bluuebunny/crossref_metadata_2025 huggingface dataset:
A novel allele arising from c.912C>A mutation in the α‐1,3‐N‐acetylgalactosaminyltransferase gene in a Chinese individual
Authors: Zhang Xu , Li Xiaofeng , Liu Ying , Li Jianping
Published: October 2020

Background

The Am phenotype, which arises from mutations of the α‐1,3‐N‐acetylgalactosaminyltransferase gene, is rare in the Chinese population. The present study focuses on a novel mutation with the Am phenotype in a Chinese individual.

Study design and methods

The sample with ABO blood group discrepancy was analyzed by serologic techniques. The full coding and flanking regions of the ABO gene, including the Intron 1 transcription factor–binding site, were identified through direct sequencing of polymerase chain reaction (PCR)‐amplified products. PCR products of Exons 6 and 7 were validated to isolate the ABO gene haplotypes by cloning and sequencing individual colonies. The impact of the novel mutation on enzyme function was predicted with Polymorphism Phenotyping algorithm V2 and bioinformatic software programs.

Results

The serologic characteristics of ABO blood typing showed the rare Am phenotype. The c.467C/T and c.912C/A heterozygous sites in Exon 7 were identified by direct sequencing analysis. Further TA cloning and sequencing revealed that the patient carried an ABO*O.01.01 allele and a novel ABO*A allele. The new allele sequence had one nucleotide alteration (C>A) at position 912 on the background of the ABO*A1.02 allele. The c.912C>A mutation was predicted to be “probably damaging” and “deleterious” by PolyPhen‐2 and PROVEAN algorithms, respectively.

Conclusion

A novel mutation c.912C>A in α‐1,3‐N‐acetylgalactosaminyltransferase gene resulting in Am phenotype was identified in a Chinese individual.
Evaluating the Impact of Central Venous Catheter Materials and Design on Thrombosis: A Systematic Review and Meta‐Analysis
Authors: Slaughter Eugene , Kynoch Kathryn , Brodribb Megan , Keogh Samantha J.
Published: October 2020

Background

Thrombosis is a common complication associated with central venous catheter (CVC) insertion. Several antithrombogenic materials and alterations to catheter design have been developed to lower thrombosis rates.

Aim

To systematically evaluate the effectiveness and safety of antithrombogenic materials and alterations to CVC design on thrombosis rates.

Methods

A systematic search was completed of main databases (CINAHL, EMBASE, MEDLINE, and PubMed) as well as trial registries and gray literature. Randomized controlled trials conducted in any age group, published in English language since 2008 reporting impact of different CVC designs or materials on thrombosis were included, to capture studies that reflect contemporary products and practice. Cochrane systematic review methodology was followed, including independent study selection and data extraction. Quality appraisal was conducted using the Cochrane risk of bias tool. A narrative synthesis and meta‐analysis in RevMan were conducted.

Results

From a possible 232 studies, nine studies met the inclusion criteria. Four studies (n = 1,320) assessed different catheter materials; four studies (n = 591) compared different CVC designs, and one study (n = 150) evaluated impact of combined design and material on outcomes. Meta‐analysis demonstrated that neither catheter material nor design alone or in combination had a significant impact on thrombosis (RR: 0.98 [95% CI 0.87, 1.11]). Different catheter materials and design also had no significant impact on occlusion or CRBSI. Studies were of mixed quality overall.

Linking Evidence to Action

Different CVC materials and designs were not associated with a reduction in the risk of either catheter‐related thrombosis or infection. Overall reporting and small sample sizes make it difficult to draw firm conclusions. Larger, quality randomized trials are required to provide evidence about the possible merits of innovative catheter design and materials on patient outcomes.
PCR and culture for diagnosis ofAcanthamoebakeratitis
Authors: Yera Helene , Ok Vichita , Lee Koy Kuet Fiona , Dahane Naima , Ariey Frédéric , Hasseine Lilia , Delaunay Pascal , Martiano David , Marty Pierre , Bourges Jean Louis
Published: October 2020

Background/Aims

Acanthamoebakeratitis (AK) is a rare but sight-threatening infection. Molecular diagnosis of corneal scraping has improved the diagnosis of AK. Different molecular targets and conditions have been used in diagnosis thus far. In this study, we prospectively compared the performance of five PCR assays on corneal samples for the diagnosis of AK.

Methods

1217 corneal scraping samples were obtained from patients, for whom an AK was suspected. Sample processing involved both molecular diagnostics and culture.AcanthamoebaPCR assays detected different regions of theAcanthamoebanuclear small-subunit rRNA gene: three final point PCR assays using Nelson, ACARNA and JDP1–JDP2 pairs of primers, and two real-time PCR assays using Acant primer-probe. Human DNA and internal control were co-amplified in the real-time PCR assay to ensure scraping quality and the absence of inhibitors. In the absence of a gold standard, the performance of each test was evaluated using latent class analysis. Genotypes ofAcanthamoebaisolates were also characterised.

Results

Estimated prevalence of AK was 1.32%. The sensitivity ofAcanthamoebadiagnostic PCRs (73.3% to 86.7%) did not differ significantly from that of culture (66.7%), or according to the target sequence or the technology. Sensitivity could be increased to 93.8% or 100% by combining two or three assays, respectively. PCR specificity (99.3% to 100%) differed between the assays. T4 was the predominantAcanthamoebagenotype (84.6%).

