Overexpression of GmPAP4 Enhances Symbiotic Nitrogen Fixation and Seed Yield in Soybean under Phosphorus-Deficient Condition.

Legume crops establish symbiosis with nitrogen-fixing rhizobia for biological nitrogen fixation (BNF), a process that provides a prominent natural nitrogen source in agroecosystems; and efficient nodulation and nitrogen fixation processes require a large amount of phosphorus (P). Here, a role of GmPAP4, a nodule-localized purple acid phosphatase, in BNF and seed yield was functionally characterized in whole transgenic soybean (Glycine max) plants under a P-limited condition. GmPAP4 was specifically expressed in the infection zones of soybean nodules and its expression was greatly induced in low P stress. Altered expression of GmPAP4 significantly affected soybean nodulation, BNF, and yield under the P-deficient condition. Nodule number, nodule fresh weight, nodule nitrogenase, APase activities, and nodule total P content were significantly increased in GmPAP4 overexpression (OE) lines. Structural characteristics revealed by toluidine blue staining showed that overexpression of GmPAP4 resulted in a larger infection area than wild-type (WT) control. Moreover, the plant biomass and N and P content of shoot and root in GmPAP4 OE lines were also greatly improved, resulting in increased soybean yield in the P-deficient condition. Taken together, our results demonstrated that GmPAP4, a purple acid phosphatase, increased P utilization efficiency in nodules under a P-deficient condition and, subsequently, enhanced symbiotic BNF and seed yield of soybean.

Integrated physical and mental management for China's elderly: insights from Long-gang District, Shenzhen.

China is in a period of rapid population aging. The total population of the elderly aged 60 and above in mainland China was 264 million in 2020, and is the country with the largest elderly population in the world, which is home to 1/5 of the world's older people. The urgency of actively coping with the aging population has never been greater, and China has raised it to the height of national strategy. To this end, China has issued several plans and projects on aging work. Many of them include multiple overlapping components. The management of physical illness and mental illness in the elderly is over-differentiated and segmented. However, it is common for older adults with complex health problems. The body and mind are inherently integrated and interact with each other, and should not be separated. There is an urgent need for integrated healthcare services for the physical and mental health of the elderly population. The national basic public health services play an important role in early detection and awareness of health problems for the elderly in community health services. This paper introduces the elderly health management services, one of the national basic public health projects, and the psychological care project for the elderly in Shenzhen, Guangdong Province, China. Taking Long-gang District's exploration of the joint management of physical and mental health of the elderly as an example, this review discusses the difficulties of the elderly health work, and the feasibility of integrating the elderly mental health and physical health in medical care. We outlook to build an integrated platform for physical and mental health of the elderly in China. Focus on the needs of older population, strengthen community health services, build a integrative team, fully publicize and improve health literacy of the elderly, link up and down and work together, improve coordination between providers of medical care and social services. It is of great significance to construct a strong public health system for the elderly and promote the realization of the grand goal of Healthy China.

Revealing the "Yin-Jing" mystery veil of Platycodon grandiflorum by potentiating therapeutic effects and lung-oriented guidance property.

