The regulatory role of Pin1 in neuronal death

Regulated cell death predominantly involves apoptosis, autophagy, and regulated necrosis. It is vital that we understand how key regulatory signals can control the process of cell death. Pin1 is a cis-trans isomerase that catalyzes the isomerization of phosphorylated serine or threonine-proline motifs of a protein, thereby acting as a crucial molecular switch and regulating the protein functionality and the signaling pathways involved. However, we know very little about how Pin1-associated pathw...     

CCPG1 involved in corneal Aspergillus fumigatus infection

AIM: To investigate whether non-canonical autophagy transport receptor cell cycle progression 1 (CCPG1) is involved in the corneal antifungal immune response. METHODS: Human corneal epithelial cells (HCECs) and human myeloid leukemia mononuclear cells (THP-1) macrophages stimulated by Aspergillus fumigatus (A. fumigatus) were used as cell models. The expression of CCPG1 mRNA was detected by qRT-PCR. Western blot was used to determine the protein expression of CCPG1 and interleukin-1β (IL-1β). The dectin-1 neutralizing antibody was used to detect the association between dectin-1 and CCPG1. Immunofluorescence was used to observe the colocalization of CCPG1 and C-type lectin-like receptor-1 (CLEC-1) in THP-1 macrophages. RESULTS: The expression of CCPG1 started to increase at 4h after infection and increased in a time-dependent manner in HCECs and THP-1 macrophages. With dectin-1 neutralizing antibody pretreatment, the expression of IL-1β was down-regulated. CCPG1 up-regulation in response to A. fumigatus infection was independent of dectin-1. Immunofluorescence showed the colocalization of CCPG1 and CLEC-1 in THP-1 macrophages. CONCLUSION: As a specific autophagy protein of non-canonical autophagy pathway, CCPG1 is involved in corneal infection with A. fumigatus.     

Maraviroc promotes recovery from traumatic brain injury in mice by suppression of neuroinflammation and activation of neurotoxic reactive astrocytes

Neuroinflammation and the NACHT, LRR, and PYD domains-containing protein 3 inflammasome play crucial roles in secondary tissue damage following an initial insult in patients with traumatic brain injury(TBI). Maraviroc, a C-C chemokine receptor type 5 antagonist, has been viewed as a new therapeutic strategy for many neuroinflammatory diseases. We studied the effect of maraviroc on TBI-induced neuroinflammation. A moderate-TBI mouse model was subjected to a controlled cortical impact device. Mara...     

Knockout of Sirt2 alleviates traumatic brain injury in mice

Sirtuin 2(SIRT2) inhibition or Sirt2 knocko ut in animal models protects against the development of neurodegenerative diseases and cerebral ischemia.However,the role of SIRT2 in traumatic brain injury(TBI) remains unclear.In this study,we found that knockout of Sirt2 in a mouse model of TBI reduced brain edema,attenuated dis ruption of the blood-brain barrie r,decreased expression of the nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)inflammasome,reduced the activity of ...     

Simultaneous Determination of Six Compounds in Rat Plasma by Ultra‑Performance Liquid Chromatography with Tandem Mass Spectrometry: Application in the Pharmacokinetic Study of Qing Gan‑Shu Yu‑Fang

A rapid and high selective ultra?performance liquid chromatography (UPLC) with tandem mass spectrometry method for simultaneous determination of six compounds including albiflorin, paeoniflorin, picroside I, picroside II, saikosaponin A, and saikosaponin D in rat plasma was developed and validated using butyl p-hydroxybenzoate as an internal standard. One-step direct protein precipitation with acetonitrile was used to extract the compounds from the rat plasma samples. Chromatographic separation was achieved using an ACQUITY UPLC BEH C18 column (100 mm × 2.1 mm, 1.7 µm) at a flow rate of 0.4 mL/min, using gradient mode containing 0.1% formic acid in water and acetonitrile were used as the Mobile phase A and B. Electrospray ionization in negative ion mode and multiple reaction monitoring were used to identify and quantify active components. Calibration curves showed good linearity (R2 > 0.9908) over a wide concentration range for all compounds. The intra- and interday precision (relative standard deviation) ranged 2.4%–7.0% and 2.6%–8.0%, respectively. The accuracy (relative error) was from ?13.0% to 13.2% at all quality control levels. The recovery ranged from 81.1% to 92.5%. The validated method was successfully applied to pharmacokinetic study in rats after oral administration of Qing Gan?Shu Yu?Fang. The results show that one can draw a conclusion that these six active ingredients can be quickly absorbed and play a pharmacodynamic role rapidly in vivo.     