Conclusions

Culture and a single PCR assay could lead to misdiagnosing AK. A combination of different PCR assays and improved sample quality could increase diagnosis sensitivity.
Lipopolysaccharide-binding protein is a distinctive biomarker of abnormal pain threshold in the general Japanese population
Authors: Kudoh Kazuhiro , Mizukami Hiroki , Itabashi Chieko , Fuke Nobuo , Osonoi Sho , Takeuchi Yuki , Wada Kanichiro , Igawa Akiko , Ogasawara Saori , Ishibashi Yasuyuki , Hakamada Kenichi , Yagihashi Soroku , Nakaji Shigeyuki
Published: October 2020

Introduction

Small fiber neuropathy (SFN) is an early manifestation in diabetic polyneuropathy (DPN); however, the mechanisms are not fully understood. In diabetes, SFN is presumed to be common in individuals with overt DPN, enhancing activation of polyol pathway, oxidative stress, advanced glycation end products (AGEs), and inflammation. We explored the relationship between clinicohematological factors related to DPN and pain sensation in the Japanese population.

Research design and methods

We conducted a population-based study, recruiting 1030 individuals (average age 54.4±0.5 years), in 2017, to participate in our Iwaki project. After initial screening by fasting blood glucose and glycohemoglobin A1c (HbA1c) measurements, the subjects were categorized into control (n=894), type 2 diabetes (n=81), and impaired fasting glucose (n=55) groups. Clinical data were gathered, and relationships between pain threshold from intraepidermal electrical stimulation (PINT) and DPN were examined by analysis of variance, post hoc test, and χ2tests to study correlations among and between groups of the clinical data and DPN.

Results

Univariate linear regression analyses showed significant correlations between PINT and serum lipopolysaccharide-binding protein (LBP) level (ß=0.1025, p=0.001). Adjustments for the clinical measurements confirmed a positive correlation (ß=0.070, p=0.034). Logistic regression analysis revealed high LBP value (>6.7 mg/dL) as a significant risk factor toward abnormal PINT (≥0.35 mA). LBP significantly correlated with the high-sensitivity C reactive protein, inflammation marker, elevated similarly in both pre-diabetic and overt-diabetic groups, compared with controls, but it did not correlate with a decreased Achilles tendon reflex. In contrast, urine 8-hydroxy-2'-deoxyguanosine, oxidative stress marker, and pentosidine, AGEs, markedly increased in individuals with type 2 diabetes with high HbA1c.

Conclusions

Individuals with high LBP exhibited an elevated PINT in the Japanese population. Low level of inflammation evoked by metabolic endotoxemia is possibly implicated in the pathophysiology of SFN from pre-diabetic stage.
Non-communicable diseases are the leading cause of mortality in rural Birbhum, West Bengal, India: a sex-stratified analysis of verbal autopsies from a prospective cohort, 2012–2017
Authors: Rai Rajesh Kumar , Barik Anamitra , Mazumdar Saibal , Chatterjee Kajal , Kalkonde Yogeshwar V , Mathur Prashant , Chowdhury Abhijit , Fawzi Wafaie W
Published: October 2020

Objectives

There is a dearth of data on causes of death in rural India, which impedes identification of public health priorities to guide health interventions. This study aims to offer insights from verbal autopsies, to understand the pattern and distribution of causes of death in a rural area of Birbhum District, West Bengal, India.

Design

Causes of death data were retrieved from a prospective vital event surveillance system.

Setting

The Birbhum Population Project, a Health and Demographic Surveillance System, West Bengal, India.

Participants

Between January 2012 and December 2017, all deaths were recorded.

Main outcome measures

Trained Surveyors tracked all deaths prospectively and used a previously validated verbal autopsy (VA) tool to record causes of death. Experienced physicians reviewed completed VA forms, and assigned cause of death using the 10th version of International Classification of Diseases. In addition to cause-specific mortality fraction, cause-specific crude death rate (CDR) among males and females were estimated.

Results

A total of 2320 deaths (1348 males and 972 females) were recorded. An estimated CDR was 708/100 000. Over half of all deaths (1176 deaths, 50.7%) were attributed to non-communicable diseases (NCDs), with nearly 30% of all deaths attributed to circulatory system disorders; whereas 24.2% and 3.9% deaths were due to cerebrovascular diseases and ischaemic heart disease, respectively. Equal percent (13%) of males died from external causes and from infectious and parasitic diseases, and 11% died from respiratory system-related diseases. Among females, 12% died from infectious and parasitic diseases. Among children aged 0–4 years, 50% of all male deaths and 45% of all female deaths were attributed to conditions in the perinatal period.

Conclusions

NCDs are the leading cause of death among adults in a select population of rural Birbhum, India. Health programmes for rural India should prioritise plans to mitigate deaths due to NCDs.
Cardiometabolic risk factors and mental health status among truck drivers: a systematic review
Authors: Guest Amber J , Chen Yu-Ling , Pearson Natalie , King James A , Paine Nicola J , Clemes Stacy A
Published: October 2020

Objective

This study aimed to systematically review and summarise the literature on cardiometabolic risk factors, lifestyle health behaviours and mental health status of truck drivers globally to ascertain the scale of these health concerns.

Design

Systematic review reported using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.

Data sources

PubMed, Scopus, PsycINFO and Web of Science were searched in January 2019 and updated in January 2020, from the date of inception to 16 January 2020.

Eligibility criteria for selecting studies

Papers were included if they (1) reported independent data on truck drivers, (2) included quantitative data on outcomes related to cardiometabolic markers of health, mental health and/or health behaviours, (3) were written in English and (4) were published in a peer-reviewed journal. Grey literature was ineligible for this review.

