bluuebunny/crossref_metadata_2025 huggingface dataset:
Transient potential groundwater recharge under surface irrigation in semiarid environment: An experimental and numerical study
Authors: Altafi Dadgar Majid , Nakhaei Mohammad , Porhemmat Jahangir , Biswas Asim , Rostami Mohammad
Published: September 2018

Groundwater recharge, a key component of the global water cycle, is critical in understanding water dynamics in managed and natural ecosystems. In this study, an experimental and numerical method was used to investigate potential groundwater recharge (PGR) in a semiarid region in Iran. A large soil column with four distinct layers was constructed using soil from an agricultural farm in the area. A 140‐day experiment with 10 applications of irrigation was carried out, and soil water was measured at different depths. Deep drainage started around 40 days after the first irrigation and increased with more water applications. The soil water dynamics for different irrigation tests were modelled using the HYDRUS‐1D software package, and the model was calibrated using laboratory collected data. Good agreement was achieved between the HYDRUS‐1D simulated and laboratory measurement data. The calibrated model was used to simulate PGR using meteorological station data between November 2008 and 2012. Three scenarios were applied, including fully cropped land with irrigation and precipitation water (R1), irrigation water (R2), and bare soil with precipitation water (R3) only. Results showed that the average annual PGR rates were 32.42%, 10.8%, and 4.26% for the three scenarios, respectively. Temporal variability of recharge for the R1 showed that recharge increased with a 2‐month delay corresponding to the increased water infiltration during harvest time. Recharge flux started after high precipitation values for R3. A clear relation between monthly precipitation and recharge rate was not found even after a 2‐month shifted recharge, but a relatively high correlation was observed between monthly 2‐month shifted recharge and precipitation after a threshold value cut‐off. Additionally, the results showed that the traditional recharge estimation in semiarid regions with episodic natural precipitation may not be as simplified as generally assumed.
Cancer incidence in older adults in selected regions of sub‐Saharan Africa, 2008–2012
Authors: Pilleron Sophie , Soerjomataram Isabelle , Charvat Hadrien , Chokunonga Eric , Somdyala Nontuthuzelo I. M. , Wabinga Henry , Korir Anne , Bray Freddie , Jemal Ahmedin , Maxwell Parkin D.
Published: September 2018

Although the countries of Sub‐Sharan Africa represent among the most rapidly growing and aging populations worldwide, no previous studies have examined the cancer patterns in older adults in the region as a means to inform cancer policies. Using data from Cancer Incidence in Five Continents, we describe recent patterns and trends in incidence rates for the major cancer sites in adults aged ≥60 years and in people aged 0–59 for comparison in four selected population‐based cancer registries in Kenya (Nairobi), the Republic of South Africa (Eastern Cape Province), Uganda (Kyadondo country), and Zimbabwe (Harare blacks). Over the period 2008–2012, almost 9,000 new cancer cases were registered in older adults in the four populations, representing one‐third of all cancer cases. Prostate and esophageal cancers were the leading cancer sites in older males, while breast, cervical and esophageal cancers were the most common among older females. Among younger people, Kaposi sarcoma and non‐Hodgkin lymphoma were common. Over the past 20 years, incidence rates among older adults have increased in both sexes in Uganda and Zimbabwe while rates have stabilized among the younger age group. Among older adults, the largest rate increase was observed for breast cancer (estimated annual percentage change: 5% in each country) in females and for prostate cancer (6–7%) in males. Due to the specific needs of older adults, tailored considerations should be given to geriatric oncology when developing, funding and implementing national and regional cancer programmes.
The moderating role of race/ethnicity on associations between insurance status and HPV vaccination among women in the USA
Authors: Marshall Colin , Chavan Bhakti , Haile Zelalem T.
Published: September 2018

Objective

To evaluate associations between insurance status and HPV vaccination.

Methods

The present cross‐sectional study analyzed data from women aged 18–26 years who participated in the National Health and Nutritional Examination Surveys 2009–2012 in the USA.

Results

The study included 621 women; 424 (68.3%) had some type of insurance and 198 (30.6%) had received the HPV vaccine. In the multivariable model, we found significant interactions between race/ethnicity and insurance status on receiving HPV vaccination. Compared with individuals with no insurance, non‐Hispanic black women with any type of insurance demonstrated increased likelihood of HPV vaccination (adjusted odds ratio [aOR] 3.63, 95% confidence interval [CI] 1.60–8.21; P=0.002). Among Mexican Americans, there was a negative association between having some insurance and HPV vaccination (aOR 0.35, 95% CI 0.15–0.81; P=0.007). For non‐Hispanic black women, the association remained significant across all insurance types (private [aOR 4.29, 95% CI 1.67–11.00; P=0.003], Medicaid [aOR 2.86, 95% CI 1.15–7.13; P=0.025], and other [aOR 4.74, 95% CI 1.06–21.15; P=0.042]). Non‐Hispanic white women with insurance other than private or Medicaid had a higher likelihood of HPV vaccination compared with uninsured individuals (aOR 8.36, 95% CI 2.79–25.05; P<0.001).

Conclusion

The present findings help to identify at‐risk populations less likely to receive the HPV vaccine.
Challenges in delivery and performance of a cervical cancer prevention program in the Kurdistan Region of the Iraq health system
Authors: Rasul Vian H. , Moghdam Zahra B. , Karim Muaf A. , Cheraghi Mohhammad A.
Published: September 2018

Objective

To investigate health‐system challenges responsible for the poor performance of a cervical cancer prevention program in the Kurdistan Region of Iraq.

Method

A qualitative study was conducted among a purposive sample of healthcare providers and female volunteers in Erbil, Kurdistan Region of Iraq, between December 10, 2014, and July 23, 2016. Data were collected from participants using in‐depth semi‐structured interviews. The interviews were then transcribed and analyzed with an inductive content analysis approach.

