bluuebunny/crossref_metadata_2025 huggingface dataset:
Epilepsy at different ages—Etiologies in a Norwegian population
Authors: Dahl‐Hansen Eline , Koht Jeanette , Syvertsen Marte
Published: December 2018

The causes of epilepsy are age related, but confirmative data from population‐based studies are scarce. Our aim was to describe the typical causes of epilepsy in the different age groups of a defined population. The study was cross‐sectional, based on a review of all medical files containing a diagnostic code for epilepsy at Drammen Hospital from 1999‐2013. Drammen Hospital serves the population of Buskerud County, with 272 228 residents (as of January 1, 2014), including 1771 people with active epilepsy. This group of persons with active epilepsy was divided into different age groups with the causes of epilepsy mapped in each group. The proportion with unknown etiology ranged from 27% (age 5‐9) to 41% (age 10‐19). Structural‐metabolic epilepsy and perinatal insults were the leading causes of epilepsy in the age group 5‐9 (46%), whereas disturbances of brain development dominated in the youngest (23% in patients ≤4 years old). In the group comprising persons with epilepsy ≥60 years old, stroke was the most common cause of epilepsy (44%). Despite recent advances in research and technology, a large number of patients in all age groups (including the youngest) still have an unknown cause of epilepsy. We conclude that an effort must be made to improve the diagnostics for and understanding of the causes of epilepsy across all ages.
From nodes to networks: How methods for defining nodes influence inferences regarding network interactions
Authors: Falco Dimitri , Chowdury Asadur , Rosenberg David R. , Diwadkar Vaibhav A. , Bressler Steven L.
Published: December 2018

Functional connectivity (FC) analysis of fMRI data typically rests on prior identification of network nodes from activation profiles. We compared Activation Likelihood Estimate (ALE) and the Experimentally Derived Estimate (EDE) approaches to network node identification and functional inference for both verbal and visual forms of working memory. ALE arrives at canonical activation maxima that are assumed to reliably represent peaks of brain activity underlying a psychological process (e.g., working memory). By comparison, EDEs of activation maxima are typically derived from individual participant data, and are thus sensitive to individual participant activation profiles. Here, nodes were localized by both ALE and EDE methods for each participant, and subsequently extracted time series were compared using connectivity analysis. Two sets of significance tests were performed: (1) correlations computed between nodal time series of each method were compared, and (2) correlations computed between network edges (functional connections) of each network node pair were compared. Large proportions of edge correlations significantly differed between methods. ALE effectively summarizes working memory network node locations across studies and subjects, but the sensitivity to individual functional loci suggest that EDE methods provide individualized estimates of network connectivity. We suggest that a hybrid method incorporating both ALE and EDE is optimal for network inference.
Ototoxicity in locally advanced head and neck cancer patients treated with induction chemotherapy followed by intermediate or high‐dose cisplatin‐based chemoradiotherapy
Authors: Driessen Chantal M. L. , Leijendeckers Joop , Snik Ad , van der Graaf Winette T. A. , de Boer Jan Paiul , Gelderblom Hans , Kaanders Johannes H. A. M. , Takes Robert , van Herpen Carla M. L.
Published: December 2018

Background

This study evaluated ototoxicity in locally advanced head and neck cancer patients treated in the CONDOR study with docetaxel/cisplatin/5‐fluorouracil (TPF) followed by conventional radiotherapy with concomitant cisplatin 100 mg/m2 on days 1, 22, and 43 (cis100+RT) versus accelerated radiotherapy with concomitant cisplatin weekly 40 mg/m2 (cis40+ART).

Methods

Sixty‐two patients were treated in this study. Audiometry was performed at baseline, during TPF, before start of chemoradiotherapy, and 1, 4, 8, and 12 months after treatment.

Results

A complete dataset of audiometric data was available of 12 patients treated with high‐dose cisplatin and of 11 patients treated with intermediate‐dose cisplatin. Patients in the high‐dose group showed significant more hearing loss than in the intermediate group at 4 kHz ([z = 1.98; P = .04] and 8 kHz [z = 2.07; P < .03]). Interindividual variation was high in both groups.

Conclusion

After induction TPF, more ototoxicity was observed in chemoradiotherapy with cis100+RT than after chemoradiotherapy with cis40+ART.
Pattern of urine iodine excretion with low iodine diet during preparation for radioactive iodine ablation in patients with thyroid cancer
Authors: Kang Sang‐Wook , Yap Zeng Z. , Lee Cho Rok , Lee Jandee , Jeong Jong Ju , Nam Kee‐Hyun , Yun Mi Jin , Lee Eun Jig , Chung Woong Youn , Park Cheong Soo
Published: December 2018

Background

The optimal period of low iodine diet during preparation for radioactive iodine (RAI) ablation in an area with iodine‐rich diet was investigated.

Methods

Ninety‐four patients with thyroid cancer who underwent low iodine diet and RAI were prospectively allocated into 2 groups—thyroxine withdrawal or using recombinant human thyroid stimulating hormone (rhTSH) for TSH stimulation. Their urinary iodine excretion (UIE) patterns were analyzed.

Results

There was no clinicopathological difference between the 2 groups except for tumor size and lymph node status. The UIE (median iodine to creatinine ratio, I/Cr) in the withdrawal group on the 7th and 14th day were 18.3 and 17.9 μg/gCr, respectively, with adequate preparation rate of 93.3% on both days (cutoff value 100 μg/gCr). In the rhTSH group, the median I/Cr on the 7th and 14th day were 48.0 and 45.7 μg/gCr (adequate preparation rates 91.8% and 93.8%), respectively.

