[Effect of miltirone on proliferation and apoptosis of leukemia THP-1 cells].

To investigate the toxicity and related mechanism of miltirone to human acute myeloid leukemia THP-1 cells. To be specific, the active components and targets of miltirone were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), and the target proteins were converted into standard gene names with UniProt. Acute leukemia-rela-ted target genes were screened from GeneCards and DisGeNET. Venn diagram was constructed with Venny 2.1 to yield the common targets of the disease and the drug. The protein-protein interaction(PPI) network was constructed by STRING and Cytoscape 3.8.2. THP-1 cells in the logarithmic growth phase were treated with dimethyl sulfoxide(DMSO), and 2.5, 5, 10, 15, and 20 µmol·L~(-1) miltirone for 24 h, respectively. The proliferation rate of cells was analyzed by carboxyfluorescein diacetate succinimidyl ester(CFSE), apoptosis rate by flow cytometry with Annexin V-PE/7 AAD staining, and cell morphology by acridine orange staining. Real-time quantitative PCR(qPCR) was employed to detect the mRNA levels of nuclear receptor coactivator 2(NCOA2), poly(ADP-ribose) polymerase-1(PARP1), B-cell lymphoma-2(Bcl-2)-associated X protein(Bax), Bcl-2, and cysteine aspartyl protease-3(caspase-3). The effect of miltirone on apoptosis was detected in presence of caspase inhibitor Z-VAD-FMK. A total of 26 targets of miltirone, 1 046 genes related to acute leukemia, and 6 common targets of the two were screened out. Flow cytometry result showed miltirone at 10 µmol·L~(-1) can inhibit proliferation and promote apoptosis of THP-1 cells. The typical manifestations of apoptosis, such as cell shrinkage, nuclear rupture, and chromatin agglomerate were displayed by acridine orange staining. The decreased mRNA levels of NCOA2 and PARP1 and increased Bax/Bcl-2 ratio and the activity of pro-apoptotic protein caspase-3 were observed. Z-VAD-FMK can attenuate the apoptosis-inducing effect of miltirone. This study indicates that miltirone can inhibit the proliferation and promote the apoptosis of THP-1 cells, by down-regulating NCOA2 and PARP1, raising Bax/Bcl-2 ratio, and activating caspase-3.

Cationic Pillar[6]arene Induces Cell Apoptosis by Inhibiting Protein Tyrosine Phosphorylation Via Host-Guest Recognition.

We reported for the first time that cationic pillar[6]arene (cPA6) could tightly bind to peptide polymer (MW~20-50 kDa), an artificial substrate for tyrosine (Tyr) phosphorylation, and efficiently inhibit Tyr protein phosphorylation through host-guest recognition. We synthesized a nanocomposite of black phosphorus nanosheets loaded with cPA6 (BPNS@cPA6) to explore the effect of cPA6 on cells. BPNS@cPA6 was able to enter HepG2 cells, induced apoptosis, and inhibited cell proliferation by reducing the level of Tyr phosphorylation. Furthermore, BPNS@cPA6 showed a stronger ability of inhibiting cell proliferation in tumor cells than in normal cells. Our results revealed the supramolecular modulation of enzymatic Tyr phosphorylation by the host-guest recognition of cPA6.

Adsorption behavior of 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin on pristine and doped black phosphorene: A DFT study.

Polychlorinated dibenzo-p-dioxins (PCDDs) are highly toxic to humans. The search for novel and effective methods and materials for detecting or removing these gas pollutants is becoming more important and urgent. With its high specific surface area, abundance, and variety of potential applications, phosphorene has attracted much research interest. In this study, density functional theory was used to study the interactions between a doped phosphorene sheet and a tetrachlorodibenzo-p-dioxin (TCDD) molecule. The initial configurations of the TCDD and metallic (Ca or Ti) or nonmetallic (S and Se) dopants were investigated during the TCDD-phosphorene interaction study. Adsorption energy, isosurface of electron density difference, and density of states analysis were utilized to explore the interactions between TCDD and phosphorene. The results indicated that Ca dopant effectively improved the interaction between TCDD and phosphorene. Se dopant reduced the interaction between TCDD and phosphorene. Combining interactions between TCDD and the pristine, Ca-doped, and Se-doped phosphorenes, phosphorene could be a promising candidate for TCDD sensing and removal.

