RESUMEN
Antler regeneration, a stem cell-based epimorphic process, has a potential as a valuable model for regenerative medicine. A pool of antler stem cells (ASCs) for antler development is located in the antlerogenic periosteum (AP). However, whether this ASC pool is homogenous or heterogeneous has not been fully evaluated. In this study, we produced a comprehensive transcriptome dataset at the single-cell level for the ASCs based on the 10× Genomics platform (scRNA-seq). A total of 4565 ASCs were sequenced and classified into a large cell cluster, indicating that the ASC resident in the AP are likely to be a homogeneous population. The scRNA-seq data revealed that tumor-related genes were highly expressed in these homogeneous ASCs, i.e., TIMP1, TMSB10, LGALS1, FTH1, VIM, LOC110126017, and S100A4. Results of screening for stem cell markers suggest that the ASCs may be considered as a special type of stem cell between embryonic (CD9) and adult (CD29, CD90, NPM1, and VIM) stem cells. Our results provide the first comprehensive transcriptome analysis at the single-cell level for the ASCs and identified only one major cell type resident in the AP and some key stem cell genes, which may hold the key to why antlers, the unique mammalian organ, can fully regenerate once lost.
Asunto(s)
Cuernos de Venado/citología , Células Madre/metabolismo , Transcriptoma , Animales , Diferenciación Celular , Células Cultivadas , Ciervos , Masculino , Medicina Regenerativa/métodos , Análisis de la Célula Individual , Células Madre/citologíaRESUMEN
Dendrobium officinale polysaccharide (DP) was prepared with lactic acid bacterium fermentation to overcome the large molecular weight and complex structure of traditional DP for improving its functional activity and application range in this work. The structure was analyzed, and then the functional activity was evaluated using a mouse model of alcoholic liver damage. The monosaccharide compositions were composed of four monosaccharides: arabinose (0.13%), galactose (0.50%), glucose (24.38%), and mannose (74.98%) with a molecular weight of 2.13 kDa. The connection types of glycosidic bonds in fermented D. officinale (KFDP) were â4)-ß-D-Manp(1â, â4)-ß-Glcp(1â, ß-D-Manp(1â, and ß-D-Glcp(1â. KFDP exhibited an excellent protective effect on alcoholic-induced liver damage at a dose of 80 mg/kg compared with polysaccharide separated and purified from D. officinale without fermentation (KDP), which increased the activity of GSH, GSH-Px, and GR and decreased the content of MDA, AST, T-AOC, and ALT, as well as regulated the level of IL-6, TNF-α, and IL-1ß to maintain the normal functional structure of hepatocytes and retard the apoptosis rate of hepatocytes. The results proved that fermentation degradation is beneficial to improving the biological activity of polysaccharides. The potential mechanism of KFDP in protecting alcoholic liver damage was inhibiting the expression of miRNA-150-5p and targeting to promote the expression of Pik3r1. This study provides an important basis for the development of functional foods.
Asunto(s)
Dendrobium , Fermentación , Hepatopatías Alcohólicas , Hígado , Polisacáridos , Animales , Ratones , Polisacáridos/química , Polisacáridos/farmacología , Polisacáridos/administración & dosificación , Dendrobium/química , Masculino , Hepatopatías Alcohólicas/prevención & control , Hepatopatías Alcohólicas/metabolismo , Hepatopatías Alcohólicas/tratamiento farmacológico , Humanos , Hígado/metabolismo , Hígado/efectos de los fármacos , Sustancias Protectoras/farmacología , Sustancias Protectoras/química , Sustancias Protectoras/administración & dosificación , Lactobacillales/metabolismo , Lactobacillales/genética , Extractos Vegetales/química , Extractos Vegetales/farmacología , Extractos Vegetales/administración & dosificaciónRESUMEN
By varying the substituents (R(1)) at the indolin-2-one scaffold, a series of indolin-2-one derivatives bearing 4-phenylpiperazine-1-carbothiohydrazide moiety at the C3-position were synthesized and evaluated for their antiproliferative activity against three human cancer cell lines. We further selected the 5-chloroindolin-2-one moiety for the extension to another series of compounds by varying the substituents (R(2)) at the phenyl group connected with the piperazine ring. Among all the compounds synthesized, 6d and 6l were most potent with IC50 values of 3.59 and 5.58 µM, respectively against A549 lung cancer cells, while 5f and 6l possessed IC50 values of 3.49 and 4.57 µM, respectively against HCT-116 colon cancer cells which were comparable to that of Sunitinib, an indolin-2-one derivative in cancer therapy.
Asunto(s)
Antineoplásicos/síntesis química , Hidrazinas/química , Indoles/química , Piperazinas/química , Antineoplásicos/química , Antineoplásicos/toxicidad , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Células HCT116 , Humanos , Hidrazinas/síntesis química , Piperazina , Relación Estructura-ActividadRESUMEN
In the title compound, C(23)H(34)N(4)O(4), the morpholine rings adopt chair conformations. The N atom of the indol-2-one group is linked to the N atom of one morpholine ring through a flexible ethyl group with an almost cif conformation. In the crystal, molecules are linked by C-Hâ¯O interactions into infinite chains along the c direction. The almost parallel infinite chains are further inter-connected via other sets of C-Hâ¯O inter-actions, forming a three-dimensional framework.
RESUMEN
In the title compound, C(16)H(12)ClNO(3), an arm-like 4-meth-oxy-benzene links to 5-chloro-indoline-2,3-dione through a methyl-ene group, with a dihedral angle between the mean planes of the benzene ring and the indole moiety of 88.44â (8)°. In the crystal, weak inter-molecular C-Hâ¯O and π-π stacking inter-actions [centroid-centroid distance = 3.383â (3)â Å] link the mol-ecules together to form a three-dimensional framework.
RESUMEN
In the title compound, C(16)H(12)FNO(3), the dihedral angle between the benzene ring and the plane of the indole ring system is 71.60â (6)°. In the crystal, mol-ecules stack along the b axis through π-π inter-actions between the adjacent indole-2,3-dione units with a centroid-centroid distance of 3.649â (3)â Å. Inter-molecular C-Hâ¯O=C and C-Hâ¯π inter-actions further stabilize the structure, forming a three-dimensional framework.