Neratinib inhibits proliferation and promotes apoptosis of acute myeloid leukemia cells by activating autophagy-dependent ferroptosis.

Acute myeloid leukemia (AML) is a hematologic malignancy with increased lethality. We focused on elucidating the role of Neratinib, a tyrosine kinase inhibitor, in the progression of AML and identify the potential mechanisms. Upon the treatment of Neratinib, autophagy suppressor 3-methyladenine (3-MA) and ferroptosis stimulator Erastin, the viability and proliferation of HL-60 cells were evaluated by cell counting kit-8 and 5-Ethynyl-20-Deoxyuridine staining assays. A flow cytometer was to observe cell cycle and apoptosis. Production of reactive oxygen species (ROS) was tested via 2,7-dichlorodihydrofluorescein diacetate  assay. Additionally, malondialdehyde (MDA) content and Fe2+ activity were examined with commercial kits. LC3-II expression was examined by using immunofluoresence staining. Western blot analysis ascertained the expression of proliferation, apoptosis, ferroptosis and autophagy-associated proteins. It was noted that Neratinib notably mitigated cell viability and proliferation, cut down Ki67 and proliferating cell nuclear antigen expression. Moreover, Neratinib hindered cell cycle at G0/G1 phase whereas exacerbated apoptosis. ROS, MDA and Fe2+ activities were elevated by Neratinib, coupled with the reduced glutathione peroxidase 4, ferritin heavy chain 1 expression and enhanced acyl-CoA synthetase long-chain family member 4 expression. Furthermore, Neratinib promoted autophagy of HL-60 cells, evidenced by raised LC3-II, ATG5, Beclin1 expression and lessened p62 expression. Importantly, 3-MA eased the impacts of Neratinib on cell ferroptosis, proliferation and apoptosis, which were offset by further administration of Erastin. To conclude, Neratinib could suppress proliferation and promote apoptosis of HL-60 cells through autophagy-dependent ferroptosis.

Sporosarcina beigongshangi sp. nov., isolated from pit mud of Baijiu.

A Gram-positive, aerobic and short rod-shaped bacterium designated REN13T, was isolated from pit mud of Baijiu, in Sichuan province, China. Strain REN13T could grow at 10-50 â„ƒ, pH 6.0-9.0 and 0-2% (w/v) NaCl, with the optimal growth occurred at 28 â„ƒ, pH 7.0, and 2% (w/v) NaCl. 16S rRNA gene sequence analysis showed that strain REN13T was closely related to Sporosarcina globispora DSM 4T (98.6%). The DNA G + C content of strain REN13T was 41.1 mol %. DDH and ANI value between strain REN13T and S. globispora DSM 4T was 24.4% and 67.6%, respectively. The major fatty acids were iso-C15:0 and antesio-C15:0. The respiratory quinone was MK-7, and the polar lipids were phosphatidylethanolamine, phospholipids, phosphatidylglycerol and diphosphatidylglycerol. Based on the above polyphasic taxonomic analysis, strain REN13T represents a novel species of the genus Sporosarcina, for which the name Sporosarcina beigongshangi sp. nov. is proposed. The type strain is strain REN13T (= JCM 34409T = GDMCC 1.2151T).

Pseudoxanthomonas beigongshangi sp. nov., a novel bacteria with predicted nitrite and nitrate reduce ability isolated from pit mud of Baijiu.

A Gram-negative and rod-shape bacterium designated REN9T, was isolated from pit mud of Baijiu in Sichuan, China. The 16S rRNA sequence of strain REN9T had a high similarity to Pseudoxanthomonas indica P15T (99.21%), P. mexicana AMX 26BT (97.74%) and P. japonensis 12-3T (97.43%). Phylogenetic analysis showed that REN9T belongs to the genus Pseudoxanthomonas and formed distinct cluster. The ANI and DDH values between strains REN9T and P15T were 80.94% and 24%, respectively. Strain REN9T grew optimally at 37 °C, pH 7.0 and 2% NaCl. PE (phosphatidylethanolamine), PG (phosphatidylglycerol) and DPG (diphosphatidylglycerol) were the major polar lipids of REN9T. Ubiquinone 8 (Q-8) was the predominant quinone, and Iso-C15:0 (64.32%), anteiso-C15:0 (12.04%) and Iso-C14:0 (4.56%) were the majority fatty acids. The DNA G + C content of strain REN9T was 67.3 mol%. Genomic analysis showed that strain REN9T had two secondary metabolite biosynthesis gene clusters. Moreover, strain REN9T had 43 glycoside hydrolases, 41 glycosyl transferases and 41 carbohydrate esterases. Based on the polyphasic taxonomic analysis, strain REN9T is recommended as a novel species within the genus Pseudoxanthomonas, for which the name Pseudoxanthomonas beigongshangi is proposed. The type stain is REN9T (= JCM 33961T = GDMCC 1.2210T).

Umezawaea beigongshangensis sp. nov., Isolated From the Mash of Baijiu.