ETHNIC PHARMACOLOGICAL RELEVANCE: "Yin-Jing" medicine (YJM) has been widely used by both ancient and modern Chinese medicine practitioners during long-term clinical practice. However, it remains unclear how to best guide other medicines to the targeted organs in a traditional Chinese medicine (TCM) prescription. Here, in an attempt to explain the scientific connotation of the YJM property (YJMP) attributed to a basic TCM theory, Platycodon grandiflorum (PG) was chosen as a case study to reveal the mystery of YJMP theory. AIM OF THE STUDY: The main purpose of this study is to employ modern chemical and molecular biology methods to confirm the "Yin-Jing" effect of PG, and further clarify its material basis and related possible mechanism. MATERIALS AND METHODS: The ammonia-induced lung injury rat model was utilized to determine the optimal dosage of traditional prescription Hui Yan Zhu Yu decoction (HYZYD) using Wright Giemsa staining, HE staining, Masson staining, and TUNEL analysis. With the same way, PG was confirmed to have potentiating therapeutic effect (PTE) by comparison with HYZYD and [HYZYD-PG]. TMT proteomics was used to reveal the "Yin-Jing" mechanism of action. Western blot assay (WB) was employed for verification of differentially expressed proteins. Additionally, four non-crossing fragmentations (Fr. A-D) were characterized by RPLC/SEC-ELSD and HILIC-ESI--Q-OT-IT-MS techniques. The PTE and guidance property assays were utilized to evaluate "Yin-Jing" functions by a compatible combination of hydroxysafflor yellow A (HYA) using qPCR, FCM, WB, HPLC, high content cell imaging (HCI) and high-resolution live-cell imaging (HRLCI) techniques. RESULTS: The HYZYD-M (medium dose group) significantly improved the lung injury level in a pneumonia model of rats. PG enhanced the therapeutic effect of HYZYD ascribed to Yin-Jing PTE functions. TMT proteomics revealed a category of differentially expressed proteins ascribed to Golgi-ER between HYZYD and [HYZYD-PG]. Fr. C (i.e., saponins) and Fr. D (i.e., lipids) were determined as therapeutic fragmentations via the LPS-induced A549 cell injury model; however, Fr. B (fructooligosaccharides and small Mw fructans) had no therapeutic effect. Further compatibility PTE assays confirmed Fr. B significantly improved efficiency by a combination of HYA. The guidance assays showed Fr. B could significantly increase the uptake and distribution of HYA into lung cells and tissues. HCI assays showed that Fr. B increased uptake of HYA accompanied by significant activation of Golgi-ER. Unlike Fr. B, HRLCI showed that Fr. A, C and D were not only unobvious activations of Golgi-ER but also insignificant facilitation of colocalizations between HYA and Golgi-ER. CONCLUSIONS: Fr. B is believed to be a key YJMP material basis of PG attributed to Yin-Jing PTE with characteristic of lung-oriented guidance property, whereas another abound Fr. C was determined to have synergistic effects rather than Yin-Jing material basis.

Gemcitabine enhances pharmacokinetic exposure of the major components of Danggui Buxue Decoction in rat via the promotion of intestinal permeability and down-regulation of CYP3A for combination treatment of non-small cell lung cancer.

CONTEXT: Danggui Buxue Decoction (DBD), a traditional Chinese medicine formula, has the potential to enhance the antitumor effect of gemcitabine in non-small cell lung cancer (NSCLC) treatment by increasing gemcitabine's active metabolites. However, whether gemcitabine affects the pharmacokinetics of DBD's major components remains unclear. OBJECTIVE: This study evaluates the herb-drug interaction between DBD's major components and gemcitabine and validates the underlying pharmacokinetic mechanism. MATERIALS AND METHODS: The pharmacokinetics of 3.6 g/kg DBD with and without a single-dose administration of 50 mg/kg gemcitabine was investigated in Sprague-Dawley rats. The effects of gemcitabine on intestinal permeability, hepatic microsomal enzymes in rat tissues, and CYP3A overexpressing HepG2 cells were determined using western blot analysis. RESULTS: The combination of gemcitabine significantly altered the pharmacokinetic profiles of DBD's major components in rats. The Cmax and AUC of calycosin-7-O-ß-d-glucoside notably increased through sodium-glucose transporter 1 (SGLT-1) expression promotion. The AUC of ligustilide and ferulic acid was also significantly elevated with the elimination half-life (t1/2) prolonged by 2.4-fold and 7.8-fold, respectively, by down-regulating hepatic CYP3A, tight junction proteins zonula occludens-1 (ZO-1) and occludin expression. DISCUSSION AND CONCLUSIONS: Gemcitabine could modulate the pharmacokinetics of DBD's major components by increasing intestinal permeability, enhancing transporter expression, and down-regulating CYP3A. These findings provide critical information for clinical research on DBD as an adjuvant for NSCLC with gemcitabine and help make potential dosage adjustments more scientifically and rationally.

Network pharmacology-based analysis of heat clearing and detoxifying drug JC724 on the treatment of colorectal cancer.

