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Rosa roxburghii Tratt. is an important commercial horticultural crop endemic to China, which is recognized for its extremely high content of L-ascorbic acid (AsA). To understand the mechanisms underlying AsA overproduction in fruit of R. roxburghii, content levels, accumulation rate, and the expression of genes putatively in the biosynthesis of AsA during fruit development have been characterized. The content of AsA increased with fruit weight during development, and AsA accumulation rate was found to be highest between 60 and 90 days after anthesis (DAA), with approximately 60% of the total amount being accumulated during this period. In vitro incubating analysis of 70DAA fruit flesh tissues confirmed that AsA was synthesized mainly via the L-galactose pathway although L-Gulono-1, 4-lactone was also an effective precursor elevating AsA biosynthesis. Furthermore, in transcript level, AsA content was significantly associated with GDP-L-galactose phosphorylase (RrGGP2) gene expression. Virus-induced RrGGP2 silencing reduced the AsA content in R. roxburghii fruit by 28.9%. Overexpressing RrGGP2 increased AsA content by 8-12-fold in tobacco leaves and 2.33-3.11-fold in tomato fruit, respectively, and it showed enhanced resistance to oxidative stress caused by paraquat in transformed tobacco. These results further justified the importance of RrGGP2 as a major control step to AsA biosynthesis in R. roxburghii fruit.

The long noncoding RNA (lncRNA) nuclear-enriched abundant transcript 1 (NEAT1) has been implicated in many tumors risk including gastric cancer. However, the association of single nucleotide polymorphisms (SNPs) at NEAT1 with gastric cancer risk has not been studied. The aim of this study was to investigate the association between SNPs in NEAT1 and gastric cancer susceptibility. In this study, four SNPs in lncRNA NEAT1 were selected for genotyping in 484 gastric cancer patients and 484 controls in Chinese Han population. Quantitative real-time PCR (qRT-PCR) was conducted to evaluate the potential function of rs3825071. Attributable risk percentage (ARP) and population attributable risk percentage (PARP) were used to assess the epidemiological effect. In the dominant model (GG), the genotypes AG + AA of rs3825071 and rs7943779 were associated with an increased risk of gastric cancer (OR = 1.72, 95%CI = 1.27–2.32 and OR = 1.63, 95%CI = 1.19–2.22). Individuals harboring ≥ 3 risk alleles have higher risk of gastric cancer (OR = 1.88, 95% CI = 1.26–2.80, P = 0.002). ARP and PARP associated with gastric cancer were 42.53% and 10.88% for rs3825071, and were 33.78% and 6.26% for rs7943779, respectively. Furthermore, compared with the genotype GG of rs3825071, the genotypes AG and AA had higher expression of NEAT1. We found that the genetic variations in NEAT1 were significantly associated with risk of gastric cancer. The G > A variant of rs3825071 may confer gastric cancer susceptibility by changed biological effects to increase the expression of NEAT1.

Owing to their characteristic structures, metal-organic frameworks (MOFs) are considered as the leading candidate for drug-delivery materials. However, controlling the synthesis of MOFs with uniform morphology and high drug-loading/release efficiencies is still challenging, which greatly limits their applications and promotion. Herein, a multifunctional MOF-based drug-delivery system (DDS) with a controlled pore size of 100-200 nm for both therapeutic and bioimaging purposes was successfully synthesized in one step. Fe-MOF-based microcapsules were synthesized through a competitive coordination method, which was profited from the intrinsic coordination characteristics of the Fe element and the host-guest supramolecular interactions between Fe3+ and polyoxometalates anions. This as-synthesized macroporous DDS could greatly increase the drug-loading/release rate (77%; 83%) and serve as a magnetic resonance (MR) contrast agent. Because an Fe-containing macroporous DDS presents ultrahigh drug loading/release, the obtained 5-FU/Fe-MOF-based microcapsules displayed good biocompatibility, extremely powerful inhibition of tumor growth, and satisfactory MR imaging capability. Given all these advantages, this study integrates high therapeutic effect and diagnostic capability via a simple and effective morphology-controlling strategy, aiming at further facilitating the applications of MOFs in multifunctional drug delivery.