Antitumor Effect of By-1 from Spent Broth from Submerged Cultures of Stout Camphor Medicinal Mushroom, Taiwanofungus camphoratus (Higher Basidiomycetes), on A549 Adenocarcinoma Cells.

By-1 was obtained from spent broth from submerged cultures of Taiwanofungus camphoratus. This report evaluates the effects of By-1 on plate clone formation, wound healing, cell cycle, activated caspase-3 expression, and ROS release in A549 lung cancer cells. The result of plate clone formation assay revealed that By-1 could dramatically inhibit the viability of A549 cells in vitro. The inhibitory effect of By-1 on cell migration was tested using a wound healing assay. Proliferation rates of A549 cells were significantly inhibited following exposure to By-1 (12.5, 50, and 80 µg/mL). Flow cytometry revealed that the extracts increased, in a concentration-dependent manner, the number of cells in the G0/G1 phases of the cell cycle. The results of the caspase-3 experiment suggested that By-1 could induce A549 cells apoptosis, and this apoptosis was related to the release of reactive oxygen species by the A549 cells. All these results indicate that By-1 has potential in anti-lung cancer drug development.

Evaluation of Vitamin C Supplementation on Kidney Function and Vascular Reactivity Following Renal Ischemic Injury in Mice.

BACKGROUND/AIMS: Renal ischemia/reperfusion injury (IRI) is a very common clinical event and usually leads to ischemic acute renal failure (ARF). In the present study, we investigated the protective role of vitamin C in renal function and renal arterial relaxation following ischemic injury. METHODS: IRI model in mice was used. Various biochemical parameters including nitric oxide (NO), reduced glutathione (GSH), total reactive oxygen species (ROS) level and superoxide dismutase (SOD) were examined. Doppler was used to investigate renal arterial resistance. The isolated renal arterial rings served for hypoxia/reoxygenation analysis. Acetylcholine (ACh) and sodium nitroprusside (SNP)-induced relaxations of isolated renal arterial rings were exerted. RESULTS: Vitamin C supplementation preserved kidney morphology and renal function following IRI. It was shown that pretreatment with vitamin C for mice subjected to IRI significantly elevated renal NO and GSH levels after reperfusion. Meanwhile, vitamin C administration decreased resistance index of renal artery and ameliorated oxidative stress secondary to IRI. The total ROS level in renal artery was decreased whereas the renal arterial SOD expression was increased by vitamin C supplementation following IRI. Pretreatment with vitamin C significantly potentiated the ACh and SNP-induced relaxations in both control and hypoxic renal arterial rings. CONCLUSION: Vitamin C protects kidney function and renal arterial reactivity against IRI. The protective role of vitamin C is linked to ROS, SOD, GSH and NO levels in renal ischemic injury.

[Features of Syndrome Patterns of Chinese Medicine in Elderly AIDS Patients in Guangxi Zhuang Autonomous Region].

Objective To observe the features of syndrome patterns of Chinese medicine (CM) in elderly human immunodeficiency virus/acquired immune deficiency syndrome ( HIV/AIDS) patients in Guangxi Zhuang Autonomous Region. Methods According to a case-control study, a clinical question- naire was designated in elderly HIV/AIDS patients older than 50 years and healthy examinees with age and sex match. Their syndrome information of CM were collected from designated medical institutions in Guangxi Zhuang Autonomous Region from October 2013 to April 2014. Analyses of syndrome factors were conducted using WF-I[A Diagnosis and Treatment System of Traditional Chinese Medicine (Auxilia- ry). The disease location of CM and nature of diseases were compared between elderly HIV/AIDS patients and the controls. The features of syndrome patterns of CM in elderly HIV/AIDS patients were summarized. Results A total of 417 elderly HIV/AIDS patients and 362 examinees were enrolled. In elderly patients with HIV/AIDS, established syndrome factors of disease nature were qi deficiency, yang deficiency, yin deficiency, blood deficiency, dampness, and phlegm , and established syndrome factors of disease loca- tion included Shen, Fei, Pi, and Gan. There were statistical differences in established syndrome factors of disease location or nature between elderly patients with HIV/AIDS and the controls (P <0. 05). Conclu- sions Elderly HIV/AIDS patients were characterized by deficiency of qi, yang, yin, and blood in Shen, Fei, Pi, and Gan, as well as endogenous production of pathogenic factors such as dampness and phlegm. Intermingled deficiency and excess was dominated in elderly HIV/AIDS patients, and mainly man- ifested as deficiency syndrome.