Data extraction and synthesis

One reviewer independently extracted data and assessed methodological quality using a checklist based on the National Heart, Lung and Blood Institute Quality Assessment tool. 20% were independently assessed for eligibility and quality by a second reviewer. Due to heterogeneity of the outcomes, results were narratively presented.

Results

3601 titles and abstracts were screened. Seventy-three studies met the inclusion criteria. Truck driving is associated with enforced sedentarism, long and irregular working hours, lack of healthy foods, social isolation and chronic time pressures. Strong evidence was observed for truck drivers to generally exhibit poor cardiometabolic risk profiles including overweight and obesity, hypertension, hypercholesterolaemia, high blood glucose, poor mental health and cigarette smoking.

Conclusions

Improving truck driver health is vital for the longevity of the trucking industry, and for the safety of all road users. The workplace plays a vital role in truck driver health; policies, regulations and procedures are required to address this health crisis.

PROSPERO registration number

CRD42019124499.
Disordered eating and eating disorders in male elite athletes: a scoping review
Authors: Karrer Yannis , Halioua Robin , Mötteli Sonja , Iff Samuel , Seifritz Erich , Jäger Matthias , Claussen Malte Christian
Published: October 2020

Background

Eating disorders (ED) and disordered eating (DE) among male elite athletes share some of the characteristics seen in female elite athletes and the population, but also exhibit some key differences.

Objective

Scoping review of ED and DE in male elite athletes.

Methods

In May 2020, a comprehensive systematic literature search was conducted for DE and ED in male elite athletes.

Results

We identified 80 studies which included 47 uncontrolled, 14 controlled studies, one interventional trial and 18 reviews.

Discussion

There was a wide range of definitions of DE and a high level of heterogeneity regarding competitive level, age and sport type. In adult male elite athletes, ED prevalence rates up to 32.5% were found, higher than in the general population. Prevalence was not higher in young/adolescent male elite athletes. The most frequently associated factor was competing in weight-sensitive sports. Male elite athletes tended to exhibit less body dissatisfaction than controls and were not always associated with DE. There were no studies looking at the prognosis or reporting an evidence-based approach for the management of DE in male elite athletes.

Conclusion

Existing literature indicates high prevalence of DE and ED in male elite athletes, with a wide range of aetiopathogenesis. There is a need for longitudinal studies to characterise the pathology and long-term outcomes, as well as develop standardised tools for assessment and treatments.
Deprivation is associated with anxiety and stress. A population-based longitudinal household survey among Chinese adults in Hong Kong
Authors: Chung Roger Yat-Nork , Marmot Michael , Mak Jonathan Ka-Long , Gordon David , Chan Dicken , Chung Gary Ka-Ki , Wong Hung , Wong Samuel Y S
Published: October 2020

Background

Mental illness is a major disease burden in the world and disproportionately affects the socially disadvantaged, but studies on the longitudinal association of poverty with anxiety and stress are rare, especially in Asia. Using data from Hong Kong, we aimed to (1) assess the cross-sectional association of poverty with anxiety and stress at baseline, and (2) to examine whether baseline poverty and change in poverty status over time are associated with a subsequent change in anxiety and stress.

Methods

Data were obtained from two waves of a territory-wide longitudinal survey in Hong Kong, with sample sizes of n=1970 and n=1224 for baseline and follow-up, respectively. Poverty was measured with a Deprivation Index and income-poverty. Anxiety and stress symptoms were assessed using Chinese Depression, Anxiety and Stress Scale—21 Items. We conducted cross-sectional and longitudinal analyses on the association of poverty with anxiety and stress.

Outcomes

Deprivation, but not income-poverty, was significantly associated with both outcomes at baseline. Increased deprivation over time was associated with greater score and increased risk of anxiety and stress. Persistent deprivation over time was associated with greater anxiety and stress, and increased risk of incident anxiety.

Interpretation

Deprivation could have significant independent effects on anxiety and stress, even after adjusting for the effects of income-poverty. Greater attention should be paid to deprivation in policymaking to tackle the inequalities of mental health problems, especially since stress and anxiety are precursors to more severe forms of mental illness and other comorbidities.
Thidiazuron suppresses breast cancer via targeting miR-132 and dysregulation of the PI3K–Akt signaling pathway mediated by the miR-202-5p–PTEN axis
Authors: Ibrahim Hairul-Islam Mohamed , Ismail Mohammad Bani , Ammar Rebai Ben , Ahmed Emad A.
Published: October 2020

Chemo-resistance and metastasis are the most common causes of breast cancer recurrence and death. Thidiazuron (TDZ) is a plant growth regulator (phytohormone) whose biological effects on humans and animals has not yet been determined. In this study, we investigated the anticancer activity of this phytohormone on the drug resistant-triple negative breast cancer cell line MDA-MB-231. Treatment of the breast cancer cells with TDZ (1–50 μmol/L) caused more stressful environment and induced a significant increase in active caspase-positive cells. In addition, TDZ treatment (5 and 10 μmol/L) significantly attenuated the migration and the invasiveness of these highly metastatic cancer cells. Mechanistically, TDZ reduces cancer progression and invasiveness by targeting miR-202-5p, which stimulates the expression of phosphatase and tensin homolog (PTEN), the tumor suppressor that downregulates the PI3K–Akt signaling pathway. Treatment with TDZ significantly upregulates miRNA-132, the suppressor of breast cancer proliferation, which is also implicated in dysregulation of the TEN-Akt–NFκB signaling pathway. Interestingly, our molecular docking analysis revealed a potential non-covalent interaction between TDZ and Akt, PTEN, and PI3K. These findings suggest that TDZ suppresses breast cancer metastasis by targeting miRNA-132, the miR-202-5p–PTEN axis, and the PI3K–Akt signaling pathway downstream.
The genetic composition of wild recruits in a recovering lake trout population in Lake Michigan
Authors: Larson Wesley A. , Kornis Matthew S. , Turnquist Keith N. , Bronte Charles R. , Holey Mark E. , Hanson S. Dale , Treska Theodore J. , Stott Wendylee , Sloss Brian L.
Published: October 2020

