Case report: Application of metagenomic next-generation sequencing in the diagnosis of visceral leishmaniasis and its treatment evaluation.

Visceral leishmaniasis is a vector-borne infection by the Leishmania spp., a parasite. Although the overall incidence of visceral leishmaniasis is low, the disease still occurs frequently in some high-risk areas. In our study, two patients were admitted to the hospital with an unprovoked and recurrent high fever, and the condition was not improved after antibiotics administration. Meanwhile, bone marrow aspiration smears failed to find out any pathogen. Finally, Leishmania-specific nucleic acid sequences were successfully detected in the peripheral blood of two patients through metagenomic next-generation sequencing (mNGS), which was further confirmed by bone marrow smear microscopy and antibody tests. After targeted treatment for visceral leishmaniasis in the patients, mNGS reported a decrease in the reads number of Leishmania sequence. The results indicate the feasibility of mNGS in detecting Leishmania spp. in peripheral blood samples. Its therapeutic effect evaluation may be achieved through a comparative analysis of the number of reads before and after the treatment.

Access to acridones by tandem copper(I)-catalyzed electrophilic amination/Ag(I)-mediated oxidative annulation of anthranils with arylboronic acids.

An efficient and practical approach for the synthesis of medicinally important acridones was developed from anthranils and commercially available arylboronic acids by a tandem copper(I)-catalyzed electrophilic amination/Ag(I)-mediated oxidative annulation strategy. This new and straightforward protocol displayed a broad substrate scope (25 examples) and high functional group tolerance. What's more, a possible mechanistic proposal was also presented.

Lyciyunin, a new dimer of feruloyltyramine and five bioactive tyramines from the root of Lycium yunnanense Kuang.

Lyciyunin, a new dimer of feruloyltyramine (1), together with five known tyramines (2-6), was isolated from the water-soluble fraction of an EtOH extract of the root of L. yunnanense. Based on HR-TOF-MS, NMR spectral data and quantum chemistry ECD calculations, the structure of this new compound was determined, including its absolute configuration. Compounds (1-6) were tested for their antioxidant activity using in vitro DPPH radical scavenging assay, and 1-6 showed the moderate antioxidant activities with IC50 values of 12.44 ± 0.39, 21.29 ± 0.75, 24.44 ± 1.63, 21.15 ± 0.66, 21.15 ± 0.66 and 45.15 ± 0.56 µM, respectively. Compounds (5-6) showed anti-inflammatory activity in LPS-induced RAW 264.7 macrophages with the IC50 values of 43.95 ± 6.11 and 33.50 ± 2.04 µM, respectively.

Retrospective analysis of the effectiveness and tolerability of nab-paclitaxel in Chinese elderly patients with advanced non-small-cell lung carcinoma.

BACKGROUND: Previous trials have suggested that elderly patients with non-small-cell lung cancer (NSCLC) could benefit from nanoparticle albumin-bound paclitaxel (nab-paclitaxel). Real-world data on the elderly Chinese population are lacking. This study aimed to analyze the effectiveness and tolerability of nab-paclitaxel in Chinese elderly patients (≥65 years) with advanced NSCLC. METHODS: This study included 76 patients with a primary diagnosis of IIIB-IV NSCLC from January 2010 to December 2017 at Peking University Cancer Hospital, who received nab-paclitaxel (125 or 130 mg/m2 i.v.) every three weeks. The overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and adverse events (AEs) were analyzed. RESULTS: There were 12 patients who received nab-paclitaxel as the first-line treatment (seven also received carboplatin), and 64 received nab-paclitaxel as the latter-line treatment. The overall ORR, DCR, median PFS, and median OS were 14.5%, 69.7%, 5.2 months, and 12.2 months, respectively. The Eastern Cooperative Oncology Group performance status of one and the age of 70-74 years were independently associated with longer OS, while early treatment line of nab-paclitaxel and age of 70-74 years were independently associated with longer PFS. The most common AEs were anemia, leukopenia, gastrointestinal reaction, fatigue, and peripheral neuropathy, which were all manageable. Dose adjustment or treatment discontinuation was encountered in 10 patients because of AEs. The incidence of AEs was not different among age subgroups. CONCLUSIONS: Nab-paclitaxel has a good clinical response profile in Chinese elderly patients with stage IIIB-IV NSCLC. Prospective clinical trials are needed to confirm these results. KEY POINTS: Significant findings of the study Nanoparticle albumin-bound paclitaxel (nab-paclitaxel) has a good clinical response profile in Chinese elderly (≥65 years) patients with stage IIIB-IV non-small-cell lung cancer (NSCLC), with acceptable and manageable adverse events. What this study adds Preliminary evidence shows a good clinical response from treatment with nab-paclitaxel in Chinese elderly patients with advanced NSCLC.

