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Context: The effects of Rhodiola rosea L. (Crassulaceae) polysaccharides (RRPs) on haematopoiesis are poorly understood. Objective: To determine the effects of RRPs on haematopoiesis in mice with aplastic anaemia. Materials and methods: Aplastic anaemia was induced in Kunming mice by 60Coγ (2.0 Gy) irradiation and cyclophosphamide administration (50 mg/kg/day for 3 consecutive days; intraperitoneal injection). The in vivo effects of RRPs (10, 20, and 40 mg/kg; intraperitoneal injection) on haematopoiesis were analyzed using peripheral blood tests, histopathological examination of haematopoietic tissues, culture of haematopoietic progenitors and bone marrow stromal cells (BMSCs), and Western blotting of Fas and Fas ligand (FasL). The in vitro effects of RRPs on bone-marrow haematopoietic progenitors and BMSCs were also evaluated. Results: Compared to anaemic controls, high-dose RRPs (40 mg/kg) significantly increased red blood cells (8.21 ± 0.57835 versus 6.13 ± 1.34623 × 1012/L), white blood cells (5.11 ± 1.6141 versus l.54 ± 1.1539 × 109/L), and BMSCs (10.33 ± 1.5542 versus 5.87 ± 3.1567 × 1012/L) in mice with aplastic anaemia (all p < 0.01). High-dose RRPs significantly increased the formation of colony-forming unit-granulocyte macrophage (CFU-GM), burst-forming unit-erythroid (BFU-E), and colony-forming unit-erythroid (CFU-E; p < 0.01). Fas and FasL protein expression in BMSCs decreased after RRPs administration. Especially at the high dose, RRPs (150 μg/mL) significantly promoted in vitro CFUs-E, BFUs-E, and CFUs-GM formation. RRPs (150-300 μg/mL) also promoted BMSC proliferation. Discussion and conclusions: RRPs helped to promote haematopoietic recovery in mice with aplastic anaemia, facilitating haematopoietic tissue recovery. This study indicated some mechanisms of the haematopoietic regulatory effects of RRPs. Our findings provide a laboratory basis for clinical research on RRPs. [ABSTRACT FROM AUTHOR]

Proliferation of the neural/neuronal progenitor cells (NPCs) at the ventricular zone of the dorsal spinal cord requires the stimuli of Wnt and bone morphogenic protein (BMP). However, how these two signaling pathways are regulated to initiate differentiation in the NPCs as they enter the intermediate zone is not known. Here, we show that Smad6, a negative regulator of BMP signaling, is expressed in the intermediate zone of the chick dorsal spinal cord. Knockdown experiments show that Smad6 is required for promoting NPCs to exit the cell cycle and differentiate into neurons. Although we find that Smad6 inhibits BMP signaling, as expected, we also find that Smad6 unexpectedly inhibits the Wnt/β-catenin pathway. The inhibition of the Wnt/β-catenin pathway by Smad6 is independent of its effect on the BMP pathway. Rather, Smad6 through its N-terminal domain and link region enhances the interaction of C-terminal binding protein with the β-catenin/T cell factor (TCF) complex and the TCF-binding element to inhibit β-catenin-mediated transcriptional activation. Our study provides evidence that transition of NPCs from a proliferative state to a differentiating state is controlled by the dual inhibitory role of Smad6 to both BMP and Wnt signaling at the level of transcription. [ABSTRACT FROM AUTHOR]

Accumulation of senile plaques composed of amyloid β-peptide (Aβ) is a pathological hallmark of Alzheimer disease (AD), and Aβ is generated through the sequential cleavage of amyloid precursor protein (APP) by β- and γ-secretase. Although oxidative stress has been implicated in the AD pathogenesis by inducing Aβ production, the underlying mechanism remains elusive. Here we show that the pro-oxidant H2O2 promotes Aβ production through c-Jun N-terminal kinase (JNK)-dependent activation of γ-secretase. Treatment with H2O2 induced significant increase in the levels of intracellular and secreted Aβ in human neuroblastoma SH-SY5Y cells. Although γ-secretase-mediated cleavage of APP or C99 was enhanced upon H2O2 treatment, expression of APP or its α/β-secretase-mediated cleavage was not affected. Silencing of the stress-activated JNK by small interfering RNA or the specific JNK inhibitor SP600125 reduced H2O2-induced γ-secretase-mediated cleavage of APP. JNK activity was augmented in human brain tissues from AD patients and active JNK located surrounding the senile plaques in the brain of AD model mouse. Our data suggest that oxidative stress-activated JNK may contribute to senile plaque expansion through the promotion of γ-secretase-mediated APP cleavage and Aβ production. [ABSTRACT FROM AUTHOR]