Diarrhea is considered to be associated with microbial dysbiosis caused by infection of pathogens but poorly understood. We herein characterized the colonic microbiota of diarrheal early-weaning piglets infected with porcine circovirus type 2 (PCV2) and Campylobacter. Campylobacter infection significantly decreased species richness and Shannon diversity index of colonic microbiota together with a significant increase in the proportion of Campylobacter and Enterobacteriaceae, whereas no significant difference on the above indexes was observed in piglets infected with PCV2 compared with healthy piglets. PCV2 and Campylobacter infection could disturb the homeostasis of colonic microbiota through deterioration of ecological network within microbial community, and specially Campylobacter performed as a module hub in ecological networks. The microbial dysbiosis caused metabolic dysfunction and led to a remarkable reduction in production of short chain fatty acids, following by a higher pH level in colon cavity. Campylobacter infection disturbed the function of colonic tract barrier observed in terms of significant lower relative expression of claudin-1, occluding, and zonula occludens protein-1 genes, and PCV2 infection induced intestinal inflammation together with a higher permeability of colon. Generally, these results suggested that PCV2 and Campylobacter infection could induce microbial dysbiosis and metabolic dysfunction, and cause intestinal disorder, all of which finally were associated to contribute to the diarrhea of early-weaning piglets.

Calorie restriction (CR) ameliorates various diseases including cardiovascular disease. However, its protection and underlying mechanisms against atherosclerosis remain un-fully elucidated. In this study, we fed apoE deficient (apoE-/-) mice in Control group a high-fat diet (HFD, 21% fat plus 0.5% cholesterol) or in CR group a CR diet (CRD, 2% fat plus 0.5% cholesterol, ∼40% calorie restriction and same levels of cholesterol, vitamins, minerals and amino acids as in HFD). After 16 weeks feeding, compared with HFD, CRD substantially reduced atherosclerosis in mice. CRD increased SMC and collagen content but reduced macrophage content, necrotic core and vascular calcification in lesion areas. Mechanistically, CRD attenuated bodyweight gain, improved lipid profiles but had little effect on macrophage lipid metabolism. CRD also inhibited expression of inflammatory molecules in lesions. Taken together, our study demonstrates CRD effectively reduces atherosclerosis in apoE-/- mice, suggesting it as a potent and reproducible therapy for atherosclerosis management.

Endothelial dysfunction is an initial and essential step in vascular-remodeling diseases, including atherosclerosis and neointima formation. During vascular remodeling, activated endothelial cells can release pro-inflammatory factors that promote phenotypic switching of vascular smooth muscle cells (VSMCs) to the proliferative phenotype. We previously reported that MEK1/2 inhibitor, U0126, has a protective effect on the development of atherosclerosis and vascular calcification. However, the effect of MEK1/2 inhibitors on neointimal formation and the underlying mechanism is not fully understood. We determined that MEK1/2 inhibitor reduced carotid artery ligation-induced neointimal formation, while increased collagen and elastin levels and vascular integrality. Mechanistically, MEK1/2 inhibitor or ERK1/2 siRNA increased miR-126-3p level in endothelial cells, thereby inhibiting expression of regular of G-protein signaling 16 (RGS16), a miR-126-3p target gene, to activate the C-X-C motif chemokine ligand 12 (CXCL12)/C-X-C motif chemokine receptor 4 (CXCR4) signaling pathway. Accordingly, miR-126-3p was also increased by U0126 in serum and carotid artery. RGS16 was inhibited while CXCR4 and CXCL12 was increased by U0126 in neointimal areas, especially in the endothelium. Moreover, similar results were observed in atherosclerotic plaques of high-fat diet-fed apolipoprotein E deficiency (apoE−/−) mice. In addition, vascular cell adhesion molecule 1 (VCAM-1), another miR-126-3p target gene, was reduced by U0126 in the neointimal areas, resulting reduced monocytes/macrophages accumulation. Taken together, our results indicate that MEK1/2 inhibitor can reduce neointima formation by activating endothelial miR-126-3p production to facilitate endothelium repair while reduce monocyte adhesion/infiltration.