A Gram-positive, aerobic and non-motile actinobacterial strain, designated REN6T, was isolated from the mash of Baijiu (Chinese spirits, a kind of distilling liquor is made by cooking, saccharification, fermentation and distillation) collected from Sichuan Province Region, China, and characterized using a polyphasic approach. Morphological and chemotaxonomic properties of strain REN6T were consistent with the description of the genus Umezawaea, such as the spore arrangement, the abundant aerial mycelium and the fragmented substrate mycelium. The diamino acid of peptidoglycan is meso-diaminopimelic acid. The diagnostic phospholipids were DPG (diphosphatidylglycerol), PG (phosphatidylglycerol), PI (phosphatidylinositol), PE (phosphatidylethanolamine). The major fatty acids were C16:0, C17:0, Iso-C16:0, Iso-C16:1 H, C17:1ω6c and C17:1 ω8c. Menaquinone-9 (MK-9) (H4) was the predominant menaquinones. The genomic DNA G + C contents were 72.7 mol%. Phylogenetic analysis based on 16S rDNA gene sequences demonstrated that strain REN6T should also be classified in the genus Umezawaea, with U. tangerina (98.7%) and U. endophytica (98.7%). However, it can be distinguished from the closest strains U. tangerina JCM 10302T based on the low levels of DNA-DNA hybridization 22.1%. Based upon the morphological, physiological, chemotaxonomic and molecular characteristics differences from other members of the genus, a novel species, Umezawaea beigongshangensis sp. nov., is proposed, with REN6T (= JCM 33954T = CGMCC 19205T) as the type strain.

Lncrna ANGPTL1-3 and its target microRNA-30a exhibit potency as biomarkers for bortezomib response and prognosis in multiple myeloma patients.

OBJECTIVE: Long non-coding RNA ANGPTL1-3 (lnc-ANGPTL1-3) is previously observed to induce bortezomib resistance via targeting microRNA-30a (miR-30a) in multiple myeloma (MM). Hence, this study aimed to further explore the relationship between lnc-ANGPTL1-3 and miR-30a and their linkage with disease properties and prognosis in bortezomib-treated MM patients. METHODS: Fifty-nine MM patients underwent treatment with the bortezomib-based regimen, and 30 healthy donors were consecutively enrolled. Bone marrow samples were collected from MM patients (before therapy) and healthy donors; then, plasma cells were separated for lnc-ANGPTL1-3 and miR-30a detection by RT-qPCR. Then treatment response, progression-free survival (PFS), and overall survival (OS) of MM patients were assessed. RESULTS: Lnc-ANGPTL1-3 was upregulated while miR-30a was downregulated in MM patients compared to healthy donors (both P < 0.001), then a negative correlation between lnc-ANGPTL1-3 and miR-30a was found in MM patients (P < 0.001) instead of in health donors (P = 0.188). In MM patients, lnc-ANGPTL1-3 correlated with increased t (4;14) (P = 0.033), Del (17p) (P = 0.018), ISS stage (P = 0.020), R-ISS stage (P = 0.025) but not t (14;16) (P = 0.255) or Durie-Salmon stage (P = 0.186); while miR-30a only related to decreased t (14;16) (P = 0.025) and R-ISS stage (P = 0.006). Besides, lnc-ANGPTL1-3 predicted lower complete response (CR) (P = 0.034), poor PFS (P = 0.016) and OS (P = 0.041) but not objective response rate (ORR) (P = 0.128). However, miR-30a forecasted higher CR (P = 0.013), prolonged PFS (P = 0.014), and OS (P = 0.045) but not ORR (P = 0.407). CONCLUSION: Lnc-ANGPTL1-3 negative correlates with miR-30a, which links with key cytogenetic features, ISS/R-ISS stage, and prognosis in MM patients who underwent treatment of bortezomib-based regimen.

CD45 correlates with adverse risk stratification, decreased treatment response and unfavorable survival profiles in elderly acute myeloid leukemia patients.

OBJECTIVE: This study aimed to explore the correlation of CD45 expression with clinicopathological features and treatment outcomes in elderly acute myeloid leukemia (AML) patients. METHODS: One hundred and twenty one elderly patients with de novo AML were consecutively recruited in this prospective cohort study, bone marrow samples from all patients were collected and CD45 expression were measured with flow cytometry. Complete remission (CR), event-free survival (EFS) and overall survival (OS) were evaluated. The median follow-up duration was 15.0 (range 2.0-36.0) months. RESULTS: CD45 high expression (CD45high) was associated with higher risk stratification in elderly AML patients (P= 0.021). The percentage of CD45high cases in CR patients was 16.4%, which was lower compared to non-CR patients (35.2%, P= 0.017), while no difference in percentage of CD45high cases was found between allogeneic hematopoietic stem cell transplantation (allo-HSCT) patients and non-allo-HSCT patients (16.7% vs. 25.7%, P= 0.492). As to survival profiles, median EFS in CD45high patients was 6.0 (95% CI: 2.9-9.1) months, which was shorter than that in CD45 low expression (CD45low) patients (10.0 (95% CI: 7.2-12.8) months) (P= 0.002), and OS in CD45high patients was 16.0 (95% CI: 13.4-18.6) months, which was worse compared to CD45low patients (22.0 (95% CI: 17.0-27.0) months) (P= 0.010). In subgroup analysis, no difference of EFS and OS was found between CD45high patients and CD45low patients in favorable, intermediate or adverse risk subgroups. CONCLUSIONS: CD45 correlates with adverse risk stratification, decreased treatment response and unfavorable survival profiles in elderly AML patients.