Anti-tumor angiogenesis therapy, targeting the suppression of blood vessel growth in tumors, presents a potent approach in the battle against cancer. Traditional therapies have primarily concentrated on single-target techniques, with a specific emphasis on targeting the vascular endothelial growth factor, but have not reached ideal therapeutic efficacy. In response to this issue, our study introduced a novel nanoparticle system known as CSsiRNA/PEITC&L-cRGD NPs. These chitosan-based nanoparticles have been recognized for their excellent biocompatibility and ability to deliver genes. To enhance their targeted delivery capability, they were combined with a cyclic RGD peptide (cRGD). Targeted codelivery of gene and chemotherapeutic agents was achieved through the use of a negatively charged lipid shell and cRGD, which possesses high affinity for integrin αv β3 overexpressed in tumor cells and neovasculature. In this multifaceted approach, co-delivery of VEGF siRNA and phenethyl isothiocyanate (PEITC) was employed to target both tumor vascular endothelial cells and tumor cells simultaneously. The co-delivery of VEGF siRNA and PEITC could achieve precise silencing of VEGF, inhibit the accumulation of HIF-1 α under hypoxic conditions, and induce apoptosis in tumor cells. In summary, we have successfully developed a nanoparticle delivery platform that utilizes a dual mechanism of action of antitumor angiogenesis and pro-tumor apoptosis, which provides a robust and potent strategy for the delivery of anti-cancer therapeutics. [ABSTRACT FROM AUTHOR]

Objectives] The study aims to explore the protective effect of Shenlingbaizhu powder on peroxidation injury and inflammatory response in mice with pneumonia. [Methods] 60 NIH mice were randomly divided into the blank group, model group, control group, large dose group, medium dose group and small dose group of Shenlingbaizhu powder. The mice in the control group were given cefixime granules, while the mice in each group of Shenlingbaizhu powder were given corresponding concentrations of Shenlingbaizhu powder water decoction by gavage. After 7 d, the content of MAD, SOD and CRP in the mice were detected by ELISA, while the content of NO was detected by fluorescence, and lung index was also detected. [Results] The medium dose and large dose of Shenlingbaizhu powder can effectively reduce the concentration of MAD and improve the level of SOD in mice with pneumonia. The effect of the large dose of Shenlingbaizhu powder is more obvious than that of the control group. Moreover, the large dose of Shenlingbaizhu powder can effectively reduce the level of NO in mice with pneumonia. In addition, the medium dose and large dose of Shenlingbaizhu powder can reduce the lung index and CRP level of mice with pneumonia, and the results are statistically significant. [Conclusions] The medium dose and large dose of Shenlingbaizhu powder can effectively reduce the concentration of MAD and improve the level of SOD in mice with pneumonia. The effect of the large dose of Shenlingbaizhu powder is more obvious than that of the control group. Moreover, the large dose of Shenlingbaizhu powder can effectively reduce the level of NO in mice with pneumonia. In addition, the medium dose and large dose of Shenlingbaizhu powder can reduce the lung index and CRP level of mice with pneumonia, and the results are statistically significant. [ABSTRACT FROM AUTHOR]

[Objectives] To explore the effect of Shenling Baizhu San combined with routine treatment on the clinical efficacy, gastrointestinal function protection, inflammatory response and immune function of children with bacterial pneumonia. [Methods] From July 2017 to January 2018, 80 children with bacterial pneumonia were randomly selected and divided into observation group and control group with 40 cases in each group. The control group was treated with conventional Western medicine, while the observation group was treated with Shenling Baizhu San on the basis of conventional treatment, with a period of 10 d. Then, we compared the clinical efficacy, incidence of gastrointestinal symptoms, WBC, CRP, CD4+ and CD8+ levels between the two groups. [Results] The clinical efficacy of the observation group was better than that of the control group（P<0.05）. After treatment, the levels of WBC and CRP in the two groups decreased, especially in the observation group（P<0.05）. After treatment, the level of CD4+ in both groups increased significantly, while the level of CD8+ decreased significantly, and the level of CD4+ in the observation group was significantly higher than that in the control group after treatment. The incidence of gastrointestinal symptoms in the observation group was significantly lower than that in the control group（P<0.01）. [Conclusions] Shenling Baizhu San can obviously improve the clinical effect of bacterial pneumonia in children and has the protective effect of gastrointestinal tract, and its mechanism may be related to its anti-inflammatory and immunomodulatory effects. [ABSTRACT FROM AUTHOR]