Background Dexmedetomidine (DEX) has a pharmacological profile that should allow rapid recovery and prevent undesirable outcomes such as pulmonary complications. Methods This large retrospective study compared the beneficial effects of perioperative infusion of DEX with propofol on the postoperative outcome after coronary artery bypass graft surgery. We reviewed patients’ medical notes at Luoyang Central Hospital from 1st January 2012 to 31st December 2019. All continuous variables, if normally distributed, were presented as mean ± SD; Otherwise, the non-normally distributed data and categorical data were presented as median (25-75 IQR) or number (percentage). The Mann-Whitney U test and Chi-square test were used to evaluate the difference of variables between the DEX and propofol groups. Multivariate logistic regression analysis was performed on the main related and differential factors in the perioperative period. Results A total of 1388 patients were included in the study; of those, 557 patients received propofol infusion, and 831 patients received dexmedetomidine. DEX significantly reduced postoperative pulmonary complications compared with propofol, 7.82% vs 13.29%; P P P = 0.001 and hospital stay, 20 (17,24) vs 22 (17,28) days; P P < 0.001, respectively. Interestingly, patients receiving DEX had significantly shorter surgical time compared to propofol; 275 (240,310) vs 280 (250,320) minutes respectively (P = 0.005) and less estimated blood loss (P = 0.001). Conclusion Perioperative infusion of dexmedetomidine improved the desirable outcomes in patients who had coronary artery bypass graft surgery compared with propofol.

Recently, the widespread use of antibiotics is becoming a serious worldwide public health challenge, which causes antimicrobial resistance and the occurrence of superbugs. In this context, MnO2 has been proposed as an alternative approach to achieve target antibacterial properties on Streptococcus mutans (S. mutans). This requires a further understanding on how to control and optimize antibacterial properties in these systems. We address this challenge by synthesizing δ-MnO2 nanoflowers doped by magnesium (Mg), sodium (Na), and potassium (K) ions, thus displaying different bandgaps, to evaluate the effect of doping on the bacterial viability of S. mutans. All these samples demonstrated antibacterial activity from the spontaneous generation of reactive oxygen species (ROS) without external illumination, where doped MnO2 can provide free electrons to induce the production of ROS, resulting in the antibacterial activity. Furthermore, it was observed that δ-MnO2 with narrower bandgap displayed a superior ability to inhibit bacteria. The enhancement is mainly attributed to the higher doping levels, which provided more free electrons to generate ROS for antibacterial effects. Moreover, we found that δ-MnO2 was attractive for in vivo applications, because it could nearly be degraded into Mn ions completely following the gradual addition of vitamin C. We believe that our results may provide meaningful insights for the design of inorganic antibacterial nanomaterials.

Recently, the widespread use of antibiotics is becoming a serious worldwide public health challenge, which causes antimicrobial resistance and the occurrence of superbugs. In this context, MnO2 has been proposed as an alternative approach to achieve target antibacterial properties on Streptococcus mutans (S. mutans). This requires a further understanding on how to control and optimize antibacterial properties in these systems. We address this challenge by synthesizing δ-MnO2 nanoflowers doped by magnesium (Mg), sodium (Na), and potassium (K) ions, thus displaying different bandgaps, to evaluate the effect of doping on the bacterial viability of S. mutans. All these samples demonstrated antibacterial activity from the spontaneous generation of reactive oxygen species (ROS) without external illumination, where doped MnO2 can provide free electrons to induce the production of ROS, resulting in the antibacterial activity. Furthermore, it was observed that δ-MnO2 with narrower bandgap displayed a superior ability to inhibit bacteria. The enhancement is mainly attributed to the higher doping levels, which provided more free electrons to generate ROS for antibacterial effects. Moreover, we found that δ-MnO2 was attractive for in vivo applications, because it could nearly be degraded into Mn ions completely following the gradual addition of vitamin C. We believe that our results may provide meaningful insights for the design of inorganic antibacterial nanomaterials.