"Out of pollen" hypothesis for origin of new genes in flowering plants: study from Arabidopsis thaliana.

New genes, which provide material for evolutionary innovation, have been extensively studied for many years in animals where it is observed that they commonly show an expression bias for the testis. Thus, the testis is a major source for the generation of new genes in animals. The source tissue for new genes in plants is unclear. Here, we find that new genes in plants show a bias in expression to mature pollen, and are also enriched in a gene coexpression module that correlates with mature pollen in Arabidopsis thaliana. Transposable elements are significantly enriched in the new genes, and the high activity of transposable elements in the vegetative nucleus, compared with the germ cells, suggests that new genes are most easily generated in the vegetative nucleus in the mature pollen. We propose an "out of pollen" hypothesis for the origin of new genes in flowering plants.

Genetic polymorphisms of ERCC1­118, XRCC1­399 and GSTP1­105 are associated with the clinical outcome of gastric cancer patients receiving oxaliplatin­based adjuvant chemotherapy.

The aim of the present study was to determine whether specific molecular parameters may serve as predictors of treatment outcomes and toxicity of oxaliplatin (OXA)­based chemotherapy, which is used as an adjuvant treatment in resected gastric cancer. All gastric cancer patients examined in the study received an OXA/5­fluorouracil chemotherapeutic regimen. Genetic polymorphisms of certain platinum­related genes were determined by the TaqMan 5' nuclease assay and direct sequencing. Relapse­free survival (RFS), overall survival (OS) and toxicity were evaluated according to each genotype. Following adjustment for the most relevant clinical variables, excision repair cross­complimentary group 1 (ERCC1)­118 and X-ray repair cross-complementing protein 1 (XRCC1­399) demonstrated significant predictive value for RFS and OS. We also demonstrated that carrying at least one variant XRCC1 Arg399Gln or glutathione S-transferase π 1 (GSTP1) Ile105Val allele significantly increased the risk of any grade 3 or 4 hematological toxicity. In particular, carrying at least one variant GSTP1 Ile105Val allele was also significantly correlated with an increased risk of grade 3 or 4 gastrointestinal toxicity and neurotoxicity. Our data suggested that gastric cancer patients harboring ERCC1­118 C/C and XRCC1­399 A/G or A/A genotypes may benefit from receiving OXA­based adjuvant chemotherapy, and carrying at least one variant XRCC1 Arg399Gln or GSTP1 Ile105Val allele may contribute to the occurrence of adverse drug effects associated with OXA­based chemotherapy.

[Treating HIV/AIDS patients by shenlin fuzheng capsule and qingdu capsule: an analysis of clinical effectiveness].

OBJECTIVE: To analyze the clinical effectiveness of Shenling Fuzheng Capsule (SFC) and Qingdu Capsule (QC) in treating HIV/AIDS patients. METHODS: Totally 220 patients with complete clinical data, who received consecutive treatment for 6 months were selected from the database. They were assigned to two groups whether they would rather receive antiretroviral drugs, the Chinese medicine (CM) treatment group and the integrative medicine (IM) group. The 129 patients in the CM group were treated with SFC or QC, while the 91 patients in the IM group were treated with SFC or QC combined highly active antiretroviral agents. Total score and single score of clinical symptoms and signs, Karnofsky Performance Status (KPS), and changes of body weight before treatment, 3 and 6 months after treatment were compared. CD4+ cell counts were compared between before treatment and 6 months after treatment. RESULTS: The total score of clinical symptoms and signs were lower at 3 and 6 months of treatment than before treatment respectively (P < 0.01). The single score of clinical symptoms and signs such as cough, weakness, shortness of breath, vomit, spontaneous perspiration, hair loss,and chest pain were also lowered at 3 and 6 months of treatment (P < 0.05, P < 0.01), and the KPS increased (P < 0.05). The body weight increased (P < 0.05) and CD4 cell counts decreased (P < 0.05) in the CM group. There was no statistical difference in body weight or CD4 cell counts in the IM group between before and after treatment. CONCLUSION: SFC and QC could improve clinical symptoms and signs of HIV/ AIDS patients, but failed to deter the decrease of CD4+ cell counts.