Conclusion

One week of low iodine diet is sufficient preparation for RAI regardless of method of TSH stimulation.
Proton therapy for skull base tumors: A review of clinical outcomes for chordomas and chondrosarcomas
Authors: Mercado Catherine E. , Holtzman Adam L. , Rotondo Ronny , Rutenberg Michael S. , Mendenhall William M.
Published: December 2018

Background

Skull base chordomas and chondrosarcomas are rare tumors traditionally treated by surgical resection and adjuvant radiation therapy (RT). We will discuss data evaluating clinical outcomes of proton therapy in the treatment of skull base chordomas and chondrosarcomas.

Methods

A literature review was performed using a MEDLINE search from January 1990 to January 2017.

Results

The published data suggest that the dose intensification allowed by proton therapy has resulted in good clinical outcomes and a tolerable toxicity profile.

Conclusion

Proton therapy is a modern RT technique that has demonstrated improved preliminary clinical outcomes in the treatment of skull base chordomas and chondrosarcomas compared to conventional radiotherapy, and comparable to other advanced photon‐based RT techniques.
Increased risk of postoperative complications after total thyroidectomy with Graves' disease
Authors: Kwon Hyungju , Kim Jong‐kyu , Lim Woosung , Moon Byung‐In , Paik Nam Sun
Published: December 2018

Background

The effect of Graves' disease on the risk of postoperative complications in patients undergoing total thyroidectomy is unclear.

Methods

The incidence of recurrent laryngeal nerve (RLN) injury and hypoparathyroidism were analyzed between 165 patients with Graves' disease (GD group) and 1:1 matched patients with euthyroid states (control group).

Results

The matched cohorts did not differ in age, sex, body mass index, pathologic diagnosis, and extent of operation. Excised thyroid weight was higher in the Graves' disease than in the control group (60.1 g vs 22.6 g; P < .001). Multivariate analysis showed that Graves' disease significantly increased risks of transient RLN injury (odds ratio [OR] = 4.7, 95% confidence interval [CI] = 1.5‐15.5; P = .010) and transient hypoparathyroidism (OR = 2.8, 95% CI = 1.3‐5.8; P = .007). Rates of permanent complications were comparable in the Graves' disease and control groups.

Conclusions

Graves' disease can be a predictive factor for postoperative RLN injury and hypoparathyroidism after total thyroidectomy.
Exploring the use of resources to support gender equality in Australian workplaces
Authors: Nally Taylor , Taket Ann , Graham Melissa
Published: December 2018

Issue addressed

Numerous resources exist to support workplaces to undertake gender equality work; however, it is often unclear which existing resources are being utilised by Australian workplaces. One group that can provide insight into the use of existing resources is the professionals who have undertaken gender equality work in their organisation.

Methods

Purposive sampling was used to identify informants with experience undertaking gender equality work. A sample of 12 informants was recruited from five employment sectors: five informants from the women('s health sector; two from other organisations in the health sector; three from local government; and one each from manufacturing and education. One in‐depth semi‐structured interview was conducted with each informant. Interview transcripts were analysed using thematic analysis.

Results

Four themes emerged from data analysis: “Organisational Context,” “Legitimising Gender Equality Work,” “Demystifying Gender Equality” and “Embedding Gender Equality into the Workplace.” Mechanisms such as drawing on the evidence base, developing internal communications strategies, establishing a working group, undertaking training, conducting an audit, and reviewing policies and procedures were used to embed gender‐based considerations into the workplace. A range of resources to underpin most of these approaches was discussed by informants.

Conclusions

Informants had a sound understanding of approaches they could use to address existing gender inequality; however, they did not always utilise existing resources to support them to undertake their chosen approach.

So what?

A clearer online database needs to be established to allow workplaces to access a compilation of existing resources and any evaluation on their use.
The risk of cancer attributable to diagnostic medical radiation: Estimation for France in 2015
Authors: Marant‐Micallef Claire , Shield Kevin D. , Vignat Jérôme , Cléro Enora , Kesminiene Ausrele , Hill Catherine , Rogel Agnès , Vacquier Blandine , Bray Freddie , Laurier Dominique , Soerjomataram Isabelle
Published: December 2018

Although medical ionizing radiation (IR) has clear clinical benefits, it is an established carcinogen. Our study estimates the number of new cancer cases in France in 2015 attributable to IR exposure from medical procedures. Exposures from external (X‐rays, CT scans, interventional radiology) and internal (nuclear medicine) sources were considered. We used 2007 national frequencies of diagnostic examinations by sex and age to estimate the lifetime organ dose exposure adjusted for changes in the use of such procedures over time. The Biological Effects of Ionizing Radiation VII risk models were used to estimate the corresponding excess cancer risk, assuming an average latency period of 10 years. Additionally, we used cancer incidence data from the French Cancer Registries Network. Of the 346,000 estimated new cancer cases in adults in France in 2015, 2300 cases (940 among men and 1360 among women) were attributable to diagnostic IR, representing 0.7% of all new cancer cases (0.5% for men and 0.9% for women). The leading cancers attributable to medical IR were female breast (n = 560 cases), lung (n = 500 cases) and colon (n = 290 cases) cancers. Compared to other risk factors, the contribution of medical IR to the cancer burden is small, and the benefits largely outweigh its harms. However, some of these IR‐associated cancer cases may be preventable through dose optimization of and enhanced justification for diagnostic examinations.
Thrombotic thrombocytopenic purpura: A 5‐year tertiary care centre experience
Authors: Swart Léanne , Schapkaitz Elise , Mahlangu Johnny N.
Published: December 2018

Introduction

Thrombotic thrombocytopenic purpura (TTP) is associated with high mortality if not managed timeously with therapeutic plasma exchange (TPE). TTP secondary to human immunodeficiency virus (HIV) infection is unique to sub‐Saharan Africa. The management and outcome of TTP in the era of improved access to therapy has not been described.