Current studies have demonstrated that significant increased LPA levels to be observed in ascites in patients with ovarian cancer. Although several studies have shown that Lysophosphatidic acid (LPA) related to the progression of ovarian cancer, which LPA receptors (LPARs) and G coupled protein subtypes mediated in LPA actions have not been clearly elucidated. This study aimed to clarify the roles of LPA and it’s subtype-specific LPARs mediating mechanisms in ovarian cancer by integrated using bioinformatic analysis and biological experimental approaches. The big data analysis shown that LPA3 was the only differentially expressed LPA receptor among the six LPARs in ovarian cancer and further verified in immunohistochemistry of tissue microarrays. Also found that LPA3 was also highly expressed in ovarian cancer tissue and ovarian cancer cells. Importantly, LPA significantly promoted the proliferation and migration of LPA3-overexpressing ovarian cancer cells, while the LPA-induced actions blocked by Ki16425, a LPAR1/3 antagonist treated, and LPA3-shRNA transfected. In vivo study indicated that the LPA3-overexpressing cell derived tumors metastasis, tumors volume and tumors mass were apparently increased in xenografted nude mice. In addition, we also observed that LPA3 was differential high-expression in ovarian cancer tissue of the patients. Our studies further confirmed the LPA3/Gi/MAPKs/NF-κB signals were involved in LPA-induced oncogenic actions in ovarian cancer cells. Our findings indicated that the LPA3 might be a novel precise therapeutic target and potential biomarker for ovarian cancer.

Background Moyamoya disease belongs to rare diseases which are arousing public awareness of its importance in China. In order to investigate the clinical features of inpatients diagnosed Moyamoya disease, the study was conducted to collect clinical information data of subjects on demographic information and clinical characteristics in Henan, China. Methods The data of 198 cases of Moyamoya disease from 56 tertiary hospitals in Henan province from January 2003 to June 2015 were collected retrospectively. Analysis was performed based on demographic, clinical and radiological characteristics of the patients. Results The mean onset age was 44.03 ± 14.45 years old. Unilateral limb weakness (36.4%) was the most common physical examination. Primary clinical manifestation was headache and dizziness (50.3%). Cranial CT showed cerebral infarction was mainly located in the frontal lobe (27.4%). MRA and DSA showed lesions mainly located in the middle cerebral artery (30.3% and 18.7%). Conclusions Clinical manifestations of Moyamoya disease varied. Early diagnosis was necessary to reduce the misdiagnosis rate of this disease. Symptoms, radiological characteristics, and lesion localization characteristics should be fully considered, especially for indicators with a certain onset age, headache and dizziness, lesion located in the frontal lobe of middle cerebral artery.

At present, the research and innovation of packaging materials are in a period of rapid development. Starch, a sustainable, low-cost, and abundant polymer, can develop environmentally friendly packaging alternatives, and it possesses outstanding degradability and reproducibility in terms of improving environmental issues and reducing oil resources. However, performance limitations, such as less mechanical strength and lower barrier properties, limit the application of starch in the packaging industry. The properties of starch-based films can be improved by modifying starch, adding reinforcing groups, or blending with other polymers. It is of significance to study starch as an active and intelligent packaging option for prolonging shelf life and monitoring the extent of food deterioration. This paper reviews the development of starch-based films, the current methods to enhance the mechanical and barrier properties of starch-based films, and the latest progress in starch-based activity, intelligent packaging, and food applications. The potential challenges and future development directions of starch-based films in the food industry are also discussed.

Background: A novel pyrrolo indole alkaloids, named Robustanoids A, was isolated from Coffea canephora beans, and it inhibits proliferation of prostate cancer (PCa) cells. However, the molecular mechanism linking Robustanoids A to the tumorigenesis of PCa is not yet clear. Methods: We investigated the expression of lncRNAs in PCa cells with Robustanoids A and control group by microarray analysis. The expression level of TCONS_00027385 in PCa tissues and cell lines was detected by qRT-PCR. Additionally, we conducted functional experiments to investigate the biological effects of TCONS_00027385 on the development of PCa both in vitro and in vivo. Furthermore, bioinformatic analysis, luciferase reporter experiment, RIP assay, pulldown assay, and protein chip were performed to investigate the oncogenic molecular mechanisms of TCONS_00027385.Results: In our current study, we focused on TCONS_00027385, which was up-regulated in PCa tissues and cell lines. The high expression of TCONS_00027385 was related to the progression of PCa. Function assays revealed that silencing TCONS_00027385 inhibited PCa cell proliferation and induced apoptosis, while over-expression of TCONS_00027385 remarkably played an opposite role. A deeper investigation showed that TCONS_00027385 acted as a sponge for hsa-miR-874-5p in PCa, and ASCC2 was a target of miR-874-5p in the downstream. Moreover, a positive association between TCONS_00027385 with ASCC2 and a negative relationship between miR-874-5p and TCONS_00027385 (or ASCC2) were also founded. According to the rescue assay, inhibiting ASCC2 could partially suppress the oncogenic effect on cell proliferation and apoptosis in PCa caused by the overexpression of TCONS_00027385.Conclusion: TCONS_00027385 acted as a competing endogenous RNA (ceRNA) for miR-874-5p to regulate the expression of ASCC2. TCONS_00027385 regulated the miR-874-5p/ASCC2 axis to promote PCa progression.

