bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of a MicroRNA-E3 Ubiquitin Ligase Regulatory Network for Hepatocyte Death in Alcohol-Associated Hepatitis
Authors: Fan Xiude , Wu Jianguo , Poulsen Kyle L. , Kim Adam , Wu Xiaoqin , Huang Emily , Miyata Tatsunori , Sanz-Garcia Carlos , Nagy Laura E. 
Published: March 2021

We aimed to identify a microRNA (miRNA)-E3 ubiquitin ligase regulatory network for protein substrates enriched in cell death pathways and investigate the underlying molecular mechanisms in alcohol-associated hepatitis (AH). An miRNA-E3 ubiquitin ligase regulatory network for protein substrates enriched in cell death pathways was constructed using integrated bioinformatics analysis. Differentially expressed hub miRNAs (GSE59492) and their validated miRNA target genes (GSE28619) were identified in the liver of patients with AH compared with healthy controls. Liver samples from patients with AH and healthy individuals and mice exposed to Gao-binge (acute on chronic) ethanol were used for experimental validation. Using hub miRNAs identified by weighted correlation network analysis, a miRNA-E3 ubiquitin ligase regulatory network was established based on 17 miRNAs and 7 E3 ligase genes targeted by these miRNAs that were down-regulated in AH. Among the miRNAs in this regulatory network, miR-150-5p was the only miRNA regulating the E3 ligase cytokine-inducible SH2 containing protein (CISH), the E3 ligase that regulates the largest number of substrates among all E3 ligase family members. Therefore, the CISH regulatory pathway for ubiquitinated substrates was selected for subsequent experimental validation. Consistent with the bioinformatics analysis results, expression of miR-150-5p was markedly increased, while CISH was decreased, in the livers of patients with AH and mice exposed to Gao-binge ethanol. Moreover, ubiquitination of Fas-associated protein with death domain, a predicted CISH substrate involved in the regulation of programmed cell death, was reduced in livers from mice after Gao-binge ethanol. Conclusion: Identification of the miRNA-E3 ubiquitin ligase regulatory network for protein substrates enriched in the cell death pathways provides insights into the molecular mechanisms contributing to hepatocyte death in AH.
This study identifies a microRNA-E3 ubiquitin ligase regulatory network for protein substrates enriched in cell death pathways. We report that expression of miR-150-5p was elevated in AH and experimentally verified the changes in the key components in this miR-150-5p-CISH-FADD regulatory network in the liver from both patients with AH and a murine model of acute-on-chronic ethanol exposure.
Plateau is a prognostic factor of lenalidomide therapy for previously treated multiple myeloma
Authors: Takakuwa Teruhito , Ohta Kensuke , Nakatani Eiji , Ito Tomoki , Kaneko Hitomi , Fuchida Shin‐Ichi , Shimura Yuji , Yagi Hideo , Shibayama Hirohiko , Kanda Junya , Uchiyama Hitoji , Kosugi Satoru , Tanaka Hirokazu , Kawata Eri , Uoshima Nobuhiko , Ishikawa Jun , Shibano Masaru , Karasuno Takahiro , Shindo Maki , Shimizu Yoshifumi , Imada Kazunori , Kanakura Yuzuru , Kuroda Junya , Hino Masayuki , Nomura Shosaku , Takaori‐Kondo Akifumi , Shimazaki Chihiro , Matsumura Itaru 
Published: March 2021

AbstractThe plateau phase emerging during the treatment of multiple myeloma (MM) is known to last steadily for a certain period, even without treatment. Therefore, the treatment started at plateau phase is expected to be associated with a better outcome. In this study, this hypothesis was evaluated retrospectively for previously treated MM patients in Kansai Myeloma Forum database who received lenalidomide (LEN) with or without dexamethasone for the first time. Disease stability index (DSI) was defined as (maximum – minimum values of M protein during the 90 days before the start of LEN) divided by M‐protein values at the start of LEN. The patients were classified into three groups: stable (S), DSI ≤ 0.25; increasing (I), DSI > 0.25 with increasing M protein; decreasing (D), DSI > 0.25 with decreasing M protein. In univariate analysis of 352 patients, DSI group "I", non‐IgG type, serum albumin<3.5 g/dL, and age≥70 were statistically significant prognostic factors for both progression‐free survival and overall survival. In multivariate analysis, the former 3 risk factors were statistically significant for poor overall survival. Thus, DSI is an independent prognostic factor for the treatment with LEN for previously treated MM.
Diagnostic accuracy of the Gaussian first‐trimester combined screening for pre‐eclampsia to predict small‐for‐gestational‐age neonates
Authors: Mendoza Manel , Serrano Berta , Bonacina Erika , Capote Sira , Garcia‐Manau Pablo , Regincós Laia , Murcia Maria Teresa , Barberan Lidia , Míguez Marta , Carreras Elena 
Published: March 2021

