Tumor necrosis factor-α small interfering RNA alveolar epithelial cell-targeting nanoparticles reduce lung injury in C57BL/6J mice with sepsis

BackgroundThe role of tumor necrosis factor (TNF)-α small interfering (si)RNA alveolar epithelial cell (AEC)-targeting nanoparticles in lung injury is unclear.MethodsSixty C57BL/6J mice with sepsis were divided into normal, control, sham, 25 mg/kg, 50 mg/kg, and 100 mg/kg siRNA AEC-targeting nanoparticles groups (n = 10 per group). The wet:dry lung weight ratio, and hematoxylin and eosin staining, western blotting, and enzyme-linked immunosorbent assays for inflammatory factors were conducted to compare differences among groups.ResultsThe wet:dry ratio was significantly lower in control and sham groups than other groups. TNF-α siRNA AEC-targeting nanoparticles significantly reduced the number of eosinophils, with significantly lower numbers in the 50 mg/kg group than in 25 mg/kg and 100 mg/kg groups. The nanoparticles also significantly reduced the expression of TNF-α, B-cell lymphoma-2, caspase 3, interleukin (IL)-1β, and IL-6, with TNF-α expression being significantly lower in the 50 mg/kg group than in 25 mg/kg and 100 mg/kg groups.ConclusionTNF-α siRNA AEC-targeting nanoparticles appear to be effective at improving lung injury-related sepsis, and 50 mg/kg may be a preferred dose option for administration.     

活性多酚化合物LM49对RAW264.7巨噬细胞极化的影响

目的初步探讨LM49(2,4'三羟基-5,2'-二溴二苯甲酮)对脂多糖(LPS)联合干扰素γ(IFN-γ)诱导的小鼠单核巨噬细胞(RAW264.7)M1/M2极化的影响及其调控机制。方法四曱基偶氮唑蓝(MTT)法测定LM49对细胞活力的影响;流式细胞术、实时荧光定量聚合酶链反应(PCR)和Westem-blot法测定LM49(5,10,20μmol·L^-1)与LPS/INF-γ共同作用于RAW264.7细胞后,巨噬细胞亚型标志物的表达情况及对核因子(NF)-κB和JAK/STAT信号通路的影响。结果与LPS/INF-γ造模组相比,LM49显著抑制CD16/32^+细胞数及诱导型一氧化氮合酶(iNOS)、白细胞介素(IL)4和肿瘤坏死因子(TNF)-αmRNA的表达,升高CD206^+细胞数及Arg-1和IL-10 mRNA的表达,且降低巨噬细胞M1/M2的比值;Westem-blot法验证LM49可显著降低TLR4、Myd88、NF-κB和STAT1蛋白的表达量,同时抑制p-JAK2和p-STATl蛋白磷酸化水平。结论LM49通过抑制TLR4-Myd88-NF-κB和JAK2-STAT1信号通路,抑制巨噬细胞Ml型极化及促进巨噬细胞M2型极化,调节巨噬细胞M1/M2的平衡。     

Niche-Specific Reprogramming of Epigenetic Landscapes Drives Myeloid Cell Diversity in Nonalcoholic Steatohepatitis

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Prostaglandin D2 synthase modulates macrophage activity and accumulation in injured peripheral nerves

We have previously reported that prostaglandin D2 Synthase (L-PGDS) participates in peripheral nervous system (PNS) myelination during development. We now describe the role of L-PGDS in the resolution of PNS injury, similarly to other members of the prostaglandin synthase family, which are important for Wallerian degeneration (WD) and axonal regeneration. Our analyses show that L-PGDS expression is modulated after injury in both sciatic nerves and dorsal root ganglia neurons, indicating that it might play a role in the WD process. Accordingly, our data reveals that L-PGDS regulates macrophages phagocytic activity through a non-cell autonomous mechanism, allowing myelin debris clearance and favoring axonal regeneration and remyelination. In addition, L-PGDS also appear to control macrophages accumulation in injured nerves, possibly by regulating the blood–nerve barrier permeability and SOX2 expression levels in Schwann cells. Collectively, our results suggest that L-PGDS has multiple functions during nerve regeneration and remyelination. Based on the results of this study, we posit that L-PGDS acts as an anti-inflammatory agent in the late phases of WD, and cooperates in the resolution of the inflammatory response. Thus, pharmacological activation of the L-PGDS pathway might prove beneficial in resolving peripheral nerve injury.     

