Response to pegylated interferon in a COVID-19-positive elderly woman with primary myelofibrosis treated with ruxolitinib.

An 83-year-old female had asymptomatic SARS-CoV-2 infection while taking ruxolitinib. She remained RT-PCR positive for viral RNA for >120 days, and Pegylated interferon for 4 weeks led to viral RNA clearance. The observations support combination therapy of ruxolitinib + interferon for COVID-19.

Ferulic acid attenuates oxidative DNA damage and inflammatory responses in microglia induced by benzo(a)pyrene.

Over-activation of microglia disrupts the physiological homeostasis of the brain, and induces inflammatory response and other processes which are implicated in neurodegenerative diseases. Therefore, theoretically, suppression of neuroinflammation would slow the progression of neurodegenerative disease. In this study, we investigated the possible protective effects of Ferulic acid (FA) against benzo(a)pyrene (BaP)-induced microglial activation using BV2 cells as the model system. Exposure of BV2 cells to BaP (10 µM) significantly increased DNA damage and the production of pro-inflammatory mediators, including nitric oxide (NO), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), reactive oxygen species (ROS), malondialdehyde (MDA), and cytokines (interleukins-1ß and -6). On the other hand, when BaP-treated BV2 cells were further incubated with FA (10, 20, 40, or 80 mg/mL) for another 24 h, a significant reduction in BaP-induced DNA damage and the release of multiple pro-inflammatory and cytotoxic factors (including interleukin-1ß, interleukin-6, NO, and ROS) was observed in a dose-dependent manner. Further study revealed that the microglial NOD-like receptor (NLR) family pyrin domain-containing 3 (NLRP3) signaling pathway was involved in the protective effect of FA. Taken together, these results suggested that FA suppressed BaP-induced toxicity in microglia, and thus may exert neuroprotective effects by inhibiting microglia-mediated pro-inflammatory response.

MiR-28-5p relieves neuropathic pain by targeting Zeb1 in CCI rat models.

MicroRNAs (miRNAs) are recognized as significant regulators of neuropathic pain. Moreover, neuroinflammation can contribute a lot to the progression of neuropathic pain. MiR-28-5p has been reported to be involved in many pathological diseases. However, little is known about the function of miR-28-5p in neuropathic pain development. Our current study was designed to investigate the biological roles of miR-28-5p in neuropathic pain in a rat model established by chronic sciatic nerve injury (CCI). Here, we observed that miR-28-5p was decreased in CCI rats. MiR-28-5p overexpression was able to alleviate neuropathic pain behaviors including mechanical and thermal hyperalgesia. Meanwhile, inflammation-correlated biomarkers such as Cyclooxygenase 2 (Cox-2), interleukin-6 (IL-6), and IL-1ß were greatly promoted in CCI rats and they were inhibited by miR-28-5p upregulation. In addition, zinc finger E-box-binding homeobox 1 (Zeb1) is a kind of transcription factor that is involved in various diseases. Here, in our study, Zeb1 was predicted as a downstream target of miR-28-5p. miR-28-5p can bind with the 3'-untranslated region of Zeb1, which was validated by carrying out dual-luciferase reporter assay. Moreover, we found that Zeb1 was significantly increased in CCI rats and miR-28-5p can modulate Zeb1 expression negatively. Theoverexpression of Zeb1 can disturb neuropathic pain development, which was repressed by the increase of miR-28-5p by upregulating Cox-2, IL-6, and IL-1ß levels. By taking all of these together, it was indicated in our study that miR-28-5p can reduce neuropathic pain progression by targeting Zeb1 in vivo. Our data implied that miR-28-5p/Zeb1 axis can be a novel therapeutic target for neuropathic pain treatment.