AbstractObjectivePre‐eclampsia and delivery of small‐for‐gestational‐age (SGA) neonates can be predicted from the first trimester. A Gaussian model for prediction of PE has recently been described, although its capacity to predict SGA is still unknown.MethodsThis was a secondary analysis of a prospective cohort study conducted at Vall d’Hebron University Hospital (Barcelona) in 2483 single pregnancies from October 2015 to September 2017. Mean arterial blood pressure and mean uterine artery pulsatility index were recorded at the first‐trimester scan. Serum concentrations of placental growth factor and pregnancy‐associated plasma protein‐A were assessed between 8+0 and 13+6 weeks. The predictive capacities of early (<32 weeks) and preterm (<37 weeks) SGA were tested.ResultsFor SGA without pre‐eclampsia, detection rates of 25.0% (95% confidence interval [CI] 0–75.0) for early SGA and 14.3% (95% CI 3.6–28.6) for preterm SGA were achieved. For SGA with pre‐eclampsia, the algorithm showed detection rates of 100.0% (95% CI 25.0–100.0) for early SGA and 56.3% (95% CI 31.3–81.3) for preterm SGA.ConclusionThis algorithm identifies 62.5% of early SGA and 27.3% of preterm SGA. Combined screening for predicting both pre‐eclampsia and SGA by using the Gaussian algorithm is feasible and would simplify clinical practice.
Role of a cysteine residue in substrate entry and catalysis inMtHIBADH: Analysis by chemical modifications and site‐directed mutagenesis
Authors: Singh Amrita , Badepally Nagendar Goud , Surolia Avadhesha 
Published: March 2021

AbstractDespite sharing conserved substrate‐binding residues, members of 3‐hydroxyisobutyrate dehydrogenase (HIBADH) superfamily show remarkable differences in substrate preference. Cysteine residues were identified within a radius of 6 Å surrounding both the active site and the substrate entry site of HIBADH enzyme fromMycobacterium tuberculosis(MtHIBADH). Chemical modification with thiol‐modifying reagents, pCMB and DTNB, abrogated the dehydrogenase activity of the enzyme. The loss in activity followed pseudo‐first‐order kinetics as a function of the concentration of pCMB. S‐HIBA (substrate) binding provided partial protection, while NAD (cofactor) binding provided ~70% protection from thiol‐modifying reagent. Site‐directed mutagenesis of cysteine residues present in the MtHIBADH enzyme identified the indispensable role of Cys‐210 residue, located at C‐terminal domain, for its dehydrogenase activity. Cys‐210 mutation to serine reduced the dehydrogenase activity by ~2‐fold while mutation to alanine strikingly reduced the activity by ~140‐fold. C210A mutation did not perturb the state of oligomerization of the enzyme but perturbed the secondary structure content. Structural analysis revealed the involvement of Cys‐210 residue in inter‐chain interaction with Gln‐178, which acts as hydrogen bond donor and coordinates with Cys‐210 and Gly‐208 of the adjacent subunit. The data demonstrate a critical role of Cys‐210 residue in maintaining the conformation and rigidity of loop composed of substrate‐interacting residues involved in the entry of S‐HIBA substrate in MtHIBADH.
Chronic Nonbacterial Osteomyelitis of the Sternocostoclavicular Region in Adults: A Single‐Center Dutch Cohort Study
Authors: Ramautar Ashna IE , Appelman‐Dijkstra Natasha M , Lakerveld Shannon , Schroijen Marielle A , Snel Marieke , Winter Elizabeth M , Hamdy Neveen AT 
Published: March 2021

