Myocardial infarction (MI) is one of the leading causes of death in the world. With the improvement of clinical therapy, the mortality of acute MI has been significantly reduced. However, as for the long-term impact of MI on cardiac remodeling and cardiac function, there is no effective prevention and treatment measures. Erythropoietin (EPO), a glycoprotein cytokine essential to hematopoiesis, has anti-apoptotic and pro-angiogenetic effects. Studies have shown that EPO plays a protective role in cardiomyocytes in cardiovascular diseases, such as cardiac ischemia injury and heart failure. EPO has been demonstrated to protect ischemic myocardium and improve MI repair by promoting the activation of cardiac progenitor cells (CPCs). This study aimed to investigate whether EPO can promote MI repair by enhancing the activity of stem cell antigen 1 positive stem cells (Sca-1⁺ SCs). Darbepoetin alpha (a long-acting EPO analog, EPO_anlg) was injected into the border zone of MI in adult mice. Infarct size, cardiac remodeling and performance, cardiomyocyte apoptosis and microvessel density were measured. Lin^- Sca-1⁺ SCs were isolated from neonatal and adult mouse hearts by magnetic sorting technology, and were used to identify the colony forming ability and the effect of EPO, respectively. The results showed that, compared to MI alone, EPO_anlg reduced the infarct percentage, cardiomyocyte apoptosis ratio and left ventricular (LV) chamber dilatation, improved cardiac performance, and increased the numbers of coronary microvessels in vivo. In vitro, EPO increased the proliferation, migration and clone formation of Lin^- Sca-1⁺ SCs likely via the EPO receptor and downstream STAT-5/p38 MAPK signaling pathways. These results suggest that EPO participates in the repair process of MI by activating Sca-1⁺ SCs.
Animals ; Mice ; Ventricular Remodeling ; Erythropoietin ; Myocardial Infarction ; Heart ; Stem Cells

ObjectiveTo improve the current standard of Belladonnae Herba in the 2020 edition of Chinese Pharmacopoeia. MethodTaking hyoscyamine sulfate， atropine sulfate and scopoletin as reference substances， and ethyl acetate-methanol-concentrated ammonia（17∶4∶2）as developing solvent， thin layer chromatography （TLC） was applied in the qualitative identification of Belladonnae Herba. The moisture， total ash and ethanol-soluble extract of Belladonnae Herba were determined based on the general principles in the 2020 edition of Chinese Pharmacopoeia （volume Ⅳ）. The contents of hyoscyamine sulfate and scopolamine hydrobromide were analyzed by high performance liquid chromatography （HPLC） with mobile phase of acetonitrile-54 mmol·L^-1 phosphate buffer solution （14∶86）， flow rate of 1.0 mL·min^-1 and detection wavelength at 210 nm. ResultThe spots in the TLC were clear with good separation and specificity. Hyoscyamine sulfate and scopolamine hydrobromide showed a good linearity with peak area in the range of 0.024 7-0.789 6 g·L^-1 （r=0.999 9） and 0.003 9-0.124 0 g·L^-1 （r=0.999 9）， the average recoveries of these two ingredients were 100.29% （RSD 1.6%） and 99.04% （RSD 1.4%）， respectively. The limits for moisture， total ash in Belladonnae Herba should be less than 13.0% and the limit for the ethanol-soluble extract should be more than 10.0%. Due to the low content and wide variation of scopolamine hydrobromide， the content of hyoscyamine sulfate should not be less than 0.098%. ConclusionThe established method is simple， specific and reproducible， which can be used to improve the quality control standard of Belladonnae Herba.