Strain performance evaluations are vital for developing successful fishery management and restoration strategies. Here, we utilized genotypes from 36 microsatellites to investigate hatchery strain contribution to collections of naturally produced lake trout (Salvelinus namaycush) sampled across Lake Michigan. Strain composition varied by area, with recoveries of Seneca Lake strain exceeding expectations based on stocking records in northern Lake Michigan but performing similarly to other strains in southern Lake Michigan. Interstrain hybrids were present at moderate frequencies similar to expectations based on simulations, suggesting that strains are interbreeding randomly. We hypothesize that the superior performance of the Seneca Lake strain in northern Lake Michigan is partially due to adaptive advantages that facilitate increased survival in areas with high mortality from sea lamprey (Petromyzon marinus) predation, such as northern Lake Michigan. However, when this selective pressure is lessened, the Seneca Lake strain performs similarly to other strains. Our study demonstrates that strain performance can vary across small spatial scales and illustrates the importance of conducting thorough strain evaluations to inform management and conservation.
Sharp estimates for homogeneous semigroups in homogeneous spaces. Applications to PDEs and fractional diffusion in ℝN
Authors: Cholewa Jan W. , Rodriguez-Bernal Anibal
Published: October 2020

In this paper, we analyze evolution problems associated to homogenous operators. We show that they have an homogenous associated semigroup of solutions that must satisfy some sharp estimates when acting on homogenous spaces and on the associated fractional power spaces. These sharp estimates are determined by the homogeneity alone. We also consider fractional diffusion problems and Schrödinger type problems as well. We apply these general results to broad classes of PDE problems including heat or higher order parabolic problems and the associated fractional and Schrödinger problems or Stokes equations. These equations are considered in Lebesgue or Morrey spaces.
Construction of solutions for a critical problem with competing potentials via local Pohozaev identities
Authors: He Qihan , Wang Chunhua , Wang Da-Bin
Published: October 2020

In this paper, we consider the following critical equation: [Formula: see text] where [Formula: see text], [Formula: see text] and [Formula: see text] are two nonnegative and bounded functions. Using a finite-dimensional reduction argument and local Pohozaev type of identities, we show that if [Formula: see text], [Formula: see text] has a stable critical point [Formula: see text] with [Formula: see text] and [Formula: see text], then the above equation has infinitely many positive solutions, where [Formula: see text] is the unique positive solution of [Formula: see text] with [Formula: see text]. Combining the results of [S. Peng, C. Wang and S. Wei, Constructing solutions for the prescribed scalar curvature problem via local Pohozaev identities, to appear in J. Differential Equations; S. Peng, C. Wang and S. Yan, Construction of solutions via local Pohozaev identities, J. Funct. Anal. 274 (2018) 2606–2633], it implies that the role of stable critical points of [Formula: see text] in constructing bump solutions is more important than that of [Formula: see text] and that [Formula: see text] can influence the sign of [Formula: see text], i.e. [Formula: see text] can be nonnegative, different from that in [S. Peng, C. Wang and S. Wei, Constructing solutions for the prescribed scalar curvature problem via local Pohozaev identities, to appear in J. Differential Equations]. The concentration points of the solutions locate near the stable critical points of [Formula: see text] which include the case of a saddle point.
Solving Generalized Wave and Heat Equations Using Linear Canonical Transform and Sampling Formulae
Authors: Bahri Mawardi , Ashino Ryuichi
Published: October 2020

Several essential properties of the linear canonical transform (LCT) are provided. Some results related to the sampling theorem in the LCT domain are investigated. Generalized wave and heat equations on the real line are introduced, and their solutions are constructed using the sampling formulae. Some examples are presented to illustrate our results.
The Power of Words: A Study of How Search Contents Can Affect Financial Decisions
Authors: Ni Du , Li Xingzhi , Xiao Zhi , Gong Ke
Published: October 2020

Search engines play an important role in providing us with the main information of our daily life. The research on the search behavior on the Internet enjoys greater and greater popularity, for the search behavior has been proved to affect our daily decisions in purchasing, traveling, and even defining beauty. However, there is still a lack of full appreciation of the relation between the search behavior itself in terms of the emotional meaning and the decisions thus generated. Therefore, this study was carried out to analyze the emotional meanings of 13,915 English words obtained from Google Trends and the profits gained from the US house market by automatic transactions and discovered that the emotional meanings of the search contents could modulate the financial decision with unsupervised machine learning methods.
Dendrobium officinale Flower Extraction Mitigates Alcohol‐Induced Liver Injury in Mice: Role of Antisteatosis, Antioxidative, and Anti‐Inflammatory
Authors: Wu Yu-Lin , Huang Si-Han , He Chun-Mei , Qiu Bo , Liu Jing-Jing , Li Jia , Lin Ying , Yu Sheng-Lu , Wang Hong-Feng , Zhang Gui-Fang
Published: October 2020