BACKGROUND: Heat-clearing and detoxifying drugs has protective effect on colorectal cancer (CRC). Given the complicated features of Traditional Chinese medicine formulas, network pharmacology is an effective approach for studying the multiple interactions between drugs and diseases. AIM: To systematically explore the anticancer mechanism of heat-clearing and detoxifying drug JC724. METHODS: This study obtained the active compounds and their targets in JC724 from Traditional Chinese Medicine System Pharmacology Database. In addition, the CRC targets were obtained from Drugbank, TTD, DisGeNET and GeneCards databases. We performed transcriptome analysis of differentially expressed genes in CRC treated with JC724. Venn diagram was used to screen the JC724-CRC intersection targets as candidate targets. Core targets were selected by protein-protein interaction network and herb ingredient-target-disease network analysis. The functional and pathway of core targets were analysed by enrichment analysis. RESULTS: We found 174 active ingredients and 283 compound targets from JC724. 940 CRC-related targets were reserved from the four databases and 304 CRC differentially expressed genes were obtained by transcriptome analysis. We constructed the network and found that the five core ingredients were quercetin, ß Beta sitosterol, wogonin, kaempferol and baicalein. The core JC724-CRC targets were CYP1A1, HMOX1, CXCL8, NQO1 and FOSL1. JC724 acts on multiple signaling pathways associated with CRC, including the Nrf2 signaling pathway, oxidative stress, and the IL-17 signaling pathway. CONCLUSION: In this study, we systematically analyzed the active ingredients, core targets and main mechanisms of JC724 in the treatment of CRC. This study could bring a new perspective to the heat-clearing and detoxifying therapy of CRC.

SbWRKY55 regulates sorghum response to saline environment by its dual role in abscisic acid signaling.

KEY MESSAGE: SbWRKY55 functions as a key component of the ABA-mediated signaling pathway; transgenic sorghum regulates plant responses to saline environments and will help save arable land and ensure food security. Salt tolerance in plants is triggered by various environmental stress factors and endogenous hormonal signals. Numerous studies have shown that WRKY transcription factors are involved in regulating plant salt tolerance. However, the underlying mechanism for WRKY transcription factors regulated salt stress response and signal transduction pathways remains largely unknown. In this study, the SbWRKY55 transcription factor was found to be the key component for reduced levels of salt and abscisic acid in SbWRKY55 overexpression significantly reduced salt tolerance in sorghum and Arabidopsis. Mutation of the homologous gene AtWRKY55 in A. thaliana significantly enhanced salt tolerance, and SbWRKY55 supplementation in the mutants restored salt tolerance. In the transgenic sorghum with SbWRKY55 overexpression, the expression levels of genes involved in the abscisic acid (ABA) pathway were altered, and the endogenous ABA content decreased. Yeast one-hybrid assays and dual-luciferase reporter assay showed that SbWRKY55 binds directly to the promoter of SbBGLU22 and inhibits its expression level. In addition, both in vivo and in vitro biochemical analyses showed that SbWRKY55 interacts with the FYVE zinc finger protein SbFYVE1, blocking the ABA signaling pathway. This could be an important feedback regulatory pathway to balance the SbWRKY55-mediated salt stress response. In summary, the results of this study provide convincing evidence that SbWRKY55 functions as a key component in the ABA-mediated signaling pathway, highlighting the dual role of SbWRKY55 in ABA signaling. This study also showed that SbWRKY55 could negatively regulate salt tolerance in sorghum.

Daming capsule protects against myocardial infarction by promoting mitophagy via the SIRT1/AMPK signaling pathway.

Myocardial infarction (MI) is a myocardial injury caused by coronary thrombosis or persistent ischemia and hypoxia. Due to its high morbidity and mortality, a safer and more effective treatment strategy is urgently needed. Daming capsule (DMC), a hypolipidemic drug, reportedly exerts cardioprotective effects in clinical and basic research, although its protective mechanism remains unknown. To investigate the mechanism underlying DMC-mediated improvement of cardiac function post-MI, C57/BL6 mice subjected to coronary artery ligation were administered DMC for 4 weeks. Our data demonstrated that DMC significantly improved cardiac structure and function compared to the saline group. Moreover, DMC inhibited inflammatory response and oxidative stress and improved mitochondrial structure and function in MI mice and hypoxia-stressed cardiomyocytes. Next, our research proved that DMC increased the expression of mitophagy receptor NLRX1. Interestingly, with the administration of DMC and siNLRX1, NLRX1 expression, mitochondria and lysosome colocalization, and mitochondrial membrane potential decreased, while mitochondrial ROS accumulation increased, suggesting that DMC promoted mitophagy to improve mitochondrial function via NLRX1 regulation. Further analysis showed that DMC activated the SIRT1/AMPK signaling pathway in vivo and in vitro. Our data showed that SIRT1 knockdown downregulated NLRX1 expression, leading to structural damage and functional impairment in mitochondria, as well as increased oxidative stress, inflammatory response, and decreased cardiac function in MI mice. Collectively, our findings reveal that DMC improves cardiac function post-MI by increasing mitophagy and inhibiting oxidative stress and inflammotory response in cardiomyocytes through the SIRT1/AMPK signaling pathway.