Methods

The present study describes the clinical presentation, treatment, therapeutic endpoints, and outcome of TTP patients at the Charlotte Maxeke Johannesburg Academic Hospital, South Africa. The inpatient and outpatient records of 41 consecutive adults with TTP were reviewed between 2012 and 2016. Patients were classified according to aetiology and treatment response.

Results

TTP was the initial presenting feature of HIV infection in 78.0%, and 12.5% were noncompliant with antiretroviral therapy (ART). Most study patients were of black ethnicity (95%) and female gender (78.1%). Treatment included initial TPE (87.8%), plasma infusion (78.1%), antiretroviral therapy (78.3%), corticosteroids (61.0%) intensive care admission (41.5%), renal dialysis (12.2%), and other immunosuppressive agents (4.9%). The median (range) number of TPEs was 10.0 (7.0‐15.0). A high rate of refractory disease (63.4%) was reported. Haemoglobin, platelet count, lactate dehydrogenase, red cell distribution width, and creatinine were reliable therapeutic end‐points (P < .05). The relapse rate was 9.8% and the mortality rate was 29.3%.

Conclusion

The high mortality rate emphasises the importance of early diagnosis, referral, and appropriate management of TTP. Anti‐retroviral therapy and adherence monitoring are essential to TTP management associated with HIV. Future studies to identify patients at risk for refractory disease are indicated.
Literature review of apheresis procedures performed perioperatively in cardiac surgery for ASFA category indications
Authors: Kanellopoulou Theoni , Kostelidou Theodora
Published: December 2018

Background

Perioperative therapeutic plasma exchange in patients with cardiovascular diseases poses several challenges, including alterations in intravascular volume, serum electrolytes, the coagulation cascade, and drug pharmacokinetics.

Methods

This review article summarizes different indications of plasma exchange for patients requiring cardiac surgery based on reported case reports and case series.

Results

The most common reported indication is plasma exchange for the management of allosensitized cardiac transplant candidate patients in combination with immunosuppressive regimens, which increases the likelihood of obtaining a cross‐match‐negative allograft, improving post‐transplant clinical outcome. The second most common indication is for patients with a history of heparin‐induced thrombocytopenia syndrome that permits the use of heparin in cardiopulmonary bypass in an urgent cardiac surgery. Less common indications are restoration of clotting factors for patients with congenital bleeding disorders or removal of cold agglutinins. No severe complications were described in reported cases.

Conclusion

Therapeutic plasma exchange is an effective and safe procedure that could be performed preoperatively and intraoperatively in urgent cardiac surgery for the management of antibody‐mediated disorders including allosensitized cardiac transplant candidate patients or patients with heparin‐induced thrombocytopenia syndrome.
Exploring effects of childhood parentification on adult‐depressive symptoms in Korean college students
Authors: Cho AhRa , Lee SoYean
Published: December 2018

Objective

This study explored parentification dimensions, the age of onset, duration, and family circumstances to better understand the characteristics of parentification and its impact on depressive symptoms among Korean college students.

Method

A sample of South Korean college students (N = 316, aged 18–29 years, 66.1% female) rated their childhood parentification experiences and current depressive symptoms.

Results

Overall, there were few significant differences in parentification dimensions and depressive symptoms regarding family circumstances that contributed to parentification. Longer duration and earlier onset of parentification were significantly associated with higher depressive symptom scores in adulthood. However, only perceived unfairness was associated with depressive symptoms after controlling for the age of onset, duration, and other parentification dimensions.

Conclusions

These findings suggest the importance of examining situational contexts of parentification to better capture the effects of childhood parentification on depressive symptoms in adulthood.
Effects of inhibitors of the renin‐angiotensin system on reducing blood pressure and expression of inflammatory factors in CHD patients: A network meta‐analysis
Authors: Pang Xue‐Feng , Liu Run‐Mei , Xia Yun‐Feng
Published: December 2018

The renin‐angiotensin system (RAS) is an ever‐evolving endocrine system with considerable checks and balances on the production and catabolism of angiotensin peptides most likely due to the manifold effects of angiotensins. We aimed to explore the effects of different inhibitors of RAS on blood pressure and expression of inflammatory factors in patients with coronary heart disease (CHD). We initially searched PubMed, EMBASE and Cochrane Library electronic databases with nine eligible randomized controlled trials enrolled. Direct and indirect evidence was combined to calculate the weighted mean difference value and draw surface under the cumulative ranking curves. The results demonstrated that, compared with placebo and enalapril, ramipril had a better effect on reducing systolic blood pressure after short‐term usage of drugs (<12 months), while perindopril had better effects on reducing diastolic blood pressure and C‐reactive protein expression. Furthermore, after long‐term usage of drugs (≥12 months), there was no significant difference among olmesartan, quinapril and candesartan in the treatment of patients with CHD. Perindopril and ramipril had better effects on inhibiting blood pressure and expression of inflammatory factors among eight inhibitors after short‐term usage of drugs (<12 months); while quinapril had better effects on reducing blood pressure and expression of inflammatory factor after long‐term usage of drugs, and there was little difference in the effects between olmesartan and candesartan (≥12 months). Perindopril may have better short‐term effects on reducing blood pressure and expression of inflammatory factor, while quinapril may have better long‐term effects on reducing blood pressure and expression of inflammatory factor.
Retracted: Downregulation of long noncoding RNA H19 rescues hippocampal neurons from apoptosis and oxidative stress by inhibiting IGF2 methylation in mice with streptozotocin‐induced diabetes mellitus
Authors: Yu Jin‐Lu , Li Chao , Che Li‐He , Zhao Yu‐Hao , Guo Yun‐Bao
Published: December 2018

