bluuebunny/crossref_metadata_2025 huggingface dataset:
Nutrient composition of fish protein powder developed from Brycinus nurse (Rüppell, 1832)
Authors: Kasozi Nasser , Asizua Denis , Iwe Gerald , Namulawa Victoria Tibenda
Published: October 2018

A new product in the form of edible fish powder was developed from small pelagic fish (Brycinus nurse) which constitutes one of the major commercial fisheries in Lake Albert, Uganda. The objective of the study was to determine the proximate and mineral composition of the newly developed fish powder and also to compare it with Nile tilapia powder already on market. Results indicated that the changes in the amount of protein and ash were found to be significantly higher (p < 0.05) in fish powder than in fried samples. The increase in fat content of fried fish samples was found to be significant compared to other fish samples. No significant changes (p > 0.05) were observed in carbohydrate content for raw, fried, and powdered samples. Vitamin A decreased significantly in powdered samples. Comparing the B. nurse powder and tilapia powder (made from juvenile tilapia as raw material), the results indicated that B. nurse had higher levels of iron and manganese. Extracting proteins from B. nurse provides an opportunity to increase the utilization of harvested catch.
Skin anti‐inflammatory activity of rose petal extract (Rosa gallica) through reduction of MAPK signaling pathway
Authors: Lee Myung‐hee , Nam Tae Gyu , Lee Inil , Shin Eun Ju , Han Ah‐ram , Lee Pomjoo , Lee Sung‐Young , Lim Tae‐Gyu
Published: October 2018

The aim of this study was to investigate the skin anti‐inflammatory activity of rose petal extract (RPE) and the mechanisms underlying this phenomenon. Recently, flowers have been considered as dietary resources owing to their biological activities, such as inhibition of nephritis and hemorrhoids. The Rosa plant exerts various biological functions, including antioxidant and anti‐microbiological activities. Herein, we confirmed the skin anti‐inflammatory activity of RPE upon solar UV (sUV) exposure. RPE reduced sUV‐induced COX‐2 expression as well as expressions of several cytokines. Activation of MKK4‐JNK, MEK‐ERK, and MKK3‐p38 signaling pathways, which are associated with cytokine production, was also attenuated by RPE treatment. We hypothesized these RPE‐induced changes are because of its antioxidant activity, because RPE displayed drastic radical scavenging and oxygen radical absorbance capacity (ORAC). Furthermore, high anthocyanins, polyphenols, and flavonoids contents were found in RPE. Hence, these results indicated the skin anti‐inflammatory activity of RPE is because of antioxidant activity.
Effect of medicinal plant type and concentration on physicochemical, antioxidant, antimicrobial, and sensorial properties of kombucha
Authors: Shahbazi Hossein , Hashemi Gahruie Hadi , Golmakani Mohammad‐Taghi , Eskandari Mohammad H. , Movahedi Matin
Published: October 2018

The aim of this study was to evaluate the effects of adding various medicinal plants to kombucha medium and to analyze the changes that occur to its physicochemical, antimicrobial, and sensorial properties. In the first part, measurements were made to determine IC50 value, total phenolic content, total flavonoid content, minimum inhibitory concentration, pH, organic acids, and sensorial properties of kombucha that contained cinnamon, cardamom, or Shirazi thyme. Results showed that kombucha samples containing cinnamon exhibited higher antioxidant and antimicrobial activities, more organic acids, and better sensorial scores. In the second part, properties of kombucha containing 25%–100% concentrations of cinnamon were evaluated. The result showed that by increasing the cinnamon concentration, certain increases were observed in the amounts of organic acids and in the magnitudes of antioxidants and antimicrobial activities. In conclusion, antioxidant and antimicrobial activities of kombucha can be increased by adding medicinal plants, especially at higher concentrations.
Co‐Producing Interdisciplinary Knowledge and Action for Sustainable Water Governance: Lessons from the Development of a Water Resources Decision Support System in Pernambuco, Brazil
Authors: White Dave D. , Lawless Krista L. , Vivoni Enrique R. , Mascaro Giuseppe , Pahle Robert , Kumar Ipsita , Coli Pedro , Castillo Raúl Muñoz , Moreda Fekadu , Asfora Marcelo
Published: October 2018

One of the most pressing global challenges for sustainable development is freshwater management. Sustainable water governance requires interdisciplinary knowledge about environmental and social processes as well as participatory strategies that bring scientists, managers, policymakers, and other stakeholders together to cooperatively produce knowledge and solutions, promote social learning, and build enduring institutional capacity. Cooperative production of knowledge and action is designed to enhance the likelihood that the findings, models, simulations, and decision support tools developed are scientifically credible, solutions‐oriented, and relevant to management needs and stakeholders' perspectives. To explore how interdisciplinary science and sustainable water management can be co‐developed in practice, the experiences of an international collaboration are drawn on to improve local capacity to manage existing and future water resources efficiently, sustainably, and equitably in the State of Pernambuco in northeastern Brazil. Systems are developed to model and simulate rainfall, reservoir management, and flood forecasting that allow users to create, save, and compare future scenarios. A web‐enabled decision support system is also designed to integrate models to inform water management and climate adaptation. The challenges and lessons learned from this project, the transferability of this approach, and strategies for evaluating the impacts on management decisions and sustainability outcomes are discussed.
The Early Aptian volcanic episode of Gutiolo (N Spain): Expression of the Bilbao Rift Fault Zone
Authors: García‐Mondéjar Joaquín , Carracedo‐Sánchez Manuel , Owen Hugh G. , Fernández‐Mendiola Pedro Angel
Published: October 2018