Bacillus subtilis Attenuates Hepatic and Intestinal Injuries and Modulates Gut Microbiota and Gene Expression Profiles in Mice Infected with Schistosoma japonicum.

Parasitic infection can induce pathological injuries and impact the gut microbiota diversity and composition of the host. Bacillus subtilis is a nonpathogenic and noninvasive probiotic bacterium for humans and other animals, playing an important role in improving the host immune system's ability to respond to intestinal and liver diseases and modulating gut microbiota. However, whether B. subtilis can impact biological functions in Schistosoma japonicum-infected mice is unclear. This study used oral administration (OA) of B. subtilis to treat mice infected with S. japonicum. We evaluated changes in the gut microbiota of infected mice using 16 S rRNA gene sequencing and differentially expressed gene profiles using transcriptome sequencing after OA B. subtilis. We found that OA B. subtilis significantly attenuated hepatic and intestinal pathological injuries in infected mice. The gut microbiota of mice were significantly altered after S. japonicum infection, while OA B. subtilis remodel the diversity and composition of gut microbiomes of infected mice. We found that the S. japonicum-infected mice with OA B. subtilis had an overabundance of the most prevalent bacterial genera, including Bacteroides, Enterococcus, Lactobacillus, Blautia, Lachnoclostridium, Ruminiclostridium, and Enterobacter. Transcriptomic analysis of intestinal tissues revealed that OA B. subtilis shaped the intestinal microenvironment of the host responding to S. japonicum infection. Differentially expressed genes were classified into KEGG pathways between S. japonicum-infected mice and those without included cell adhesion molecules, intestinal immune network for IgA production, hematopoietic cell lineage, Fc epsilon RI signaling pathway, Th1 and Th2 cell differentiation, Th17 cell differentiation, calcium signaling pathway, Fc gamma R-mediated phagocytosis, chemokine signaling pathway, phospholipase D signaling pathway, NF-kappa B signaling pathway, B cell receptor signaling pathway, pancreatic secretion, and phagosome. In conclusion, our findings showed that OA B. subtilis alleviates pathological injuries and regulates gene expression, implying that B. subtilis supplementation may be a potential therapeutic strategy for schistosomiasis. Our study may highlight the value of probiotics as a beneficial supplementary therapy during human schistosomiasis, but further studies are needed.

Effect of Songlingxuemaikang on mild essential hypertension in patients: a randomized parallel-controlled study.

OBJECTIVE: To evaluate the effect of songlingxuemaikang (SLXMK) on mild essential hypertension in patients in terms of endothelial function. METHODS: We enrolled 90 patients with mild essential hypertension in Xuanwu Hospital from January 2016 to December 2016. To evaluate the effects of SLXMK, the 90 patients were randomly assigned at a 2∶1 ratio into 2 groups: the SLXMK group (500 mg per capsule, 4500 mg/d, n = 60) and the losartan potassium group (50 mg per table, 50 mg/d, n = 30). The total study period was 12 weeks, and the changes of blood pressure, laboratory test and endothelium function were compared between two groups. RESULTS: After 12 weeks of treatment with SLXMK, blood pressure (BP) and plasma lipid levels significantly improved (P < 0.05). Meanwhile, the reactive hyperemia index (RHI) increased in the SLXMK group (P < 0.05). The results of multivariate logistic regression analyses examining the association of selected variables with showed that high level of oxidized low density lipoprotein (ox-LDL) was positively associated with endothelial dysfunction. CONCLUSION: SLXMK not only effectively decreased BP and plasma lipid levels, but also reduced ox-LDL and RHI in patients with mild essential hypertension. And SLXMK might improve endothelial function through decreasing the circulating ox-LDL.

[Raw Materials and End Treatment-based Emission Factors for Volatile Organic Compounds (VOCs) from Typical Solvent Use Sources].