Influence of Fuzheng Huayu Tablet on mental state and social function of patients with post-hepatitis B liver cirrhosis.

OBJECTIVE: To observe the influence of Fuzheng Huayu Tablet on mental state and social activity of patients with post-hepatitis B liver cirrhosis (LC-HB). METHODS: Adopting grouped randomized double-blinded control method, 180 LC-HB patients in 3 research centers were distributed to 2 groups, the treated group and the control group, 90 in each group. Patients in the treated group were administered with FZHYT; while those in the control group treated with conventional therapy combined with placebo, the course for all patients were 6 months. Their mental state and social activity were evaluated before treatment, after 3 months' treatment and at terminal of the 6-month therapeutic course by estimating with Zung self-rating anxiety scale (SAS), self-rating depression scale (SDS) and social deficit screening scale (SDSS). Additionally, the basic demographic materials, liver function, cirrhosis index, hepatic and splenic images, blood coagulation function, etc. in the patients were tested and compared as well. RESULTS: As compared with before treatment, the normal rate of SAS and SDS scores increased and the social deficit rate decreased in the treated group significantly after treatment, showing statistical significance (P<0.05 or P<0.01); while in the control group, change was only shown in the social deficit (P<0.01), inter-group comparisons after treatment showed significant differences in all the three indexes (P<0.05 or P<0.01). Additionally, after treatment, levels of liver function, cirrhosis, blood coagulation function and splenomegaly in the treated group were all improved significantly P<0.05 or P<0.01), and the improvements were better than those in the control group (P<0.01) in levels of total bilirubin (TBIL), albumin (ALB), type IV collagen (IV-C), prothrombin time (PT), prothrombin activity (PTA). CONCLUSION: Most patients of LC-HB have mental disturbance and social activity deficit, which could definitely be improved by intervention with Chinese FZHYT.

[Effect of aconiti lateralis radix praeparata and taraxaci herba on Chinese medicine signs and symptoms of urethane-induced lung cancer in mice].

OBJECTIVE: To study Chinese medicine (CM) signs and symptoms of urethane-induced lung cancer in mice, and observe the effect of Aconiti Lateralis Radix Praeparata and Taraxaci Herba on symptoms in mice and tumor progress. METHOD: The mice were intraperitoneally injected with urethane twice a week for consecutively five weeks to establish a lung cancer model. The changes in their appearance, body temperature and auricle microcirculation were observed in carcinogenic process. CM signs and symptoms of urethane-induced lung cancer in mice were evaluated with energy metabolism, erythrocytic ATP emzymatic activity and hemorrheological index. During the tumor model was induced, Aconiti Lateralis Radix Praeparata and Taraxaci Herba were used to treat the mice and observe their effect on symptoms in mice and tumor progress. RESULT: During urethane was used to induce lung cancer, the mice had gradually become chill, lazy, hunched, with reduction in temperature, cyanosis in auricle and tail. Meanwhile, their energy metabolism and erythrocytic ATP enzymatic activity reduced, whereas their whole blood viscosity and erythrocytic aggregate index increased. Taraxaci Herba showed an effect on enhancing above symptoms and signs but had no effect on tumor progress. Aconiti Lateralis Radix Praeparata showed an effect on reducing above symptoms and signs and preventing tumor progress. CONCLUSION: Mice with urethane-induced lung cancer show CM signs and symptoms of congealing cold with blood stasis. The treatment with Aconiti Lateralis Radix Praeparata can alleviate symptoms and signs in mice and prevent tumor progress.

[Chinese medicine prevention and treatment of AIDS in terms of constitution theory].

The significant effects of constitutional factor on AIDS were addressed. Acquired immunodeficiency syndrome (AIDS), caused by HIV, is mainly characterized as decreased immune function or immune deficiency. It has strong infectiousness and higher mortality, so it is one of the diseases that attract great attention to clinical prevention and treatment. The constitution not only exerts significant effect on the immune function of patients with AIDS, but also plays important roles in the development, prognosis, and outcomes of AIDS. Therefore, it is of great referential significance in both clinical and scientific studies of AIDS by exploring Chinese medicine prevention and treatment of AIDS from the angle of constitution.