The Gutiolo volcanic unit belongs to the Aptian Bilbao Formation and crops out 6 km SE of Bilbao (N Spain) within marine marlstones. It is 300 m thick and up to 1 km long. The volcanics consist of lava in the lower part and volcaniclastic sediments above, with metatrachytes and metatrachybasalts, similar to others of the alkali Cretaceous sequence in the Basque–Cantabrian Basin. The palaeontological age is top early Aptian (Dufrenoyia furcata Zone) near the Bedoulian–Gargasian substage transition, and the isotopic age (K–Ar) is 123 ± 3 Ma but most probably, 122 Ma. E–W and N–S trending faults bounding the Gutiolo volcanics controlled magma eruption. Other NW‐ and SE‐oriented major faults in the Bilbao area favoured several Valanginian to Santonian eruptions including Gutiolo. The eruptions moved progressively in space and time from SW to NE. These faults make up a 15‐km‐wide tectonic belt, the magma‐leaky Bilbao Fault Zone. A similar magmatic fault zone NE of Bilbao, Gernika‐Elgoibar, poured magma onto the sea floor during the late Albian–Cenomanian up to the Santonian, continuing the north‐easterly younging trend of volcanic inceptions recognized in Bilbao. All this Cretaceous volcanism is related to the Bay of Biscay opening processes, and the Gutiolo event is correlated with the first appearance of oceanic crust in the Bay of Biscay. From stratigraphic, volcanic, geochemical, and mineralization evidence, we attribute Gutiolo to an early phase of mafic intrusion emplacement in the Bilbao area, underplated by magmatism during the Valanginian to Santonian (Cretaceous). Volcanic hydrothermal fluids associated to the Gutiolo event are considered responsible for metallic ore emplacement in the Basque–Cantabrian Basin during the early Aptian.
Serum Hepatitis B Virus RNA: A New Potential Biomarker for Chronic Hepatitis B Virus Infection
Authors: Liu Shi , Zhou Bin , Valdes Juan D. , Sun Jian , Guo Haitao
Published: October 2018

Chronic hepatitis B infection is one of the major etiological causes of liver failure, cirrhosis, and hepatocellular carcinoma (HCC) worldwide. This condition cannot be completely cured by currently available drugs due to the persistent existence of hepatitis B virus (HBV) covalently closed circular DNA (cccDNA), the bona fide transcription template for HBV RNAs, in infected hepatocytes. Because quantifying cccDNA per se requires an invasive procedure, serum biomarkers reflecting intrahepatic cccDNA activity are warranted. Recently, a growing body of research suggests that the circulating HBV RNA may serve as a serum biomarker for HBV infection, treatment, and prognosis. In order to delineate the molecular and clinical characteristics of serum HBV RNA, we systematically reviewed the available literature on serum HBV RNA dating back to the early 1990s. In this review, we summarize the reported serum HBV RNA quantification methods and discuss the potential HBV RNA species in patient serum. We also compare the reported correlations of serum HBV RNA with other serological markers, including HBV DNA, hepatitis B surface antigen, e antigen, and core‐related antigen, as well as their correlations with intrahepatic cccDNA, to assess their potential in clinical applications. Future directions for serum HBV RNA research are also discussed.
PAPD5/7 Are Host Factors That Are Required for Hepatitis B Virus RNA Stabilization
Authors: Mueller Henrik , Lopez Anaïs , Tropberger Philipp , Wildum Steffen , Schmaler Josephine , Pedersen Lykke , Han Xingchun , Wang Yongguang , Ottosen Søren , Yang Song , Young John A.T. , Javanbakht Hassan
Published: October 2018

RG7834 is a potent, orally bioavailable small‐molecule inhibitor of hepatitis B virus (HBV) gene expression that belongs to the dihydroquinolizinone (DHQ) chemical class and uniquely blocks production of both viral DNA and antigens. In this study, we used DHQ compounds as tools in a compound‐based adaptation version of the yeast three‐hybrid screen to identify the cognate cellular protein targets, the non‐canonical poly(A) RNA polymerase associated domain containing proteins 5 and 7 (PAPD5 and PAPD7). Interaction with RG7834 was mapped to the catalytic domains of the two cellular enzymes. The role of PAPD5 and PAPD7 in HBV replication was confirmed by oligonucleotide‐mediated knockdown studies that phenocopied the result seen with RG7834‐treated HBV‐infected hepatocytes. The greatest effect on HBV gene expression was seen when PAPD5 and PAPD7 mRNAs were simultaneously knocked down, suggesting that the two cellular proteins play a redundant role in maintaining HBV mRNA levels. In addition, as seen previously with RG7834 treatment, PAPD5 and PAPD7 knockdown led to destabilization and degradation of HBV mRNA without impacting production of viral RNA transcripts. Conclusion: We identify PAPD5 and PAPD7 as cellular host factors required for HBV RNA stabilization and as therapeutic targets for the HBV cure.
Applying a developmental lens to examine injury mortality in young people in Australia, 2001‐2013
Authors: Seah Rebecca , Mitchell Rebecca J.
Published: October 2018

Issue addressed

As injuries are preventable, understanding the age profile of specific injury mechanisms is critical for developing injury prevention strategies. This study examined the profile and temporal trends of injury mortality of young people aged ≤24 years in Australia across developmental life stages.

Method

A retrospective analysis of injury deaths of young people aged ≤24 years was conducted using closed cases from the National Coronial Information System during 2001‐2013. Negative binomial regression was used to examine temporal trends in mortality rates by age group.

Results

There were 7749 injury deaths of young people in Australia. The mortality rates were estimated to decline each year for young people aged 0‐4 years (by 3.4%; 95% CI: −5.10 to −1.67), 10‐14 years (by 3.7%; 95% CI: −6.29 to −1.09), 15‐19 years (by 4.4%; 95% CI: −5.90 to −2.85) and 20‐24 years (by 4.5%; 95% CI: −5.61 to −3.37). Motor vehicle incidents were a frequent mechanism of fatal injury for all ages. For children aged ≤9 years, drowning and submersion and other threats to breathing were also frequent mechanisms of fatal injury. Young people aged 15‐24 years were also frequently fatally injured as a motorcyclist or a pedestrian.

