Liposomes trigger bone marrow niche macrophage "foam" cell formation and affect hematopoiesis in mice.

Liposomes are the most widely used nanocarrier platform for the delivery of therapeutic and diagnostic agents, and a number of liposomes have been approved for use in clinical practice. After systemic administration, most liposomes are cleared by macrophages in the mononuclear phagocyte system, such as the liver and bone marrow (BM). However, the majority of studies have focused on investigating the therapeutic results of liposomal drugs, and too few studies have evaluated the potential side effects of empty nanocarriers on the functions of macrophages in the mononuclear phagocyte system. Here, we evaluate the potential effects of empty liposomes on the functions of BM niche macrophages. Following liposome administration, we observed lipid droplet (LD) accumulation in cultured primary macrophages and BM niche macrophages. We found that these LD-accumulating macrophages, similar to foam cells, exhibited increased expression of inflammatory cytokines, such as IL-1ß and IL-6. We further provided evidence that liposome deposition and degradation induced LD biogenesis on the endoplasmic reticulum membrane and subsequently disturbed endoplasmic reticulum homeostasis and activated the inositol-requiring transmembrane kinase/endoribonuclease 1α/NF-κB signaling pathway, which is responsible for the inflammatory activation of macrophages after liposome engulfment. Finally, we also showed the side effects of dysfunctional BM niche macrophages on hematopoiesis in mice, such as the promotion of myeloid-biased output and impairment of erythropoiesis. This study not only draws attention to the safety of liposomal drugs in clinical practice but also provides new directions for the design of lipid-based drug carriers in preclinical studies.

Hydrangeaxinfeniae (Hydrangeaceae), a new species from Sichuan, China.

Hydrangeaxinfeniae W.B.Ju & J.Ru, a new species of Hydrangeaceae from Sichuan Province, China, is described and illustrated. The new species belongs to Hydrangeasect.Dichroa (Lour.) Y.De Smet & Samain, with its distinctive characteristic being the nearly superior ovary. It shares morphological similarities with H.yaoshanensis (Y.C.Wu) Y.De Smet & C.Granados, but can be distinguished by its hirsute trichomes densely covered on the branchlets, leaves, peduncles and pedicels, broadly elliptic to rectangular-elliptic leaf blade with nearly rounded base, coarse teeth leaf margins, 3-4 pairs of lateral veins, corymbose cyme with few and loose branches, lanceolate bract, the calyx tube and lobes margin with sparsely hirsute trichomes, adaxially glabrous and abaxially sparsely hirsute petal, outer whorl filaments are linear, inner ones are awl-shaped, glabrous styles, and the nearly superior ovary. H.xinfeniaesp. nov. currently known from only three relatively small populations of the type locality, and its conservation status is assessed as Data Deficient (DD).

Mazusmotuoensis (Mazaceae), a new species from Xizang, China.

Mazusmotuoensis W.B.Ju, Bo Xu bis & X.F.Gao is a newly described species found in Xizang Autonomous Region, China. Morphologically, this species differs from all the other known Mazus species by having erect perennial herb form with a rhizome, presence of multicellular hairs, without basal leaves, opposite arrangement of stem leaves, and corolla lobes with erose-toothed margins. Molecular phylogenetic analysis using nuclear and cpDNA genes suggests that this new species occupies a basal position within Mazus. In conclusion, both morphological evidence and molecular phylogenetic analyses support that this species belongs to Mazus and represents an as-yet-unreported new species with distinct differences from other species within the genus.

Cytotoxicity of water-soluble mPEG-SH-coated silver nanoparticles in HL-7702 cells.

