Punicalagin alleviates the hyperproliferation of keratinocytes in psoriasis through inhibiting SKP2 expression.

Psoriasis is a chronic inflammatory skin disorder characterized by abnormal keratinocytes proliferation and multiple immune cells infiltration in the dermis and epidermis. Although most psoriasis-related researches have been concentrated on the interleukin-23 (IL-23)/interleukin-17 (IL-17) axis, new data suggest that keratinocytes also play a pivotal role in psoriasis. Previously, we found that punicalagin (PUN), a bioactive ellagitannin extracted from Pericarpium Granati (the pericarpium of Punica granatum L.), exerts a therapeutic effect on psoriasis. However, the underlying mechanism, especially its potential modulatory effect on keratinocytes, remains obscure. Our study aims to reveal the potential regulatory effect and its underlying cellular mechanism of PUN on the hyperproliferation of keratinocytes. We used tumor necrosis factor α (TNF-α), IL-17A and interleukin-6 (IL-6) to induce abnormal proliferation of HaCaT cells (Human Keratinocytes Cells) in vitro. Then, we evaluated the effects of PUN through MTT assay, EdU staining and cell cycle detection. Finally, we explored the underlying cellular mechanisms of PUN via RNA-sequencing, WB in vitro and in vivo. Here, we found that PUN can directly and dose-dependently decrease TNF-α, IL-17A and IL-6-induced abnormal proliferation of HaCaT cells in vitro. Mechanically, PUN suppresses the hyperproliferation of keratinocytes through repressing S-phase kinase-associated protein 2 (SKP2) expression in vitro and in vivo. Moreover, overexpression of SKP2 can partly abolish PUN-mediated inhibition of aberrantly proliferative keratinocytes. These results illustrate that PUN can reduce the severity of psoriasis through directly repressing SKP2-mediated abnormal proliferation of keratinocytes, which gives new insight into the therapeutic mechanism of PUN on psoriasis. Moreover, these findings imply that PUN might be a promising drug candidate for the treatment of psoriasis.

Post-hospitalization rehabilitation alleviates long-term immune repertoire alteration in COVID-19 convalescent patients.

The global pandemic of Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an once-in-a-lifetime public health crisis. Among hundreds of millions of people who have contracted with or are being infected with COVID-19, the question of whether COVID-19 infection may cause long-term health concern, even being completely recovered from the disease clinically, especially immune system damage, needs to be addressed. Here, we performed seven-chain adaptome immune repertoire analyses on convalescent COVID-19 patients who have been discharged from hospitals for at least 6 months. Surprisingly, we discovered lymphopenia, reduced number of unique CDR3s, and reduced diversity of the TCR/BCR immune repertoire in convalescent COVID-19 patients. In addition, the BCR repertoire appears to be activated, which is consistent with the protective antibody titres, but serological experiments reveal significantly lower IL-4 and IL-7 levels in convalescent patients compared to those in healthy controls. Finally, in comparison with convalescent patients who did not receive post-hospitalization rehabilitation, the convalescent patients who received post-hospitalization rehabilitation had attenuated immune repertoire abnormality, almost back to the level of healthy control, despite no detectable clinic demographic difference. Overall, we report the potential long-term immunological impairment for COVID-19 infection, and correction of this impairment via post-hospitalization rehabilitation may offer a new prospect for COVID-19 recovery strategy.

Punicalagin Alleviates Psoriasis by Inhibiting NF-κB-Mediated IL-1ß Transcription and Caspase-1-Regulated IL-1ß Secretion.

Psoriasis is a chronic and inflammatory skin disorder characterized by inflammation and epidermal hyperplasia. Punicalagin (PUN) is a main active ingredient of pomegranate (Punica granatum L.) peel with multiple biological activities, such as antibacterial, antioxidant and anti-tumor effects. However, the potential effect of PUN on psoriasis remains unknown. In this study, we want to investigate the pharmacological effect of PUN on psoriasis by using imiquimod (IMQ)-induced psoriatic mice model in vivo and tumor necrosis factor a (TNF-α) and interleukin-17A (IL-17A)-stimulated HaCaT cells in vitro. Our results showed that PUN can effectively alleviate the severity of psoriasis-like symptoms. Mechanistically, PUN potently suppresses the aberrant upregulation of interleukin-1ß (IL-1ß) and subsequent IL-1ß-mediated inflammatory cascade in keratinocytes by inhibiting the nuclear factor kappa B (NF-κB) activation and cleaved caspase-1 expression in vitro and in vivo. Taken together, our findings indicate that PUN can relieve psoriasis by repressing NF-κB-mediated IL-1ß transcription and caspase-1-regulated IL-1ß secretion, which provide evidence that PUN might represent a novel and promising candidate for the treatment of psoriasis.

System for Operating Electric Wheelchairs Using Only the Remaining Functions of the Thumbs of Muscular Dystrophy Patients.

For patients with muscular dystrophy, a motor dysfunction, who have difficulty operating an electric wheelchair with joysticks, a simplified one-input device is used. However, avoiding obstacles can be time-consuming. In this study, we analyzed the motor functions of the thumb of a patient with severe muscular dystrophy and identified the operations that did not cause physical fatigue. Then, we developed an operation support system to continuously operate. Finally, we conducted experiments comparing the proposed system with the conventional system and verified the effectiveness of the proposed system based on the steering accuracy of the electric wheelchair and the task completion time.