bluuebunny/crossref_metadata_2025_split huggingface dataset:
Persistent organic pollutants in pregnant women potentially affect child development and thyroid hormone status
Authors: Krönke Anna A. , Jurkutat Anne , Schlingmann Maike , Poulain Tanja , Nüchter Matthias , Hilbert Anja , Kiviranta Hannu , Körner Antje , Vogel Mandy , Söder Olle , Bornehag Carl G. , Kiess Wieland 
Published: April 2021

Abstract
Background
Potentially harmful effects of persistent organic pollutants (POPs) such as polychlorinated biphenyls (PCBs) and dichlorodiphenyltrichloroethane (DDT) on prenatal development and the endocrine system have been controversially discussed.

Methods
Working with a German cohort of 324 pregnant women, we assessed POP levels and used robust linear regression models to determine potential associations between maternal POP concentrations and pre- and postnatal development in the children, as well as the thyroid hormone status of the mother and child.

Results
Maternal p,p′-dichlorodiphenyldichloroethylene (p,p′-DDE) and most measured PCBs positively correlated with postnatal weight gain. We detected no correlation between newborn birth weight and head circumference, respectively, and maternal PCB and p,p′-DDE serum levels, while body length at birth was negatively associated with the maternal serum concentration of PCB 183. Maternal p,p′-DDE and nearly all PCB serum levels showed a negative correlation with maternal free triiodothyronine (FT3). p,p′-DDE and PCB 74 and 118 were negatively associated with maternal thyroid-stimulating hormone levels. In addition, we identified significant associations between maternal POP levels and thyroid hormone parameters of the child.

Conclusions
These results indicate that POP exposure likely affects different aspects of pre- and postnatal development and impacts the thyroid hormone status of both mother and child.

Impact

Pregnant women in a German cohort display a substantial accumulation of POPs.

Body mass index and age influence maternal serum POP levels.

Maternal POP levels show correlations with the child’s length at birth and weight gain, and FT3 levels in the mother and child.

Our data provide additional evidence for the potentially harmful influence of POPs.

Our data indicate that POPs influence pre- and postnatal development.
Antibiotics at birth and later antibiotic courses: effects on gut microbiota
Authors: Ainonen Sofia , Tejesvi Mysore V , Mahmud Md. Rayhan , Paalanne Niko , Pokka Tytti , Li Weizhong , Nelson Karen E , Salo Jarmo , Renko Marjo , Vänni Petri , Pirttilä Anna Maria , Tapiainen Terhi 
Published: April 2021

Abstract
Background
Intrapartum antibiotic prophylaxis (IAP) is widely used, but the evidence of the long-term effects on the gut microbiota and subsequent health of children is limited. Here, we compared the impacts of perinatal antibiotic exposure and later courses of antibiotic courses on gut microbiota.

Methods
This was a prospective, controlled cohort study among 100 vaginally delivered infants with different perinatal antibiotic exposures: control (27), IAP (27), postnatal antibiotics (24), and IAP and postnatal antibiotics (22). At 1 year of age, we performed next-generation sequencing of the bacterial 16S ribosomal RNA gene of fecal samples.

Results
Exposure to the perinatal antibiotics had a clear impact on the gut microbiota. The abundance of the Bacteroidetes phylum was significantly higher in the control group, whereas the relative abundance of Escherichia coli was significantly lower in the control group. The impact of the perinatal antibiotics on the gut microbiota composition was greater than exposure to later courses of antibiotics (28% of participants).

Conclusions
Perinatal antibiotic exposure had a marked impact on the gut microbiota at the age of 1 year. The timing of the antibiotic exposure appears to be the critical factor for the changes observed in the gut microbiota.

Impact

Infants are commonly exposed to IAP and postnatal antibiotics, and later to courses of antibiotics during the first year of life.

Perinatal antibiotics have been associated with an altered gut microbiota during the first months of life, whereas the evidence regarding the long-term impact is more limited.

Perinatal antibiotic exposure had a marked impact on the infant’s gut microbiota at 1 year of age.

Impact of the perinatal antibiotics on the gut microbiota composition was greater than that of the later courses of antibiotics at the age of 1 year.
Cesarean delivery and metabolic health and inflammation biomarkers during mid-childhood and early adolescence
Authors: Mínguez-Alarcón Lidia , Rifas-Shiman Sheryl L. , Mitchell Caroline , Sordillo Joanne , Aris Izzuddin M. , Hivert Marie-France , Oken Emily , Chavarro Jorge E. 
Published: April 2021

Abstract
Background
We assessed differences in plasma levels of metabolic health and inflammation biomarkers during mid-childhood and early adolescence between children born by cesarean section vs. vaginal delivery.