A database of refined raw materials and end treatment-based VOCs emission factors for typical solvent use sources was developed for the Pearl River Delta. For this, the impact of composition and the content of raw materials, production process, and comprehensive end treatment on the emission of VOCs was analyzed. The solvent use sources included printing, furniture manufacturing, and electronic component and equipment manufacturing. The results showed that the main VOCs in the raw materials used in printing were ethyl acetate, propyl acetate, isopropanol, propanol, and ethanol, which contributed 60%-80% to the total amount of VOCs. Ethyl acetate and butyl acetate were the main oxygenated VOCs (OVOCs) from the raw materials used in furniture manufacturing, contributing 45%-65% of the total. The main VOCs from the raw materials used in electronic component and equipment manufacturing were OVOCs such as alcohols, ethers and phenols, BTEX, and halohydrocarbons. The uncontrolled and controlled emission factors for VOCs from printing were 415.2 kg·t-1 and 184.3 kg·t-1, respectively. Of these, solvent-based raw materials accounted for 704.9 kg·t-1 and 200.1 kg·t-1, water-based raw materials accounted for 325.6 kg·t-1 and 230.3 kg·t-1, UV raw materials accounted for 197.0 kg·t-1 and 129.0 kg·t-1, and plant-based raw materials accounted for 89.0 kg·t-1 and 89.0 kg·t-1, respectively. The uncontrolled and controlled emission factors for VOCs from furniture manufacturing were 379.0 kg·t-1 and 290.2 kg·t-1, respectively. Of these, solvent-based raw materials accounted for 603.0 kg·t-1 and 448.5 kg·t-1, water-based raw materials accounted for 80.0 kg·t-1 and 80.0 kg·t-1, and powder raw materials accounted for 230.0 kg·t-1 and 184.0 kg·t-1, respectively. In electronic component and equipment manufacturing, the uncontrolled and controlled emission factors (unit:kg·million-1) for VOCs from AC ceramic capacitors, CC ceramic capacitors, varistors, and aluminum electrolytic capacitors were 59.7 and 40.8, 394.1 and 269.6, 282.4 and 193.2, and 1.2 and 1.0, respectively. The uncontrolled and controlled emission factors for VOCs from the manufacturing of continuous terminals, enameled wire, and printed circuit boards were 56.3 kg·t-1 and 42.8 kg·t-1, 87.2 kg·t-1 and 28.3 kg·t-1, and 26.4 kg·(100 m2)-1 and 11.6 kg·(100 m2)-1, respectively.

Tanshinone IIA attenuates demyelination and promotes remyelination in A. cantonensis-infected BALB/c mice.

BACKGROUND: Angiostrongylus cantonensis infection can cause demyelination in the central nervous system, and there is no effective treatment. METHODS: We used dexamethasone, Tanshinone IIA (TSIIA) and Cryptotanshinone(Two traditional Chinese medicine monomers) in combination with albendazole (AB, a standard anti-helminthic compound) to observe their therapeutic effect on demyelination in A. cantonensis-infected mice. Luxol fast blue staining and electron microscope of myelin sheath, Oligodendrocyte (OL) number and myelin basic protein (MBP) expression in brain was detected in above groups. RESULTS: TSIIA+AB facilitated OL proliferation and significantly increased both myelin sheath thickness and the population of small-diameter axons. In addition, TSIIA treatment inhibited the expression of inflammation-related factors (interleukin [IL]-6, IL-1ß, tumor necrosis factor [TNF]-α, inducible nitric oxide synthase [iNOS]) rather than inhibiting eosinophil infiltration in brain. TSIIA also decreased microglial activation and shifted their phenotype from M1 to M2. CONCLUSIONS: Taken together, these results provide evidence that TSIIA combined with AB may be an effective treatment for demyelination caused by A. cantonensis infection and other demyelinating diseases.

Anthocyanin is involved in the activation of pyroptosis in oral squamous cell carcinoma.