Do positional changes of the inferior alveolar canal after sagittal split mandibular osteotomy affect neurosensory recovery?

The purpose of this study was to assess the pre- and postoperative position and dimensions of the inferior alveolar canal (IAC) following sagittal split osteotomy (SSO) and identify any association with postoperative neurosensory deficit (NSD) at 1 year. This retrospective cohort study enrolled consecutive patients who had SSO performed to correct skeletal malocclusion. The pre- and postoperative cone beam computed tomography data were superimposed to visualize differences in IAC position and dimensions. Subjective and objective neurosensory tests were used to determine NSD in the inferior alveolar nerve distribution. A total of 20 subjects were included. The preoperative distance from the lateral cortex of the IAC to the inner aspect of the lateral cortex of the mandible was significantly greater in sides with NSD when compared to sides without NSD (P = 0.01). A significantly greater reduction in the postoperative distance measurement was seen in sides with NSD when compared to sides without NSD (P = 0.01). The magnitude of mandibular movement was significantly increased in sides with NSD (P = 0.02). The preoperative location of the IAC, as well as certain changes in the mediolateral and vertical positions as a result of SSO, are risk factors for postoperative NSD.     

Short implants (≤8 mm) compared to standard length implants (>8 mm) in conjunction with maxillary sinus floor augmentation: a systematic review and meta-analysis

The objective was to test the hypothesis of no difference in the treatment outcome after the installation of short implants (≤8 mm) in the posterior part of the maxilla compared to standard length implants (>8 mm) in conjunction with maxillary sinus floor augmentation (MSFA) using the lateral window technique, after an observation period of ≥3 years. A search of the MEDLINE, Embase, and Cochrane Library databases, in combination with a hand-search of relevant journals, was conducted. The search yielded 1102 titles. Finally, three studies that fulfilled the inclusion criteria were included. All were considered to have a low risk of bias. Meta-analyses revealed no significant differences in implant survival or peri-implant marginal bone loss between the two treatment modalities. However, the use of standard length implants in conjunction with MSFA was characterized by a tendency towards more peri-implant marginal bone loss. There was no statistically significant difference between the two treatment modalities with regard to overall patient satisfaction. Short implants seem to be a suitable alternative to standard length implants in conjunction with MSFA. However, further randomized controlled trials with larger patient samples and an observation period of more than 3 years are needed before one treatment modality might be considered superior to the other.     

Immune-pineal axis protects rat lungs exposed to polluted air

Environmental pollution in the form of particulate matter <2.5 μm (PM_2.5) is a major risk factor for diseases such as lung cancer, chronic respiratory infections, and major cardiovascular diseases. Our goal was to show that PM_2.5 eliciting a proinflammatory response activates the immune-pineal axis, reducing the pineal synthesis and increasing the extrapineal synthesis of melatonin. Herein, we report that the exposure of rats to polluted air for 6 hours reduced nocturnal plasma melatonin levels and increased lung melatonin levels. Melatonin synthesis in the lung reduced lipid peroxidation and increased PM_2.5 engulfment and cell viability by activating high-affinity melatonin receptors. Diesel exhaust particles (DEPs) promoted the synthesis of melatonin in a cultured cell line (RAW 264.7 cells) and rat alveolar macrophages via the expression of the gene encoding for AANAT through a mechanism dependent on activation of the NFκB pathway. Expression of the genes encoding AANAT, MT1, and MT2 was negatively correlated with cellular necroptosis, as disclosed by analysis of Gene Expression Omnibus (GEO) microarray data from the human alveolar macrophages of nonsmoking subjects. The enrichment score for antioxidant genes obtained from lung gene expression data (GTEx) was significantly correlated with the levels of AANAT and MT1 but not the MT2 melatonin receptor. Collectively, these data provide a systemic and mechanistic rationale for coordination of the pineal and extrapineal synthesis of melatonin by a standard damage-associated stimulus, which activates the immune-pineal axis and provides a new framework for understanding the effects of air pollution on lung diseases.