IL-37 is a potent inhibitor of innate immunity by shifting the cytokine equilibrium away from excessive inflammation. Psoriasis is thought to be initiated by abnormal interactions between the cutaneous keratinocytes and systemic immune cells, triggering keratinocyte hyperproliferation. In the current study, we assessed IL-37 in two well-known psoriasis models: a human keratinocyte cell line (HaCaT) and the keratin 14 VEGF-A–transgenic mouse model. First, we used the HaCaT cell line, which was transiently transfected with an overexpressing IL-37 vector, and tested the effect of IL-37 on these cells using a mixture of five proinflammatory cytokines. IL-37 was effective in suppressing the production of CXCL8, IL-6, and S100A7, which were highly upregulated by the mixture of five proinflammatory cytokines. Keratin 14 VEGF-A–transgenic mice were treated with plasmid coding human IL-37 sequence–formulated cationic liposomes, and we observed potent immunosuppressive effects over the 18-d period. In this model, we observed reduced systemic IL-10 levels, local IFN-γ gene transcripts, as well as mild mast cell infiltration into the psoriatic lesions of the mice. Immunohistochemical analysis indicated that IL-37 was expressed by effector memory T cells, as well as macrophages, in human psoriatic plaques. In conclusion, our studies strongly indicate that IL-37 plays a potent immunosuppressive role in the pathogenesis of both experimental psoriasis models in vitro and in vivo by downregulating proinflammatory cytokines. Importantly, our findings highlight new therapeutic strategies that can be designed to use this immunosuppressive anti-inflammatory cytokine in psoriasis and other inflammatory cutaneous diseases.

Objective Illness uncertainty is a significant source of psychological distress that affects cancer patients' quality of life (QOL). Mishel's uncertainty in illness theory (UIT) proposes that illness uncertainty influences an individual's use of coping strategies, and directly and indirectly influences their QOL. This study tested the relationships depicted in the adapted UIT in cancer patients. Methods This cross‐sectional study is a secondary analysis of the baseline data from a randomized clinical trial (N = 263 prostate cancer patients). Patients were diagnosed with localized (64.6%), biochemical recurrent (12.6%), or advanced (22.8%) prostate cancer. Uncertainty, coping (avoidant and active coping strategies), and QOL (physical and mental well‐being) were measured using the Mishel's uncertainty of illness scale, Brief COPE, and the Medical Outcomes Study 12‐item short form (SF‐12), respectively. We used path analysis to achieve the research aim. Results Patients' illness uncertainty directly, negatively influenced their physical well‐being (P < .001) and mental well‐being (P < .05). Patients' illness uncertainty was positively related to their avoidant coping strategies (P < .001). Patients' active and avoidant coping strategies influenced their mental well‐being (P < .001). Uncertainty also negatively influenced mental well‐being through avoidant coping strategies. The model had excellent fit to the data. Conclusions Our findings have indicated the potential of improving QOL by decreasing illness uncertainty and reducing avoidant coping strategies. Future research is needed to better understand the complex relationships between illness uncertainty, coping strategies, and domains of QOL among patients with different types of cancer using longitudinal research.

Cancer biomarkers with a strong predictive power for diagnosis/prognosis and a potential to be therapeutic targets have not yet been fully established. Here we employed a loss-of-function screen in glioblastoma (GBM), an infiltrative brain tumor with a dismal prognosis, and identified 20 survival kinase genes (SKGs). Survival analyses using The Cancer Genome Atlas (TCGA) datasets revealed that the expression of CDCP1, CDKL5, CSNK1E, IRAK3, LATS2, PRKAA1, STK3, TBRG4, and ULK4 stratified GBM prognosis with or without temozolomide (TMZ) treatment as a covariate. For the first time, we found that GBM patients with a high level of NEK9 and PIK3CB had a greater chance of having recurrent tumors. The expression of CDCP1, IGF2R, IRAK3, LATS2, PIK3CB, ULK4, or VRK1 in primary GBM tumors was associated with recurrence-related prognosis. Notably, the level of PIK3CB in recurrent tumors was much higher than that in newly diagnosed ones. Congruent with these results, genes in the PI3K/AKT pathway showed a significantly strong correlation with recurrence rate, further highlighting the pivotal role of PIK3CB in the disease progression. Importantly, 17 SKGs together presented a novel GBM prognostic signature. SKGs identified herein are associated with recurrence rate and present prognostic significance in GBM, thereby becoming attractive therapeutic targets.

Uteroplacental insufficiency and poor postnatal nutrition impair adult glucose tolerance and insulin secretion in male rat offspring, which can be partially ameliorated by improving postnatal nutrition. Uteroplacental insufficiency was induced in the WKY rat on day 18 of pregnancy (Restricted) compared to sham-operated Controls. Pups were then cross-fostered onto Control or Restricted mothers one day after birth resulting in: (Pup-on-Mother) Control-on-Control, Control-on-Restricted, Restricted-on-Control and Restricted-on-Restricted. Endocrine pancreatic morphology and markers of intrinsic β-cell function and glucose homeostasis were assessed in male offspring at 6 months. Pancreatic and hepatic gene expression was quantified at postnatal day 7 and 6 months. Restricted pups were born 10-15% lighter than Controls and remained lighter at 6 months. Relative islet and β-cell mass were 51-65% lower in Restricted-on-Restricted compared to Controls at 6 months. Non-fasting plasma C-reactive protein levels were also increased, suggestive of an inflammatory response. Overall, the average number of islets, small islets and proportion of β-cells per islet correlated positively with birth weight. Intrinsic β-cell function, estimated by insulin secretion relative to β-cell mass, was unaffected by Restriction, suggesting that the in vivo functional deficit was attributable to reduced mass, not function. Importantly, these deficits were ameliorated when lactational nutrition was normalized in Restricted-on-Control offspring, who also showed increased pancreatic Igf1r, Pdx1 and Vegf mRNA expression at 7 days compared to Control-on-Control and Restricted-on-Restricted. This highlights lactation as a critical period for intervention following prenatal restraint, whereby deficits in endocrine pancreatic mass and associated impaired in vivo insulin secretion can be ameliorated.

The study suggests that there is a major need for further improvement of both medical care and ongoing psychosocial support for PWH in China.