Results

In total, 23 individuals completed the interviews. The participants included 8 (35%) female volunteers; 5 (22%) nurses; 4 (17%) managers; 3 (13%) doctors; and 3 (13%) gynecologists. The health‐system challenges were classified into three main categories: existence of an official reminder system, public information delivery programs, and infrastructures of facilities, which included three subcategories—cervical cancer screening center, material resources, and human resources.

Conclusions

The Kurdistan Region of Iraq health system faced several challenges in delivering a cervical cancer prevention program. These challenges must be addressed to improve the coverage of cervical cancer screening, diagnosis, and treatment.
Cultural value mismatch in urbanizing China: A large‐scale analysis of collectivism and happiness based on social media and nationwide survey
Authors: Wu Michael Shengtao , Zhou Chan , Chen Hao , Cai Huajian , Sundararajan Louise
Published: September 2018

Throughout history, collectivism has contributed much to social bonding and human wellness. However, it remains unclear whether the collectivism‐wellness equation still applies, when there is a mismatch between the collectivistic values and the ecological environment of urbanisation. Testing the hypothesis of cultural value mismatch (e.g., high urbanised & high collectivistic, or low urbanised & low collectivistic), two studies were designed to examine the relationship between collectivism and emotional wellbeing in China, with urbanisation as moderator. Based on the emotion analysis of tweets among 1.6 millions of Weibo users, Study 1 found that the province‐level collectivism scores were significantly and positively related to negative emotions in high urbanised provinces, but this relationship was not significant in low or middle urbanised provinces. Using a nationwide survey dataset, Study 2 showed that, on the individual level, those with higher collectivism reported less negative emotions, but only in low‐ and middle‐urbanised provinces, not in high‐urbanised provinces. On positive emotions in all areas, the positive effect of collectivism was observed on individual level, but not on province level. These findings support the value mismatch hypothesis of urbanisation, suggesting that the purchasing power of collectivism on wellbeing is compromised in urbanising China.
A review of environmental enrichment as treatment for problem behavior maintained by automatic reinforcement
Authors: Gover Holly C. , Fahmie Tara A. , McKeown Ciobha A.
Published: September 2018

We reviewed studies that used environmental enrichment as treatment for problem behavior maintained by automatic reinforcement. A search of behavior analytic journals produced 71 publications with a total of 265 applications of environmental enrichment used alone or in conjunction with alternative behavior manipulations (e.g., prompting, reinforcement) and problem behavior manipulations (e.g., blocking, restraint). Environmental enrichment, as a sole intervention, was efficacious in 41% of the sample. Alternative behavior manipulations, problem behavior manipulations, and a combination of both improved the overall efficacy of environmental enrichment. We discuss factors that may influence the efficacy of environmental enrichment, current trends in research on this topic, and implications for both practitioners and researchers.
Ascorbic acid supplementation ameliorates testicular hormonal signaling, sperm production and oxidative stress in male rats exposed to rosuvastatin during pre‐puberty
Authors: Leite Gabriel Adan Araujo , de Barros Jorge Willian Franco , Martins Airton da Cunha , Anselmo‐Franci Janete Aparecida , Barbosa Fernando , Kempinas Wilma De Grava
Published: September 2018

Dyslipidemias are occurring earlier in the population due to the augmentation of obesity. Rosuvastatin reduces cholesterol and triglycerides; however, previous studies have shown that it may affect male reproduction. Ascorbic acid (AA), an antioxidant compound, plays a protective role in the male reproductive system. This study aimed to evaluate whether pre‐pubertal exposure to rosuvastatin may impair testicular structure and antioxidant status in male rats and if supplementation with AA may alleviate these damages. Male rats were randomly divided into six experimental groups (n = 10) on postnatal day (PND) 23 and received the different treatments by gavage from PND 23 to 53. The experimental groups received vehicle (saline solution 0.9%), 3 or 10 mg/kg/day of rosuvastatin diluted in saline solution 0.9%, supplementation with 150 mg/day of AA, 3 mg/kg/day of rosuvastatin in association with 150 mg/day of AA or 10 mg/kg/day of rosuvastatin associated with 150 mg/day of AA. Testicular parameters were assessed on PND 53 and 110. There were diminished androgen receptors staining in the Sertoli cells and increased germ cell death in rosuvastatin‐exposed groups, in both periods. Spermatids showed lower estrogen alpha‐receptors staining in the group exposed to 10 mg of statin at adulthood. There were androgen depletion and increased lipid peroxidation and catalase activity in statin‐exposed groups. Rosuvastatin exposure during pre‐puberty impaired testicular structure, steroid receptor distribution and increased oxidative stress; however, AA was able to ameliorate the impairment provoked by statin exposure.
Thrombogenicity assessment of Pipeline Flex, Pipeline Shield, and FRED flow diverters in an in vitro human blood physiological flow loop model
Authors: Girdhar Gaurav , Andersen Arielle , Pangerl Elizabeth , Jahanbekam Reza , Ubl Samantha , Nguyen Kevin , Wainwright John , Wolf Michael F.
Published: September 2018

