on treatment day-5, delactation rate, relieving pain rate, and number of needle aspirations until day-28. The experimental group's 5-day cure rate (43.1%) was significantly higher (p < 0.05). Breastfeeding continuation on day-5 did not differ significantly (experimental group: 88.2%, control group: 96.0%, p = 0.269). In the experimental and control groups, 19.6% and 14.0% of patients experienced moderate to severe pain on day-5, respectively, with no statistically significant differences (p = 0.451). Four patients in each group developed diarrhea, with adverse reaction rates of 7.84% and 8.0%, respectively. No adverse reactions were reported in the infants. L. fermentum can shorten the healing time in patients with lactational breast abscesses. Trial registration This study was registered in the Chinese Clinical Trial Registry (http://www.chictr.org.cn), registration number: ChiCTR2000032682, registration date: 6/May/ 2020; first entry date: 11/May/2020. [ABSTRACT FROM AUTHOR]

In human immunity, the spleen is a major organ, being central to humoral and cellular immunity. In vitro and in vivo, inflammation is regulated by ubiquitin-specific protease 8 (USP8); however, to the best of our knowledge, the effect of USP8 on spleen injury remains unknown. The present study aimed to investigate the protection offered by USP8 against spleen injury in lipopolysaccharide (LPS)-induced mice via attenuation of inflammation. A total of 119 C57BL/6J mice were placed into the following groups: Control group, saline group, LPS group, USP8 group, USP8 + LPS group and negative control (NC) + LPS group. A USP8 lentivirus was injected into mice at 1×108 TU/ml intracerebroventricularly for 7 days before LPS was administered via intraperitoneal injection at 750 µg/kg. From each group, serum and spleen samples were collected for analysis. Histological imaging was used to examine the spleen structure. Western blotting was used to detect the expression levels of proteins associated with the mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-κB signaling pathways. Pro-inflammatory cytokines were detected using enzyme-linked immunosorbent assays. Compared with that in the saline, control and USP8 + LPS groups, the spleen volume in the LPS group was markedly increased, and the width of the splenic cord and sinus exhibited morphological damage in the LPS group. Compared with that in the saline, control and USP8 + LPS groups, the protein expression levels of USP8 in the spleen were decreased in the LPS group. Furthermore, the production of LPS-induced pro-inflammatory cytokines (e.g., interleukin-1β and tumor necrosis factor-α) was reduced in serum and spleen homogenates by USP8. Related inflammatory pathways, including the NF-κB and MAPK pathways, were downregulated in the USP8 + LPS group compared with those in the LPS group. In conclusion, the anti-inflammatory effect of USP8 on LPS-induced spleen injury may be mediated by the inhibition of MAPK and NF-κB signaling pathways. [ABSTRACT FROM AUTHOR]