Tracing the origins of Hakka and Chaoshanese by mitochondrial DNA analysis.

Hakka and Chaoshanese are two unique Han populations residing in southern China but with northern Han (NH) cultural traditions and linguistic influences. Although most of historical records indicate that both populations migrated from northern China in the last two thousand years, no consensus on their origins has been reached so far. To shed more light on the origins of Hakka and Chaoshanese, mitochondrial DNAs (mtDNAs) of 170 Hakka from Meizhou and 102 Chaoshanese from Chaoshan area, Guangdong Province, were analyzed. Our results show that some southern Chinese predominant haplogroups, e.g. B, F, and M7, have relatively high frequencies in both populations. Although median network analyses show that Hakka/Chaoshanese share some haplotypes with NH, interpopulation comparison reveals that both populations show closer affinity with southern Han (SH) populations than with NH. In consideration of previous results from nuclear gene (including Y chromosome) research, it is likely that matrilineal landscapes of both Hakka and Chaoshanese have largely been shaped by the local people during their migration southward and/or later colonization in southern China, and factors such as cultural assimilation, patrilocality, and even sex-bias in the immigrants might have played important roles during the process.

Mitochondrial genome evidence reveals successful Late Paleolithic settlement on the Tibetan Plateau.

Due to its numerous environmental extremes, the Tibetan Plateau--the world's highest plateau--is one of the most challenging areas of modern human settlement. Archaeological evidence dates the earliest settlement on the plateau to the Late Paleolithic, while previous genetic studies have traced the colonization event(s) to no earlier than the Neolithic. To explore whether the genetic continuity on the plateau has an exclusively Neolithic time depth, we studied mitochondrial DNA (mtDNA) genome variation within 6 regional Tibetan populations sampled from Tibet and neighboring areas. Our results confirm that the vast majority of Tibetan matrilineal components can trace their ancestry to Epipaleolithic and Neolithic immigrants from northern China during the mid-Holocene. Significantly, we also identified an infrequent novel haplogroup, M16, that branched off directly from the Eurasian M founder type. Its nearly exclusive distribution in Tibetan populations and ancient age (>21 kya) suggest that M16 may represent the genetic relics of the Late Paleolithic inhabitants on the plateau. This partial genetic continuity between the Paleolithic inhabitants and the contemporary Tibetan populations bridges the results and inferences from archaeology, history, and genetics.

[Protection effect of Salvia miltiorrhiza on model of acute lung injury in rats].

OBJECTIVE: To investigate the effect of SM on aquaporin-1 (AQP1) expression in rats with acute lung injury (ALI), and study protection against ALI. METHODS: 48 SD rats were randomly divided into normal group, ALI 7-day group, ALI 8-hour group, SM prevention group, SM 7-day treatment group, and SM 8-hour treatment group. At 8 hours and 7 days after treatment, lung wet-to-dry weight ratio, lung pathology, electron microscope, AQP1 immunohistochemistry, and AQP1 Western blot were performed. RESULTS: The model group rats all appeared ALI symptom. Compared with the 7-day ALI group, the degree of lung edema statement alleviated in SM 7-day treatment group. But the expression of AQP-1 was not significant between the two groups (P < 0.05). Compared with the 8-hour ALI group, the degree of lung edema statement alleviated in SM 8-hour treatment group and SM prevention group. The expression of AQP-1 was significantly expression in the group of SM prevention group (P < 0.01). CONCLUSION: SM may improve the body fluid metabolism and alleviate the degree of the lung edema by regulating the expression of AQP-1. The results suggest SM can regulate the activity of AQP-1 to improve the water metabolism of ALI.

[Research on the identification of penis et testis cervi with molecular taxonomy].

OBJECTIVE: To make the kit with witch to identify Penis et Testis Cervi with molecular taxonomy. METHOD: The mtDNA of sika and red deer from different areas was amplified by PCR and sequenced. Compared with the mtDNA of bovine and horse from witch the false medicines were made, characteristic segments of deer were found. We selected one as the species distinctive PCR primer of deer. RESULT: The kit made up with this primer and related reagents could be used to discern Penis et Testis Cervi from the false medicine. CONCLUSION: It is a scientific, steady, accurate and convenient way to identify Penis et Testis Cervi with molecular taxonomy.