The study aimed to evaluate the protective effect of Dendrobium officinale flower extraction (DOFE) on alcohol‐induced liver injury and its probable mechanisms in mice. The chemical composition of DOFE was performed via UPLC/MS. Male Kunming mice were used to establish alcohol‐induced liver injury models by oral gavage of 56% alcohol. Results showed that DOFE dramatically attenuated the increased serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), and triacylglycerol (TG). Meanwhile, hematoxylin and eosin and Oil Red O staining showed that DOFE attenuated degeneration, inflammatory infiltration, and lipid droplet accumulation. DOFE was also found to suppress the activity of malonaldehyde (MDA) and enhanced the level of glutathione (GSH) and the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH‐Px), and catalase (CAT) in the liver. The protection of DOFE against oxidative stress was associated with the downregulation of hepatic cytochrome P450 2E1 (CYP2E1) and upregulation of nuclear factor erythroid 2‐related factor 2 (Nrf2), heme oxygenase‐1 (HO‐1), and NAD(P)H quinone oxidoreductase l (NQO1). Additionally, DOFE suppressed inflammation via downregulating Toll‐like receptor‐4 (TLR‐4) and nuclear factor kappa‐B P65 (NF‐κB P65). Thus, DOFE exhibited a significant protective effect against alcohol‐induced liver injury through its antisteatosis, antioxidative, and anti‐inflammatory effect.
Irvingia gabonensis Seed Extract: An Effective Attenuator of Doxorubicin-Mediated Cardiotoxicity in Wistar Rats
Authors: Olorundare Olufunke , Adeneye Adejuwon , Akinsola Akinyele , Kolo Phillip , Agede Olalekan , Soyemi Sunday , Mgbehoma Alban , Okoye Ikechukwu , Albrecht Ralph , Mukhtar Hasan
Published: October 2020

Cardiotoxicity as an off-target effect of doxorubicin therapy is a major limiting factor for its clinical use as a choice cytotoxic agent. Seeds of Irvingia gabonensis have been reported to possess both nutritional and medicinal values which include antidiabetic, weight losing, antihyperlipidemic, and antioxidative effects. Protective effects of Irvingia gabonensis ethanol seed extract (IGESE) was investigated in doxorubicin (DOX)-mediated cardiotoxicity induced with single intraperitoneal injection of 15 mg/kg of DOX following the oral pretreatments of Wistar rats with 100-400 mg/kg/day of IGESE for 10 days, using serum cardiac enzyme markers (cardiac troponin I (cTI) and lactate dehydrogenase (LDH)), cardiac tissue oxidative stress markers (catalase (CAT), malonyldialdehyde (MDA), superoxide dismutase (SOD), glutathione-S-transferase (GST), glutathione peroxidase (GSH-Px), and reduced glutathione (GSH)), and cardiac histopathology endpoints. In addition, both qualitative and quantitative analyses to determine IGESE’s secondary metabolites profile and its in vitro antioxidant activities were also conducted. Results revealed that serum cTnI and LDH were significantly elevated by the DOX treatment. Similarly, activities of tissue SOD, CAT, GST, and GSH levels were profoundly reduced, while GPx activity and MDA levels were profoundly increased by DOX treatment. These biochemical changes were associated with microthrombi formation in the DOX-treated cardiac tissues on histological examination. However, oral pretreatments with 100-400 mg/kg/day of IGESE dissolved in 5% DMSO in distilled water significantly attenuated increases in the serum cTnI and LDH, prevented significant alterations in the serum lipid profile and the tissue activities and levels of oxidative stress markers while improving cardiovascular disease risk indices and DOX-induced histopathological lesions. The in vitro antioxidant studies showed IGESE to have good antioxidant profile and contained 56 major secondary metabolites prominent among which are γ-sitosterol, Phytol, neophytadiene, stigmasterol, vitamin E, hexadecanoic acid and its ethyl ester, Phytyl palmitate, campesterol, lupeol, and squalene. Overall, both the in vitro and in vivo findings indicate that IGESE may be a promising prophylactic cardioprotective agent against DOX-induced cardiotoxicity, at least in part mediated via IGESE’s antioxidant and free radical scavenging and antithrombotic mechanisms.
Activating CD137 Signaling Promotes Sprouting Angiogenesis via Increased VEGFA Secretion and the VEGFR2/Akt/eNOS Pathway
Authors: Li Bo , Zhang Yue , Yin Runting , Zhong Wei , Chen Rui , Yan Jinchuan
Published: October 2020

Combination of antiangiogenesis and immunotherapy may be an effective strategy for treatment of solid tumors. Our previous work reported that activation of CD137 signaling promotes intraplaque angiogenesis. A number of studies have demonstrated that vascular endothelial growth factor receptor 2 (VEGFR2) is a key target for angiogenesis. However, it is unknown whether CD137-mediated angiogenesis is related to VEGFR2. In this study, we investigated the effect of CD137 on the VEGFR2 expression and explored the underlying mechanisms of CD137-mediated angiogenesis. Knock-out of CD137 in ApoE-/- mice significantly decreased neovessel density in atherosclerotic plaques. CD137 silencing or inhibition attenuated endothelial cell (ECs) proliferation, migration, and tube formation. We found activation of CD137 signaling for increased VEGFR2 transcription and translation steadily. Moreover, CD137 signaling activated phosphorylated VEGFR2 (Tyr1175) and the downstream Akt/eNOS pathway, whereas neutralizing CD137 signaling weakened the activation of VEGFR2 and the downstream Akt/eNOS pathway. The aortic ring assay further demonstrated that CD137 signaling promoted ECc sprouting. Inhibition of VEGFR2 by siRNA or XL184 (cabozantinib) and inhibition of downstream signaling by LY294002 (inhibits AKT activation) and L-NAME (eNOS inhibitor) remarkably abolished proangiogenic effects of CD137 signaling both in vitro and ex vivo. In addition, the condition medium from CD137-activated ECs and vascular endothelial growth factor A (VEGFA) had similar effects on ECs that expressed high VEGFR2. Additionally, activating CD137 signaling promoted endothelial secretion of VEGFA, while blocking CD137 signaling attenuated VEGFA secretion. In conclusion, activation of CD137 signaling promoted sprouting angiogenesis by increased VEGFA secretion and the VEGFR2/Akt/eNOS pathway. These findings provide a basis for stabilizing intraplaque angiogenesis through VEGFR2 intervatioin, as well as cancer treatment via combination of CD137 agonists and specific VEGFR2 inhibitors.
The Role of Notch3 Signaling in Kidney Disease
Authors: Yuan Cheng , Ni Lihua , Zhang Changjiang , Wu Xiaoyan
Published: October 2020