Endovascular treatment of intracranial aneurysms with endoluminal flow diverters (single or multiple) has proven to be clinically safe and effective, but is associated with a risk of thromboembolic complications. Recently, a novel biomimetic surface modification with covalently bound phosphorylcholine (Shield Technology™) has shown to reduce the material thrombogenicity of the Pipeline flow diverter. Thrombogenicity of Pipeline Flex, Pipeline Shield, and Flow Redirection Endoluminal Device (FRED) in the presence of human blood under physiological flow conditions—in addition to relative increase in thrombogenicity with multiple devices—remains unknown and was investigated here. Thrombin generation (mean ± SD; μg/mL; thrombin–antithrombin complex or TAT) was measured as FRED (30.3 ± 2.9), Pipeline (13.9 ± 4.4), Pipeline Shield (0.4 ± 0.3), and negative control (no device; 0.1 ± 0.0). Platelet activation (mean ± SD; IU/μL; beta‐thromboglobulin or βTG) was measured as FRED (148 ± 45), Pipeline (92.8 ± 41), Pipeline Shield (16.2 ± 3.5), and negative control (2.70 ± 0.16). FRED was significantly more thrombogenic than Pipeline and Pipeline Shield (p < 0.05) for TAT. Additionally, Pipeline Shield had significantly lower TAT and βTG than the other devices tested (p < 0.05) and these were comparable to the negative control (p > 0.05). TAT and βTG scaled proportionately with multiple Pipeline devices (N = 6) but was unaffected by multiple Pipeline Shield (N = 6) devices—the latter being statistically similar to negative control (p > 0.05). © 2018 The Authors. Journal Of Biomedical Materials Research Part A Published By Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 3195–3202, 2018.
Injectable hydrogels based on glycyrrhizin, alginate, and calcium for three‐dimensional cell culture in liver tissue engineering
Authors: Tong Xiao‐Fang , Zhao Fa‐Quan , Ren Ying‐Zong , Zhang Yi , Cui Yuan‐Lu , Wang Qiang‐Song
Published: September 2018

Injectable hydrogels have been paid more attentions on cell therapy and tissue regeneration resulting from the applications in minimally invasive surgical procedures with ease of handling and complete filling of defect area. Here, a biodegradable and injectable in situ hydrogel formed by glycyrrhizin (GL), alginate (Alg), and calcium (Ca) was developed for three‐dimensional (3D) cell culture. Differential scanning calorimetry (DSC), X‐ray diffraction (XRD), scanning electron microscope (SEM) and rheology analysis were performed to characterize GL‐Alg‐Ca hydrogel and evaluate its formation mechanism, properties, and morphology. The biocompatibility of hydrogel was investigated by cell viability, morphology, and liver specific functions. The results of DSC, XRD, and rheology suggested that hydrogel was homogenous complex with stable structure and well viscoelasticity. Human hepatoma HepG2 cells cultured in hydrogels showed well morphology. Compared with the control group, cells in hydrogels showed good biocompatibility, and could maintain the viability, proliferation and liver function for longer periods of time. Furthermore, the hydrogel improved the mRNA expression of cytochrome P450, which were key enzyme to the metabolization of hepatocytes. The GL‐Alg‐Ca hydrogel could be a potential 3D cells culture system for liver tissue engineering. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 3292–3302, 2018.
Antiplatelet and anticoagulant activities of two phospholipase A2s purified from Cerastes cerastes venom: Structure‐function relationship
Authors: Fatah Chérifi , Samah Saoud , Fatima Laraba‐Djebari
Published: September 2018

This study aimed to elucidate anticoagulant/antiplatelet mechanisms of two previously purified PLA2s from Cerastes cerastes venom, here, termed Cc1‐PLA2 and Cc2‐PLA2. Both PLA2s present close molecular weights of 13,534 and 13,430 Da and Isoectric pH (pI) 7.38 and 7.86 respectively, for Cc1‐PLA2 and Cc2‐PLA2. These Ca2+‐dependent enzymes showed a high catalytic activity upon phospholipids, inducing indirect hemolysis, since they conserve the catalytic domain of PLA2s 26CYCGWGGKG34. They exhibited dual inhibition of platelet aggregation by targeting P2Y12 and TPα receptors preventing Adenosine diphosphate/arachidonate binding and blood clotting. These effects are due to the interaction of Cc1‐PLA2s/Cc2‐PLA2s with factor FXa through a noncatalytic PL‐independent mechanism leading to nonreleased thrombin. Both proteins consist of 120 amino acid residues and share similar three‐dimensional structures close to other SV‐PLA2s. Structural data of PLA2s allowed the relevant residues involved in binding to FXa and platelet receptors. These findings may lead to the design of novel noncompetitive FXa inhibitors.
Optimizing methods for human testicular tissue cryopreservation and spermatogonial stem cell isolation
Authors: Moraveji Seyedeh‐Faezeh , Esfandiari Fereshteh , Sharbatoghli Mina , Taleahmad Sara , Nikeghbalian Saman , Shahverdi Abdolhossein , Baharvand Hossein
Published: September 2018

Cryopreservation of testicular tissue before cancer therapy for fertility preservation in prepubertal boys with cancer is of great interest in reproductive medicine. Isolation of spermatogonial stem cells (SSCs) from cryopreserved tissues would be a suitable cell source to re‐establish spermatogenesis after cancer therapy. We herein establish optimized protocols for cryopreservation of human testicular tissue and isolation of SSCs from cryopreserved tissue. We developed a freezing protocol that provided high testicular cell viability and supported structural integrity and tubular epithelium coherence similar to fresh tissue. Then, we established a protocol that allowed efficient isolation of functional SSCs from cryopreserved tissues. Isolated cells were found on the testicular basement membrane after xenotransplantation. Our results demonstrated the preservation of testicular tissue structure and high cell viability with efficient isolation of SSCs after testicular cryopreservation, which is promising for future therapeutic applications in fertility preservation.
CRISPR/Cas9‐mediated sheep MSTN gene knockout and promote sSMSCs differentiation
Authors: Zhang Yani , Wang Yingjie , Yulin Bi , Tang Beibei , Wang Man , Zhang Chen , Zhang Wenhui , Jin Jing , Li Tingting , Zhao Ruifeng , Yu Xinjian , Zuo Qisheng , Li Bichun
Published: September 2018

