The Zinc Transporter SLC39A10 Plays an Essential Role in Embryonic Hematopoiesis.

The role of zinc in hematopoiesis is currently unclear. Here, SLC39A10 (ZIP10) is identified as a key zinc transporter in hematopoiesis. The results show that in zebrafish, Slc39a10 is a key regulator of the response to zinc deficiency. Surprisingly, both slc39a10 mutant zebrafish and hematopoietic Slc39a10-deficient mice develop a more severe form of impaired hematopoiesis than animals lacking transferrin receptor 1, a well-characterized iron gatekeeper, indicating that zinc plays a larger role than iron in hematopoiesis, at least in early hematopoietic stem cells (HSCs). Furthermore, it is shown that loss of Slc39a10 causes zinc deficiency in fetal HSCs, which in turn leads to DNA damage, apoptosis, and G1 cell cycle arrest. Notably, zinc supplementation largely restores colony formation in HSCs derived from hematopoietic Slc39a10-deficient mice. In addition, inhibiting necroptosis partially restores hematopoiesis in mouse HSCs, providing mechanistic insights into the requirement for zinc in mediating hematopoiesis. Together, these findings indicate that SLC39A10 safeguards hematopoiesis by protecting against zinc deficiency-induced necroptosis, thus providing compelling evidence that SLC39A10 and zinc homeostasis promote the development of fetal HSCs. Moreover, these results suggest that SLC39A10 may serve as a novel therapeutic target for treating anemia and zinc deficiency-related disorders.

[Preparation and intestinal absorption of Panax notoginseng saponins chitosan nanoparticles].

In this experiment, Panax notoginseng saponins chitosan nanoparticles(PNS-NPs) were prepared by self-assembly and their appearance, particle size, encapsulation efficiency, drug loading, polydispersity index(PDI), Zeta potential, and microstructure were characterized. The prepared PNS-NPs were intact in structure, with an average particle size of(209±0.258) nm, encapsulation efficiency of 42.34%±0.28%, a drug loading of 37.63%±0.85%, and a Zeta potential of(39.8±3.122) mV. The intestinal absorption of PNS-NPs in rats was further studied. The established HPLC method of PNS was employed to investigate the effects of pH, perfusion rate, and different drugs(PNS raw materials, Xuesaitong Capsules, and PNS-NPs). The absorption rate constant(K_a) and apparent permeability coefficient(P_(app)) in the duodenum, jejunum, ileum, and colon were calculated and analyzed. As illustrated by the results, the intestinal absorption of PNS-NPs was increased in the perfusion solution at pH 6.8(P<0.05), and perfusion rate had no significant effect on the K_a and P_(app) of PNS-NPs. The intestinal absorption of PNS-NPs was significantly different from that of PNS raw materials and Xuesaitong Capsules(P<0.05), and the intestinal absorption of PNS-NPs was significantly improved.

Optimization of Fermentation Process of Pomegranate Peel and Schisandra Chinensis and the Biological Activities of Fermentation Broth: Antioxidant Activity and Protective Effect Against H2O2-induced Oxidative Damage in HaCaT Cells.

In this study, the lactobacillus fermentation process of pomegranate (Punica granatum L.) peel and Schisandra chinensis (Turcz.) Baill (PP&SC) was optimized by using the response surface method (RSM) coupled with a Box-Behnken design. The optimum fermentation condition with the maximal yield of ellagic acid (99.49 ± 0.47 mg/g) was as follows: 1:1 (w:w) ratio of pomegranate peel to Schisandra chinensis, 1% (v:v) of strains with a 1:1 (v:v) ratio of Lactobacillus Plantarum to Streptococcus Thermophilus, a 37 °C fermentation temperature, 33 h of fermentation time, 1:20 (g:mL) of a solid-liquid ratio and 3 g/100 mL of a glucose dosage. Under these conditions, the achieved fermentation broth (FB) showed stronger free radical scavenging abilities than the water extract (WE) against the ABTS+, DPPH, OH- and O2- radicals. The cytotoxicity and the protective effect of FB on the intracellular ROS level in HaCaT cells were further detected by the Cell Counting Kit-8 (CCK-8) assay. The results showed that FB had no significant cytotoxicity toward HaCaT cells when its content was no more than 8 mg/mL. The FB with a concentration of 8 mg/mL had a good protective effect against oxidative damage, which can effectively reduce the ROS level to 125.94% ± 13.46% (p < 0.001) compared with 294.49% ± 11.54% of the control group in H2O2-damaged HaCaT cells. The outstanding antioxidant ability and protective effect against H2O2-induced oxidative damage in HaCaT cells promote the potential for the FB of PP&SC as a functional raw material of cosmetics.

Tanshinone I, a new EZH2 inhibitor restricts normal and malignant hematopoiesis through upregulation of MMP9 and ABCG2.