Rebalancing of the gut flora and microbial metabolism is responsible for the anti-arthritis effect of kaempferol

Kaempferol is a natural flavonol that possesses various pharmacological activities,including anti-arthritis effects,yet the underlying mechanisms remain controversial.To evaluate the anti-arthritis efficacy and the underlying mechanisms of kaempferol,collagen-induced arthritis(CIA)mice were treated with kaempferol intragastrically(200 mg·kg^−1·d^−1)and intraperitoneally(20 mg·kg^−1·d^−1).Pharmacodynamic and pharmacokinetic studies showed that the oral administration of kaempferol produced distinct anti-arthritis effects in model mice with arthritis in terms of the spleen index,arthritis index,paw thickness,and inflammatory factors;the bioavailability(1.5%,relative to that of the intraperitoneal injection)and circulatory exposure of kaempferol(Cmax=0.23±0.06 ng/mL)and its primary metabolite kaempferol-3-O-glucuronide(Cmax=233.29±89.64 ng/mL)were rather low.In contrast,the intraperitoneal injection of kaempferol caused marginal anti-arthritis effects,although it achieved a much higher in vivo exposure.The much higher kaempferol content in the gut implicated a potential mechanism involved in the gut.Analysis of 16S ribosomal RNA revealed that CIA caused imbalance of 14 types of bacteria at the family level,whereas kaempferol largely rebalanced the intestinal microbiota in CIA mice.A metabolomics study showed that kaempferol treatment significantly reversed the perturbation of metabolites involved in energy production and the tryptophan,fatty acid and secondary bile acid metabolisms in the gut contents of the CIA mice.In conclusion,we demonstrate for the first time that the high level of kaempferol in the gut regulates the intestinal flora and microbiotic metabolism,which are potentially responsible for the anti-arthritis activities of kaempferol.     

The potential application of the traditional Chinese herb Exocarpium Citri grandis in the prevention and treatment of COVID-19

Huajuhong(Exocarpium Citri grandis,ECG)is a traditional Chinese herbal medicine and has been used for the treatment of respiratory diseases for hundreds of years.Recently,ECG has been listed in a traditional Chinese medicine formula in the Guidelines for the Diagnosis and Treatment of Coronavirus Disease 2019(sixth edition)in China.To date,the effect and mechanism of ECG against respiratory diseases have not been systematically reviewed.In this paper,the researchers summarized the effects of ECG and its pharmacologically active compound naringin in functioning as an antitussive and expectorant,improving lung function,alleviating acute lung injury,attenuating pulmonary fibrosis,and enhancing antiviral immune response,so as to provide a reference for its clinical application in the prevention and treatment of multiple respiratory diseases,including coronavirus disease 2019.     

Antiviral Properties of Traditional Chinese Medicine against Coronavirus: Research Clues for Coronavirus Disease-2019

The objective of this study was to provide research clues for the prevention and treatment of coronavirus disease?2019 (COVID?19) and coronavirus (CoV) infection using Traditional Chinese Medicine (TCM). A review on research and clinical trials that using TCM extracts and active ingredients against CoV was performed, and a table of TCM agents and their effects on CoV were summarized. Relevant analysis was performed and visual expression of the data included summarizing the types of TCM and treatment methods for COVID?19. TCM fighting against CoV is mainly used in the lung and heart channels, and its medicinal properties are mainly cold and mild, while its taste is mainly bitter and sweet. The majority of research focused on treatments that clear away heat and toxic materials and those that strengthen body resistance and tonify deficiencies. TCM has unique advantages to fight against CoV. The development of new anti?CoV therapy using TCM is of great significance for the prevention and treatment of COVID?19 pneumonia and various viral infectious diseases.