Chronic diseases, especially cardiovascular diseases (CVD), have become one of the main causes affecting human health. Hypertension is a prominent representative of CVD. The formation and development of hypertension is closely related to people's daily diet. A large number of studies have shown that excessive intake of salt (NaCl) could increase the risk of hypertension. In recent years, more and more investigations have focused on other cations that may be contained in edible salt, exploring whether they have an effect on hypertension and the underlying mechanism. This article focuses on the relationship between four metal elements (potassium, calcium, magnesium, and zinc) and hypertension, by discussing the main metabolic pathway, the impact of diet intake on blood pressure, and especially the regulation mechanisms on blood pressure in detail. At the same time, some opinions and suggestions are put forward, combined with the current hot topics "salt reduction" and "salt substitution".

The bioactive lipid sphingosine 1-phosphate (S1P) is implicated in many pivotal processes for the physiological and pathological actions via activating five types of G-protein-coupled S1P receptors (S1PR1-5). The role of S1P in renal cell carcinoma (RCC) and its receptor subtype specific mediating mechanism are poorly studied. So we focus on the regulatory role of S1P in RCC progression and the receptor subtypes involved in S1P-induced actions, intending to further clarify a novel therapeutic target for RCC. Analysis of The Cancer Genome Atlas (TCGA) databases showed that the patients with high expression of S1PR3 had significantly worse overall than with low expression. We further demonstrated that S1P could promote proliferation, migration, and epithelial-mesenchymal transition (EMT) of renal cancer cells in vitro, and the actions were enhanced with the increase of S1PR3 expression. Meanwhile, the results in animal experiments also showed that S1PR3 could accelerate tumorigenesis and metastasis of RCC. Our study also clarified the mechanism for S1P induced cell proliferation is mediated by S1PR3/Gi/p38/Akt/p65/cyclin D1-CDK4 pathway and the main pathway for migration is S1PR3/Gi/q/ERK/p38/p65. In addition, S1PR3 was involved in epidermal growth factor (EGF)-induced actions by enhancing protein expression, not by transactivation of epidermal growth factor receptor (EGFR). These results also further supported our conclusion that the carcinogenic role of S1P/S1PR3 axis. Thus, our findings provide that S1PR3 may be a promising small molecular therapeutic target for S1PR3 expressed cancers.

Five Mn(I) photo-activated carbon monoxide-releasing molecules (photo-CORMs) with benzimidazole coligands, namely [MnBr(CO)3L1] (1, L1 = 2-(2-pyridyl)benzimidazole), [Mn(CO)2L1(PPh3)2](ClO4) (2), [MnBr(CO)3L2] (3, L2 = 2,2′-bisbenzimidazole), [MnBr(CO)3L3]·CH3OH (4, L3 = 2,6-bis(benzimidazole-2′-yl)pyridine) and fac-[MnBr(CO)3L4] (5, L4 = 2,4-bis(benzimidazole-2′-yl) pyridine) were synthesized by reactions of MnBr(CO)5 with complexes L1–L4, respectively, and characterized via single crystal X-ray diffraction, elemental analysis, 1H-NMR, 13C-NMR, IR, UV-vis and fluorescence spectroscopy. The CO-release properties of 1–5 were investigated using the myoglobin assay and CO detection, and the results show that all of the complexes could release CO rapidly upon exposure to 365 nm UV light. Comparing their half-lives of CO release, we found that increasing the degree of unsaturation and conjugation of the ligand frame could be advantageous for prolonging the time of CO-release, and that the luminescence intensity of 1–5 could gradually be enhanced. The cellular fluorescence imaging tests demonstrate that these Mn(I) photo-CORMs can be taken up by human liver cells (HL-7702) and liver cancer cells (SK-Hep1), and exhibit good capabilities for bioimaging. A cell viability assay for SK-Hep1 shows that the anticancer activity of 3 is better than that of other complexes.