Myostatin (MSTN) is an important gene involved in the regulation of embryonic muscle cells and adult muscle development; it has a good application prospect in transgenic animal production by improving the yield of muscle. The purpose of this study is to construct
MSTN gene knockout vector using clustered regularly interspaced short palindromic repeats (
CRISPR)/CRISPR‐associated protein 9 (
Cas9). The knockout efficiency was evaluated in sheep ear fibroblasts (SEFs) by cleavage activity of transcription of guide RNA (
gRNA), luciferase‐single‐strand annealing assay, T7 endonuclease I assay (T7E1), and TA clone sequence (10/38); and above all, detection showed that the cleavage activity of
CRISPR/Cas9‐mediated
MSTN reached 29%.
MSTN‐Cas9/gRNA4 was transfected into sheep skeletal muscle satellite cell (sSMSC) to confirm the function of
MSTN in myotomes formation induced by starvation in low‐serum medium. The results showed that myotubes formation efficiency were 11.2 ± 1.3% and 19.5 ± 2.1% in the control group and knockout group, respectively. The average length of myotomes was 22 ± 5.3 and 47 ± 3.6 μm, displaying that
MSTN knockout can promote sSMSC differentiation in number and length. The unlabeled
MSTN‐Cas9/gRNA4 was transfected into SEFs and monoclonal positive cells was obtained after 48 hours transfection. The MSTN‐positive cells were used as donor cells to perform somatic cell nuclear transplantation to produce transgenic sheep. A total of 20 embryos were transplanted into surrogate mothers, four of them normally produce offspring. The genomic DNA of surviving lambs were used as a template, three positive individuals were identified by T7E1 digestion. All the results demonstrated that the
CRISPR/Cas9 system has the potential to become an important and applicable gene engineering tool in animal breeding.
Whole transcriptome sequencing reveals biologically significant RNA markers and related regulating biological pathways in cardiomyocyte hypertrophy induced by high glucose
Authors: Meng Zheying , Chen Cui , Cao Hongli , Wang Jingyi , Shen E
Published: September 2018

Cardiomyocyte hypertrophy is a physiological adaptation used in an attempt to augment or preserve cardiac function for short periods. Long‐term cardiomyocyte hypertrophy often progresses to heart failure. Previous studies have presented comprehensive mechanisms underlying cardiomyocyte hypertrophy, such as signaling pathways, marker genes, and marker miRNAs or lncRNAs. However, the mechanism in RNA level is still unclear. In this study, we used the whole transcriptome technology on cardiomyocety hypertrophy cells, which were cultured with a high concentration of d‐glucose. Many differentially expressed markers, including genes, lncRNAs, miRNAs, and circRNAs were identified. Further quantitative real‐time PCR verified the highly specific expressed genes, such as Eid1, Timm8b, Mrpl50, Dusp18, Abrc1, Klf13, and Igf1. Moreover, the functional pathways were also enriched with the differentially expressed lncRNA, miRNA, and circRNA. Our study gives new insights into cardiomyocyte hypertrophy and makes great progress in comprehending its mechanism.
Stabilizing proteins to prevent conformational changes required for amyloid fibril formation
Authors: Siddiqi Mohammad Khursheed , Alam Parvez , Malik Sadia , Majid Nabeela , Chaturvedi Sumit Kumar , Rajan Sudeepa , Ajmal Mohd Rehan , Khan Mohsin Vahid , Uversky Vladimir N , Khan Rizwan Hasan
Published: September 2018

Amyloid fibrillation is associated with several human maladies, such as Alzheimer’s, Parkinson’s, Huntington’s diseases, prions, amyotrophic lateral sclerosis, and type 2 diabetes diseases. Gaining insights into the mechanism of amyloid fibril formation and exploring novel approaches to fibrillation inhibition are crucial for preventing amyloid diseases. Here, we hypothesized that ligands capable of stabilizing the native state of query proteins might prevent protein unfolding, which, in turn, may reduce the propensity of proteins to form amyloid fibrils. We demonstrated the efficient inhibition of amyloid formation of the human serum albumin (HSA) (up to 85%) and human insulin (up to 80%) by a nonsteroidal anti‐inflammatory drug, ibuprofen (IBFN). IBFN significantly increases the conformational stability of both HSA and insulin, as confirmed by differential scanning calorimetry (DSC). Moreover, increasing concentration of IBFN boosts its amyloid inhibitory propensity in a linear fashion by influencing the nucleation phase as assayed by thioflavin T fluorescence, transmission electron microscopy, and dynamic light scattering. Furthermore, circular dichroism analysis supported the DSC results, showing that IBFN binds to the native state of proteins and almost completely prevents their tendency to lose secondary and tertiary structures. Cell toxicity assay confirms that species formed in the presence of IBFN are less toxic to neuronal cells (SH‐SY5Y). These results demonstrate the feasibility of using a small molecule to stabilize the native state of proteins, thereby preventing the amyloidogenic conformational changes, which appear to be the common link in several human amyloid diseases.
Role of angiotensin‐converting enzyme insertion/deletion polymorphism in sudden cardiac arrest
Authors: Liu Aifen , Wang Sai , Zhang Chunxiao , Sun Di , Song Xiaozheng
Published: September 2018

Objective

This study aimed to investigate the relationship between angiotensin‐converting enzyme (ACE) insertion/deletion (I/D) polymorphism and to understand sudden cardiac arrest (SCA) in the Chinese population.