Notch receptors are transmembrane proteins that are members of the epidermal growth factor-like family. These receptors are widely expressed on the cell surface and are highly conserved. Binding to ligands on adjacent cells results in cleavage of these receptors, and their intracellular domains translocate into the nucleus, where target gene transcription is initiated. In the mammalian kidney, Notch receptors are activated during nephrogenesis and become silenced in the normal kidney after birth. Reactivation of Notch signaling in the adult kidney could be due to the genetic activation of Notch signaling or kidney injury. Notch3 is a mammalian heterodimeric transmembrane receptor in the Notch gene family. Notch3 activation is significantly increased in various glomerular diseases, renal tubulointerstitial diseases, glomerular sclerosis, and renal fibrosis and mediates disease occurrence and development. Here, we discuss numerous recently published papers describing the role of Notch3 signaling in kidney disease.
The Protective Effect of Qishen Granule on Heart Failure after Myocardial Infarction through Regulation of Calcium Homeostasis
Authors: Yang Xiaomin , Wang Qiyan , Zeng Zifan , Zhang Qian , Liu Fang , Chang Hong , Li Chun , Wang Wei , Wang Yong
Published: October 2020

Qishen granule (QSG) is a frequently prescribed traditional Chinese medicine formula, which improves heart function in patients with heart failure (HF). However, the cardioprotective mechanisms of QSG have not been fully understood. The current study aimed to elucidate whether the effect of QSG is mediated by ameliorating cytoplasmic calcium (Ca2+) overload in cardiomyocytes. The HF rat model was induced by left anterior descending (LAD) artery ligation surgery. Rats were randomly divided into sham, model, QSG‐low dosage (QSG‐L) treatment, QSG‐high dosage (QSG‐H) treatment, and positive drug (diltiazem) treatment groups. 28 days after surgery, cardiac functions were assessed by echocardiography. Levels of norepinephrine (NE) and angiotensin II (AngII) in the plasma were evaluated. Expressions of critical proteins in the calcium signaling pathway, including cell membrane calcium channel CaV1.2, sarcoendoplasmic reticulum ATPase 2a (SERCA2a), calcium/calmodulin‐dependent protein kinase type II (CaMKII), and protein phosphatase calcineurin (CaN), were measured by Western blotting (WB) and immunohistochemistry (IHC). Echocardiography showed that left ventricular ejection fraction (EF) and fractional shortening (FS) value significantly decreased in the model group compared to the sham group, and illustrating heart function was severely impaired. Furthermore, levels of NE and AngII in the plasma were dramatically increased. Expressions of CaV1.2, CaMKII, and CaN in the cardiomyocytes were upregulated, and expressions of SERCA2a were downregulated in the model group. After treatment with QSG, both EF and FS values were increased. QSG significantly reduced levels of NE and AngII in the plasma. In particular, QSG prevented cytoplasmic Ca2+ overload by downregulating expression of CaV1.2 and upregulating expression of SERCA2a. Meanwhile, expressions of CaMKII and CaN were inhibited by QSG treatment. In conclusion, QSG could effectively promote heart function in HF rats by restoring cardiac Ca2+ homeostasis. These findings revealed novel therapeutic mechanisms of QSG and provided potential targets in the treatment of HF.
The Approach of Hierarchical Linear Model to Exploring Individual and Team Creativity: A Perspective of Cultural Intelligence and Team Trust
Authors: Huang Chenhan , He Changqing , Zhai Xuesong
Published: October 2020

How to promote the creativity of interorganizational teams has always been the focus among scholars and management practitioners. From the perspective of leadership, this study explores the influence of shared leadership on creativity in interorganizational teams. Specifically, this study integrates leadership perspective with trust perspective and explores the mediating role of team trust between shared leadership and creativity at both team and individual level. In addition, this study examines the moderating effect of the leader’s cultural intelligence between shared leadership and team trust based on the perspective of leadership situation. The data comes from 275 employees within 54 interorganizational teams. The results show that shared leadership will promote team trust and team trust plays a key mediating role between shared leadership and creativity. Moreover, the relationship between shared leadership and team trust is moderated by the cultural intelligence of leader, such that the positive relationship will be stronger with high cultural intelligence and weaker with low cultural intelligence.
The Role of the Patient Information Leaflet in Patients’Medication Therapy: A Case Study within the Kumasi Metropolis of Ghana
Authors: Owusu Frederick W. A. , Yeboah Genevieve Naana , Aboagye Rahel Adutwiwah , Amengor Cedric Dzidzor K. , Entsie Philomena
Published: October 2020