Conclusions

The age‐specific injury mortality profiles reflect the changing vulnerabilities of young people influenced by physical, cognitive and social characteristics associated with different stages of their development. By focusing on different ages, targeted injury prevention interventions can be developed.

So what?

While policies play a key role in reducing injury mortality, secondary interventions that aim to shift attitudes to injury prevention activities will also be critical to influence positive behaviour change.
Clinical, pathological and loss of heterozygosity differences in Wilms tumors between Asian and non‐Asian children
Authors: Loke Benjamin N. , Wong Meng Kang , Tawng Khawn D. , Kuick Chick Hong , Jain Sudhanshi , Lian Derrick , Wagner Elizabeth , Zou Yuhan , Ganesan Visveswari , Sim Siam Wee , Lee York Tien , Chin Francis , Chan Mei Yoke , Tan Ah Moy , Teh Bin Tean , Soh Shui Yen , Chang Kenneth T.E. , Loh Amos H.P.
Published: October 2018

Wilms tumor demonstrates significant interethnic epidemiological, histological and outcome differences, and is rare and poorly studied among Asians. We compared the clinicopathological, and loss of heterozygosity (LOH) profile and survival outcomes of Asian and non‐Asian patients with Wilms tumor. Clinical charts and histological slides from patients with malignant renal tumors over a period of 20 years were retrospectively reviewed. We adapted a genotyping assay to determine 1p36 and 16q21‐22 LOH in formalin‐fixed paraffin‐embedded (FFPE) specimens, and compared these characteristics between Asian and non‐Asian patients. Fifty‐three (79.1%) Asian and 14 (20.9%) non‐Asian patients had Wilms tumors. Compared to non‐Asians, Asians were younger (mean 4.6 and 4.0 years, respectively), had more equal gender distribution (female: male = 1.8 and 1.0, respectively), fewer tumors with unfavorable histology (25.0% and 4.1%, respectively, p = 0.05), and less advanced disease at presentation, yet similar nodal metastases rates (16.7% and 18.4%, respectively). No Asian patients had bilateral tumors. Our adapted genotyping assay accurately determined LOH in FFPE specimens <10 years post‐fixation. Among 30 Asian patients, 1p and 16q LOH were each detected in 5 (16.7%) patients, respectively—similar to rates reported in other ethnicities. Yet after similar treatment with National Wilms Tumor Study regimens, 15‐year event‐free and overall survival for Asian patients was 95.7% and 96.3% respectively. In summary, despite similar nodal metastasis and LOH rates, Asian patients had fewer unfavorable histology tumors, lower‐stage disease, and better survival outcomes. The bases for these differences and implications on treatment strategy for these patients warrant further study.
Nonaspirin NSAIDs and contralateral breast cancer risk
Authors: Bens Annet , Cronin‐Fenton Deirdre , Dehlendorff Christian , Jensen Maj‐Britt , Ejlertsen Bent , Kroman Niels , Friis Søren , Mellemkjær Lene
Published: October 2018

Laboratory studies suggest that inhibition of the cyclooxygenase (COX)‐2 enzymes inhibits breast cancer development. We aimed to evaluate whether postdiagnosis use of COX‐2 selective or other nonaspirin nonsteroidal anti‐inflammatory drugs (NSAIDs) reduce the risk of contralateral breast cancer (CBC) among Danish breast cancer patients. From the clinical database of the Danish Breast Cancer Group, we identified 52,723 women diagnosed with breast cancer between 1996 and 2012. Data on nonaspirin NSAID use, CBC and potential confounding variables were obtained from nationwide registries. We defined postdiagnosis use (two or more prescriptions) as a time‐varying covariate with a one‐year lag. Cox proportional hazard regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for CBC associated with nonaspirin NSAID use. During a median follow‐up of 4.8 years (interquartile range: 2.3–9 years), 1,444 patients were diagnosed with CBC. Overall, postdiagnosis use of nonaspirin NSAID was associated with an adjusted HR for CBC of 0.98 (95% CI: 0.87–1.11). The HRs did not vary substantially with duration or intensity of nonaspirin NSAID use. Moreover, similar associations were found for COX‐2 selective (HR: 1.02; 95% CI: 0.85–1.23) and nonselective (HR: 0.96; 95% CI: 0.82–1.13) nonaspirin NSAIDs. In conclusion, our nationwide cohort study of breast cancer patients does not suggest a reduced risk of CBC with nonaspirin NSAID use regardless of the COX‐2 selectivity.
Preparation and Applications of Chiral Polymeric Particles
Authors: Zhang Yingjie , Huang Huajun , Zhao Biao , Deng Jianping
Published: October 2018

Chiral polymeric particles (CPPs) have been gathering increasing interest as typical functional polymeric particles in recent decades. This article presents a review on the preparation and applications of CPPs. The methods for preparing CPPs are classified into two major groups: The first one is the direct polymerization of monomers and the other is the post‐treatment of preformed polymers. CPPs have been explored as a unique type of chiral materials in various fields like asymmetric catalysis, enantioselective release, enantioselective crystallization, and enantioseparation. This review article is expected to accelerate the progress of scientific research dealing with CPPs and their applications in chirality‐related fields.
Stimuli‐Responsive Polyurethane Dispersions – Aqueous Auto‐Dispersion
Authors: Gupta Harshit , Texter John
Published: October 2018