Methods

In this study, 232 patients were divided into the SCA group and the coronary disease group with coronary disease, but no SCA occurred during the treatment period. After comparing the genotype frequencies of the two groups, all patients were further divided into three groups as the II homozygotes, ID heterozygotes, and DD homozygotes to investigate the relationship in ACE I/D polymorphism and other risk factors of SCA.

Results

The frequencies of DD genotype in the SCA group were significantly higher than the coronary disease group, as well as the D allele frequencies in the SCA group were high when compared with the coronary disease group. According to the genotypes of the ACE I/D polymorphism, the distribution of patients’ characteristics had no significant differences among all the characteristics. Both, the patients who survived SCA, with II genotype and the ones who died of SCA, with DD genotype had significant higher percentages.

Conclusion

The DD genotype was associated with a higher prevalence of SCA and might be a risk factor of survival rate in sudden cardiac death.
Liver stiffness assessed by transient elastography as a potential indicator of chronic kidney disease in patients with nonalcoholic fatty liver disease
Authors: Qin Shaoyou , Wang Song , Wang Xu , Wang Jiangbin
Published: September 2018

Background

This study was designed to determine the diagnostic value of liver stiffness measured by transient elastography (TE) in identifying chronic kidney disease (CKD) in individuals with ultrasonography‐diagnosed NAFLD.

Methods

A total of 1439 adult patients with ultrasonography‐diagnosed NAFLD between October 2015 and August 2017 in China‐Japan union hospital of Jilin university were initially eligible. According to the exclusion criteria, 24 patients were excluded, and eventually, a total of 1415 patients were included in the study. The AST/ALT ratio and FIB‐4 score were calculated from blood tests, and liver stiffness was measured using TE.

Results

The liver stiffness measured by TE, FIB‐4 score, ALT/AST ratio were significantly elevated in CKD patients, compared with those without CKD (P < 0.001). The areas under the curve (AUROC) of liver stiffness, FIB‐4 score and AST/ALT ratio were 0.694 (0.670‐0.718), 0.707 (0.682‐0.730), 0.712 (0.688‐0.736), showing no statistically significant difference between these three tests. Further, multivariate analysis identified four independent risk factors for CKD: age, diabetes mellitus, serum uric acid, and liver stiffness. Also, the performance of these four independent variables taken together in a logistic regression model for identifying CKD was 0.834 (AUROC; 95%CI: 0.814‐0.853), showing a higher diagnostic performance than that of a single application of liver stiffness.

Conclusions

Liver stiffness assessed by TE is a potential indicator for CKD in ultrasonography‐diagnosed NAFLD patients. Further, a four‐variable model (liver stiffness, age, serum uric acid, and diabetes mellitus) could be a useful tool for identifying subjects at high risk for CKD in NAFLD patients.
Teeth‐derived stem cells: A source for cell therapy
Authors: Baniebrahimi Ghazaleh , Khanmohammadi Razieh , Mir Fatemeh
Published: September 2018

Cell therapy is one of the important therapeutic approaches in the treatment of many diseases such as cancer, degenerative diseases, and cardiovascular diseases. Among various cell types, which could be used as cell therapies, stem cell therapy has emerged as powerful tools in the treatment of several diseases. Multipotent stem cells are one of the main classes of stem cells that could originate from different parts of the body such as bone marrow, adipose, placenta, and tooth. Among several types of multipotent stem cells, tooth‐derived stem cells (TDSCs) are associated with special properties such as accessible, easy isolation, and low invasive, which have introduced them as a good source for using in the treatment of several diseases such as neural injuries, liver fibrosis, and Cohrn’s disease. Here, we provided an overview of TDSCs particular stem cells from human exfoliated deciduous teeth and clinical application of them. Moreover, we highlighted molecular mechanisms involved in the regulation of dental stem cells fate.
Ephrin A1 promotes proliferation of bovine endometrial cells with abundant expression of proliferating cell nuclear antigen and cyclin D1 changing the cell population at each stage of the cell cycle
Authors: Lim Whasun , Bae Hyocheol , Bazer Fuller W. , Song Gwonhwa
Published: September 2018

Ephrin A1 has a role in a variety of biological events, including cell proliferation, differentiation, migration, and angiogenesis. Ephrin A1 expression is abundant in trophoblasts and endometrial cells during the implantation period; however, its intracellular activities have not yet been reported in bovine endometrial (BEND) epithelial cells. The aim of this study was to identify the functional role of ephrin A1 in BEND cells, which have served as a good model system for investigating the regulation of signal transduction following treatment with interferon‐τ (IFNT) in vitro. Supplementation of ephrin A1 to BEND cells increased cell proliferation and increased levels of proliferating cell nuclear antigen and cyclin D1 protein in BEND cell nuclei. To investigate intracellular mechanisms regulated by ephrin A1, we performed Western blot analysis focused on mitogen‐activated protein kinase (MAPK) and phosphoinositide 3‐kinase (PI3K) signaling, which are significantly involved in the successful maintenance of pregnancy. Ephrin A1 dose‐dependently increased phosphorylation of extracellular signal‐regulated kinases (ERK)1/2, c‐Jun N‐terminal kinases (JNK), P38, protein kinase B (AKT), P70S6K, S6, and cyclin D1, and the activated proteins were suppressed by pharmacological inhibitors including wortmannin (a PI3K inhibitor), U0126 (an ERK1/2 inhibitor), and SP600125 (a JNK inhibitor). Among ephrin A1 receptors, abundant expression of EPHA2 and EPHA4 messenger RNA was detected in BEND cells by reverse transcription polymerase chain reaction analysis. Furthermore, tunicamycin‐induced endoplasmic reticulum (ER) stress was inactivated by ephrin A1 treatment of BEND cells. Our findings suggest that ephrin A1 promotes the development of BEND cells and likely enhances uterine capacity and maintenance of pregnancy by activating MAPK and PI3K signaling cascades and by restoring ER stress.
A genetic variant in CDKN2A/2B locus was associated with poor prognosis in patients with esophageal squamous cell carcinoma
Authors: Ghobadi Niloofar , Mehramiz Mehrane , ShahidSales Soodabeh , Rezaei Borojerdi Arezoo , Anvari Kazem , Khazaei Majid , Rezayi Majid , Sadegh Khorrami Mohammad , Joudi‐Mashhad Mona , Ramshini Hassan , Ahmadi‐Simab Saeideh , Moradi Ali , Hassanian Seyed Mahdi , Ghayour‐Mobarhan Majid , Boroushaki Mohammad Taher , Ferns Gordon A. , Avan Amir
Published: September 2018