Methods
Mother–child pairs (N = 942) enrolled during pregnancy in obstetric practices and child follow-up started at birth. Risk biomarkers were assessed in blood samples collected at the mild-childhood (median = 7 years) and early adolescence (median = 13 years) in-person visits.

Results
Two hundred and six children (22%) were born by cesarean section. There were no significant differences in biomarker levels between children born by cesarean and children born vaginally in mid-childhood. However, adolescents born by cesarean section had significantly lower adiponectin [% difference (95% confidence interval (CI)) = −11.3 (−18.1, −4.0) µg/mL] compared to vaginal delivery. We also found some suggestion of higher insulin resistance [insulin levels % difference (95% CI) = 11.5 (−0.40, 25.0) µU/mL and HOMA-IR (homeostatic model assessment of insulin resistance) % difference (95% CI) = 9.1 (−2.30, 21.8) U] in adolescents born by cesarean section compared to those born vaginally.

Conclusions
We found suggestive evidence that adolescents born by cesarean section show differences in certain metabolic health biomarkers relative to adolescents born by vaginal delivery. Further studies are needed to reevaluate these associations since the clinical significance of these differences is unclear.

Impact

Multiple studies show that children born by cesarean section are at higher risk of obesity compared to those born vaginally.

It is unclear yet to what extent this elevated risk may extend to a more adverse profile of biomarkers of metabolic health and inflammation.

Adolescents born by cesarean section show small differences in adiponectin and insulin relative to adolescents born by vaginal delivery.

Adolescents born by cesarean section may be at higher risk to a more adverse profile of biomarkers of metabolic health and inflammation, but the clinical significance of these differences is uncertain.
Breast cancer as an example of tumour heterogeneity and tumour cell plasticity during malignant progression
Authors: Lüönd Fabiana , Tiede Stefanie , Christofori Gerhard 
Published: April 2021

AbstractHeterogeneity within a tumour increases its ability to adapt to constantly changing constraints, but adversely affects a patient’s prognosis, therapy response and clinical outcome. Intratumoural heterogeneity results from a combination of extrinsic factors from the tumour microenvironment and intrinsic parameters from the cancer cells themselves, including their genetic, epigenetic and transcriptomic traits, their ability to proliferate, migrate and invade, and their stemness and plasticity attributes. Cell plasticity constitutes the ability of cancer cells to rapidly reprogramme their gene expression repertoire, to change their behaviour and identities, and to adapt to microenvironmental cues. These features also directly contribute to tumour heterogeneity and are critical for malignant tumour progression. In this article, we use breast cancer as an example of the origins of tumour heterogeneity (in particular, the mutational spectrum and clonal evolution of progressing tumours) and of tumour cell plasticity (in particular, that shown by tumour cells undergoing epithelial-to-mesenchymal transition), as well as considering interclonal cooperativity and cell plasticity as sources of cancer cell heterogeneity. We review current knowledge on the functional contribution of cell plasticity and tumour heterogeneity to malignant tumour progression, metastasis formation and therapy resistance.
Sunglasses to hide behind may also prevent melanoma of the eyes
Authors: Dhomen Nathalie , Mundra Piyushkumar A. , Marais Richard 
Published: April 2021

SummaryIn 1967, Sandy Posey pronounced that sunglasses are essential beachwear (https://www.youtube.com/watch?v=4HVBEb-GA1Y). Now, whole-genome sequencing reveals that ultraviolet radiation (UVR) can contribute to melanomas in the iris and conjunctiva, data that provide a molecular explanation for why it is important to protect our eyes from exposure to UVR.
Tumour neoantigen mimicry by microbial species in cancer immunotherapy
Authors: Boesch Maximilian , Baty Florent , Rothschild Sacha I. , Tamm Michael , Joerger Markus , Früh Martin , Brutsche Martin H. 
Published: April 2021