The present study investigated the pharmaceutical effect and underlying mechanism of Zexie Decoction(ZXD) on nonalcoholic fatty liver disease(NAFLD) in vitro and in vivo via the LKB1/AMPK/PGC-1α pathway based on palmitic acid(PA)-induced lipid accumulation model and high-fat diet(HFD)-induced NAFLD model in mice. As revealed by the MTT assay, ZXD had no effect on HepG2 activity, but dose-dependently down-regulated alanine aminotransferase(ALT) and aspartate aminotransferase(AST) in the liver cell medium induced by PA, and decreased the plasma levels of ALT and AST, and total cholesterol(TC) and triglyceride(TG) levels in the liver. Nile red staining showed PA-induced intracellular lipid accumulation, significantly increased lipid accumulation of hepatocytes induced by PA, suggesting that the lipid accumulation model in vitro was properly induced. ZXD could effectively improve the lipid accumulation of hepatocytes induced by PA. Oil red O staining also demonstrated that ZXD improved the lipid accumulation in the liver of HFD mice. JC-1 staining for mitochondrial membrane potential indicated that ZXD effectively reversed the decrease in mitochondrial membrane potential caused by hepatocyte injury induced by PA, activated PGC-1α, and up-regulated the expression of its target genes, such as ACADS, CPT-1α, CPT-1β, UCP-1, ACSL-1, and NRF-1. In addition, as revealed by the Western blot and immunohistochemistry, ZXD up-regulated the protein expression levels of LKB1, p-AMPK, p-ACC, and PGC-1α in vivo and in vitro. In conclusion, ZXD can improve NAFLD and its mechanism may be related to the regulation of the LKB1/AMPK/PGC-1α pathway.
AMP-Activated Protein Kinases/metabolism* ; Alanine Transaminase/metabolism* ; Animals ; Diet, High-Fat ; Liver/metabolism* ; Mice ; Mice, Inbred C57BL ; Non-alcoholic Fatty Liver Disease/genetics* ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha

OBJECTIVES: To investigate the incidence of extrauterine growth retardation (EUGR) and its risk factors in very preterm infants (VPIs) during hospitalization in China. METHODS: A prospective multicenter study was performed on the medical data of 2 514 VPIs who were hospitalized in the department of neonatology in 28 hospitals from 7 areas of China between September 2019 and December 2020. According to the presence or absence of EUGR based on the evaluation of body weight at the corrected gestational age of 36 weeks or at discharge, the VPIs were classified to two groups: EUGR group (n=1 189) and non-EUGR (n=1 325). The clinical features were compared between the two groups, and the incidence of EUGR and risk factors for EUGR were examined. RESULTS: The incidence of EUGR was 47.30% (1 189/2 514) evaluated by weight. The multivariate logistic regression analysis showed that higher weight growth velocity after regaining birth weight and higher cumulative calorie intake during the first week of hospitalization were protective factors against EUGR (P<0.05), while small-for-gestational-age birth, prolonged time to the initiation of total enteral feeding, prolonged cumulative fasting time, lower breast milk intake before starting human milk fortifiers, prolonged time to the initiation of full fortified feeding, and moderate-to-severe bronchopulmonary dysplasia were risk factors for EUGR (P<0.05). CONCLUSIONS It is crucial to reduce the incidence of EUGR by achieving total enteral feeding as early as possible, strengthening breastfeeding, increasing calorie intake in the first week after birth, improving the velocity of weight gain, and preventing moderate-severe bronchopulmonary dysplasia in VPIs.
Female ; Fetal Growth Retardation ; Gestational Age ; Hospitalization ; Humans ; Incidence ; Infant ; Infant, Newborn ; Infant, Premature ; Infant, Very Low Birth Weight ; Prospective Studies ; Risk Factors

Taking lipophagy as the breakthrough point, we explored the mechanism of Zexie Decoction(ZXD) in improving lipid metabolism in the hepatocyte model induced by palmitic acid(PA) and in the animal model induced by high-fat diet(HFD) on the basis of protein kinase B(Akt)/transcription factor EB(TFEB) signaling pathway. Co-localization was carried out for the microtubule-associated protein light chain 3(LC3) plasmid labeled with green fluorescent protein(GFP) and lipid droplets(LDs), and immunofluorescence co-localization for liver LC3 of HFD mice and perilipin 2(PLIN2). The results showed that ZXD up-regulated the expression of LC3, reduced lipid accumulation in hepatocytes, and increased the co-localization of LC3 and LDs, thereby activating lipo-phagy. Western blot results confirmed that ZXD increased autophagy-related protein LC3Ⅱ/LC3Ⅰ transformation ratio and lysosome-associated membrane protein 2(LAMP2) in vivo and in vitro and promoted the degradation of sequestosome-1(SQSTM1/p62)(P<0.05). The results above jointly explained that ZXD regulated lipophagy. Furthermore, ZXD activated TFEB expression(P<0.05) and reversed the PA-and HFD-induced decrease of TFEB nuclear localization in hepatocytes(P<0.05). Meanwhile, ZXD activated liver TFEB to up-regulate the expression of the targets Lamp2, Lc3 B, Bcl2, and Atg5(P<0.05). Additionally, ZXD down-regulated the protein level of p-Akt upstream of TFEB in vivo and in vitro. In conclusion, ZXD may promote lipophagy by regulating the Akt/TFEB pathway.
Animals ; Mice ; Autophagy/drug effects* ; Hepatocytes/metabolism* ; Microtubule-Associated Proteins/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Signal Transduction ; Drugs, Chinese Herbal/pharmacology*