Silver nanoparticles (AgNPs) are being used widely and increasingly in various products and medical supplies due to their antibacterial activity. However, little is known about the impacts of the AgNPs. Herein, The primary purpose of this study was to investigate the cytotoxic effect of AgNPs in the human liver cell line (HL-7702). The water-soluble α-Methoxy-poly (ethylene glycol)-ω-mercapto (mPEG-SH)-coated AgNPs (40 nm) were synthesized, which showed superior stabilization and uniform dispersion in culture medium. The effect of mPEG-SH-coated silver nanoparticles on cell viability, leakage of lactate dehydrogenase (LDH), oxidative stress, mitochondrial membrane potential (MMP), and cell cycle was evaluated after the cells were treated with nanoparticles. The results showed that the coated AgNPs could be taken up by cells, decreased cell viability in dose- and time-dependent manners at dosage levels between 6.25 and 100.00 µg/mL, caused membrane damage (LDH leakage), and decreased the activities of superoxide dismutase and glutathione peroxides. The level of malondialdehyde, an end product of lipid peroxidation, was also increased in AgNPs-exposed cells. Moreover, flow cytometric analysis showed that AgNP exposure decrease MMP and cause G2/M phase arrest. Thus, our data suggest that mPEG-SH-coated AgNPs have the potential toxicity that is associated with oxidative stress, apoptosis, and DNA damage.

Hymenaspleniumtholiformis (Aspleniaceae), a new fern species from southeastern Xizang, China based on morphological and molecular evidence.

A new species of Aspleniaceae, Hymenaspleniumtholiformis sp. nov., is described from Medog County in southeastern Xizang, China. The new species is morphologically similar to H.apogamum and H.szechuanense, but the former has ascending pinnae, pinna apex obtuse to rounded, pinna-marginal teeth entire, and veins terminating just below marginal teeth. Phylogenetic analysis based on five plastid markers confirmed that this new species represents a diverging lineage in the H.excisum subclade of Hymenasplenium.

Clodronate-liposomes aggravate irradiation-induced myelosuppression by promoting myeloid differentiation.

PURPOSE: Clodronate-liposomes (Clod-Lip) is an effective candidate drug for treating chronic myelomonocytic leukemia, autoimmune hemolytic anemia and immune thrombocytopenic purpura in mice experiments. But its role in hematopoietic recovery after acute myelosuppression is still unknown. We aim to explore the function and underlining mechanisms of Clod-Lip on hematopoietic reconstitution after sublethal dose irradiation in mice. MATERIALS AND METHODS: Mice at 8-10 weeks received a total-body sublethal dose γ-irradiation (TBI) and injected with Clod-Lip or PBS-Liposomes (PBS-Lip) every 4 days after TBI. The survival rate of each group was recorded. Flow cytometry was used to analyze changes in hematopoietic stem cells and their progenies in bone marrow. ELISA and RT-qPCR were used for the analysis of hematopoietic regulatory factors. Regarding IL-1ß inhibition, 25 mg/kg diacerein or an equal volume of DMSO was intraperitoneally injected into mice every day after TBI. RESULTS: In sublethal dose-irradiated mice, Clod-Lip reduced the survival rate, the total number of bone marrow and hematopoietic stem cells, delayed peripheral blood recovery of red blood cells and platelets. However, it could increase the number of CMP, MEP and myeloid cells, which suggested that Clod-Lip could induce HSC to myeloid differentiation in vivo. We further verified that Clod-Lip may induce myeloid differentiation by bone marrow microenvironmental factor IL-1ß. CONCLUSIONS: In summary, this study suggested that Clod-Lip may aggravate inhibitor effect of hematopoietic function and promote myeloid differentiation in myelosuppression mice model.

Sorbus gongshanensis (Rosaceae), a new species from the Hengduan Mountains, China.

Sorbus gongshanensis sp. nov., a new species from the Hengduan Mountains China, is described and illustrated. It is similar to S. kurzii from China (Yunnan & Xizang), Nepal, and Sikkim in the size of the leaflets, glabrous veins, persistent (sometimes) herbaceous stipules and reddish brown villous inflorescences and red fruits, but differs in its serrate leaflet margins toothed in the distal half or often almost to their base, reddish brown villous to glabrous hypanthium and reddish brown villous infructescences, among other characteristics.