Background: A lot of time and money was needed during the diagnosis and treatment process of leprosy, the delayed leprosy would also impair the labor capability of patients as well, and these put a heavy burden for the leprosy patients. The migrant leprosy patient is a special group and need more concern. Our goal was to assess the economic burden of leprosy on migrant and resident patient populations in Guangdong province, China.Methods: We conducted a population-based cross-sectional survey from February to July of 2016. A self-designed questionnaire was administered to leprosy patients who: (1) had registered in Leprosy Management Information System in China (LEPMIS) by the end of February 2016, (2) had received multiple drug treatment (MDT) drugs at a local leprosy control institution for three consecutive months or had had at least one physical check in the past half year, and (3) were willing to take part in the investigation and give informed written consent. Demographic characteristics, Financial and disease information, and costs before and after leprosy diagnosis were collected and compared using t-test and χ2 test.Results: A total of 254 participants completed the questionnaires, including 168 males and 86 females. Migrants and residents accounted for 33.9% and 66.1% of patients, respectively. Among migrant patients, the median cost before diagnosis was $131.6 (39.2-450.9), the median yearly cost of leprosy treatment after diagnosis was $300.6 (158.4-868.5), and the median yearly cost of leprosy complications was $69.5 (11-178.4). In comparison, among residents the median yearly costs were $152.4 (30.7-770.9) pre-diagnosis, $309.7 (103.2-1016.7) after diagnosis, and $91.9 (32.6-303.1) for leprosy complications. Base on this, we determined that the median yearly total expense after diagnosis amounted to 15% of migrant and 38% of resident patients' annual income.Conclusion: Leprosy places a heavy economic burden on both migrant and resident leprosy patients and governmental policies and programs could substantially alleviate this. Measures to implement more active surveillance and early diagnosis would benefit both populations, while labor protection and medical insurance are urgently needed for migrant patients and easier access to medical services and social aids could substantially decrease the burden of leprosy for resident patients. [ABSTRACT FROM AUTHOR]

Cell proliferation was inhibited following forced over-expression of miR-30a in the ovary cancer cell line A2780DX5 and the gastric cancer cell line SGC7901R. Interestingly, miR-30a targets the DNA replication protein RPA1, hinders the replication of DNA and induces DNA fragmentation. Furthermore, ataxia telangiectasia mutated (ATM) and checkpoint kinase 2 (CHK2) were phosphorylated after DNA damage, which induced p53 expression, thus triggering the S-phase checkpoint, arresting cell cycle progression and ultimately initiating cancer cell apoptosis. Therefore, forced miR-30a over-expression in cancer cells can be a potential way to inhibit tumour development. [ABSTRACT FROM AUTHOR]

During early embryonic development, bone morphogenetic protein (BMP) signaling is essential for neural/non-neural cell fate decisions. BMP signaling inhibits precocious neural differentiation and allows for proper differentiation of mesoderm, endoderm, and epidermis. However, the mechanisms underlying theBMPpathway-mediated cell fate decision remain largely unknown. Here, we show that the expression of Ovol2, which encodes an evolutionarily conserved zinc finger transcription factor, is down-regulated during neural differentiation of mouse embryonic stem cells. Knockdown of Ovol2 in embryonic stem cells facilitates neural conversion and inhibits mesendodermal differentiation, whereas Ovol2 overexpression gives rise to the opposite phenotype. Moreover, Ovol2 knockdown partially rescues the neural inhibition and mesendodermal induction by BMP4. Mechanistic studies further show that BMP4 directly regulates Ovol2 expression through the binding of Smad1/5/8 to the second intron of the Ovol2 gene. In the chick embryo, cOvol2 expression is specifically excluded from neural territory and is up-regulated by BMP4. In addition, ectopic expression of cOvol2 in the prospective neural plate represses the expression of the definitive neural plate marker cSox2. Taken together, these results indicate that Ovol2 acts downstream of the BMP pathway in the cell fate decision between neuroectoderm and mesendoderm to ensure proper germ layer development. [ABSTRACT FROM AUTHOR]

Nestin is a molecular marker for neural progenitor cells. Rat and human nestin genes possess a central nervous system-specific enhancer within their second introns, However, the transcription factors that bind to the nestin enhancer have not been fully elucidated. Here, we show that the second intron of the mouse nestin gene is sufficient to drive reporter gene expression in the developing nervous system. The core sequence of this central nervous system-specific enhancer localizes to the 3' 320-bp region. The cis-elements for Sox and POU family transcription factors and the hormone-responsive element are essential for nestin expression during embryonic carcinoma P19 cell neural differentiation and in the developing chick neural tube. Interestingly, different transcription factors bind to the nestin enhancer at different stages of P19 cell neural differentiation and central nervous system development. Sox2 and SF1 may mediate basal nestin expression in undifferentiated P19EC cells, whereas Sox2, Brn1, and Brn2 bind to the enhancer in P19 neural progenitor cells. Similarly, in vivo, Octl binds to the nestin enhancer in embryonic day 8.5 (E8.5) mouse embryos, and Oct1, Brn1, and Brn2 bind to this enhancer in E10.5 and E12.5 mouse embryos. Our studies therefore suggest a temporal coordination of transcription factors in determining nestin gene expression. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 36-year-old man with multiple, disseminated, violaceous nodules and maculopapules on the skin of his extremeties and trunk. Physical examination revealed disseminated solid, nodules, multiple and violaceous plaques on the skin of the trunk and on the lower and upper limbs as well as the face. Treatment with prednisone 30 milligrams (mg)/day was administered for five days and the lesions nearly disappeared.