In the superficial study, the complete response rate of 87% in the 3 days per week with occlusion group was similar to that of daily and 5 days per week dosing without occlusion in a previous 12-week study and one study of daily dosing without occlusion for 6 weeks. All treatment groups had acceptable safety profiles in both studies. Occlusion did not have a statistically significant effect on efficacy for either superficial or nodular BCC tumours.

Reprograming of metabolic pathways is critical in governing the polarization of macrophages into classical proinflammatory M1 or alternative anti-inflammatory M2 phenotypes in metabolic diseases, such as diabetes. Porphyromonas gingivalis, a keystone pathogen of periodontitis, causes an imbalance in M1/M2 activation, resulting in a hyperinflammatory environment that promotes the pathogenesis of periodontitis. However, whether P. gingivalis infection modulates metabolic pathways to alter macrophage polarization remains unclear. Bone-marrow-derived macrophages (BMDMs) were collected from 6-week-old female C57BL/6 mice and stimulated with P. gingivalis, P. gingivalis-derived LPS or IL-4. Relative gene expression and protein production were measured by quantitative real-time PCR, RNA sequencing and western blotting. Colorimetric assays were also performed to assess the amounts of α-ketoglutarate (α-KG) and succinate. P. gingivalis or P. gingivalis-derived LPS-induced inflammatory responses enhanced M1 macrophages and suppressed M2 macrophages, even in the presence of IL-4. P. gingivalis inhibited Idh1/2 and Gpt1/2 mRNA expression, and increased Akgdh mRNA expression, thus decreasing the ratio of α-KG/succinate. Supplementation of cell-permeable dimethyl-α-KG dramatically restored M2 activation during P. gingivalis infection. Our study suggests that P. gingivalis maintains a hyperinflammatory state by suppressing the production of α-KG by M2 macrophages.

Background Porphyromonas gingivalis is the main pathogen of periodontal disease affecting over half of the worldwide adult population. Recent studies have shown that P. gingivalis is related to the development of non‐alcoholic fatty liver disease (NAFLD), a global major chronic liver disease, especially in developed countries. However, how P. gingivalis contributes to the pathogenesis of NAFLD has not been fully clarified. We aimed to conduct a preliminary exploration of the underlying mechanism of P. gingivalis infection in the development of NAFLD. Methods Human hepatocellular cells HepG2 were incubated with/without oleic acid (OA) and tested for lipid accumulation upon stimulation by lipopolysaccharide (LPS) derived from P. gingivalis or Escherichia coli. Intracellular lipid droplet formation was analyzed and quantified by Oil Red O staining. The involvement of signaling pathway molecules and pro‐inflammatory cytokines related to NF‐κB and MAPKs were examined with Western blot and quantitative real‐time PCR (qRT‐PCR) analyses and further evaluated with inhibitor treatment and RNA interference. Results HepG2 cells accumulated more intracellular lipids when stimulated with P. gingivalis LPS, as compared to cells treated with E. coli LPS or control. Further pathway analysis demonstrated that after stimulation with P. gingivalis LPS, cells displayed significantly upregulated MyD88 expression, increased phosphorylation of p65 and JNK, and more release of pro‐inflammatory cytokines, such as IL‐1, IL‐8, and TNF‐α. In addition, suppression of phosphorylation of p65 and JNK by inhibitors and RNA interference resulted in a reduction in lipid accumulation upon P. gingivalis LPS treatment. Conclusions These results suggest that P. gingivalis‐derived LPS may contribute to intracellular lipid accumulation and inflammatory reaction of HepG2 cells via the activation of NF‐κB and JNK signaling pathways. This study offers a possible explanation to the functional involvement of P. gingivalis infection in the pathological progression of NAFLD. These findings may help design new treatment strategies in NAFLD.

Using data from the China Health and Nutrition Survey (CHNS), this study analyses changes in bodyweight (BMI and waist circumference) distributions between 1991 and 2011 among adults aged 20+ in China. To do so, we quantify the source and extent of temporal changes in bodyweight and then decompose the increase in obesity prevalence into two components: a rightward shift of the bodyweight distribution (mean growth) and a (re)distributional skewing.Our analysis reveals a clear rightward distributional shift combined with a leftward skewing.Although the relatively large size of this skewing in the first decade analysed reflects an increase in obesity inequality, this inequality growth subsides in the second decade.Nevertheless, over the entire 20-year period, obesity inequality increases significantly, especially among females, younger age groups, rural residents and individuals with low socioeconomic status.