BACKGROUND: The anti-carcinogenic effects of anthocyanin are well documented. Oral squamous cell carcinoma is one of the most common and lethal cancer types due to its high degree of malignancy and poor prognosis. The main purpose of the current study was to investigate the potential inhibitory effects of anthocyanin on oral squamous cell carcinoma and identify effective targets for therapy. METHODS: Cell viability was measured using cell counting kit-8 (CCK8). Cell migration and invasion abilities were determined using scratch-wound and Transwell invasion assays, respectively. mRNA and protein expression patterns of nucleotide-binding oligomerization domain-like receptor pyrin domain containing 3 (NLRP3), caspase-1 and IL-1ß were detected using qRT-PCR, immunofluorescence and western blot. The gasdermin D (GSDMD) level was determined via confocal microscopy and western blot. RESULTS: Anthocyanin reduced the viability of oral squamous cell carcinoma cells and inhibited migration and invasion abilities. Simultaneously, activation of pyroptosis was associated with enhanced expression of NLRP3, caspase-1, and IL-1ß. Upon administration of caspase-1 inhibitors, anthocyanin-activated pyroptosis was suppressed and cell viability, migration, and invasion rates concomitantly enhanced. CONCLUSION: Anthocyanin promotes the death of oral squamous cell carcinoma cells through activation of pyroptosis and inhibits tumor progression.

Long non-coding RNA, Bmcob, regulates osteoblastic differentiation of bone marrow mesenchymal stem cells.

Disordered osteoblastic differentiation of bone marrow mesenchymal stem cells (BMSCs) contributes to bone loss. The underlying mechanisms are complicated and not fully understood. Long non-coding RNAs (lncRNAs) are emerging as an important regulatory factors on bone metabolism. Here, we discovered a novel lncRNA, Bmcob, which modulated osteogenic differentiation of primary mouse BMSCs. Expression levels of Bmcob were significantly upregulated in early-to-mid stages during osteoblast differentiation. Silencing of Bmcob suppressed osteoblastic differentiation of BMSCs in vitro, whereas its overexpression protected BMSCs from oxidative stress induced inhibition on osteogenesis. Subsequently, we discovered that selenoprotein P (Sepp1), which is located next to the Bmcob gene, was partly responsible for the regulatory effects of Bmcob. In addition, a series of selenoproteins were downregulated in BMSCs with Bmcob knockdown. Mechanistically, we found Bmcob was associated with selenocysteine insertion sequence binding protein 2 (SBP2), a critical trans-acting factor for selenoprotein synthesis. Finally, we suggest an explanatory hypothesis that through modulating nucleocytoplasmic shuttling of SBP2, Bmcob regulates a number of selenoproteins expression, including sepp1, and then mediates osteogenesis of BMSCs. Taken together, our results revealed a novel mechanism regulating osteogenesis of BMSCs and may function as a potential target for treating osteoporosis.

A hederagenin saponin isolated from Clematis ganpiniana induces apoptosis in breast cancer cells via the mitochondrial pathway.

Natural plants offer a treasure trove of resources for anticancer drug development. Clematis are widely used in Traditional Chinese Medicine. However, studies on the active substances in Clematis are scarce. In the present study, four monomer compounds were successfully extracted from this species and their inhibitory effects on the growth of breast cancer cells were investigated using bioactivity tests. Among them, Clematis hederagenin saponin (CHS) belongs to the class of triterpenoid saponins. CHS showed cytotoxic effects on breast cancer cells in a dose- and time-dependent manner. The compound also induced apoptosis in breast cancer cells in a time-dependent manner. Further investigation into the underlying mechanisms of apoptosis induction in breast cancer cells showed that the compound significantly reduced mitochondrial Apaf-1 and cytochrome c proteins in breast cancer cells. In addition, it upregulated the activities of caspase-3 and -9. In conclusion, CHS induced apoptosis in breast cancer cells through regulation of the mitochondrial apoptosis pathway. The results suggest that the hederagenin saponin extracted from Clematis ganpiniana offers great potential as a novel anti-breast cancer drug.

Dihydrocelastrol inhibits multiple myeloma cell proliferation and promotes apoptosis through ERK1/2 and IL-6/STAT3 pathways in vitro and in vivo.