Estimating population attributable risks of potential modifiable risk factors for stroke and (or) myocardial infarction may be useful for planning cardiovascular disease (CVD) preventive strategies. A population of 17,292 adults aged 18 years and older from a cross-sectional survey was included in the study. The binary logistic regression was used to evaluate the association between risk factors with disease events, then population attributable fraction according to prevalence and odds ratios were calculated to identify and compare the effects at different subpopulations. We found that the main risk factor for CVD events was hypertension with about 50% of population attributable fraction; prehypertension (22.24%) only acts at rural older females; the efficiency of low- and moderate-level physical activities were higher in males (over 20%) than females (under 20%); ever smoked contributed to CVDs in rural older populations (males, 19.25%; females, 5.57%) and urban younger males (54.52%); while as for high body mass index, overweight (12.59%) only made contribution to rural males over 60 years. In conclusion, hypertension control in the whole population, physical activity increasing in males and older females, smoking prevention in rural elders and urban younger males, and slimming in rural elder males might be effective to reduce the burden of CVDs in Henan.

The lysosome inhibitors bafilomycin A1 and chloroquine have both lysosomotropic properties and autophagy inhibition ability, and are promising clinical agents to be used in combination with anticancer drugs. In order to investigate this combination effect, HepG2 cells were treated with bafilomycin A1, chloroquine, or/and doxorubicin, and their proliferative ability, induction of apoptosis, and the changes of lysosomal membrane permeabilization and mitochondrial membrane potential were studied. The results demonstrate that treatment with bafilomycin A1 or chloroquine alone at a relatively low concentration promotes the inhibitory effect of doxorubicin on cell growth and apoptosis. Further studies reveal that bafilomycin A1 and chloroquine promote lysosomal membrane permeabilization and the reduction of mitochondrial membrane potential induced by doxorubicin. Our findings suggest that bafilomycin A1 and chloroquine potentiate the anticancer effect of doxorubicin in hepatic cancer cells and that supplementation of conventional chemotherapy with lysosome inhibitors may provide a more efficient anticancer therapy.

As a tool for modifying the genome, gene editing technology has developed rapidly in recent years, especially in the past two years. With the emergence of new gene editing technologies, such as transposon editing tools, numerous advancements have been made including precise editing of the genome, double base editing, and pilot editing. This report focuses on the development of gene editing tools in recent years, elaborates the progress made in classic editing tools, base editor and other new editing tools, and provides insights into challenges and opportunities.

Powdery mildew (PM) is considered a major cause of yield losses and reduced quality in cucumber worldwide, but the molecular basis of PM resistance remains poorly understood. A segment substitution line, namely, SSL508-28, was developed with dominant PM resistance in the genetic background of PM-susceptible cucumber inbred line D8. The substituted segment contains 860 genes. An iTRAQ-based comparative proteomic technology was used to map the proteomes of PM-inoculated and untreated (control) D8 and SSL508-28. The number of differentially regulated proteins (DRPs) in SSL508-28 was almost three times higher than that in D8. Fourteen DRPs were located in the substituted segment interval. Comparative gene expression analysis revealed that nodulin-related protein 1 (NRP1) may be a good candidate for PM resistance. Gene Ontology enrichment analysis showed that DRPs functioning in tetrapyrrole biosynthetic process, sulfur metabolic process and cell redox homeostasis were specifically enriched in the resistant line SSL508-28. DRPs categorized in the KEGG term photosynthesis increased in both lines upon PM infection, suggesting that the strategies used by cucumber may be different from those used by other crops to react to PM attacks at the initial stage. The measurement of hydrogen peroxide and superoxide anion production and net photosynthetic rate were consistent with the changes in protein abundance, suggesting that the proteomic results were reliable. There was a poor correlation between DRPs measured by iTRAQ and the corresponding gene expression changes measured by RNA-seq with the same experimental design. Taken together, these findings improve the understanding of the molecular mechanisms underlying the response of cucumber to PM infection.