AbstractTumour neoantigens arising from cancer-specific mutations generate a molecular fingerprint that has a definite specificity for cancer. Although this fingerprint perfectly discriminates cancer from healthy somatic and germline cells, and is therefore therapeutically exploitable using immune checkpoint blockade, gut and extra-gut microbial species can independently produce epitopes that resemble tumour neoantigens as part of their natural gene expression programmes. Such tumour molecular mimicry is likely not only to influence the quality and strength of the body’s anti-cancer immune response, but could also explain why certain patients show favourable long-term responses to immune checkpoint blockade while others do not benefit at all from this treatment. This article outlines the requirement for tumour neoantigens in successful cancer immunotherapy and draws attention to the emerging role of microbiome-mediated tumour neoantigen mimicry in determining checkpoint immunotherapy outcome, with far-reaching implications for the future of cancer immunotherapy.
The long-noncoding RNA SOCS2-AS1 suppresses endometrial cancer progression by regulating AURKA degradation
Authors: Jian Fangfang , Che Xiaoxia , Zhang Jingjing , Liu Chang , Liu Gedan , Tang Yujing , Feng Weiwei 
Published: April 2021

AbstractAberrant long-noncoding RNA (lncRNA) expression has been shown to be involved in the pathogenesis of endometrial cancer (EC). Herein, we report a novel tumor suppressor lncRNA SOCS2-AS1 in EC. Quantitative real-time PCR was performed to detect RNA expression. In situ hybridization and nuclear/cytoplasmic fractionation assays were used to detect the subcellular location. We found that SOCS2-AS1 was downregulated in EC tissues. Its reduced expression was correlated with advanced clinical stage and poor prognosis. Forced expression of SOCS2-AS1 suppressed EC cell proliferation and induced cell-cycle arrest and apoptosis. SOCS2-AS1-binding proteins were detected using RNA pull-down assay and mass spectrometry. Mechanistically, SOCS2-AS1 bound to Aurora kinase A (AURKA) and increased its degradation through the ubiquitin-proteasome pathway. In conclusion, SOCS2-AS1 may thus serve as a prognostic predictor and a biomarker for AURKA-inhibitor treatment in EC patients.
CREG ameliorates the phenotypic switching of cardiac fibroblasts after myocardial infarction via modulation of CDC42
Authors: Liu Dan , Tian Xiaoxiang , Liu Yanxia , Song Haixu , Cheng Xiaoli , Zhang Xiaolin , Yan Chenghui , Han Yaling 
Published: April 2021

AbstractPhenotype switching of cardiac fibroblasts into myofibroblasts plays important role in cardiac fibrosis following myocardial infarction (MI). Cellular repressor of E1A-stimulated genes (CREG) protects against vascular and cardiac remodeling induced by angiotensin-II. However, the effects and mechanisms of CREG on phenotype switching of cardiac fibroblasts after MI are unknown. This study aimed to investigate the role of CREG on the phenotype switching of cardiac fibroblasts following MI and its mechanism. Our findings demonstrated that, compared with littermate control mice, cardiac function was deteriorated in CREG+/− mice on day 14 post-MI. Fibrosis size, αSMA, and collagen-1 expressions were increased in the border regions of CREG+/− mice on day 14 post-MI. Conversely, exogenous CREG protein significantly improved cardiac function, inhibited fibrosis, and reduced the expressions of αSMA and collagen-1 in the border regions of C57BL/6J mice on day 14. In vitro, CREG recombinant protein inhibited αSMA and collagen-1 expression and blocked the hypoxia-induced proliferation and migration of cardiac fibroblasts, which was mediated through the inhibition of cell division control protein 42 (CDC42) expression. Our findings could help in establishing new strategies based on the clarification of the role of the key molecule CREG in phenotype switching of cardiac fibroblasts following MI.
ADCK1 activates the β-catenin/TCF signaling pathway to promote the growth and migration of colon cancer cells
Authors: Ji Yong , Liu Yiqian , Sun Changchun , Yu Lijiang , Wang Zhao , Du Xu , Yang Wu , Zhang Chenggong , Tao Chunmu , Wang Jianjiang , Yang Xi , Di Sun , Huang Yufeng 
Published: April 2021

AbstractAs a result of mutations in the upstream components of the Wnt/β-catenin signaling pathway, this cascade is abnormally activated in colon cancer. Hence, identifying the activation mechanism of this pathway is an urgent need for the treatment of colon cancer. Here, we found an increase in ADCK1 (AarF domain-containing kinase 1) expression in clinical specimens of colon cancer and animal models. Upregulation of ADCK1 expression promoted the colony formation and infiltration of cancer cells. Downregulation of ADCK1 expression inhibited the colony formation and infiltration of cancer cells, in vivo tumorigenesis, migration, and organoid formation. Molecular mechanistic studies demonstrated that ADCK1 interacted with TCF4 (T-cell factor 4) to activate the β-catenin/TCF signaling pathway. In conclusion, our research revealed the functions of ADCK1 in the development of colon cancer and provided potential therapeutic targets.
ADGRA1 negatively regulates energy expenditure and thermogenesis through both sympathetic nervous system and hypothalamus–pituitary–thyroid axis in male mice
Authors: Zhang Xiao-Hong , Tang Ling-Yun , Wang Xi-Yi , Shen Chun-Ling , Xiong Wen-Feng , Shen Yan , Wan Ying-Han , Wu You-Bing , Wang Yi-Cheng , Zhang Hong-Xin , Lu Shun-Yuan , Fei Jian , Wang Zhu-Gang 
Published: April 2021