Multiple myeloma (MM) is the second most frequent malignant hematological disease. Dihydrocelastrol (DHCE) is synthesized by hydrogenated celastrol, a treterpene isolated from Chinese medicinal plant Tripterygium regelii. In this study, we first reported the anti-tumor activity of DHCE on MM cells. We found that DHCE could inhibit cell proliferation and promote apoptosis through caspase-dependent way in vitro. In addition, DHCE could inactivate the expression of interleukin (IL)-6 and downregulate the phosphorylation of extracellular regulated protein kinases (ERK1/2) and the signal transducer and activator of transcription 3 (STAT3) in MM. It also retained its activity against MM cell lines in the presence of IL-6. Furthermore, treatment of MM cells with DHCE resulted in an accumulation of cells in G0/G1 phase of the cell cycle. Notably, DHCE reduced the expression of cyclin D1 and cyclin-dependent kinases 4 and 6 in MM cell lines. Additionally, its efficacy toward the MM cell lines could be enhanced in combination with the histone deacetylase inhibitor panobinostat (LBH589), which implied the possibility of the combination treatment of DHCE and LBH589 as a potential therapeutic strategy in MM. In addition, treatment of NCI-H929 tumor-bearing nude mice with DHCE (10 mg/kg/d, i.p., 1-14 days) resulted in 73% inhibition of the tumor growth in vivo. Taken together, the results of our present study indicated that DHCE could inhibit cellular proliferation and induce cell apoptosis in myeloma cells mediated through different mechanisms, possibly through inhibiting the IL-6/STAT3 and ERK1/2 pathways. And it may provide a new therapeutic option for MM patients.

[A study of global ecological adaptability and field selection practices of Panax ginseng].

Through the development of ecological suitability analysis of producing area and the selection criteria of farmland cultivation in the global range of ginseng, we aim to provide scientific basis for rational planning, production layout and standardized planting of farmland. We analyze the data based on the ecological factors from 271 sample plots of Panax ginseng, including both the traditional producing regions recorded in past dynasties medicinal works and the popular production regions in the world, using global geographic information system for medicinal plant(GMPGIS) developed by ICMM (Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences). We concluded that the suitable producing areas in global for P. ginseng mainly included America, Canada, China, Russia, Japan, North Korea, France, Italy, Ukraine, and South Korea. In addition, the suitable producing areas in China mainly included Heilongjiang, Jilin, Liaoning, Shanxi, Gansu, Hubei, Sichuan, Inner Mongolia, Shandong, and Shanxi. Besides, based on the references and the experience of ginseng-producing and our many years' work on the 1,000-hectare plantation of P. ginseng, we established a standard land selection protocol for cultivation of P. ginseng. The use of GMPGIS to select the most optimum ginseng production regions provides a new scientific basis for introduction, cultivation, tending, protection, cultivation normalization for P. ginseng and the standard land selection protocol would lay a solid foundation for the high quality P. ginseng production.

Nausea and vomiting in early pregnancy and the risk of neural tube defects: a case-control study.

There has been considerable professional debate on the association between nausea and vomiting in early pregnancy (NVP) and neural tube defects (NTDs) risk. This study explored the association between NVP and NTDs risk, and the effect of folic acid supplements on the association. A 1:1 matched case-control study was conducted and conditional logistic regression model was used to analyze the associations. The result showed the odds ratio (OR) of severe NVP for NTDs was 2.403 (95%CI 1.437,4.017; P<0.001) and that of moderate NVP was 1.469 (95%CI 1.063,2.031; P = 0.020) compared with light NVP when adjusted by the potential confounders. Stratified by intake of folic acid supplements, the ORs for severe and moderate NVP turned to 2.147 (95%CI 1.140, 4.043; P = 0.018) and 2.055 (95%CI 1.320, 3.199; P = 0.001) in the stratum of non-intake of folic acid supplements while ORs reduced to 1.851 (95%CI 0.729, 4.699; P = 0.195) and 1.003 (95%CI 0.594, 1.694; P = 0.992) in the stratum of intake of folic acid supplements, respectively. We conclude that severe/moderate NVP has an association with the risk of NTDs, which was not found in the group with intake of folic acid supplements. Folic acid supplements should be recommended to use for the prevention of NTDs.

Arsenite binding-induced zinc loss from PARP-1 is equivalent to zinc deficiency in reducing PARP-1 activity, leading to inhibition of DNA repair.