ABSTRACTSternocostoclavicular hyperostosis (SCCH) is a rare autoinflammatory bone disorder caused by chronic nonbacterial osteomyelitis (CNO), which is associated with sclerosis and hyperostosis primarily affecting the sternum, the medial end of the clavicles, and the first ribs. Other areas of the axial skeleton may also be affected. The more severe synovitis–acne–pustulosis–hyperostosis–osteitis (SAPHO) syndrome is additionally associated with dermatoses and joint manifestations. This Dutch retrospective cross‐sectional single‐center cohort study characterizes the spectrum of clinical features in adult CNO/SCCH patients at the time of diagnosis. The only inclusion criteria was the availability of complete sets of clinical and imaging data systematically collected over three decades using in‐house protocols. Data from 213 predominantly female patients (88%) with a median age of 36 years at presentation were studied. The mean diagnostic delay was 5 ± 5 years. The main symptoms were chronic pain (92%), bony swelling (61%), and restricted shoulder girdle function (46%); 32% had palmoplantar pustulosis and 22% had autoimmune disease. The majority (73%) had isolated SCCH; 59 (27%) had additional localizations in vertebrae (19%), the mandible (9%), or both (2%); 4 had SAPHO. The prevalence of current or past smoking was high (58%), particularly for patients with palmoplantar pustulosis (76%). There was a significant relationship between delay in diagnosis and both the extent of affected skeletal sites (p = 0.036) and erythrocyte sedimentation rate levels (p = 0.023). Adult‐onset CNO is characterized by distinctive clinical and radiological features, but diverse aspects of its spectrum are currently not fully captured by a comprehensive classification. Delayed diagnosis is still common and potentially associated with irreversible structural changes and debilitating chronic symptoms, increasing the burden of illness and negatively impacting on quality of life. It is hoped that findings from this study will dispel confusion about nomenclature and classification of adult‐onset CNO and increase awareness of its distinctive clinical and radiological features, and thus facilitate early diagnosis and referral for treatment, which should positively impact prognosis by preventing disease progression, although this remains to be established. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
Phyllanthin inhibits MOLT‐4 leukemic cancer cell growth and induces apoptosis through the inhibition of AKT and JNK signaling pathway
Authors: Wang Hui , Chinnathambi Arunachalam , Alahmadi Tahani Awad , Alharbi Sulaiman Ali , Veeraraghavan Vishnu Priya , Krishna Mohan Surapaneni , Hussain Sardar , Ramamoorthy Kavitha , Rengarajan Thamaraiselvan 
Published: March 2021

AbstractAmong cancers, leukemia is a multistep progression that involves genetic modifications of normal hematopoietic progenitor cells to cancerous cells. In recent times, leukemia cases and their mortality rate have increased rapidly. Therefore, the immense need for a therapeutic approach is crucial that can control this type of cancer. Phyllanthin is a lignan compound constituent from the Phyllanthus species and has numerous beneficial effects as a dietary component. The present study aims to determine the impact of phyllanthin on the MOLT‐4 cytotoxic effect. MOLT‐4 cells and MS‐5 cells were cultured at different concentrations of phyllanthin (5, 10, 25, 50, 75, and 100 μM/ml), and the viability was assessed by the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide method. The level of reactive oxygen species, the membrane potential of mitochondria, apoptosis by 2',7'‐dichlorofluorescin‐diacetate (DCF‐DA), rhodamine, acridine orange (AO)/ethidium bromide (EB), 4′,6‐diamidino‐2‐phenylindole (DAPI)/propidium iodide (PI) staining, gene expression of signaling molecules, and protein levels were assessed by reverse‐transcription polymerase chain reaction and western blot analysis. Phyllanthin did not show toxicity toward MS‐5 cells and significantly decreased the cell viability of MOLT‐4 cells with an IC50 value of 25 µM/ml. Also, phyllanthin induced the production of reactive oxygen species and led to the loss of mitochondrial membrane potential. AO/EB and DAPI/PI staining fluorescent image confirmed the induction of apoptosis by phyllanthin treatment. The messenger RNA (mRNA) expression of cell cycle regulator cyclin D1, antiapoptotic gene Bcl‐2, NF‐κB, and TNF‐α decreased, but the proapoptotic Bax mRNA expression was increased. The phosphorylated protein levels of p‐PI3K1/2, p‐ERK1/2, and p‐AKT were decreased, whereas the levels of p‐p38 and p‐JNKT1/2 increased. Our results confirmed that phyllanthin inhibits the MOLT‐4 cells, increases apoptosis, and inhibits MOLT‐4 migration and cell invasion. Therefore, phyllanthin can be used as a potential target for leukemia treatment.
Deodorizing the king of fruits: Durian stalk deodorizes the aroma of durian
Authors: Tan Ke Qi , Lim Zhi Kheng , Fang Esther Zi Hui , Pui Carmen Sze Min , Lv Yunbo , Zhang Hua Jun , Chua Chun Kiang 
Published: March 2021

