Preliminary verification of the anti-hypoxia mechanism of Gentiana straminea maxim based on UPLC-triple TOF MS/MS and network pharmacology.

BACKGROUND: Anoxia is characterized by changes in the morphology, metabolism, and function of tissues and organs due to insufficient oxygen supply or oxygen dysfunction. Gentiana straminea Maxim (G.s Maxim) is a traditional Tibetan medicine. Our previous work found that G.s Maxim mediates resistance to hypoxia, and we found that the ethyl acetate extract had the best effect. Nevertheless, the primary anti-hypoxia components and mechanisms of action remain unclear. METHODS: Compounds from the ethyl acetate extraction of G.s Maxim were identified using UPLC-Triple TOF MS/MS. Then Traditional Chinese Medicine Systematic Pharmacology Database was used to filtrate them. Network pharmacology was used to forecast the mechanisms of these compounds. Male specific pathogen-free Sprague Dawley rats were randomly divided into six groups: (1) Control; (2) Model; (3) 228 mg/kg body weight Rhodiola capsules; (4) 6.66 g/kg body weight the G.s Maxim's ethyl acetate extraction; (5) 3.33 g/kg body weight the G.s Maxim's ethyl acetate extraction; (6) 1.67 g/kg body weight the G.s Maxim's ethyl acetate extraction. After administering intragastric ally for 15 consecutive days, an anoxia model was established using a hypobaric oxygen chamber (7000 m, 24 h). Then Histology, enzyme-linked immunosorbent assays, and western blots were performed to determine these compounds' anti-hypoxic effects and mechanisms. Finally, we performed a molecular docking test to test these compounds using Auto Dock. RESULTS: Eight drug-like compounds in G.s Maxim were confirmed using UPLC-Triple TOF MS/MS and Lipinski's rule. The tumor necrosis factor (TNF) signaling pathway, the hypoxia-inducible factor 1 (HIF-1) signaling pathway, and the nuclear factor kappa-B (NF-κB) signaling pathway was signaling pathways that G.s Maxim mediated anti-anoxia effects. The critical targets were TNF, Jun proto-oncogene (JUN), tumor protein p53 (TP53), and threonine kinase 1 (AKT1). Animal experiments showed that the ethyl acetate extraction of G.s Maxim ameliorated the hypoxia-induced damage of hippocampal nerve cells in the CA1 region and reversed elevated serum expression of TNF-α, IL-6, and NF-κ B in hypoxic rats. The compound also reduced the expression of HIF-1α and p65 and increased the Bcl-2/Bax ratio in brain tissue. These findings suggest that G.s Maxim significantly protects against brain tissue damage in hypoxic rats by suppressing hypoxia-induced apoptosis and inflammation. Ccorosolic acid, oleanolic acid, and ursolic acid had a strong affinity with core targets. CONCLUSIONS: The ethyl acetate extraction of G.s Maxim mediates anti-hypoxic effects, possibly related to inhibiting apoptosis and inflammatory responses through the HIF-1/NF-κB pathway. The primary active components might be corosolic, oleanolic, and ursolic acids.

Metabolomic and transcriptomic profiling of three types of litchi pericarps reveals that changes in the hormone balance constitute the molecular basis of the fruit cracking susceptibility of Litchi chinensis cv. Baitangying.

Many Litchi chinensis cv. Baitangying orchards are suffering from a serious fruit cracking problem, but few studies have improved our understanding of the mechanism or the molecular basis of cracking susceptibility in 'Baitangying'. We conducted metabolome and transcriptome analyses of three types of litchi pericarps. To prevent passive progression after fruit cracking from affecting the results, we mainly focused on 11 metabolites and 101 genes that showed the same regulatory status and overlap in pairwise comparisons of cracking 'Baitangying' versus noncracking 'Baitangying' and noncracking 'Baitangying' versus noncracking 'Feizixiao'. Compared with the cracking-resistant cultivar 'Feizixiao', the 'Baitangying' pericarp has higher abscisic acid contents, and the presence of relevant metabolites and genes suggests increased biosynthesis of ethylene and jasmonic acid and decreased auxin and brassinosteroid biosynthesis. The fruit cracking-susceptible trait in 'Baitangying' might be associated with differences in the balance of these five types of hormones between the pericarp of this cultivar and that of 'Feizixiao'. Additionally, combined analyses showed a correspondence between the metabolite profiles and transcript patterns. qRT-PCR validation indicated the reliability of our high-throughput results. The acquired information might help in further studying the mechanisms that mediate fruit cracking susceptibility in 'Baitangying' and other litchi cultivars.

Blastic plasmacytoid dendritic cell neoplasm: A case report.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN), formerly known as agranular cluster of differentiation (CD)4+/CD56+ hematodermic neoplasm, is a rare and aggressive type of lymphoma, with only ~100 cases reported worldwide. BPDCN is a hematological malignancy derived from precursors of plasmacytoid dendritic cells and is clinically characterized by cutaneous manifestations involving the lymph nodes and peripheral blood, a leukemia-like dissemination and a poor prognosis. The present study reports the case of a 54-year-old male who presented with symptoms characteristic of BPDCN. Pathological and immunohistochemical analysis of abdominal skin lesion biopsies were used to determine a diagnosis of stage IIIE BPDCN. Although cyclophosphamide, doxorubicin, vincristine and prednisolone chemotherapy was administered, the patient succumbed to BPDCN nine days after the discontinuation of chemotherapy. Thus, the period from BPDCN presentation to mortality was ≤3 months. The case reported in the present study was characterized by rapid development and poor prognosis, and displayed additional features of BPDCN, including systemic dissemination and a short survival period.

[Efficacy of clonidine transdermal patch for treatment of Tourette's syndrome in children].

OBJECTIVE: Children with Tourette's syndrome (TS) have a poor treatment compliance due to side effects and inconvenient administration of oral drugs. This study explored the efficacy and safety of clonidine transdermal patch for treating TS in children. METHODS: A total of 119 children with TS were randomly treated with the clonidine transdermal patch (n=65) or with oral haloperidol (n=54). The therapeutic efficacy was assessed based on the results of the Yale Global Tic Severity Scale (YGTSS) 4 weeks after treatment. RESULTS: The clonidine transdermal patch group showed a higher reduction in the overall tic symptom scores (61.5+/-7.5%) than that in the haloperidol group (41.0+/-6.3%; p<0.05). Clonidine transdermal patch treatment was effective in 53 patients (81.5%) and 36 patients (67.5%) showed effective to oral haloperidol (p>0.05). Mild side effects (decrease of blood pressure and dizziness) were observed in 1 patient in the clonidine transdermal patch group. Mild hypermyotonia, drowsiness or lassitude as side effects occurred in 6 patients in the haloperidol group. CONCLUSIONS: Clonidine transdermal patch is effective for the treatment of TS in children and its side effects are mild and rare.