AbstractAdhesion G protein-coupled receptor A1 (ADGRA1, also known as GPR123) belongs to the G protein-coupled receptors (GPCRs) family and is well conserved in the vertebrate lineage. However, the structure of ADGRA1 is unique and its physiological function remains unknown. Previous studies have shown that Adgra1 is predominantly expressed in the central nervous system (CNS), indicating its important role in the transduction of neural signals. The aim of this study is to investigate the central function of Adgra1 in vivo and clarify its physiological significance by establishing an Adgra1-deficient mouse (Adgra1−/−) model. The results show that Adgra1−/− male mice exhibit decreased body weight with normal food intake and locomotion, shrinkage of body mass, increased lipolysis, and hypermetabolic activity. Meanwhile, mutant male mice present elevated core temperature coupled with resistance to hypothermia upon cold stimulus. Further studies show that tyrosine hydroxylase (TH) and β3-adrenergic receptor (β3-AR), indicators of sympathetic nerve excitability, are activated as well as their downstream molecules including uncoupling protein 1 (UCP1), coactivator 1 alpha (PGC1-α) in brown adipose tissue (BAT), and hormone-sensitive lipase (HSL) in white adipose tissue (WAT). In addition, mutant male mice have higher levels of serum T3, T4, accompanied by increased mRNAs of hypothalamus–pituitary–thyroid axis. Finally, Adgra1−/− male mice present abnormal activation of PI3K/AKT/GSK3β and MEK/ERK pathways in hypothalamus. Overexpression of ADGRA1 in Neuro2A cell line appears to suppress these two signaling pathways. In contrast, Adgra1−/− female mice show comparable body weight along with normal metabolic process to their sex-matched controls. Collectively, ADGRA1 is a negative regulator of sympathetic nervous system (SNS) and hypothalamus–pituitary–thyroid axis by regulating PI3K/AKT/GSK3β and MEK/ERK pathways in hypothalamus of male mice, suggesting an important role of ADGRA1 in maintaining metabolic homeostasis including energy expenditure and thermogenic balance.
The effect of extracellular vesicles on the regulation of mitochondria under hypoxia
Authors: Zhang Yaodan , Tan Jin , Miao Yuyang , Zhang Qiang 
Published: April 2021

AbstractMitochondria are indispensable organelles for maintaining cell energy metabolism, and also are necessary to retain cell biological function by transmitting information as signal organelles. Hypoxia, one of the important cellular stresses, can directly regulates mitochondrial metabolites and mitochondrial reactive oxygen species (mROS), which affects the nuclear gene expression through mitochondrial retrograde signal pathways, and also promotes the delivery of signal components into cytoplasm, causing cellular injury. In addition, mitochondria can also trigger adaptive mechanisms to maintain mitochondrial function in response to hypoxia. Extracellular vesicles (EVs), as a medium of information transmission between cells, can change the biological effects of receptor cells by the release of cargo, including nucleic acids, proteins, lipids, mitochondria, and their compositions. The secretion of EVs increases in cells under hypoxia, which indirectly changes the mitochondrial function through the uptake of contents by the receptor cells. In this review, we focus on the mitochondrial regulation indirectly through EVs under hypoxia, and the possible mechanisms that EVs cause the changes in mitochondrial function. Finally, we discuss the significance of this EV-mitochondria axis in hypoxic diseases.
Somatic CG6015 mediates cyst stem cell maintenance and germline stem cell differentiation via EGFR signaling in Drosophila testes
Authors: Zheng Qianwen , Chen Xia , Qiao Chen , Wang Min , Chen Wanyin , Luan Xiaojin , Yan Yidan , Shen Cong , Fang Jie , Hu Xing , Zheng Bo , Wu Yibo , Yu Jun 
Published: April 2021