AbstractDurian fruit is well‐known for its strong aroma due to the presence of esters and sulfur compounds. Although the usage of durian husk as a deodorizing agent of durian aroma has been a known practice, there is a lack of scientific evidence. Here, we investigated the effect of using durian stalk extract to deodorize durian aroma. Static‐headspace gas chromatography–mass spectrometry technique is used to semi‐quantitatively track the variation of 13 esters and sulfur compounds found in durian. Durian stalk extract reduced the amount of esters and sulfur compounds in headspace up to 45 and 55%, respectively. NaCl, CaCl2, and Na2SO4 provided a similar effect on sulfur compounds. In addition, lemon and ginger extracts were evaluated and the latter performed as well as durian stalk extract. This study has implications for the application of durian husk as a biomass feedstock for the development of plant‐based deodorizers.
Recent advances of carbazole‐based nonfullerene acceptors: Molecular design, optoelectronic properties, and photovoltaic performance in organic solar cells
Authors: Chen Tsung‐Wei , Karapala Vamsi Krishna , Chen Jiun‐Tai , Hsu Chain‐Shu 
Published: March 2021

AbstractIn this review, the properties, performance, advantages, and applications of carbazole‐based nonfullerene acceptors (NFAs) are summarized and categorized by fused‐ring number. The recent advances of carbazole‐based NFAs are depicted with their decent photovoltaic performance, enabled by the versatality of elegant molecular design. These literature precedents sufficiently validate that carbazole can be exploited as a promising building block embedded in functional, high‐performance NFAs. The structure‐to‐performance relation of carbazole‐based NFAs is systematically studied, which is believed to facilitate the development of photovoltaic technology.
The biogenetic law and the Gastraea theory: From Ernst Haeckel's discoveries to contemporary views
Authors: Levit Georgy S. , Hoßfeld Uwe , Naumann Benjamin , Lukas Paul , Olsson Lennart 
Published: March 2021

AbstractMore than 150 years ago, in 1866, Ernst Haeckel published a book in two volumes called Generelle Morphologie der Organismen (General Morphology of Organisms) in the first volume of which he formulated his biogenetic law, famously stating that ontogeny recapitulates phylogeny. Here, we describe Haeckel's original idea as first formulated in the Generelle Morphologie der Organismen and later further developed in other publications until the present situation in which molecular data are used to test the “hourglass model,” which can be seen as a modern version of the biogenetic law. We also tell the story about his discovery, while traveling in Norway, of an unknown organism, Magosphaera planula, that was important in that it helped to precipitate his ideas into what was to become the Gastraea theory. We also follow further development and reformulations of the Gastraea theory by other scientists, notably the Russian school. Elias Metchnikoff developed the Phagocytella hypothesis for the origin of metazoans based on studies of a colonial flagellate. Alexey Zakhvatin focused on deducing the ancestral life cycle and the cell types of the last common ancestor of all metazoans, and Kirill V. Mikhailov recently pursued this line of research further.
Ultrasound irradiation in heterocycle synthesis: An overview
Authors: Saranya Salim , Radhika Sankaran , Afsina Abdulla Cheriya Mukkolakkal , Anilkumar Gopinathan 
Published: March 2021

AbstractThe synthesis of heterocyclic compounds has been a hot topic for several decades. Synthetic organic chemists are always in search of new methodologies which are greener for the synthesis of heterocyclic compounds. The ultrasound‐assisted reactions have contributed much to this field. This review focuses on the impact of sonochemistry in the synthesis of heterocyclic compounds and covers the literature from 2009 to 2020.
Estimating HIV transmissions in a large U.S. clinic‐based sample: effects of time and syndemic conditions
Authors: Satyanarayana Satyanand , Safren Steven A , Rogers Brooke G , Bainter Sierra A , Christopoulos Katerina A , Fredericksen Rob J , Mathews William C , Moore Richard D , Mugavero Michael J , Napravnik Sonia , Carrico Adam W , Mimiaga Matthew J , Mayer Kenneth H , Crane Heidi M 
Published: March 2021