We report a single‐pot synthesis of polyurethanes (PUs) in solvent that utilizes an hydroxyl imidazolium bromide salt (ionic liquid) as a chain terminating group. This material, after being desolvated under activation, spontaneously disperses in water to form auto‐dispersing polyurethane dispersions (PUDs). These PUDs comprise aggregates, that separate under further activation (sonication) to form sub‐micron to sub‐100‐nm dispersions that are stable. Their size changes during such (auto) dispersion processing are examined by dynamic light scattering. Anion‐dependent stimuli‐responsiveness is observed upon anion exchange. This stimuli‐responsiveness is based on imidazolium‐anion pair solubility changes induced by anion exchange. Dispersion destabilization can be induced by selection and anion exchange for particular “hydrophobic” anions. Film formation and wetting are observed to exhibit stimuli‐responsiveness to anion exchange. Coatings based on PUD comprising tripropylene glycol are less hydrophilic than coatings incorporating PEO‐based PUDs.
Lignin Based Molecular Materials – a Zinc Vanillate with a Hydrogen Bonded 4‐ and 8‐connected Net with a New Topology
Authors: Spekreijse Jurjen , Inge A. Ken , Öhrström Lars
Published: October 2018

Vanillic acid, C8H8O4, is a possible product from a future biorefinery with lignin as raw material. Two coordination compounds with this ligand in two different protonation states were prepared: 1 [Zn(C8H7O4)2(H2O)2] and 2 [Co2(C8H6O4)2(H2O)6] ⋅ 2H2O. Both compounds form extended 3D structures with strong hydrogen bonds. A high symmetry 8‐ and 4‐connected network topology, jus, is found in 1. The dinuclear coordination entity in 2 hints at a potentially useful SBU for MOF synthesis from lignin based bridging ligands.
Neutrophil‐to‐lymphocyte ratio and platelet indices in pre‐eclampsia
Authors: Gogoi Priyanka , Sinha Pallavi , Gupta Bindiya , Firmal Priyanka , Rajaram Shalini
Published: October 2018

Objective

To compare the neutrophil‐to‐lymphocyte ratio (NLR), platelet‐to‐lymphocyte ratio (PLR), and platelet indices between women with pre‐eclampsia and normotensive pregnant women.

Methods

A cross‐sectional study conducted from January to July 2017 at a tertiary care hospital in Delhi, India. The study compared pregnant women aged 18–40 years with pre‐eclampsia diagnosed at term with healthy pregnant women matched for gestational age. Venous blood samples were drawn and complete blood count was analyzed. The parameters recorded were hemoglobin, red cell distribution width (RDW), platelet count, mean platelet volume (MPV), plateletcrit, and platelet distribution width.

Results

There were 67 women included in each group. NLR was higher in women with pre‐eclampsia compared with the control group (6.8 ± 7.6 vs 3.0 ± 0.98; P=0.001). Both PLR (14.18 ± 14.4 vs 9.54 ± 3.6; P=0.012) and MPV (9.45 ± 1.19 vs 9.02 ± 1.1; P=0.029) were higher in the study group compared with the control group. Platelet count was lower in pre‐eclamptic women compared with the control group (188 ± 89.7 vs 200.1 ± 62.36; P=0.014). RDW was also higher in the study group (P=0.025).

Conclusions

The present study found that the inflammatory markers NLR, PLR, RDW, and MPV were higher in women with pre‐eclampsia. Measuring NLR and PLR may be useful in predicting pre‐eclampsia among women at high risk during prenatal follow‐up.
Transfection efficiency and cytotoxicity of polyethyleneimine‐coated magnetic iron oxide nanoparticles in rooster sperm cells
Authors: Katebi Samira , Esmaeili Abolghasem , Ghaedi Kamran , Salimi Parvin
Published: October 2018

Since the morphology of the rooster spermatozoa is different to other animal spermatozoa, the aim of the current study was to investigate the transfection efficiency and cytotoxicity of polyethyleneimine (PEI) coated magnetic iron oxide nanoparticles (MION) on these cells. Liposome/nucleic acid (NA) complexes and PEI‐coated MION linked to the labeled oligonucleotides were used. Viability and percentage of exogenous nucleic acid uptake of spermatozoa were measured by flow cytometry analyses. The results showed a significant increase in exogenous nucleic acid uptake by rooster spermatozoa (P < 0.001) when treated with MION‐NA complexes in comparison to liposome/NA. There were no significant differences between efficiency of lipid‐based transfection agent and MION (P > 0.05) during short incubation period. MION with or without magnetic field, did not show significant cytotoxicity while the lipid‐based transfection agent significantly decreased (P < 0.05) the viability of rooster spermatozoa. Results of this study showed that magnetofection and lipofection were both effective methods which increased exogenous nucleic acid uptake by rooster spermatozoa. However, the magnetofection method was more successful in maintaining the cell's survival than lipofection method.
Evaluation of the two polymorphisms rs1801133 in MTHFR and rs10811661 in CDKN2A/B in breast cancer
Authors: Hesari Amirreza , Maleksabet Amir , Tirkani Abolfazl Nosrati , Ghazizadeh Hamideh , Iranifar Elmira , Mohagheg Fatoalah , Anoshrvani Ali Arash , Ghasemi Faezeh
Published: October 2018