The diabetes mellitus (DM)‐induced reduction of neurogenesis in the hippocampus is consequently accompanied by cognitive decline. The present study set out to define the critical role played by long noncoding RNA H19 (lncRNA H19) in the apoptosis of hippocampal neurons, as well as oxidative stress (OS) in streptozotocin (STZ)‐induced DM mice through regulation of insulin‐like growth factor 2 (IGF2) methylation. The expression of lncRNA H19 in the hippocampal neurons and surviving neurons were detected. Hippocampal neurons were cultured and transfected with oe‐H19, sh‐H19, oe‐IGF2, or sh‐IGF2, followed by detection of the expressions of IGF2 and apoptosis‐related genes. Determination of the lipid peroxide and glutathione levels was conducted, while antioxidant enzyme activity was identified. The IGF2 methylation, the binding of lncRNA H19 to DNA methyltransferase, and the binding of lncRNA H19 to IGF2 promoter region were detected. DM mice exhibited high expressions of H19, as well as a decreased hippocampal neurons survival rate. Higher lncRNA H19 expression was found in DM. Upregulated lncRNA H19 significantly increased the expression of Bax and caspase‐3 but decreased that of Bcl‐2, thus promoting the apoptosis of hippocampal neuron. Besides, upregulation of lncRNA H19 induced OS. LncRNA H19 was observed to bind specifically to the IGF2 gene promoter region and promote IGF2 methylation by enriching DNA methyltransferase, thereby silencing IGF2 expression. Taken together, downregulated lncRNA H19 reduces IGF2 methylation and enhances its expression, thereby suppressing hippocampal neuron apoptosis and OS in STZ‐induced (DM) mice.
Retracted: IRAK3 gene silencing prevents cardiac rupture and ventricular remodeling through negative regulation of the NF‐κB signaling pathway in a mouse model of acute myocardial infarction
Authors: Ge Zhen‐Wei , Wang Bao‐Cai , Hu Jun‐Long , Sun Jun‐Jie , Wang Sheng , Chen Xian‐Jie , Meng Shu‐Ping , Liu Lin , Cheng Zhao‐Yun
Published: December 2018

Cardiac rupture and ventricular remodeling are recognized as the severe complications and major risk factors of acute myocardial infarction (AMI). This study aims to evaluate the regulatory roles of interleukin‐1 receptor‐associated kinase 3 (IRAK3) and nuclear factor‐κB (NF‐κB) signaling pathway in cardiac rupture and ventricular remodeling. Microarray analysis was performed to screen AMI‐related differentially expressed genes and IRAK3 was identified. The models of AMI were established in male C57BL/6 mice to investigate the functional role of IRAK3. Afterwards, lentivirus recombinant plasmid si‐IRAK3 was constructed for IRAK3 silencing. Next, cardiac function parameters were measured in response to IRAK3 silencing. The regulatory effects that IRAK3 had on myocardial infarct size and the content of myocardial interstitial collagen were analyzed. The regulation of IRAK3 silencing on the NF‐κB signaling pathway was further assayed. The obtained results indicated that highly expressed IRAK3 and activated NF‐κB signaling pathway were observed in myocardial tissues of mouse models of AMI, accompanied by increased expression of matrix metalloproteinase (MMP)‐2/9 and tissue inhibitor of metalloproteinase 2 (TIMP‐2). Notably, IRAK3 gene silencing inhibited the activation of NF‐κB signaling pathway. Furthermore, IRAK3 gene silencing led to the decreased thickness of infarct area and collagen content of myocardial interstitium, alleviated diastolic, and systolic dysfunctions, as well as, facilitated cardiac functions in mice with AMI, corresponding to decreased expression of MMP‐2/9 expression and increased expression of TIMP‐2. Taken together, silencing of IRAK3 inactivates the NF‐κB signaling pathway, and thereby impeding the cardiac rupture and ventricular remodeling, which eventually prevents AMI progression.
Effects of obesity and diabetes on the epigenetic modification of mammalian gametes
Authors: Ou Xiang‐Hong , Zhu Cheng‐Cheng , Sun Shao‐Chen
Published: December 2018

Obesity and diabetes are closely associated with numerous reproductive disorders, including termination of ovulation, irregular menstruation, low fertility, abortion, and risky pregnancy, which are now regarded as global health problems. Paternal/maternal obesity and diabetes can also be transmitted to the subsequent generation via gametes, suggesting the association of epigenetic inheritance with obesity and diabetes, particularly for its effects on offspring. Recent studies indicate that both obesity and diabetes change DNA and histone methylation levels, histone acetylation, and noncoding RNAs such as microRNAs (miRNAs) in oocytes and sperm. Several important genes, such as PPAR‐α, Igf2, H19, Fyn, Stella, Sirt3, Sirt6, and Peg3 as well as miRNAs, such as let‐7c, reportedly participate in the regulation of epigenetic modifications in mammalian gametes. This review summarizes the recent progress that links obesity/diabetes and reproductive disorders from the perspective of gamete epigenetic modifications.
Long noncoding RNA ABHD11‐AS1 promote cells proliferation and invasion of colorectal cancer via regulating the miR‐1254‐WNT11 pathway
Authors: He Dedong , Yue Zhongyi , Liu Lingling , Fang Xiangjie , Chen Liping , Han Huanhuan
Published: December 2018