AbstractIntroductionLittle is known about onward HIV transmissions from people living with HIV (PLWH) in care. Antiretroviral therapy (ART) has increased in potency, and treatment as prevention (TasP) is an important component of ending the epidemic. Syndemic theory has informed modelling of HIV risk but has yet to inform modelling of HIV transmissions.MethodsData were from 61,198 primary HIV care visits for 14,261 PLWH receiving care through the Centers for AIDS Research (CFAR) Network of Integrated Clinical Systems (CNICS) at seven United States (U.S.) sites from 2007 to 2017. Patient‐reported outcomes and measures (PROs) of syndemic conditions – depressive symptoms, anxiety symptoms, drug use (opiates, amphetamines, crack/cocaine) and alcohol use – were collected approximately four to six months apart along with sexual behaviours (mean = 4.3 observations). Counts of syndemic conditions, HIV sexual risk group and time in care were modelled to predict estimated HIV transmissions resulting from sexual behaviour and viral suppression status (HIV RNA < 400/mL) using hierarchical linear modelling.ResultsPatients averaged 0.38 estimated HIV transmissions/100 patients/year for all visits with syndemic conditions measured (down from 0.83, first visit). The final multivariate model showed that per 100 patients, each care visit predicted 0.05 fewer estimated transmissions annually (95% confidence interval (CI): 0.03 to 0.06; p < 0.0005). Cisgender women, cisgender heterosexual men and cisgender men of undisclosed sexual orientation had, respectively, 0.47 (95% CI: 0.35 to 0.59; p < 0.0005), 0.34 (95% CI: 0.20 to 0.49; p < 0.0005) and 0.22 (95% CI: 0.09 to 0.35; p < 0.005) fewer estimated HIV transmissions/100 patients/year than cisgender men who have sex with men (MSM). Each within‐patient syndemic condition predicted 0.18 estimated transmissions/100 patients/year (95% CI: 0.12 to 0.24; p < 0.0005). Each between‐syndemic condition predicted 0.23 estimated HIV transmissions/100 patients/year (95% CI: 0.17 to 0.28; p < 0.0005).ConclusionsEstimated HIV transmissions among PLWH receiving care in well‐resourced U.S. clinical settings varied by HIV sexual risk group and decreased with time in care, highlighting the importance of TasP efforts. Syndemic conditions remained a significant predictor of estimated HIV transmissions notwithstanding the effects of HIV sexual risk group and time in care.
The regulatory role of insulin in energy metabolism and leukocyte functions
Authors: Cruz-Pineda Walter David , Parra-Rojas Isela , Rodríguez-Ruíz Hugo Alberto , Illades-Aguiar Berenice , Matia-García Inés , Garibay-Cerdenares Olga Lilia 
Published: March 2021

AbstractInsulin is the hormone responsible for maintaining glucose homeostasis in the body, in addition to participating in lipid metabolism, protein synthesis, and the inhibition of gluconeogenesis. These functions are well characterized in the classic organ target cells that are responsible for general energy regulation: the liver, skeletal muscle, and adipose tissue. However, these actions are not restricted to these tissues because insulin has been shown to affect most cells in the body. This review describes the role of insulin in leukocyte signaling pathways, metabolism and functions, and how insulin resistance could affect this signaling and deteriorate leukocyte metabolism and function, in addition to showing evidence that suggests leukocytes may substantially contribute to the development of systemic insulin resistance.
Metallothioneins alter macrophage phenotype and represent novel therapeutic targets for acetaminophen-induced liver injury
Authors: Devisscher Lindsey , Van Campenhout Sanne , Lefere Sander , Raevens Sarah , Tilleman Laurentijn , Van Nieuwerburgh Filip , Van Eeckhoutte Hannelore P , Hoorens Anne , Lynes Michael A , Geerts Anja , Laukens Debby , Van Vlierberghe Hans 
Published: March 2021

AbstractAcetaminophen (APAP) intoxication is the foremost cause of drug-induced liver failure in developed countries. The only pharmacologic treatment option, N-acetylcysteine (NAC), is not effective for patients who are admitted too late and/or who have excessive liver damage, emphasizing the need for alternative treatment options. APAP intoxication results in hepatocyte death and release of danger signals, which further contribute to liver injury, in part by hepatic monocyte/macrophage infiltration and activation. Metallothionein (MT) 1 and 2 have important danger signaling functions and might represent novel therapeutic targets in APAP overdose. Therefore, we evaluated hepatic MT expression and the effect of anti-MT antibodies on the transcriptional profile of the hepatic macrophage population and liver injury following APAP overdose in mice. Hepatic MT expression was significantly induced in APAP-intoxicated mice and abundantly present in human livers. APAP intoxication in mice resulted in increased serum transaminase levels, extended necrotic regions on liver histology and induced expression of proinflammatory markers, which was significantly less pronounced in mice treated with anti-MT antibodies. Anti-MT antibody therapy attenuated proinflammatory macrophage polarization, as demonstrated by RNA sequencing analyses of isolated liver macrophages and in LPS-stimulated bone marrow-derived macrophages. Importantly, NAC and anti-MT antibodies were equally effective whereas administration of anti-MT antibody in combination with NAC exceeded the efficiency of both monotherapies in APAP-induced liver injury (AILI). We conclude that the neutralization of secreted MTs using a monoclonal antibody is a novel therapeutic strategy as mono- or add-on therapy for AILI. In addition, we provide evidence suggesting that MTs in the extracellular environment are involved in macrophage polarization.