The 5,10‐Methylenetetrahydrofolate reductase (MTHFR) was the rate‐limiting enzyme in the methyl cycle, which was encoded by the MTHFR gene. MTHFR played a key role in homocysteine plasma level and was associated with the risk of breast cancer. The cyclin‐dependent kinase (CDK) inhibitor (CDKN2A/B) was the tumor suppressor in the cell cycle regulation. The single‐nucleotide polymorphism was thought to be associated with the predisposition of breast cancer and in subsequent immune response in different populations. The current study was conducted on a peripheral blood sample of 100 Iranian women with breast carcinoma and 142 cancer‐free healthy female volunteers. The TaqMan real‐time polymerase chain reaction technique was applied for genotyping of participants. The correlation of both variants and demographic data were investigated with the risk of breast cancer. Our data showed that the MTHFR allele T and TT genotype had the higher prevalence in patients (P < 0.0001) than the control group. The frequency of risk C allele into the CDKN2A/B rs10811661 was 72%. The correlations of menarche and underlying hormonal disorder with the risk of breast cancer were investigated; also our results showed that the menopause status was statistically significant between patients and controls (P = 0.036). Our investigations demonstrated that the MTHFR rs180113 and CDKN2A/B rs10811661 had a significant correlation with the elevated risk of breast cancer and they might be potentially valuable to apply as a prognostic factor for individual health care.
Strategies for targeting energy metabolism in Kirsten rat sarcoma viral oncogene homolog ‐mutant colorectal cancer
Authors: Wang Gang , Wang Jun‐Jie , Yin Pei‐Hao , Xu Ke , Wang Yu‐Zhu , Shi Feng , Gao Jing , Fu Xing‐Li
Published: October 2018

Alterations in cellular energy metabolism play critical roles in colorectal cancer (CRC). These alterations, which correlate to KRAS mutations, have been identified as energy metabolism signatures. This review summarizes the relationship between colorectal tumors associated with mutated KRAS and energy metabolism, especially for the deregulated energy metabolism that affects tumor cell proliferation, invasion, and migration. Furthermore, this review will concentrate on the role of metabolic genes, factors and signaling pathways, which are coupled with the primary energy source connected with the KRAS mutation that induces metabolic alterations. Strategies for targeting energy metabolism in mutated KRAS CRC are also introduced. In conclusion, deregulated energy metabolism has a close relationship with KRAS mutations in colorectal tumors. Therefore, selective inhibitors, agents against metabolic targets or KRAS signaling, may be clinically useful for colorectal tumor treatment through a patient‐personalized approach.
Zellweger spectrum disorder patient–derived fibroblasts with the PEX1‐Gly843Asp allele recover peroxisome functions in response to flavonoids
Authors: MacLean Gillian E. , Argyriou Catherine , Di Pietro Erminia , Sun Xuting , Birjandian Sara , Saberian Panteha , Hacia Joseph G. , Braverman Nancy E.
Published: October 2018

Zellweger spectrum disorder (ZSD) results from biallelic mutations in PEX genes required for peroxisome biogenesis. PEX1‐G843D is a common hypomorphic allele in the patient population that is associated with milder disease. In prior work using a PEX1‐G843D/null patient fibroblast line expressing a green fluorescent protein (GFP) reporter with a peroxisome‐targeting signal (GFP‐PTS1), we demonstrated that treatments with the chemical chaperone betaine and flavonoid acacetin diacetate recovered peroxisome functions. To identify more effective compounds for preclinical investigation, we evaluated 54 flavonoids using this cell‐based phenotype assay. Diosmetin showed the most promising combination of potency and efficacy (EC50 2.5 µM). All active 5′,7′‐dihydroxyflavones showed greater average efficacy than their corresponding flavonols, whereas the corresponding flavanones, isoflavones, and chalcones tested were inactive. Additional treatment with the proteostasis regulator bortezomib increased the percentage of import‐rescued cells over treatment with flavonoids alone. Cotreatments of diosmetin and betaine showed the most robust additive effects, as confirmed by three independent functional assays in primary PEX1‐G843D patient cells, but neither agent was active alone or in combination in patient cells homozygous for the PEX1 c.2097_2098insT null allele. Moreover, diosmetin treatment increased PEX1, PEX6, and PEX5 protein levels in PEX1‐G843D patient cells, but none of these proteins increased in PEX1 null cells. We propose that diosmetin acts as a pharmacological chaperone that improves the stability, conformation, and functions of PEX1/PEX6 exportomer complexes required for peroxisome assembly. We suggest that diosmetin, in clinical use for chronic venous disease, and related flavonoids warrant further preclinical investigation for the treatment of PEX1‐G843D–associated ZSD.
Protective effect of ginsenoside Rg3 on lung injury in diabetic rats
Authors: Wang Heyuan , Wu Wei , Wang Guixia , Xu Wenzhou , Zhang Fuqiang , Wu Bing , Tian Yaping
Published: October 2018

Ginsenoside has been used to treat diabetes, while ginsenoside Rg3 is the main active ingredient component of ginseng and is used to study its effects on lung tissue damage in diabetic rats. In this paper, 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay and flow cytometry were applied to detect the proliferation and apoptosis of BEAS‐2B cells treated with different concentrations of Rg3. The inflammatory response and pathological change in the lung tissue of diabetic rats treated with Rg3 were evaluated by enzyme‐linked immunosorbent assay, quantative real‐time polymerase chain reaction, and hematoxylin and eosin staining immunohistochemistry. Meanwhile, PI3K and MAPK signaling pathway proteins in lung tissue were determined by Western blot analysis. The results showed that ginsenoside Rg3 had no significant influence on the proliferation and apoptosis of BEAS‐2B cells. Ginsenoside Rg3 can inhibit inflammatory response and promote the activation of PI3K and MAPK signaling pathways to prevent damages of lung tissues induced by hyperglycemia. The protective effect provided by ginsenoside Rg3 indicates that ginsenoside Rg3 is a potential drug for the treatment of diabetes.
Integrative analysis of mRNA and microRNA expression profiles in laryngeal squamous cell carcinoma
Authors: Ekmekci Cumhur Gokhan , Coskunpinar Ender , Avci Hakan , Farooqi Ammad Ahmad , Orhan Kadir Serkan , Akbas Fahri
Published: October 2018