The purpose of our study was to investigate the effects of the long noncoding RNA (lncRNA) ABHD11‐AS1 on colorectal cancer (CRC) progression and further explore its possible underlying mechanisms. In the study, we found that ABHD11‐AS1 was highly expressed in CRC tissues and cell lines. High ABHD11‐AS1 expression was correlated with poor overall survival of patients with CRC. ABHD11‐AS1 knockdown reduced CRC cell proliferation, in vitro invasion, and in vivo tumor growth. Investigation of the underlying mechanism showed that ABHD11‐AS1 could act as a molecular sponge of miR‐1254, and WNT11 was a downstream target of miR‐1254 in CRC. Moreover, there was a negative association between ABHD11‐AS1 expression (or WNT11) and miR‐1254 in CRC tissues. The rescue assays showed that WNT11 overexpression partially rescued the effects of ABHD11‐AS1 inhibition on CRC progression. Thus, we demonstrated that ABHD11‐AS1 promotes CRC progression through the miR‐1254‐WNT11 pathway, which provides a new insight into the therapeutic strategies for CRC.
microRNAs in cancer stem cells: Biology, pathways, and therapeutic opportunities
Authors: Asadzadeh Zahra , Mansoori Behzad , Mohammadi Ali , Aghajani Marjan , Haji‐Asgarzadeh Khalil , Safarzadeh Elham , Mokhtarzadeh Ahad , Duijf Pascal H. G. , Baradaran Behzad
Published: December 2018

Cancer stem cells (CSCs) are a small subpopulation of tumor cells that have been identified in most types of cancer. Features that distinguish them from the bulk of tumor cells include their pluripotency, self‐renewal capacity, low proliferation rate, and tumor‐initiating ability. CSCs are highly malignant, as they confer drug resistance and facilitate tumor progression, relapse, and metastasis. The molecular mechanisms underlying CSC biology are now beginning to be understood. In this context, microRNAs (miRNAs) occupy a prominent place. These endogenous, small noncoding RNA molecules control gene expression at the posttranscriptional level. This study reviews our current understanding of how the misexpression of tumor suppressor and oncogenic miRNAs in CSCs sustain their abundance and malignant properties. We discuss how they partly do so by acting on major CSC signaling pathways, including the Wnt, Notch, Hedgehog, and BMI‐1 pathways. Our current knowledge of miRNA functions in CSCs may now be used for cancer diagnostic and prognostic purposes. In addition, when combined with recent technical advances in the in vivo delivery of miRNAs, we are now in an excellent position to develop strategies that harness miRNA interference and replacement technologies for the therapeutic targeting of CSCs.
Role of the HIF‐1α/Nur77 axis in the regulation of the tyrosine hydroxylase expression by insulin in PC12 cells
Authors: Fiory Francesca , Mirra Paola , Nigro Cecilia , Pignalosa Francesca Chiara , Zatterale Federica , Ulianich Luca , Prevete Nella , Formisano Pietro , Beguinot Francesco , Miele Claudia
Published: December 2018

Tyrosine hydroxylase (TH), catalyzing the conversion of tyrosine into l‐DOPA, is the rate‐limiting enzyme in dopamine synthesis. Defects in insulin action contribute to alterations of TH expression and/or activity in the brain and insulin increases TH levels in 1‐methyl‐4‐phenylpyridinium (MPP+)‐treated neuronal cells. However, the molecular mechanisms underlying the regulation of TH by insulin have not been elucidated yet. Using PC12 cells, we show for the first time that insulin increases TH expression in a biphasic manner, with a transient peak at 2 hr and a delayed response at 16 hr, which persists for up to 24 hr. The use of a dominant negative hypoxia‐inducible factor 1‐alpha (HIF‐1α) and its pharmacological inhibitor chetomin, together with chromatin immunoprecipitation (ChIP) experiments for the specific binding to TH promoter, demonstrate the direct role of HIF‐1α in the early phase. Moreover, ChIP experiments and transfection of a dominant negative of the nerve growth factor IB (Nur77) indicate the involvement of Nur77 in the late phase insulin response, which is mediated by HIF‐1α. In conclusion, the present study shows that insulin regulates TH expression through HIF‐1α and Nur77 in PC12 cells, supporting the critical role of insulin signaling in maintaining an appropriate dopaminergic tone by regulating TH expression in the central nervous system.
Ca2+‐dependent and Ca2+‐independent somatic release from trigeminal neurons
Authors: Sforna Luigi , Franciolini Fabio , Catacuzzeno Luigi
Published: December 2018

Besides the nerve endings, the soma of trigeminal neurons also respond to membrane depolarizations with the release of neurotransmitters and neuromodulators in the extracellular space within the ganglion, a process potentially important for the cross‐communication between neighboring sensory neurons. In this study, we addressed the dependence of somatic release on Ca2+ influx in trigeminal neurons and the involvement of the different types of voltage‐gated Ca2+ (Cav) channels in the process. Similar to the closely related dorsal root ganglion neurons, we found two kinetically distinct components of somatic release, a faster component stimulated by voltage but independent of the Ca2+ influx, and a slower component triggered by Ca2+ influx. The Ca2+‐dependent component was inhibited 80% by ω‐conotoxin‐MVIIC, an inhibitor of both N‐ and P/Q‐type Cav channels, and 55% by the P/Q‐type selective inhibitor ω‐agatoxin‐IVA. The selective L‐type Ca2+ channel inhibitor nimodipine was instead without effect. These results suggest a major involvement of N‐ and P/Q‐, but not L‐type Cav channels in the somatic release of trigeminal neurons. Thus antinociceptive Cav channel antagonists acting on the N‐ and P/Q‐type channels may exert their function by also modulating the somatic release and cross‐communication between sensory neurons.
Long noncoding RNA CASC9 promotes LIN7A expression via miR‐758‐3p to facilitate the malignancy of ovarian cancer
Authors: Hu Xiaowei , Li Yang , Kong Dan , Hu Longhu , Liu Donghui , Wu Jin
Published: December 2018