Esophageal squamous cell carcinoma (ESCC) is among the leading causes of cancer related death. Despite of extensive efforts in identifying valid cancer prognostic biomarkers, only a very small number of markers have been identified. Several genetic variants in the 9p21 region have been identified that are associated with the risk of multiple cancers. Here, we explored the association of two genetic variants in the 9p21 region, CDKN2A/B, rs10811661, and rs1333049 for the first time in 273 subjects with, or without ESCC. We observed that the patients with ESCC had a higher frequency of a TT genotype for rs10811661 than individuals in the control group, and this polymorphism was also associated with tumor size. Moreover, a CC genotype for the rs1333049 polymorphism was associated with a reduced overall survival (OS) of patients with ESCC. In particular, patients with a CC (rs1333049) genotype had a significantly shorter OS (CC genotype: 34.5 ± 8.9 months vs. CG+GG: 47.7 ± 5.9 months;
p value = 0.03). We have also shown the association of a novel genetic variant in CDKN2B gene with clinical outcome of patients with ESCC. Further investigations are warranted in a larger population to explore the value of emerging markers as a risk stratification marker in ESCC.
The genetic factors contributing to hypospadias and their clinical utility in its diagnosis
Authors: Joodi Marjan , Amerizadeh Forouzan , Hassanian Seyed Mahdi , Erfani Marjan , Ghayour‐Mobarhan Majid , Ferns Gordon A. , Khazaei Majid , Avan Amir
Published: September 2018

Hypospadias is among the most common congenital malformations in male neonates. It results from abnormal penile and urethral development, but is a multifactorial disorder that is highly heterogeneous, with several genetic and environmental determinants. Monogenic and chromosomal abnormalities are present in approximately 30% of cases, although the genetic factors contributing to hypospadias remain unknown in 70% of cases. While defects in androgen synthesis can lead to this malformation, mutational analyses have shown several genes, such as sonic hedgehog, fibroblast growth factors, bone morphogenetic proteins, homeobox genes, and the Wnt family, are involved in the normal development of male external genitalia. Mutations in the genes of penile development (e.g., HOX, FGF, Shh) and testicular determination (e.g., WT1, SRY), luteinizing hormone receptor, and androgen receptor have also been proposed to be implicated in hypospadias. Here we review the recent advances in this field and discuss the potential genes that could determine the risk of hypospadias.
Stromal vascular fraction cells plus sustained release VEGF/Ang‐1‐PLGA microspheres improve fat graft survival in mice
Authors: He Yucang , Yu Xiaofang , Chen Zhuojie , Li Liqun
Published: September 2018

Autologous fat transplantation is increasingly applied in plastic and reconstructive surgery. Stromal vascular fraction cells (SVFs) combined with angiogenic factors, such as VEGF (vascular endothelial growth factor A) and Ang‐1 (angiogenin‐1), can improve angiogenesis, which is a critical factor for graft survival. However, direct transplant with such a mixture is insufficient owing to the short half‐life of angiogenic factors. In this study, we evaluated whether a double sustained release system of VEGF/ANG‐1‐PLGA (poly (lactic‐co‐glycolic acid)) microspheres plus SVFs can improve angiogenesis and graft survival after autologous fat transplantation. VEGF/ANG‐1‐PLGA‐sustained release microspheres were fabricated by a modified double emulsion–solvent evaporation technique. Human aspirated fat was mixed with SVF suspension plus VEGF/ANG‐1 sustained release microspheres (Group C), SVF suspension (Group B) alone, or Dulbecco’s modified Eagle’s medium as the control (Group A). Eighteen immunocompromised nude mice were injected with these three mixtures subcutaneously at random positions. After 8 weeks, the mean volume of grafts was greater in the SVFs plus VEGF/ANG‐1‐PLGA group than in the control and SVFs groups (1.08 ± 0.069 ml vs. 0.62 ± 0.036 ml, and 0.83 ± 0.059 ml, respectively). Histological assessments showed that lower fibrosis, but greater microvascular density in the SVFs plus VEGF/ANG‐1‐PLGA group than in the other groups, though the SVFs group also had an appropriate capillary density and reduced fibrosis. Our findings indicate that SVFs plus VEGF/ANG‐1‐PLGA‐sustained release microspheres can improve angiogenesis and graft survival after autologous fat transplantation.
Laminar shear stress‐provoked cytoskeletal changes are mediated by epigenetic reprogramming of TIMP1 in human primary smooth muscle cells
Authors: da Silva Rodrigo A. , Fernandes Célio Jr da C. , Feltran Geórgia da S. , Gomes Anderson M. , de Camargo Andrade Amanda Fantini , Andia Denise C. , Peppelenbosch Maikel P. , Zambuzzi Willian F.
Published: September 2018