Human umbilical cord mesenchymal stem cells (hUC-MSCs) are potential stromal cells which are regarded as the most feasible stem cell group in cell therapy. The maintenance of cell survival without differentiation is important in cell transplantation and stem cell therapy. However, negative factors exist in cell transplantation. Lysophosphatidic acid (LPA) is a non-antigenic small molecule phospholipid which induced several fundamental cellular responses, such as cell proliferation, apoptosis and migration. In this study we aimed to explore the effects of LPA on the survival and differentiation of MSCs and its availability in cell therapy. We found that LPA stimulated hUC-MSC proliferation and protected hUC-MSCs from lipopolysaccharide (LPS) induced apoptosis. We also observed that CD29, CD44, CD73, CD90 and CD105 were expressed, whereas CD34 and CD45 were not expressed in hUC-MSCs, and these makers have no change in LPA containing medium, which indicated that LPA accelerated the survival of hUC-MSCs in an undifferentiating status. We also demonstrated that higher expressed LPAR1 involved in LPA stimulated cell survival action. LPA stimulated cell proliferation was associated with LPAR1 mediated Gi/o-proteins/ERK1/2 pathway. On the other hand, LPA protected hUC-MSCs from LPS-induced apoptosis through suppressing caspase-3 activation by LPAR1 coupled with a G protein, but not Gi/o or Gq/11 in hUC-MSC. Collectively, this study demonstrated that LPA increased the proliferation and survival of hUC-MSCs without differentiation through LPAR1 mediated manner. Our findings provide that LPA as a anti-apoptotic agent having potential application prospect in cell transplantation and stem cell therapy. Electronic supplementary material The online version of this article (doi:10.1007/s10495-017-1399-6) contains supplementary material, which is available to authorized users.

In this paper, we utilized dimethylhydrazine (DMH)-induced colorectal cancer (CC) model rats to explore the effects of casein glycomacropeptide (CGMP) on colorectal cancer. Rats with CC were orally administrated with 10, 50, or 100 mg/kg bw d CGMP, or the same volume of phosphate-buffered saline for 15 weeks. The total numbers of aberrant crypt foci (ACF) and crypts per focus in colon were scored using a light microscope at low magnification after the colon was stained with methylene blue solutions. The methylation level of DNA extracted from colon was detected using methylation-specific PCR. The expression of p16 and mucin 2 (MUC2) proteins were measured by immunohistochemistry. The results showed that although ACF were found in rats treated with CGMP, their number was significantly decreased compared to that of model rats. In addition, methylation and expression levels of p16 and MUC2 were also inhibited by CGMP, which were more obvious in rats treated with 50 mg/kg bw d CGMP. In conclusion, CGMP has potential application as nutritional therapy for preventing colorectal cancer.

This study investigates the anti-apoptotic function of casein glycomacropeptide (CGMP) against oxazolone-induced ulcerative colitis (UC) in a mouse model. We tested the effect of CGMP on the morphological and histological damages of colon in UC mice and examined the mRNA levels of FasL, TNF-α, p53, p65 and TGF-β1 in colon tissues. Our results show that CGMP treatments alleviated oxazolone-induced body weight loss as well as morphological and histological damages. In addition, CGMP attenuated FasL and p65 mRNA level in colon tissue, while having no significant effect on the expression of TNF-α and p53. This suggests that therapeutically, the anti-apoptotic effect of CGMP is mediated through the FasR/FasL pathway and the anti-inflammation affects the NF-κB/p65 pathway. This study furthers our understanding of UC and provides sound support for the development of milk-derived therapeutics.

Chlorogenic acid (CGA) has many biological properties, including antibacterial, antioxidant and anti-inflammatory properties, and is one of the most abundant phenolic acids available in the human diet. The aim of this study was to investigate the effects of CGA on regulation of the gut microbiota, and on the levels of free amino acids and 5-hydroxytryptamine (5-HT, serotonin). Ninety-six healthy growing pigs were randomly assigned to two treatment groups: the Ctrl group (control group, standard feed) and the CGA group [standard feed plus 0.05% 3-caffeoylquinic acid (3-CQA)] for 60 days. The diversity of the gut microbiota was increased after CGA supplementation. Changes in these microbes were significantly associated with the serum free amino acid levels and colonic 5-HT level. Compared with the Ctrl group, the levels of serum aspartic acid, threonine, alanine, arginine, and colonic 5-HT were significantly increased (p .05). These data suggest important roles for CGA in regulating the gut microbiota and increasing the serum free amino acid levels.