The long noncoding RNA cancer susceptibility 9 (CASC9) has been reported to be a pivot modulator in growth and metastasis of breast cancer, liver cancer, esophageal squamous cell carcinoma, lung adenocarcinoma, gastric cancer, and nasopharyngeal cancer. However, its potential roles in ovarian cancer remain unclear. In this study, we aimed at its functions and molecular mechanism in ovarian cancer progression. We showed that CASC9 was highly expressed in ovarian cancer tissues and cell lines. An elevated level of CASC9 predicts an unfavorable prognosis in patients with ovarian cancer. Loss‐of‐function and gain‐of‐function assays illustrated that CASC9 promotes ovarian cancer cell proliferation, migration, and invasion in vitro, and accelerates tumor growth in vivo. We showed that CASC9 works as a competing endogenous RNA (ceRNA) for miR‐758‐3p which targets LIN7A. CASC9 inhibits the level of miR‐758‐3p, and in turn stimulates LIN7A expression in ovarian cancer. Overexpression of LIN7A reverses the suppressive roles of CASC9 depletion on ovarian cancer. In sum, our findings reveal a novel undefined regulatory signaling pathway, namely CASC9/miR‐758‐3p/LIN7A axis, involved in ovarian cancer progression.
What role does pyroptosis play in microbial infection?
Authors: Xia Xiaojing , Wang Xin , Zheng Yi , Jiang Jinqing , Hu Jianhe
Published: December 2018

Pyroptosis, a type of programmed cell death mediated by gasdermin, is characterized by the swelling and rupture of cells, release of cellular contents and a strong inflammatory response, which is critical for controlling microbial infection. Pattern recognition receptors recognize the intracellular and extracellular pathogenic microbial components and stimulate the organism's inflammatory response by activating the pyroptosis signaling pathway and releasing interleukin‐1β (IL‐1β), IL‐18, and other inflammatory factors to promote pathogen clearance and prevent infection. In the process of continuous evolution, pathogens have developed multiple strategies to modulate the occurrence of pyroptosis and thus enhance their ability to induce disease; that is, the competition between host cells and pathogens controls the occurrence of pyroptosis. Competition can directly affect tissue inflammation outbreaks and even alter cell survival. Studies have shown that various bacterial infections, including Shigella flexneri, Salmonella, Listeria monocytogenes, and Legionella pneumophila, can lead to pyroptosis. Pyroptosis is associated with the occurrence and development of various diseases caused by microbial infection, and the identification of molecules related to the pyroptosis signaling pathway may provide new drug targets for the treatment of related diseases. This study reviews the molecular mechanisms of pyroptosis and the role of pyroptosis in microbial infection‐related diseases.
Interleukin‐10 responses from acute exercise in healthy subjects: A systematic review
Authors: Cabral‐Santos Carolina , de Lima Junior Edson Alves , Fernandes Isabela Maia da Cruz , Pinto Rafael Zambelli , Rosa‐Neto José César , Bishop Nicolette Charllote , Lira Fábio Santos
Published: December 2018

Purpose

Interleukin 10 (IL‐10) is a cytokine that plays a critical role with potent anti‐inflammatory properties when produced during exercise, limiting host immune response to pathogens and preventing tissue damage. The purpose of this systematic review was to assess the response of IL‐10 after acute exercise session in healthy adults.

Methods

Databases of Ovid Medline (1978–2016), CINAHL (1998–2016), EMBASE (2003–2016), SportDiscus (1990–2016), and Web of Science library (1990–2016) were carefully screened. Clinical trials comparing exercise types in healthy individuals were included for pooled analysis. The trials of exercise were methodologically appraised by PEDro Scale.

Results

Twelve randomized controlled and crossover trials containing 176 individuals were identified for inclusion. The Kruskal‐Wallis test showed no significant differences between type of exercise and the corresponding values in IL‐10 [X2(4) = 2.878; p = 0.449]. The duration of exercise was significantly correlated with increase in IL‐10 changes (Pearson's r = 1.00, 95%CI: 0.015–0.042, p < 0.0001) indicating that 48% of the variation in IL‐10 levels can be explained by the duration of the exercise performed. In addition, despite a linear increase, we did not find a significant correlation with the intensity of exercise and IL‐10 changes (Pearson's r = 0.218, 95%CI: −0.554–0.042, p < 0.035).

Conclusion

Overall, the duration of the exercise is the single most important factor determining the magnitude of the exercise‐induced increase of plasma IL‐10.
Coenzyme Q10 protects against β‐cell toxicity induced by pravastatin treatment of hypercholesterolemia
Authors: Lorza‐Gil Estela , de Souza Jane C. , García‐Arévalo Marta , Vettorazzi Jean F. , Marques Ana Carolina , Salerno Alessandro G. , Trigo Jose Roberto , Oliveira Helena C. F.
Published: December 2018