Whereas endothelial responses to shear stress are well‐characterized, the cell physiological effects of shear stress in smooth muscle cells (SMCs) remain largely obscure. As SMCs are directly challenged by shear stress after endothelial denuding injury following procedures such as angioplasty or endarterectomy, characterization of these responses represents an important scientific question. Hence we decided to contrast cytoskeletal reorganization, epigenetic reprogramming, signaling transduction, and changes in miRNA (miRs) profiles in primary human aortic smooth muscle cells (AoSMCs) between unstressed cells and cells exposed to shear stress. We observed that shear stress‐provoked reorganization of the actin cytoskeleton in an apparently Cofilin‐dependent fashion and which related to altered integrin signaling, apparently caused by remodeling of the extracellular matrix. The latter appeared a downstream effect of increased expression of matrix metalloproteinases and downregulation of tissue metalloproteinase inhibitor 1 (TIMP1) protein levels. In turn, these effects related to shear stress‐provoked changes in expression and nuclear localization of the epigenetic regulators demethylases TET1, TET2, DNMT1, DNMT3A and DNMT3B, HDAC6, and SIRT1. Accordingly, TIMP1 promotor CpG hypomethylation was a prominent effect, and resulted in a significant increase in TIMP1 transcription, which may also have related increased expression of miRs involved in modulating TIMP1 translation. Thus epigenetic‐reprogramming of TIMP1 emerges as critical element in smooth muscle responses to mechanical signals and as epigenetic machinery is amendable to pharmacological manipulation, this pathway may have important clinical consequences.
Genetics and rheumatoid arthritis susceptibility in Iran
Authors: Korani Shahla , Korani Mitra , Butler Alexandra E. , Sahebkar Amirhossein
Published: September 2018

Rheumatoid arthritis (RA) is an autoimmune disorder with a number of risk factors, including both genetic and environmental. A number of RA risk associated genomic loci has been identified. In this review, we summarize the association of genetic factors with RA reported in population studies in Iran. No significant association was found between the majority of genetic factors identified in other populations and risk for RA in the Iranian subjects. This conflicting result could be due to the ethnic differences and diversity that are present in Iran. We conclude that there is a need to investigate larger groups of Iranian subjects, encompassing different regions of Iran, to either prove or refute these initial findings.
Hypoxia induces ZEB2 in podocytes: Implications in the pathogenesis of proteinuria
Authors: Nakuluri Krishnamurthy , Mukhi Dhanunjay , Nishad Rajkishor , Saleem Moin A. , Mungamuri Sathish Kumar , Menon Ram K. , Pasupulati Anil Kumar
Published: September 2018

The glomerular filtration barrier (GFB) plays a critical role in ensuing protein free urine. The integrity of the GFB is compromised during hypoxia that prevails during extreme physiological conditions. However, the mechanism by which glomerular permselectivity is compromised during hypoxia remains enigmatic. Rats exposed to hypoxia showed a decreased glomerular filtration rate, podocyte foot‐processes effacement, and proteinuria. Accumulation of hypoxia‐inducible factor‐1α (HIF1α) in podocytes resulted in elevated expression of zinc finger E‐box binding homeobox 2 (ZEB2) and decreased expression of E‐ and P‐cadherin. We also demonstrated that HIF1α binds to hypoxia response element localized in the ZEB2 promoter. Furthermore, HIF1α also induced the expression of ZEB2‐natural antisense transcript, which is known to increase the efficiency of ZEB2 translation. Ectopic expression of ZEB2 induced loss of E‐ and P‐cadherin and is associated with enhanced motility of podocytes during hypoxic conditions. ZEB2 knockdown abrogated hypoxia‐induced decrease in podocyte permselectivity. This study suggests that hypoxia leads to activation of HIF1α–ZEB2 axis, resulting in podocyte injury and poor renal outcome.
Melatonin and cancer: From the promotion of genomic stability to use in cancer treatment
Authors: Farhood Bagher , Goradel Nasser Hashemi , Mortezaee Keywan , Khanlarkhani Neda , Najafi Masoud , Sahebkar Amirhossein
Published: September 2018

Cancer remains among the most challenging human diseases. Several lines of evidence suggest that carcinogenesis is a complex process that is initiated by DNA damage. Exposure to clastogenic agents such as heavy metals, ionizing radiation (IR), and chemotherapy drugs may cause chronic mutations in the genomic material, leading to a phenomenon named genomic instability. Evidence suggests that genomic instability is responsible for cancer incidence after exposure to carcinogenic agents, and increases the risk of secondary cancers following treatment with radiotherapy or chemotherapy. Melatonin as the main product of the pineal gland is a promising hormone for preventing cancer and improving cancer treatment. Melatonin can directly neutralize toxic free radicals more efficiently compared with other classical antioxidants. In addition, melatonin is able to regulate the reduction/oxidation (redox) system in stress conditions. Through regulation of mitochondrial nction and inhibition of pro‐oxidant enzymes, melatonin suppresses chronic oxidative stress. Moreover, melatonin potently stimulates DNA damage responses that increase the tolerance of normal tissues to toxic effect of IR and may reduce the risk of genomic instability in patients who undergo radiotherapy. Through these mechanisms, melatonin attenuates several side effects of radiotherapy and chemotherapy. Interestingly, melatonin has shown some synergistic properties with IR and chemotherapy, which is distinct from classical antioxidants that are mainly used for the alleviation of adverse events of radiotherapy and chemotherapy. In this review, we describe the anticarcinogenic effects of melatonin and also its possible application in clinical oncology.
Cholesterol burden in the liver induces mitochondrial dynamic changes and resistance to apoptosis
Authors: Domínguez‐Pérez Mayra , Simoni‐Nieves Arturo , Rosales Patricia , Nuño‐Lámbarri Natalia , Rosas‐Lemus Mónica , Souza Verónica , Miranda Roxana U. , Bucio Leticia , Uribe Carvajal Salvador , Marquardt Jens U. , Seo Daekwan , Gomez‐Quiroz Luis E. , Gutiérrez‐Ruiz María Concepción
Published: September 2018