AbstractStem cell niche is regulated by intrinsic and extrinsic factors. In the Drosophila testis, cyst stem cells (CySCs) support the differentiation of germline stem cells (GSCs). However, the underlying mechanisms remain unclear. In this study, we found that somatic CG6015 is required for CySC maintenance and GSC differentiation in a Drosophila model. Knockdown of CG6015 in CySCs caused aberrant activation of dpERK in undifferentiated germ cells in the Drosophila testis, and disruption of key downstream targets of EGFR signaling (Dsor1 and rl) in CySCs results in a phenotype resembling that of CG6015 knockdown. CG6015, Dsor1, and rl are essential for the survival of Drosophila cell line Schneider 2 (S2) cells. Our data showed that somatic CG6015 regulates CySC maintenance and GSC differentiation via EGFR signaling, and inhibits aberrant activation of germline dpERK signals. These findings indicate regulatory mechanisms of stem cell niche homeostasis in the Drosophila testis.
Lysine-specific demethylase 1 inhibition enhances autophagy and attenuates early-stage post-spinal cord injury apoptosis
Authors: Gu Yang , Chen Dehui , Zhou Linquan , Zhao Xin , Lin Jiemin , Lin Bin , Lin Taotao , Chen Zhi , Chen Zhaohong , Wang Zhenyu , Liu Wenge 
Published: April 2021

AbstractNeuron death in spinal cords is caused primarily by apoptosis after spinal cord injury (SCI). Autophagy can act as a cellular response to maintain neuron homeostasis that can reduce apoptosis. Although more studies have shown that an epigenetic enzyme called Lysine-specific demethylase 1 (LSD1) can negatively regulate autophagy during cancer research, existing research does not focus on impacts related to LSD1 in nerve injury diseases. This study was designed to determine whether inhibiting LSD1 could enhance autophagy against apoptosis and provide effective neuroprotection in vitro and vivo after SCI. The results showed that LSD1 inhibition treatment significantly reduced spinal cord damage in SCI rat models and was characterized by upregulated autophagy and downregulated apoptosis. Further research demonstrated that using both pharmacological inhibition and gene knockdown could enhance autophagy and reduce apoptosis for in vitro simulation of SCI-caused damage models. Additionally, 3-methyladenine (3-MA) could partially eliminate the effect of autophagy enhancement and apoptosis suppression. These findings demonstrated that LSD1 inhibition could protect against SCI by activating autophagy and hindering apoptosis, suggesting a potential candidate for SCI therapy.
Identification of an endogenous glutamatergic transmitter system controlling excitability and conductivity of atrial cardiomyocytes
Authors: Xie Duanyang , Xiong Ke , Su Xuling , Wang Guanghua , Ji Qiang , Zou Qicheng , Wang Lingling , Liu Yi , Liang Dandan , Xue Jinfeng , Wang Luxin , Gao Xueting , Gu Xingdong , Liu Hongyu , He Xiaoyu , Li Li , Yang Jian , Lu Youming , Peng Luying , Chen Yi-Han 
Published: April 2021

AbstractAs an excitatory transmitter system, the glutamatergic transmitter system controls excitability and conductivity of neurons. Since both cardiomyocytes and neurons are excitable cells, we hypothesized that cardiomyocytes may also be regulated by a similar system. Here, we have demonstrated that atrial cardiomyocytes have an intrinsic glutamatergic transmitter system, which regulates the generation and propagation of action potentials. First, there are abundant vesicles containing glutamate beneath the plasma membrane of rat atrial cardiomyocytes. Second, rat atrial cardiomyocytes express key elements of the glutamatergic transmitter system, such as the glutamate metabolic enzyme, ionotropic glutamate receptors (iGluRs), and glutamate transporters. Third, iGluR agonists evoke iGluR-gated currents and decrease the threshold of electrical excitability in rat atrial cardiomyocytes. Fourth, iGluR antagonists strikingly attenuate the conduction velocity of electrical impulses in rat atrial myocardium both in vitro and in vivo. Knockdown of GRIA3 or GRIN1, two highly expressed iGluR subtypes in atria, drastically decreased the excitatory firing rate and slowed down the electrical conduction velocity in cultured human induced pluripotent stem cell (iPSC)-derived atrial cardiomyocyte monolayers. Finally, iGluR antagonists effectively prevent and terminate atrial fibrillation in a rat isolated heart model. In addition, the key elements of the glutamatergic transmitter system are also present and show electrophysiological functions in human atrial cardiomyocytes. In conclusion, our data reveal an intrinsic glutamatergic transmitter system directly modulating excitability and conductivity of atrial cardiomyocytes through controlling iGluR-gated currents. Manipulation of this system may open potential new avenues for therapeutic intervention of cardiac arrhythmias.