Larynx cancer is a therapeutically challenging disease. Rapidly evolving experimentally validated data have significantly improved our understanding of the complex role of numerous RNA, DNA, and proteins that play a role in the development and progression of cancer. Based on the insights from approximately two decades of research, it seems clear that microRNAs (miRNAs) have revolutionized our concepts related to the main role of noncoding RNAs in different cancers’ progression, development, and metastasis. Mechanistically, miRNAs have been reported to regulate different RNAs and finally protein‐coding genes. The expression profiling of miRNAs and messenger RNA (mRNAs) was conducted for a deeper analysis of the miRNAs and mRNAs which play an essential role in larynx cancer. Downregulation or upregulation over twofolds in the miRNAs was considered to be significant, and that of sixfolds or below was considered to be significant for the mRNAs. In accordance with this approach, the expression levels of 43 miRNAs were increased in this study, whereas the expression levels of 129 were decreased. Accordingly, all the genomic expression studies provided evidence of upregulation of 97 genes, whereas 128 genes were found to be downregulated. Among these miRNAs, hsa‐miR‐20a‐3p and hsa‐miR‐1972 were noted to be important in the etiology of larynx cancer.
Current progress in CRISPR‐based diagnostic platforms
Authors: Khambhati Khushal , Bhattacharjee Gargi , Singh Vijai
Published: October 2018

The CRISPR‐Cas system is a key technology for genome editing and regulation in a wide range of organisms and cell types. Recently, CRISPR‐Cas–based diagnostic platform has shown idealistic properties for pathogen detection. Integrating the CRISPR‐Cas platform along with lateral flow system allows rapid, sensitive, specific, cheap, and reliable diagnostic. It has the potential to be in frontline for not only pathogen detection during the epidemic outbreak, but also cancer, and genetic diseases.
Oncostatic treatment effect of triple negative breast cancer cell line with copper (I)‐nicotinate complex
Authors: Abdel‐Mohsen Mohamed A. , Toson Elshahat A. , Helal Marihan A.
Published: October 2018

The treatment of triple‐negative breast cancer (TNBC) remains a major challenge. The present study aimed to throw more light on the role of copper (I)‐nicotinate complex (CNC) as an antitumor as well as a proapoptotic agent. In this study, the HCC‐1806 cell line was used as a model for TNBC. Cell cycle, apoptosis assay, and programmed cell death protein‐1 were investigated by flowcytometry. Besides, the comet assay was performed using a fluorescence microscope. The enzyme‐linked immunosorbent assay technique was used for the detection of phospho‐Chk1 at ser 317 and caspase‐3. Moreover, the gene expression of survivin was identified by real‐time polymerase chain reaction. Finally, superoxide dismutase (SOD) was calorimetrically assayed. The viability of HCC‐1806 cells treated with CNC was decreased in a dose‐dependent manner. The tendency for apoptotic machinery was observed through the increase in the sub G0 peak, the percentage of early and late apoptotic phases, and the elevation in caspase‐3 levels associated with a downregulation of the survivin gene expression. The antioxidant property of the complex, reflected by elevated SOD activity, may contribute to mediate the cell death pathways. Low concentrations of CNC were found to favor the apoptotis‐mediated mechanism. However, one cannot neglect the abundance of cell necrosis–mediated death of cells via CNC, especially at higher concentrations.
Exosomes derived from miR‐146a‐modified adipose‐derived stem cells attenuate acute myocardial infarction−induced myocardial damage via downregulation of early growth response factor 1
Authors: Pan Junjie , Alimujiang Maimaitijiang , Chen Qiying , Shi Haiming , Luo Xinping
Published: October 2018

Multiple studies demonstrated that early growth response factor 1 (EGR1) induces myocardial damage after acute myocardial infarction (AMI). Recent evidence indicates that microRNAs (miRNA) play an important role in exosome‐mediated cardioprotection after AMI. Bioinformatics analysis has shown that miR‐146a can regulate the expression of EGR1, so the aim of this study was to determine if miR‐146a plays a role in exosome‐mediated cardioprotection by regulation of EGR1 after AMI. Exosomes were isolated from wild‐ or miR‐146a‐modified adipose‐derived stem cells (ADSCs), and the therapeutic effect of exosomes was assessed in an AMI model in rats and hypoxic‐induced H9c2 model cells. The results showed that miR‐146a containing exosomes had more effect than the exosome treatment group on the suppression of AMI‐induced apoptosis, inflammatory response, and fibrosis in an AMI rat model. Both in vivo and in vitro experiments found that miR‐146a interacted with the 3′‐untranslated region of EGR1 and suppressed posttranscriptional EGR1 expression, which was confirmed by the luciferase reporter assay. We also found that suppressed EGR1 expression reversed AMI or hypoxia‐induced TLR4/NFκB signal activation, which played an important role in the promotion of myocardial cell apoptosis, inflammatory response, and fibrosis. Taken together, these findings suggested that exosomes derived from miR‐146a‐modified ADSCs attenuated AMI‐induced myocardial damage via downregulation of EGR1.
Effects of alpha lipoic acid and its derivative “andrographolid‐lipoic acid‐1” on ulcerative colitis: A systematic review with meta‐analysis of animal studies
Authors: Moeinian Mahsa , Abdolghaffari Amir Hossein , Nikfar Shekoufeh , Momtaz Saeideh , Abdollahi Mohammad
Published: October 2018