New onset of diabetes is associated with the use of statins. We have recently demonstrated that pravastatin‐treated hypercholesterolemic LDL receptor knockout (LDLr−/−) mice exhibit reductions in insulin secretion and increased islet cell death and oxidative stress. Here, we hypothesized that these diabetogenic effects of pravastatin could be counteracted by treatment with the antioxidant coenzyme Q
10 (CoQ
10), an intermediate generated in the cholesterol synthesis pathway. LDLr
−/− mice were treated with pravastatin and/or CoQ
10 for 2 months. Pravastatin treatment resulted in a 75% decrease of liver CoQ
10 content. Dietary CoQ
10 supplementation of pravastatin‐treated mice reversed fasting hyperglycemia, improved glucose tolerance (20%) and insulin sensitivity (>2‐fold), and fully restored islet glucose‐stimulated insulin secretion impaired by pravastatin (40%). Pravastatin had no effect on insulin secretion of wild‐type mice. In vitro, insulin‐secreting INS1E cells cotreated with CoQ
10 were protected from cell death and oxidative stress induced by pravastatin. Simvastatin and atorvastatin were more potent in inducing dose‐dependent INS1E cell death (10–15‐fold), which were also attenuated by CoQ
10 cotreatment. Together, these results demonstrate that statins impair β‐cell redox balance, function and viability. However, CoQ
10 supplementation can protect the statins detrimental effects on the endocrine pancreas.
Exosomes as a novel cell‐free therapeutic approach in gastrointestinal diseases
Authors: Baghaei Kaveh , Tokhanbigli Samaneh , Asadzadeh Hamid , Nmaki Saeed , Reza Zali Mohammad , Hashemi Seyed Mahmoud
Published: December 2018

Cell communication through extracellular vesicles (EVs) has been defined for many years and it is not limited only to neighboring cells, but also distant ones in organisms receive these signals. These vesicles are secreted from the variety of cells and are composed of a distinctive component such as proteins, lipids, and nucleic acids. EVs have different classified subgroups regarding their cell origin, in this context, exosomes are the most appealing particles in cell biology, especially clinical in recent years and are represented as novel therapeutic agents with numerous advantages alongside and/or over cell therapy. However, cell therapy had a hopeful outcome in gastrointestinal diseases which have minimal alternatives in their treatments. Inflammatory bowel disease (IBD), liver fibrosis, gastrointestinal cancers are the examples that cell therapy and immunotherapy were applied in their treatment, therefore, the cell products like exosomes are the beneficial option in their treatment even cancers with promising results in animal models. In this review, we consider the main defined biogenesis, function, and component of secreted exosomes in different cells with a specific focus on the potential application of these exosomes as a cell‐free therapeutic approach in gastrointestinal diseases like IBD, gastric cancer, and colon cancer. Additionally, exosomes role as therapeutic reagents mainly mesenchymal stem cells and dendritic cell‐derived exosomes in different studies have been under intense investigation and even they are being studied in different clinical trials. Therefore, all these striking functions described for secretome implies the importance of these biocarriers.
EP2 and EP4 receptor antagonists: Impact on cytokine production and β2‐adrenergic receptor desensitization in human airway smooth muscle
Authors: Bradbury Peta , Rumzhum Nowshin N. , Ammit Alaina J.
Published: December 2018

Prostaglandin E2 (PGE2) is a key prostanoid known to have both proinflammatory and anti‐inflammatory impact in the context of chronic respiratory diseases. We hypothesize that these opposing effects may be the result of different prostanoid E (EP) receptor‐mediated signaling pathways. In this study, we focus on two of the four EP receptors, EP2 and EP4, as they are known to induce cyclic adenosine monophosphate (cAMP)‐dependent signaling pathways. Using primary human airway smooth muscle (ASM) cells, we first focussed on the PGE2‐induced production of two cAMP‐dependent proinflammatory mediators: interleukin 6 (IL‐6) and cyclo‐oxygenase 2 production. We show that PGE2‐induced IL‐6 protein secretion occurs via an EP2‐mediated pathway, in a manner independent of receptor‐mediated effects on messenger RNA (mRNA) expression and temporal activation kinetics of the transcription factor cAMP response element binding. Moreover, stimulation of ASM with PGE2 did not establish a positive, receptor‐mediated, feedback loop, as mRNA expression for EP2 and EP4 receptors were not upregulated and receptor antagonists were without effect. Our studies revealed that the EP2, but not the EP4, receptor is responsible for β2‐adrenergic desensitization induced by PGE2. We demonstrate that PGE2‐induced heterologous receptor desensitization responsible for tachyphylaxis to short‐ (salbutamol) or long‐ (formoterol) β2‐agonists (measured by cAMP release) can be reversed by the EP2 receptor antagonist PF‐04418948. Importantly, this study highlights that inhibiting the EP2 receptor restores β2‐adrenergic receptor function in vitro and offers an attractive novel therapeutic target for treating infectious exacerbations in people suffering from chronic respiratory diseases in the future.
Attenuation of aquaporin‐3 and epidermal growth factor receptor expression and activation in systemic sclerosis dermal fibroblasts
Authors: Farhadi Elham , Mahmoudi Mahdi , Rahmani Farzaneh , Yousefi Bahman , Sarafnejad Abdolfattah , Kavosi Hoda , Karimizadeh Elham , Jamshidi Ahmadreza , Gharibdoost Farhad
Published: December 2018

Objectives

Impaired wound healing and skin dehydration are the mainstay of systemic sclerosis (SSc) cutaneous manifestations. Aquaporin‐3 (AQP3) has a pivotal role in skin hydration and wound healing. Epidermal growth factor receptor (EGFR) activation is impaired in SSc fibroblasts. It is unclear whether AQP3 downregulation or epidermal growth factor (EGF) signaling are the primary points of dysregulation in SSc patients.

Methods

Skin punch biopsies were obtained from 10 SSc patients and 10 healthy subjects. The mRNA and/or protein expression levels of AQP3, EGFR/p‐EGFR, matrix metalloproteinase‐1/2/9 (MMP‐1/2/9), and tissue inhibitors of metalloproteinase‐1 (TIMP1) at baseline and after EGF and transforming growth factor‐β1 (TGF‐β1) treatment was evaluated in extracted fibroblasts using real‐time polymerase chain reaction and western blot analysis.