OBJECTIVES: TMEPAI (transmembrane prostate androgen‐induced protein) has been reported to be overexpressed during tumour progression; however, little is known concerning transcriptional mechanisms regulating TMEPAI gene expression. MATERIALS AND METHODS: In this study, the TMEPAI gene promoter has been identified and characterized, and the effects of Sp1 on TMEPAI‐induced viability of A549 cells were evaluated, using MTT and colony formation assays. RESULTS: We found that the sequence between −298 and +24 consists of basal promoter activity for TMEPAI. Further analysis indicated that two Sp1‐binding sites are crucial for maintaining basal transcriptional activity of the TMEPAI promoter, and chromatin immunoprecipitation assays confirmed direct binding of Sp1 to the TMEPAI promoter. In addition, Sp1 up‐regulated TMEPAI protein expression, as well as Sp1 promoting TMEPAI‐induced cell proliferation. CONCLUSIONS: These results indicate that the sequence between −298 and +24 consists of the basal promoter activity for TMEPAI. Sp1 promotes TMEPAI expression and contributes to cell proliferation.

Objectives The aim of this study was to elucidate the molecular mechanisms by which food-derived casein glycomacropeptide (CGMP) maintains internal homeostasis in the intestinal mucosa and to investigate the effects of CGMP on the intestinal mucosal immunological barrier and related signal transduction pathways. Methods In this study, a famoxadone (OXZ)-induced mouse experimental ulcerative colitis (UC) model was built. The experimental UC mice were intragastrically administered milk-derived CGMP for four consecutive days. The molecular mechanisms by which milk-derived CGMP improved and restored the inflammatory status in UC symptoms were elucidated by H&E staining, immunohistochemical staining and western blotting. Results The results indicated that CGMP (50 mg/(kg bw·d)) could significantly improve morphological injury to intestinal mucosa in OXZ-induced UC mice to the same extent that did sulfasalazine (SASP, 40 mg/(kg bw·d)), a medicine used to treat UC, in the control group. The study found that CGMP could significantly reduce the expression of Human mucosal addressin cell adhesion molecule-1 (MAdCAM-1), Cluster of differentiation 4 (CD4) and Cluster of differentiation 8 (CD8) in the lamina propria of the intestinal mucosa and significantly stimulate the secretion of sIgA to increase intestinal immunity. Furthermore, CGMP was found to be directly involved in inhibiting the MAPK pathway and activating the TGF-β1/Smad signal transduction cascade, which could maintain immunological regulation of the intestinal mucosa and protect the functions of the intestinal mucosal barrier. Conclusions This study elucidated the molecular mechanisms by which CGMP maintained homeostasis of the intestinal mucosa and further confirmed its pharmaceutical value as a food-derived functional component with promising potential for further exploration/utilization.

In this paper, aimed at how to solve load imbalance problem when exploiting P2P technology in telecommunications network, we propose a load balancing algorithm GALB. In GALB algorithm, the intra-domain load transfer is mainly used for temporary load imbalance. For emergency leading to a large amount of concurrent user request, we will adopt the inter-domain load transfer. Experimental results show that after using the GALB load transfer mechanism the successful rate of service can be significantly improved, and it does not bring too much maintenance overhead.

This study is aimed to evaluate the clinical application of the millimeter wave and magnetism light compound therapy. The EHF-98B MMW. RL compound therapy apparatus made in the University of Electronic Technology(Chengdu) was used in 171 patients. The superficial, skin lesions or the visceral reflected skin regions (acupoints) were directly exposed to the light from the apparatus. All the cases were divided into five groups, namely skin mucosa superficial lesions, trauma of the bone and joint soft tissue, surgical incision, ENT infections, and rare intricate diseases. The therapeutic effects observed in the groups were analyzed and evaluated by means of 4 levels. As for the 171 patients, the cure rate was 42.7% (73 patients), the effective rate 25.1%(43 patients), the improvement rate 31%(53 patients), and no effect constituted 1.2%(2 patients). The total effective rate was 98.8%. This therapy was especially effective for treating chronic cervicitis, cervical erosion, soft tissue trauma, surgical incision. Also it was effective for treating some rare intricate diseases, e.g. sterility, vitiligo, Behcet disease. So the millimeter wave and magnetism light compound therapy may find wide clinical applications.