We aimed to review and meta‐analyze the inflammatory and oxidative factors following alpha lipoic acid (ALA) and its derivative “andrographolid‐lipoic acid‐1” (AL‐1) in ulcerative colitis (UC). ALA plays an important role in scavenging intracellular radicals and inflammatory elements. AL‐1 is found in herbal medicines with potent anti‐inflammatory properties. Data were collected from the Google Scholar, PubMed, Scopus, Evidence‐based medicine/clinical trials, and Cochrane library database until 2017, which finally resulted in 22 animal studies (70 rats and 162 mice). The beneficial effects of ALA or AL‐1 on the most important parameters of UC were reviewed; also, studies were considered separately in mice and rats. Administration of ALA and AL‐1 significantly reduced the tumor necrosis factor‐α level compared with the controls, while data were not noteworthy in the meta‐analysis (mean differences = −18.57 [95% CI = −42.65 to 5.51],
P = 0.13). In spite of insignificant decrease in meta‐analysis outcomes (differences = 6.92 [95% CI = −39.33 to 53.16],
P = 0.77), a significant reduction in myeloperoxidase activity was shown following ALA or AL‐1 treatment compared with the controls. Despite significant differences in each study, we had to exclude some studies to homogenize data for meta‐analyzing as they showed insignificant results. Interleukin 6, cyclooxygenase‐2, glutathione, malondialdehyde, superoxide dismutase, histopathological score, macroscopic and microscopic scores, disease activity index, body weight change, and colon length were also reviewed. Most studies have emphasized on significant positive effects of ALA and AL‐1. Comprehensive clinical trials are obligatory to determine the precious position of ALA or AL‐1 in the management of UC.
Administration of losartan improves aortic arterial stiffness and reduces the occurrence of acute coronary syndrome in aged patients with essential hypertension
Authors: Zhang Zhi‐Mian , Wang Bing‐Xiang , Ou Wen‐Sheng , Lv Yan‐Hong , Li Ming‐Min , Miao Zhang , Wang Shuang‐Xi , Fei Jian‐Chun , Guo Tao
Published: October 2018

Backgrounds and Aims

Increased arterial stiffness may increase cardiovascular morbidity and mortality. Angiotensin II type 1 receptor blocker losartan is potentially useful in controlling the central blood pressure and arterial stiffness in mild to moderate essential hypertension, while the effects of losartan in aged patients with essential hypertension are not entirely investigated.

Methods

The carotid‐femoral arterial pulse wave velocity (PWV) was measured in aged patients with essential hypertension.

Results

In a cross‐sectional study, PWV value was significantly higher in these old patients with essential hypertension, compared with patients without essential hypertension. Logistic regression analysis indicated that age, hypertension duration, and losartan treatment are risk factors of arterial stiffness. In a perspective study, long‐term administration of losartan (50 mg/d) remarkably reduced PWV in aged patients with essential hypertension. In a longitudinal study, PWV is an independent predictor of the occurrence of acute coronary syndrome (ACS) in elderly patients with essential hypertension by using multivariate analysis. Further, the ACS occurrence was reduced by long‐term administration of losartan in aged patients with essential hypertension, compared with the old hypertensive patients without taking losartan.

Conclusion

Losartan treatment is a negative risk factor of arterial stiffness and reduces the risk of ACS in aged patients with essential hypertension.
CTRP3 inhibits high glucose–induced human glomerular mesangial cell dysfunction
Authors: Hu Tian‐ying , Li La‐mei , Pan Yan‐zi
Published: October 2018

C1q/tumour necrosis factor–related protein‐3 (CTRP3) is a member of CTRP family, and its blood level is reduced in human and rodent models of obesity and diabetes. However, the role of CTRP3 in diabetic nephropathy remains unclear. This study was designed to examine the effects of CTRP3 on cell proliferation and extracellular matrix (ECM) accumulation in human glomerular mesangial cells (MCs) in response to high glucose (HG), and explore the potential molecular mechanisms. Our results demonstrated that the expression of CTRP3 was significantly decreased by HG stimulation in MCs. In addition, CTRP3 overexpression inhibited MCs proliferation, reactive oxygen species level, and ECM production in HG‐stimulated MCs. Mechanistically, CTRP3 overexpression inhibited the activation of the Janus kinase 2/signal transducers and activators of transcription 3 (JAK2/STAT3) pathway in HG‐stimulated MCs. Taken together, these findings indicated that CTRP3 attenuated HG‐induced MC proliferation and ECM production through the inactivation of the JAK2/STAT3 signaling pathway. Thus, CTRP3 may be a potential therapeutic target for the treatment of diabetic nephropathy.
Priming with oxytocin and relaxin improves cardiac differentiation of adipose tissue–derived stem cells
Authors: Taha Masoumeh Fakhr , Javeri Arash , Karimipour Mojtaba , Yamaghani Mojtaba Saghafi
Published: October 2018

Previous studies have identified the heart as a source and a target tissue for oxytocin and relaxin hormones. These hormones play important roles in the regulation of cardiovascular function and repair of ischemic heart injury. In the current study, we examined the impact of oxytocin and relaxin on the development of cardiomyocytes from mesenchymal stem cells. For this purpose, mouse adipose tissue–derived stem cells (ADSCs) were treated with different concentrations of oxytocin or relaxin for 4 days. Three weeks after initiation of cardiac induction, differentiated ADSCs expressed cardiac‐specific genes, Gata4,
Mef2c, Nkx2.5,
Tbx5, α‐ and
β‐Mhc,
Mlc2v,
Mlc2a and
Anp, and cardiac proteins including connexin 43, desmin and α‐actinin. 10
−7 M oxytocin and 50 ng/mL relaxin induced the maximum upregulation in the expression of cardiac markers. A combination of oxytocin and relaxin induced cardiomyocyte differentiation more potently than the individual factors. In our experiment, oxytocin‐relaxin combination increased the population of cardiac troponin I‐expressing cells to 6.84% as compared with 2.36% for the untreated ADSCs, 3.7% for oxytocin treatment and 3.41% for relaxin treatment groups. In summary, the results of this study indicated that oxytocin and relaxin hormones individually and in combination can improve cardiac differentiation of ADSCs, and treatment of the ADSCs and possibly other mesenchymal stem cells with these hormones may enhance their cardiogenic differentiation and survival after transplantation into the ischemic heart tissue.
The experimental research of pregnancy immune tolerance induced by FTY720 via blocking S1P signal transduction pathway
Authors: Xiong Miao , Xu Lang , Li Li , Liu Yang , Zhou Fangfang , Wang Jun , Zhu Jieping
Published: October 2018

Objective

To investigate the effects of pregnancy immune tolerance induced by FTY720 via blocking S1P signal transduction pathway.