OBJECTIVE: To investigate the cytotoxic effect and its mechanism of the micromolecule compound on the leukemia cells. METHODS: The cytotoxic effects of 28 Nilotinib derivatives on K562, KA, KG, HA and 32D cell lines were detected by MTT assays, and the compound Nilo 22 was screen out. Cell apoptosis and cell cycle on leukemia cells were detected by flow cytometry. The effect of compound screened out on leukemogenesis potential of MLL-AF9 leukemia mice GFP RESULTS: Nilo 22 serves as the most outstanding candidate out of 28 Nilotinib derivatives, which impairs leukemia cell lines, but spares normal hematopoietic cell line. Comparing with Nilotinib, Nilo 22 could induce the apoptosis of GFP CONCLUSION Nilo 22 shows a significant cytotoxic effect on mice and human leukemia cells, especially for drug resistance cells. Nilo 22 is a promising anti-leukemia agent to solve the common clinical problems of drug resistance and relapse of leukemia.
Animals ; Apoptosis/drug effects* ; Cell Cycle/drug effects* ; Cell Line, Tumor ; Humans ; Leukemia ; Mice ; Myeloid-Lymphoid Leukemia Protein/genetics* ; Telomerase/metabolism* ; Telomere/metabolism*

Antibodies, Viral ; blood ; Betacoronavirus ; Coronavirus ; immunology ; Coronavirus Infections ; immunology ; Humans ; Immunoglobulin G ; blood ; Pandemics ; Pneumonia, Viral ; immunology

Angiotensin Receptor Antagonists ; Angiotensin-Converting Enzyme 2 ; Betacoronavirus ; COVID-19 ; Cardiovascular Agents/pharmacology* ; Cardiovascular Diseases ; Coronavirus Infections/physiopathology* ; Humans ; Pandemics ; Peptidyl-Dipeptidase A/physiology* ; Pneumonia, Viral/physiopathology* ; SARS-CoV-2

The 1-DNJ named 1-deoxynojirimycinis (2R,3R,4R,5S)-2-(hydroxymethyl) piperidine-3,4,5-triol, which is the nature active components existingin mulberryresources including leaves, stems, roots and silkworm larva, silkworm chrysalis, etc.The 1-deoxynojirimycin is a polyhydroxylated piperidine alkaloid, which was first found in Streptomyces as an antibiotic. Then the Japanese researchers isolated it from the mulberry root. 1-DNJ can inhibit postprandial hyperglycemia by suppressing intestinal alpha glucosidase. Therefore, 1-DNJ is often used to treat treating diabetes and complicating disease and to prevent obesity and weight-related disorders. With the development of the researches, 1-deoxynojirimycin and its derivtiv was discovered to possess anti-hyperglycemic, anti-virus, anti-tumor functions and so on. Therefore,based on our current studythe existing knowledge on source, technique preparation process, pharmacokinetics, bioactivties,and in silico target fishing of 1-DNJ were summarized, so that the researchers may use it to explore future perspective of research on 1-DNJ.

OBJECTIVETo investigate the effect of ADAR1 on the occurrence and development of mouse T cell acute lymphoblastic leukemia (T-ALL).

METHODSLck-Cre; ADAR1lox/lox mice were generated through interbreeding. The lineage-cells of Lck-Cre; ADAR1lox/lox mice and the control were enriched respectively by the means of MACS, and the lin- cells were transfected with retrovirus carrying MSCV-ICN1-IRES-GFP fusion gene. Then the transfection efficiency was detected by the means of FACS, and the same number of GFP+ cells were transplanted into lethally irradiated recipient mice to observe the survival of mice in 2 recipient group after transplantation.

RESULTST cell-specific knockout ADAR1 mice were generated, and Notch1-induced T-ALL mouse model was established successfully. The leukemia with T-ALL characteristics occured in the mice of control group, but did not in the ADAR1 kmockout mice after transplantation.

CONCLUSIONSADAR1 plays a key role in the incidence and development of Notch1-induced T-ALL.

Adenosine Deaminase ; genetics ; Animals ; Disease Models, Animal ; Mice ; Mice, Knockout ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ; genetics ; Receptor, Notch1 ; genetics ; T-Lymphocytes