One of the tools used in providing comprehensible medication information to patients on their medication use for improved adherence and subsequent optimal therapeutic effect is the Patient Information (PI) leaflet. In Ghana, the patient information leaflet is available through various sources including health-care professionals (HCPs) and electronic forms. The World Health Organization (WHO) estimates that more than 70% of patients, especially in the developing countries, who receive medications do not read the accompanying leaflet. This study assessed the role of the patient information leaflet in Patients’ medication therapy in the Kumasi metropolis of Ghana. A random cross-sectional survey was conducted in various hospitals and pharmacies within selected districts in the Kumasi metropolis. The survey revealed that 96.9% of the sampled respondents (n = 300) were provided with PI leaflets on their medicines while only 3.1% of them indicated otherwise. Among the proportion of respondents who were provided with PI leaflets, 66.7% of them read the information on the drug leaflets whilst the remaining 33.3% did not. Ultimately, 62.4% of those who read the PI leaflets were influenced to discontinue their medication. In conclusion, reading of the drug information leaflet was higher than that found in previous studies in Ghana. Reading the leaflet did not increase adherence but aroused anxiety and decreased adherence in some patients. A large number of the patients who were given the PI leaflets indicated that it did not provide them with the needed information.
Trifolium Flavonoids Overcome Gefitinib Resistance of Non‐Small‐Cell Lung Cancer Cell by Suppressing ERK and STAT3 Signaling Pathways
Authors: Wu Zhiqiang , Xu Bin , Yu Zhiyi , He Qin , Hu Zhuyuan , Zhou Shishi , Chen Meiqin , Zhu Liang
Published: October 2020

Gefitinib is a tyrosine kinase inhibitor of EGFR (epidermal growth factor receptor) and represents the first‐line treatment for EGFR mutation patients with NSCLC (non‐small‐cell lung cancer) therapeutics. However, NSCLC patients are inclined to develop acquired gefitinib drug resistance through nowadays, unarticulated mechanisms of chemoresistance. Here, we investigated the role of TF (Trifolium flavonoids) on sensitizing gefitinib resistance in NSCLC cells and revealed its potential mechanism of action. We demonstrated that TF exerted significantly potential chemosensitivity in gefitinib resistant NSCLC cells. MTT assay and cytological methods were used to analyze cell viability and apoptosis in NSCLC cell line PC‐9R. Both TF and gefitinib suppressed PC‐9R cell growth in a dose‐dependent manner. Subtoxic concentrations of TF did significantly augment gefitinib‐induced apoptosis in PC‐9R cell line. The TF promoted chemosensitivity was major mediated by the PARP and caspases activation. Meanwhile, the TF promoted chemosensitivity also decreased the expression of Bcl‐2 and Mcl‐1. Finally, TF significantly reduced the phosphorylation levels of STAT3 and ERK. Altogether, the results of the present study indicated the potential mechanisms of chemosensitivity of TF in gefitinib‐induced apoptosis of NSCLC by downregulating ERK and STAT3 signaling pathways and Bcl2 and Mcl‐1 expression and a promising application of TF in therapy of NSCLC with gefitinib resistant.
Oxidative Stress in Alzheimer’s Disease: In Vitro Therapeutic Effect of Amniotic Fluid Stem Cells Extracellular Vesicles
Authors: Gatti Martina , Zavatti Manuela , Beretti Francesca , Giuliani Daniela , Vandini Eleonora , Ottani Alessandra , Bertucci Emma , Maraldi Tullia
Published: October 2020

Alzheimer’s disease (AD) is characterized by abnormal protein aggregation, deposition of extracellular β-amyloid proteins (Aβ), besides an increase of oxidative stress. Amniotic fluid stem cells (AFSCs) should have a therapeutic potential for neurodegenerative disorders, mainly through a paracrine effect mediated by extracellular vesicles (EV). Here, we examined the effect of EV derived from human AFSCs (AFSC-EV) on the disease phenotypes in an AD neuron primary culture. We observed a positive effect of AFSC-EV on neuron morphology, viability, and Aβ and phospho-Tau levels. This could be due to the apoptotic and autophagic pathway modulation derived from the decrease in oxidative stress. Indeed, reactive oxygen species (ROS) were reduced, while GSH levels were enhanced. This modulation could be ascribed to the presence of ROS regulating enzymes, such as SOD1 present into the AFSC-EV themselves. This study describes the ROS-modulating effects of extracellular vesicles alone, apart from their deriving stem cell, in an AD in vitro model, proposing AFSC-EV as a therapeutic tool to stop the progression of AD.
Performance Evaluation of an Ironmaking System with Environmental Costs
Authors: Liu Huimin , Li Qiqiang
Published: October 2020

This paper proposes an exergoeconomic analysis method that considers environmental costs to make up for the lack of description of environmental costs in the traditional matrix model exergoeconomic analysis method. This method tracks the formation process of the product cost through life cycle and makes a useful exploration for revealing the true cost of the system product. According to actual needs, the principles for the construction of environmental emissions of products are proposed, and a detailed exergoeconomic analysis model is established by taking the iron smelting system as an example. Through calculation and analysis, the formation process and change rule of unit exergoeconomic cost of products in the system are revealed. Especially, considering the exergoeconomic cost of carbon emissions, the results show that the three most influential substances are sinter, coke, and pellets. When carbon dioxide emissions are considered, the total cost will increase by 165.3 CNY/t iron, and unit exergoeconomic cost gradually increases with the progress of the production process.
Potential Molecular Mechanisms of Plantain in the Treatment of Gout and Hyperuricemia Based on Network Pharmacology
Authors: Liu Pei , Xu Huachong , Shi Yucong , Deng Li , Chen Xiaoyin
Published: October 2020