Rationale: Tanshinone, a type of diterpenes derived from salvia miltiorrhiza, is a particularly promising herbal medicine compound for the treatment of cancers including acute myeloid leukemia (AML). However, the therapeutic function and the underlying mechanism of Tanshinone in AML are not clear, and the toxic effect of Tanshinone limits its clinical application. Methods: Our work utilizes human leukemia cell lines, zebrafish transgenics and xenograft models to study the cellular and molecular mechanisms of how Tanshinone affects normal and abnormal hematopoiesis. WISH, Sudan Black and O-Dianisidine Staining were used to determine the expression of hematopoietic genes on zebrafish embryos. RNA-seq analysis showed that differential expression genes and enrichment gene signature with Tan I treatment. The surface plasmon resonance (SPR) method was used with a BIAcore T200 (GE Healthcare) to measure the binding affinities of Tan I. In vitro methyltransferase assay was performed to verify Tan I inhibits the histone enzymatic activity of the PRC2 complex. ChIP-qPCR assay was used to determine the H3K27me3 level of EZH2 target genes. Results: We found that Tanshinone I (Tan I), one of the Tanshinones, can inhibit the proliferation of human leukemia cells in vitro and in the xenograft zebrafish model, as well as the normal and malignant definitive hematopoiesis in zebrafish. Mechanistic studies illustrate that Tan I regulates normal and malignant hematopoiesis through direct binding to EZH2, a well-known histone H3K27 methyltransferase, and inhibiting PRC2 enzymatic activity. Furthermore, we identified MMP9 and ABCG2 as two possible downstream genes of Tan I's effects on EZH2. Conclusions: Together, this study confirmed that Tan I is a novel EZH2 inhibitor and suggested MMP9 and ABCG2 as two potential therapeutic targets for myeloid malignant diseases.

STUDY OF ACAROID MITES POLLUTION IN STORED FRUIT-DERIVED CHINESE MEDICINAL MATERIALS.

OBJECTIVE: to investigate the species and breeding density of acaroid mites in stored fruit-derived Chinese medicinal materials in Anhui province. METHODS: samples of stored fruit-derived Chinese medicinal materials were collected from 30 herb stores and storehouses in 17 Anhui cities, where the breeding acaroids mites were detected. RESULTS: 20 species of acaroids mites were found in 33 samples, belonging to 15 genus, 5 families of the acaridae respectively, among which T. putrescentiae, A. farinae, C. lactis, and C. berlesei are predominant species. CONCLUSION: stored fruit-derived Chinese medicinal materials in Anhui areas suffer from serious acaroid mites pollution. Therefore, proactive measures should be taken to control acaroid mites from breeding in an effort to reduce the harm on medicinal materials.

Objetivo: investigar las especies y la densidad de reproducción de ácaros en productos medicinales chinos almacenados derivados de la fruta en la provincia de Anhui. Métodos: muestras de productos medicinales chinos almacenados derivados de la fruta fueron recogidos a partir de 30 herbolarios y almacenes en 17 ciudades de Anhui, donde se detectó la reproducción de ácaros. Resultados: se detectaron 20 especies de ácaros en 33 muestras, pertenecientes a 15 géneros, 5 familias de ácaros respectivamente, entre los cuales T. putrescentiae, A. farinae, C. lactis y C. berlesei son las especies predominantes. Conclusión: los productos medicinales chinos almacenados derivados de la fruta en la zona de Anhui sufren una grave contaminación por ácaros. Por lo tanto, se deben tomar medidas dinámicas para controlar la reproducción de ácaros en un esfuerzo por reducir los daños en los productos medicinales.

Study of acaroid mites pollution in stored fruit-derived Chinese medicinal materials / Estudio de la contaminación por ácaros en productos medicinales chinos almacenados derivados de la fruta

Objective: to investigate the species and breeding density of acaroid mites in stored fruit-derived Chinese medicinal materials in Anhui province. Methods: samples of stored fruit-derived Chinese medicinal materials were collected from 30 herb stores and storehouses in 17 Anhui cities, where the breeding acaroids mites were detected. Results: 20 species of acaroids mites were found in 33 samples, belonging to 15 genus, 5 families of the acaridae respectively, among which T. putrescentiae, A. farinae, C. lactis, and C. berlesei are predominant species. Conclusion: stored fruit-derived Chinese medicinal materials in Anhui areas suffer from serious acaroid mites pollution. Therefore, proactive measures should be taken to control acaroid mites from breeding in an effort to reduce the harm on medicinal materials (AU)

Objetivo: investigar las especies y la densidad de reproducción de ácaros en productos medicinales chinos almacenados derivados de la fruta en la provincia de Anhui. Métodos: muestras de productos medicinales chinos almacenados derivados de la fruta fueron recogidos a partir de 30 herbolarios y almacenes en 17 ciudades de Anhui, donde se detectó la reproducción de ácaros. Resultados: se detectaron 20 especies de ácaros en 33 muestras, pertenecientes a 15 géneros, 5 familias de ácaros respectivamente, entre los cuales T. putrescentiae, A. farinae, C. lactis y C. berlesei son las especies predominantes. Conclusión: los productos medicinales chinos almacenados derivados de la fruta en la zona de Anhui sufren una grave contaminación por ácaros. Por lo tanto, se deben tomar medidas dinámicas para controlar la reproducción de ácaros en un esfuerzo por reducir los daños en los productos medicinales (AU)

Synthesis of 1H-imidazo[1,2-b]-1,2,4-triazol-6-amines via multicomponent reaction.

A simple and effective method for the synthesis of bioactive imidazo[1,2,4]triazole analogues has been developed utilizing the MCR technique, which involved the reaction of aminotriazoles, isocyanides and aldehydes. The products were characterized by (1)H, (13)C NMR spectroscopy, MS and elemental analysis. Interestingly, compounds 19d, 21a, 21b and 21h displayed good cytotoxic activities at 10(-4) M concentration in the inhibition of tumor cell growth as evaluated by the MTT method.