Results

SSc fibroblasts expressed lower AQP3 and EGFR, compared with normal fibroblasts. Normal fibroblasts increased AQP3 expression in response to EGF whereas AQP3 expression had no change in EGF‐treated‐SSc fibroblasts. Likewise, EGFR was activated in response to EGF in the normal group but not SSc group. Baseline expression of MMP‐1/2/9 and TIMP1 was not different between SSc and controls. EGF treatment did not result in alteration of any MMPs expression in either of the groups. Combination treatment resulted in a significant upregulation of MMP‐1 in normal fibroblasts compared with SSc fibroblasts, while in SSc fibroblasts MMP‐9 expression was upregulated in response to treatment with TGF‐β1 only.

Conclusion

Downregulation of AQP3 expression in SSc fibroblasts may be related to reduced EGFR expression and activation. TGF‐β1 (alone or in combination with EGF) only can upregulate AQP3 expression in SSc fibroblasts so, TGF‐β1 affect MMP‐1 and MMP‐9 just in SSc fibroblasts.
Transforming growth factor‐β signaling: Tumorigenesis and targeting for cancer therapy
Authors: Ahmadi Amirhossein , Najafi Masoud , Farhood Bagher , Mortezaee Keywan
Published: December 2018

Transforming growth factor (TGF)‐β is a multitasking cytokine such that its aberrant expression is related to cancer progression and metastasis. TGF‐β is produced by a variety of cells within the tumor microenvironment (TME), and it is responsible for regulation of the activity of cells within this milieu. TGF‐β is a main inducer of epithelial–mesenchymal transition (EMT), immune evasion, and metastasis during cancer progression. TGF‐β exerts most of its functions by acting on TβRI and TβRII receptors in canonical (Smad‐dependent) or noncanonical (Smad‐independent) pathways. Members of mitogen‐activated protein kinase, phosphatidylinositol 3‐kinase/protein kinase B, and nuclear factor κβ are involved in the non‐Smad TGF‐β pathway. TGF‐β acts by complex signaling, and deletion in one of the effectors in this pathway may influence the outcome in a diverse way by taking even an antitumor role. The stage and the type of tumor (contextual cues from cancer cells and/or the TME) and the concentration of TGF‐β are other important factors determining the fate of cancer (progression or repression). There are a number of ways for targeting TGF‐β signaling in cancer, among them the special focus is on TβRII suppression.
Mutual inhibitions between epidermal growth factor receptor signaling and miR‐124a control pancreatic progenitor proliferation
Authors: Zhang Zhenwu , Zhai Wenjun , Liang Jie , Chen Zhenbao , Ma Mingjun , Zhao Yicheng , Liang Yang , Li Xuyan , Teng Chun‐Bo
Published: December 2018

Pancreatic stem/progenitor cells convert from a proliferative to a differentiated fate passing through proliferation cease to a resting state. However, the molecular mechanisms of cell cycle arrest are poorly understood. In this study, we demonstrated that the microRNA‐124a (miR‐124a) inhibited the proliferation of pancreatic progenitor cells both in vitro and ex vivo and promoted a quiescent state. The miR‐124a directly targeted SOS Ras/Rac guanine nucleotide exchange factor 1 (SOS1), IQ motif‐containing GTPase‐activating protein 1 (IQGAP1), signal transducer and activator of transcription 3 (STAT3), and cyclin D2 (CCND2), thereby inactivating epidermal growth factor receptor (EGFR) downstream signaling pathways including mitogen‐activated protein kinase/extracellular signal‐regulated kinase (MEK/ERK), phosphatidylinositol 3‐kinase‐protein kinase B (PI3K/AKT) and Janus kinase (JAK)/STAT3. miR‐124a blocked cell proliferation mainly through targeting STAT3 to inhibit PI3K/AKT and JAK/STAT3 signaling. Moreover, miR‐124a expression was negatively regulated by EGFR downstream PI3K/AKT signaling. These results indicated that miR‐124a and EGFR signaling mutually interact to form a regulating circuit that determines the proliferation of pancreatic progenitor cells.
Dynamic recognition and repair of DNA complex damage
Authors: Yan Junfang , Xie Yi , Zhang Qianjing , Gan Lu , Wang Fang , Li Hongyan , Si Jing , Zhang Hong
Published: December 2018

Irradiation (IR) can be used to treat cancer by inducing complex and irreparable DNA damage in the cancer cells, which may lead to their apoptotic death. However, little is known about the molecular mechanism of this DNA damage. Here, the non‐small‐cell lung cancer cell line A549 was treated with either X‐ray or carbon ion combined with bleomycin (BLM). The cell survival rate, frequency of double‐strand breaks (DSBs), dynamic changes in γH2AX, and p53 binding protein 1 (53BP1), and protein expression of Ku70, Rad51, and XRCC1 were determined by the clone formation assay, agarose gel electrophoresis, immunofluorescence, and western blot analysis. The results showed that the most obvious complex DSBs occurred in the carbon IR + BLM group. The number of γH2AX and 53BP1 foci in the 0.5 hr X‐ray IR + BLM group was the highest (p < 0.001) among all the groups. γH2AX foci were detected in the nucleus at 0.5, 1, 2, and 4 hr, but were distributed throughout the cell at 6 hr after IR in the carbon ion IR + BLM group. The expression of Ku70 increased and XRCC1 decreased at 2 and 6 hr after IR. Our data indicate that a DNA damage frequency of 13.4/Mbp is caused by clustered DNA damage and further show a correlation between γH2AX, 53BP1, and XRCC1 levels and the extent of DNA damage. The results of this study provide insights into DNA damage recognition and a rationale for the clinical use of radiotherapy.