Non‐alcoholic fatty liver disease (NAFLD) encompasses a broad spectrum of histopathological changes ranging from non‐inflammatory intracellular fat deposition to non‐alcoholic steatohepatitis (NASH), which may progress into hepatic fibrosis, cirrhosis, or hepatocellular carcinoma. Recent data suggest that impaired hepatic cholesterol homeostasis and its accumulation are relevant to the pathogenesis of NAFLD/NASH. Despite a vital physiological function of cholesterol, mitochondrial dysfunction is an important consequence of dietary‐induced hypercholesterolemia and was, subsequently, linked to many pathophysiological conditions. The aim in the current study was to evaluate the morphological and molecular changes of cholesterol overload in mouse liver and particularly, in mitochondria, induced by a high‐cholesterol (HC) diet for one month. Histopathological studies revealed microvesicular hepatic steatosis and significantly elevated levels of liver cholesterol and triglycerides leading to impaired liver synthesis. Further, high levels of oxidative stress could be determined in liver tissue as well as primary hepatocyte culture. Transcriptomic changes induced by the HC diet involved disruption in key pathways related to cell death and oxidative stress as well as upregulation of genes related to glutathione homeostasis. Impaired liver function could be associated with a decrease in mitochondrial membrane potential and ATP content and significant alterations in mitochondrial dynamics. We demonstrate that cholesterol overload in the liver leads to mitochondrial changes which may render damaged hepatocytes proliferative and resistant to cell death whereby perpetuating liver damage.
Renewal of extinguished operant behavior following changes in social context
Authors: Browning Kaitlyn O. , Shahan Timothy A.
Published: September 2018

Renewal is the reoccurrence of previously extinguished behavior following a change in the context in which extinction was conducted. Despite an extensive body of research examining renewal, little is known about the role of social stimuli in renewal. The present experiments provided a novel examination of renewal of operant behavior by changing social stimuli across phases in an ABA renewal preparation. In both experiments, social stimuli were arranged by placing another rat in a second compartment of a divided operant chamber. In Experiment 1, the presence of another rat defined the extinction context, whereas an empty second compartment defined the baseline and testing contexts. We reversed these contextual manipulations in Experiment 2 such that the presence of another rat defined the baseline and testing contexts and the second compartment was empty during extinction. Renewal of lever pressing occurred when the other rat was removed from the chamber in Experiment 1 and when the other rat was returned to the chamber in Experiment 2. Thus, social stimuli may function as contextual stimuli, and changes in social contexts may produce renewal of previously extinguished behavior.
Bibliographic title search for medical cardiological “signs” (eponyms)
Authors: Kanie Takayoshi , Mizuno Atsushi , Kawai Fujimi , Iri Takanobu , Suzuki Takahiro , Oshima Shinichirou , Fukui Sho , Son Raku , Matsuo Takahiro
Published: September 2018

Background

The word “sign” refers to important physical findings or observations that are useful in diagnosis; however, there are no scientific reviews of “signs.” The aim of this paper was to list and review these terms using a bibliographic approach.

Methods

We performed a title search of “sign” using a bibliographic search and review approach in MEDLINE and EMBASE.

Results

We detected 398 papers including 217 medical signs in cardiology.

Conclusions

This is the first literature review of eponyms specifically for signs using a bibliographic method, which is useful for the discussion of the appropriateness of eponyms.
STACKing the odds for adolescent survival: health service factors associated with full retention in care and adherence amongst adolescents living with HIV in South Africa
Authors: Cluver Lucie , Pantelic Marija , Toska Elona , Orkin Mark , Casale Marisa , Bungane Nontuthuzelo , Sherr Lorraine
Published: September 2018

Introduction

There are two million HIV‐positive adolescents in southern Africa, and this group has low retention in care and high mortality. There is almost no evidence to identify which healthcare factors can improve adolescent self‐reported retention. This study examines factors associated with retention amongst antiretroviral therapy (ART)‐initiated adolescents in South Africa.

Methods

We collected clinical records and detailed standardized interviews (n = 1059) with all 10‐ to 19 year‐olds ever initiated on ART in all 53 government clinics of a health subdistrict, and community traced to include lost‐to‐follow‐up (90.1% of eligible adolescents interviewed). Associations between full self‐reported retention in care (no past‐year missed appointments and 85% past‐week adherence) and health service factors were tested simultaneously in sequential multivariate regression and marginal effects modelling, controlling for covariates of age, gender, urban/rural location, formal/informal housing, maternal and paternal orphanhood, vertical/horizontal HIV infection, overall health, length of time on ART and type of healthcare facility.

Results

About 56% of adolescents had self‐reported retention in care, validated against lower detectable viral load (AOR: 0.63, CI: 0.45 to 0.87, p = 0.005). Independent of covariates, five factors (STACK) were associated with improved retention: clinics Stocked with medication (OR: 3.0, CI: 1.6 to 5.5); staff with Time for adolescents (OR: 2.7, CI: 1.8 to 4.1); adolescents Accompanied to the clinic (OR: 2.3, CI: 1.5 to 3.6); enough Cash to get to clinic safely (OR: 1.4, CI: 1.1 to 1.9); and staff who are Kind (OR: 2.6, CI: 1.8 to 3.6). With none of these factors, 3.3% of adolescents reported retention. With all five factors, 69.5% reported retention.

Conclusions

This study identifies key intervention points for adolescent retention in HIV care. A basic package of clinic and community services has the potential to STACK the odds for health and survival for HIV‐positive adolescents.