Methods

Immunohistochemistry was used to detect the expression of S1P in the decidua of pregnant rats. We have constructed S1P gene small interfering RNA (siRNA) lentiviral vector and overexpression
S1P gene lentiviral vector and they are transferred into dendritic cell (DC), then observing the effect of adoptive transferring of FTY720 on the embryo loss rate of spontaneous abortion mouse model after transferring this two kinds of lentiviral vectors.

Results

(1) FTY720 had no significant effect on the embryo loss rate of the normal pregnant rats; (2) Adoptive transferring of FTY720 can significantly reduce the embryo loss rate of the spontaneous abortion mouse model. The expression of S1P in the decidua of spontaneous abortion mouse model was lower than that of normal pregnant rat (P < 0.05). (3) After transferring of S1P‐siRNA lentiviral vector transfected DC, FTY720 could mild reduce the embryo loss rate of abortion mouse model (embryo loss rate was 11.5%) (
P < 0.05). However, the effect is far less than that of before adoptive transferring of S1P‐siRNA lentivirus transfected DC. After the transferring of the overexpression of
S1P gene lentiviral vector transfected DC, FTY720 can significantly reduce the rate of embryo loss in the spontaneous abortion mouse model (embryo loss rate decreased to 1.95%) (
P < 0.01). The effect was more obvious than that of no transfecting
S1P gene lentiviral vector transfected DC.

Conclusion

FTY720 is secured in inducing immune tolerance during pregnancy by blocking the S1P signaling pathway.
Overexpression of miR‐301a‐3p promotes colorectal cancer cell proliferation and metastasis by targeting deleted in liver cancer‐1 and runt‐related transcription factor 3
Authors: Zhang Liuliu , Zhang Yi , Zhu Huayun , Sun Xiaofeng , Wang Xiaohua , Wu Pingping , Xu Xinyu
Published: October 2018

Colorectal cancer (CRC) is the third most common type of cancer. MicroRNAs have been reported to participate in the progression of various cancers. In previous studies, miR‐301a‐3p expression was shown to be upregulated in CRC tissues. However, the underlying mechanism of miR‐301a‐3p in CRC has not yet been elucidated. Herein, the level of miR‐301a‐3p was found to be significantly upregulated in CRC clinical tissues and cell lines (HT29 and SW620). In addition, overexpression of miR‐301a‐3p obviously promoted cell proliferation, migration and invasion, and inhibited cell apoptosis in CRC cells. Meanwhile, upregulated miR‐301a‐3p expression also enhanced the expressions of Bax, caspase‐3, caspase‐9, matrix metalloproteinase (MMP)‐2, and MMP‐9, while the expression of Bax‐2 was decreased. Furthermore, deleted in liver cancer‐1 (DLC‐1) and runt‐related transcription factor 3 (RUNX3) were verified to be direct target genes of miR‐301a‐3p. Furthermore, overexpression of DLC‐1 and RUNX3 revealed antitumor effects in CRC cell lines with the inhibition of cell proliferation, migration and invasion, and the induction of cell apoptosis. In addition, the expressions of Bax, caspase‐3, caspase‐3, MMP‐2, and MMP‐9 could be decreased after upregulating the expressions of DLC‐1 and RUNX3, along with the upregulation of Bax‐2. Moreover, overexpression of miR‐301a‐3p could promote the growth of xenograft tumors and liver metastasis in vivo, along with reducing the expressions of DLC‐1 and RUNX3. Overall, miR‐301a‐3p might act as a tumor inducer in CRC cells through negatively regulating DLC‐1 and RUNX3.
MALAT1 promoted cell proliferation and migration via MALAT1/miR‐155/MEF2A pathway in hypoxia of cardiac stem cells
Authors: Wang Qiuyun , Lu Guoping , Chen Zhenyue
Published: October 2018

Accumulating evidence revealed that hypoxia contributed to many human diseases, including ischemic myocardium and heart failure (HF). In recent years, the roles of hypoxia in stem cell survival and cardiac biology have been studied extensively. However, the underlying molecular mechanisms remain to be elucidated. As a leading cause of HF, ischemic heart disease was correlated with hypoxia. In this study, we firstly constructed the hypoxia cell model by CoCl2 in cardiac stem cells (CSCs) and found that hypoxia induced the cell proliferation and migration potential in CSCs. Then, we demonstrated that the expression of metastasis‐associated lung adenocarcinoma transcript 1 (MALAT1) was promoted in CoCl2‐induced CSCs hypoxia model. Furthermore, we found that knockdown of MALAT1 inhibited the cell proliferation and migration in CoCl2‐induced CSCs hypoxia model. In addition, we revealed that MALAT1 regulated the microRNA‐155 (miR‐155) expression in CSCs under both the normal and hypoxia conditions and further, manipulation of the miR‐155 expression affected the role of MALAT1 in CoCl2‐induced CSCs hypoxia cell model. We then illustrated that miR‐155 regulated the myocyte enhancer factor 2A (MEF2A) expression in CSCs under both the normal and hypoxia conditions and further, changing the expression of MEF2A affected the role of miR‐155. Finally, we demonstrated that MALAT1 regulated the MEF2A expression and exerted its role via modulation of the MALAT1/miR‐155/MEF2A pathway. Taken together, our study illustrated that MALAT1 promoted the cell proliferation and migration in CoCl2‐induced CSCs hypoxia model, acting mechanistically by promoting MEF2A expression via “sponging” miR‐155.