Background. The incidence of gout and hyperuricemia is increasing year by year in the world. Plantain is a traditional natural medicine commonly used in the treatment of gout and hyperuricemia, but the molecular mechanism of its active compounds is still unclear. Based on network pharmacology, this article predicts the targets and pathways of effective components of plantain for gout and hyperuricemia and provides effective reference for clinical medication. Method. Traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP) and SymMap databases were used to screen out the active compounds and their targets in plantain. GeneCards, Therapeutic Target Database (TTD), and Online Mendelian Inheritance in Man (OMIM) databases were used to find the targets corresponding to gout and hyperuricemia. Venn diagram was used to obtain the intersection targets of plantain and diseases. The interaction network of the plantain active compounds‐targets‐pathways‐diseases was constructed by using Cytoscape 3.7.2 software. Finally, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were carried out. Result. Seven active compounds were identified by network pharmacological analysis, including dinatin, baicalein, baicalin, sitosterol, 6‐OH‐luteolin, stigmasterol, and luteolin. Plantain plays a role in gout and hyperuricemia diseases by regulating various biological processes, cellular components, and molecular functions. The core targets of plantain for treating gout are MAPK1, RELA, TNF, NFKBIA, and IFNG, and the key pathways are pathways in cancer, hypoxia‐inducible factor‐1 (HIF‐1) signaling pathway, interleukin (IL)‐17 signaling pathway, Chagas disease (American trypanosomiasis), and relaxin signaling pathway. The core targets of plantain for hyperuricemia are RELA, MAPK1, NFKBIA, CASP3, CASP8, and TNF, and the main pathways are pathways in cancer, apoptosis, hepatitis B, IL‐17 signaling pathway, and toxoplasmosis. Conclusion. This study explored the related targets and mechanisms of plantain for the treatment of gout and hyperuricemia from the perspective of network pharmacological analysis, reflecting the characteristics of multiple components, multiple targets, and multiple pathways, and it provides a good theoretical basis for the clinical application of plantain.
Antitumor Therapy under Hypoxic Microenvironment by the Combination of 2-Methoxyestradiol and Sodium Dichloroacetate on Human Non-Small-Cell Lung Cancer
Authors: Romero Yair , Castillejos-López Manuel , Romero-García Susana , Aguayo Alfonso Salgado , Herrera Iliana , Garcia-Martin Misael O. , Torres-Espíndola Luz Maria , Negrete-García Maria Cristina , Olvera Angel Camarena , Huerta-Cruz Juan Carlos , Velázquez-Cruz Rafael , Cisneros José , Soto Edgar Flores , Solís-Chagoyán Héctor , Mendoza-Milla Criselda , Cabello-Gutiérrez Carlos , Ruiz Víctor , Aquino-Gálvez Arnoldo
Published: October 2020

A hypoxic microenvironment is a hallmark in different types of tumors; this phenomenon participates in a metabolic alteration that confers resistance to treatments. Because of this, it was proposed that a combination of 2-methoxyestradiol (2-ME) and sodium dichloroacetate (DCA) could reduce this alteration, preventing proliferation through the reactivation of aerobic metabolism in lung adenocarcinoma cell line (A549). A549 cells were cultured in a hypoxic chamber at 1% O2 for 72 hours to determine the effect of this combination on growth, migration, and expression of hypoxia-inducible factors (HIFs) by immunofluorescence. The effect in the metabolism was evaluated by the determination of glucose/glutamine consumption and the lactate/glutamate production. The treatment of 2-ME (10 μM) in combination with DCA (40 mM) under hypoxic conditions showed an inhibitory effect on growth and migration. Notably, this reduction could be attributed to 2-ME, while DCA had a predominant effect on metabolic activity. Moreover, this combination decreases the signaling of HIF-3α and partially HIF-1α but not HIF-2α. The results of this study highlight the antitumor activity of the combination of 2-ME 10 μl/DCA 40 mM, even in hypoxic conditions.
Transforming Growth Factor Beta Receptor 3 Haplotypes in Sickle Cell Disease Are Associated with Lipid Profile and Clinical Manifestations
Authors: Santiago Rayra P. , Figueiredo Camylla V. B. , Fiuza Luciana M. , Yahouédéhou Sètondji C. M. A. , Oliveira Rodrigo M. , Aleluia Milena M. , Carvalho Suellen P. , Fonseca Cleverson A. , Nascimento Valma M. L. , Rocha Larissa C. , Guarda Caroline C. , Gonçalves Marilda S.
Published: October 2020

Individuals with sickle cell disease (SCD) present both chronic and acute inflammatory events. The TGF-β pathway is known to play a role in immune response, angiogenesis, inflammation, hematopoiesis, vascular inflammation, and cell proliferation. Polymorphisms in the transforming growth factor-beta receptor 3 (TGFBR3) gene have been linked to several inflammatory diseases. This study investigated associations between two TGFBR3 haplotypes and classical laboratory parameters, as well as clinical manifestations, in SCD. We found that individuals with the GG haplotype presented higher levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglycerides, non-HDL cholesterol, total proteins, and globulin than individuals with non-GG haplotypes. In addition, the GG haplotype was associated with a previous history of pneumonia. Individuals with the CGG haplotype presented increased plateletcrit, TC, LDL-C levels, and non-HDL cholesterol. The CCG haplotype was also associated with a previous history of pneumonia. Our findings suggest that individuals with the GG and CGG haplotypes of TGFBR3 present important alterations in lipid profile.