Pseudorabies virus UL13 primes inflammatory response through downregulating heat shock factor 1.

Pseudorabies virus is a swine alpha-herpesvirus. We demonstrated that alpha-herpesvirus infection downregulates HSF1, a master transcription factor in the heat shock response. The serine/threonine protein kinase activity of late viral protein UL13 is indispensable for HSF1 depletion and phosphorylation, and UL13 does not degrade HSF1 posttranslationally but inhibits the HSF1 mRNA level. Importantly, UL13 increased HSF1 activity even though it reduced HSF1 mRNA. Furthermore, viral replication markedly decreased in the HSF1 knockout cell line or in the presence of an HSF1-specific inhibitor. Interestingly, HSF1 knockout accelerated the activation of NF-κB and p38MAPK. The K96 loci of UL13 are important to induce high levels of IL-6, TNF-α, and IL-ß cytokines while playing a crucial role in promoting mild interstitial pneumonia, liver necrosis, and severe inflammatory cell infiltration in the footpad. Thus, UL13 steers the heat shock response to promote viral replication and the inflammatory response. IMPORTANCE: PRV is a ubiquitous pathogen that infects a variety of mammals, such as pigs, ruminants, carnivores, and rodents as well as human beings, causing enormous economic losses in the swine industry. Here, we employed PRV as a model to determine the relationship between α-herpesvirus and the inflammatory response. Overall, our findings indicated that PRV infection inhibits the level of HSF1 mRNA via the serine/threonine protein kinase activity of UL13. Additionally, we discovered that HSF1 was involved in NF-κB activation upon PRV infection. PRV UL13 orchestrates the level of HSF1 mRNA, HSF1 protein phosphorylation, and priming of the inflammatory response. Our study reveals a novel mechanism employed by UL13 serine/threonine protein kinase activity to promote the inflammatory response, providing novel clues for therapy against alpha-herpesvirus infection.

Establishment of pseudorabies virus latency and reactivation model in mice dorsal root ganglia culture.

Pseudorabies virus (PRV) belongs to the alpha herpesvirus family and is responsible for Aujeszky's disease in pigs. Similar to other alpha herpesviruses, PRV establishes a lifelong latent infection in trigeminal ganglion. These latently infected pigs serve as a reservoir for recurrent infections when reactivation is triggered, making the eradication of PRV a challenging task. However, the molecular mechanism underlying PRV latency and reactivation in neurons is still poorly understood due to limitations in the in vitro model. To establish a pseudorabies virus latency and reactivation model in primary neuron cultures, we isolated dorsal root ganglion (DRG) from newborn Kunming mice using a method named epineurium-pulling for DRG collection (EPDC) and cultured primary neurons in vitro. A dual-colour recombinant PRV BAC mRuby-VP16 was constructed and 0.5 multiplicity of infection (MOI) was found as an appropriate dose in the presence of aciclovir to establish latency. Reactivation was induced using UV-inactivated herpesviruses or a series of chemical inhibitors. Interestingly, we found that not only UV-PRV, but also UV-HSV-1 and UV-BHoV-5 were able to induce rapid PRV reactivation. The efficiency of reactivation for LY294002, forskolin, etoposide, dexamethasone, and acetylcholine was found to be dependent on their concentration. In conclusion, we developed a valuable model of PRV latency and reactivation, which provides a basis for future mechanism research.

A Case of Neuropsychiatric Systemic Lupus Erythematosus With Hair Loss as the First Diagnostic Symptom.

Neuropsychiatric systemic lupus erythematosus is a serious complication of systemic lupus erythematosus. A 33-year-old female patient had repeated hair loss for more than 3 years. A dermatologic examination showed several pieces of irregularly shaped hair loss patterns in the center of the patient's scalp. The systemic treatment included oral hydroxychloroquine, aspirin enteric-coated tablets and prednisone, and intrathecal injection of dexamethasone and methotrexate. The local treatment included intralesional injection of triamcinolone acetonide and lidocaine in the lesion area, 0.1% tacrolimus ointment for external use. After 2-month treatment, hair regrew in a non-scarring patchy alopecia region with no further hair loss.

Two new compounds from the fruits of Buddleja lindleyana with neuroprotective effect.

Two new triterpenoid glycosides, mimengosides H (1) and I (2), were isolated from the fruits of Buddleja lindleyana Fort. Their structures were determined by extensive spectroscopic methods. Neuroprotective effects of these isolates against 1-methyl-4-phenylpyridinium ion-induced neurotoxicity in PC12 cells were evaluated. Pretreatment with compound 1 had potential protective effect in a concentration range from 0.1 to 1 µmol l⁻¹.

[Analysis of muscone from serum and cerebrospinal fluid of rabbits after intragastric administration of tongqiao huoxue granules].

OBJECTIVE: To analyse the muscone from serum and cerebrospinal fluid (CSF) of rabbits after intragastric administration of Tongqiao Huoxue granules (TQHXG) and provide the partial experimental reference on laying down quality standard of preparation of formula and offer new ideas on studying the relation between pharmacodynamics and its effective component of formula. METHODS: Muscone from TQHXG was qualitative identified by the methods of thin-layer chromatography (TLC) and gas chromatography (GC). Muscone from blood and CSF of rabbits was examined by GC after intragastric administration of TQHXG. Compared with standard reference material of muscone, blank serum and blank CSF, the segmental component absorbed into CSF of rabbits was confirmed. RESULTS: Spots of TQHXG on the chromatomap showed the same colour at the corresponding locality of the standard reference material. Detected by GC, chromatographic peaks appeared at the retention time of 4.8 minute in the chromatomaps of the serum with TQHXG, the CSF with TQHXG and standard reference material of muscone, while there were no chromatographic peaks in the chromatomaps of the blank serum, the blank CSF and methanol at the same time. The ingredient corresponding the chromatographic peaks at the retention time of 4.8 minute in the chromatomaps of the serum, CSF with TQHXG should be muscone. CONCLUSION: Muscone from TQHXG could penetrate blood brain barrier and could be one index of quality standard of preparation of TQHXG.

[Chemical constituents of Carya cathayensis and their antitumor bioactivity].

OBJECTIVE: To investigate the chemical constituents of Carya cathayensis and their antitumor bioactivity. METHODS: The compounds were isolated by Sephadex LH-20 and silica gel column chromatography. Their structures were identified by physicochemical properties and spectroscopic analysis. Then their cytotoxic activity was studied. RESULTS: Five compounds were elucidated as chrysophanol (1), physcion (2), beta-sitosterol (3), pinostrobin(4), 4,8-dihydroxy-1-tetralone (5). CONCLUSION: Compounds 2 and 5 are isolated from Carya cathayensis for the first time. In the MTT antitumor experiments, the compounds 1,4 and 5 have the cytotoxic activity to KB cell.