Inhibition of DNA repair is a recognized mechanism for arsenic enhancement of ultraviolet radiation-induced DNA damage and carcinogenesis. Poly(ADP-ribose) polymerase-1 (PARP-1), a zinc finger DNA repair protein, has been identified as a sensitive molecular target for arsenic. The zinc finger domains of PARP-1 protein function as a critical structure in DNA recognition and binding. Since cellular poly(ADP-ribosyl)ation capacity has been positively correlated with zinc status in cells, we hypothesize that arsenite binding-induced zinc loss from PARP-1 is equivalent to zinc deficiency in reducing PARP-1 activity, leading to inhibition of DNA repair. To test this hypothesis, we compared the effects of arsenite exposure with zinc deficiency, created by using the membrane-permeable zinc chelator TPEN, on 8-OHdG formation, PARP-1 activity and zinc binding to PARP-1 in HaCat cells. Our results show that arsenite exposure and zinc deficiency had similar effects on PARP-1 protein, whereas supplemental zinc reversed these effects. To investigate the molecular mechanism of zinc loss induced by arsenite, ICP-AES, near UV spectroscopy, fluorescence, and circular dichroism spectroscopy were utilized to examine arsenite binding and occupation of a peptide representing the first zinc finger of PARP-1. We found that arsenite binding as well as zinc loss altered the conformation of zinc finger structure which functionally leads to PARP-1 inhibition. These findings suggest that arsenite binding to PARP-1 protein created similar adverse biological effects as zinc deficiency, which establishes the molecular mechanism for zinc supplementation as a potentially effective treatment to reverse the detrimental outcomes of arsenic exposure.

Maternal body mass index and the association between folic acid supplements and neural tube defects.

AIM: To study the influence of maternal body mass index (BMI) on the association between folic acid supplementation and neural tube defects (NTDs) risk in offspring. METHODS: A hospital-based, case-control study was conducted between 2006 and 2008 on 459 mothers with NTDs-affected births and 459 mothers without NTDs-affected births. Logistic regression models examined the associations between folic acid supplementation and the NTDs risk in offspring for all mothers, underweight/normal weight mothers (BMI<24.0) and overweight/obese mothers (BMI ≥24.0). The effects were evaluated by adjusted odds ratio (AOR) and 95% confidence intervals (CIs) with SAS 9.1.3 software. RESULTS: The overall AOR for periconceptional folic acid supplementation was 0.315 (95% CI = 0.172-0.577) when compared with no supplements. Stratified by maternal BMI, the AOR for periconceptional folic acid supplementation in overweight/obese mothers was greater than in underweight/normal weight mothers (0.646 vs. 0.208). The AOR for folic acid supplementation within 3 months before conception was 0.711 (95% CI = 0.323-1.563) in all mothers. Stratified by maternal BMI, the AOR for folic acid supplementation within 3 months before conception in overweight/obese mothers was greater than in underweight/normal weight mothers (0.658 vs. 0.527). CONCLUSION: The association between folic acid supplementation and the reduced NTDs risk was weaker in overweight/obese mothers (BMI ≥24.0) than in underweight/normal weight mothers (BMI <24.0).

A herbal composition of semen hoveniae, radix puerariae, and fructus schisandrae shows potent protective effects on acute alcoholic intoxication in rodent models.

This study is designed to evaluate the effects of a herbal composition of Semen Hoveniae, Radix Puerariae and Fructus Schisandrae (SRF) against acute alcoholic intoxication. The animals were treated with SRF extract (SRFE) for 14 days, and ethanol was conducted subsequent to the final treatment. The effects of SRFE on righting reflex, inebriety rates, kinetic parameters of blood ethanol and acetaldehyde were determined. In addition; levels of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), the activities of cytochrome P450 2E1 (CYP2E1), selected antioxidative enzymes, and the contents of malonaldehyde (MDA) were measured. SRFE-pretreated rodents exhibited lower rates of intoxication, longer times to loss of righting reflex, and shortened times to recovery of righting reflex than in controls. The peak concentrations and area under the time-concentration curves were lower in the pretreated animals than in controls, which corresponded to higher levels of ADH and ALDH in both gastrointestines and livers of the SRFE-treated animals. The activities of CYP2E1 were lower in SRFE-pretreated animals, which also exhibited higher activities of some antioxidant enzymes and lower hepatic MDA levels. These findings suggest that the anti-inebriation effects of SRFE may involve inhibition of ethanol absorption, promotion of ethanol metabolism, and enhancing hepatic anti-oxidative functions.