Sasanquasaponin ΙΙΙ from Schima crenata Korth induces autophagy through Akt/mTOR/p70S6K pathway and promotes apoptosis in human melanoma A375 cells.

BACKGROUND: Melanoma is a high fatality skin cancer which lacks effective drugs. Sasanquasaponin, an important sort of constituents in theaceae, has been demonstrated to have potent anti-tumor effect in breast cancer and hepatocellular carcinoma. As a sasanquasaponin, we speculate that Sasanquasaponin III (SQS III) isolated from Schima crenata Korth may also have anti-tumor activity. PURPOSE: This study aims to investigate whether SQS III has anti-melanoma activity and examine the underlying mechanisms of SQS III against melanoma. METHODS/STUDY DESIGNS: The anti-proliferative effect of SQS III was assessed by cells viability assay. Annexin V-FITC/PI double staining assay was utilized for detection of apoptosis. Mitochondrial membrane potential and reactive oxygen species (ROS) production were detected using JC-1 and DCFH-DA assay, respectively. Autophagy was monitored using transmission electron microscopy (TEM) and GFP-LC3 transfection fluorescence analysis. Autophagosome-lysosome fusion and lysosomal degradation were determined using a GFP-LC3 & LAMP1 co-localization assay and DQ-BSA staining. Proteins related to apoptosis and autophagy were analyzed by Western blotting. RESULTS: Our results demonstrated that the SQS III exhibited potent anti-cancer activity in A375 cells by inducing both apoptosis and autophagy. In melanoma cells treated with SQS III, caspases were activated and PARP was cleaved, proving the occurrence of apoptosis. Mechanistic studies indicated that the pro-apoptosis activity of SQS III was mediated by death receptor pathway and mitochondrial dysfunction which was induced by ROS accumulation and reversed by the ROS inhibitor N-acetyl-cysteine (NAC). In addition to triggering apoptosis, SQS III may also cause autophagy in melanoma cells. Our results demonstrated that SQS III induced up-regulated expression of GFP-LC3, autophagosome-lysosomal fusion and lysosomal degradation. Additionally, the ROS accumulation was also involved in the activation of autophagy. Meanwhile, it was also found that after SQS III treatment, the expression of LC3-II was up-regulated and the AKT/mTOR signaling pathway was inhibited. The autophagy inhibitor 3-MA converted cytotoxicity and apoptosis of SQS III in A375 cells, which indicated that autophagy promoted the SQS III-induced apoptosis. CONCLUSION: SQS III showed potent anti-cancer activity by inducing apoptosis and autophagy, which provides insights into its possible use as a therapy for melanoma.

Three new lignanamides from the root of Lycium chinense with anti-inflammatory activity.

Three new lignanamides, that is, a new lignanamide (1), and a pair of enantiomers (2a and 2b) were isolated from the EtOAc-soluble fraction of an EtOH extract of the root of Lycium chinense. The structures of these new compounds, including their absolute configuration, were established on the basis of HR-ESI-MS, NMR spectroscopic data and quantum chemical ECD calculations. Compound 2a showed significant anti-inflammatory activity in LPS-induced RAW 264.7 macrophages with the IC50 value of 10.77 ± 2.14 µM, comparing to that of positive control quercetin (17.21 ± 0.50 µM).

A New Lignanamide from the Root of Lycium yunnanense Kuang and Its Antioxidant Activity.

A new lignanamide (1), lyciumamide K, together with four known analogues (2-5), was isolated from the root of Lycium yunnanense Kuang. Based on HR-ESI-MS, NMR spectral data and quantum chemistry ECD calculations, the structure of this new compound was confirmed, including its absolute configuration. Evaluation of the antioxidant activity of compounds 1-5 in the oxygen radical absorption capacity (ORAC) assay showed that they all exhibited significant antioxidant activities. Particularly, compound 1 showed the best activity with ORAC values (U/mol) of 7.90 ± 0.52. Thus, the new lignanamide may be a good source of bioavtive and protective compounds.