bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synthesis and anticancer activity of two highly water-soluble and ionic Pt(IV) complexes as prodrugs for Pt(II) anticancer drugs
Authors: Gao Anli , Wu Yaxi , Jiang Jing , Gong Hongyu , Yu Juan , Yang Caihong , Liu Weiping , Qing Chen 
Published: September 2021

Abstract
Two new Pt(IV) complexes featuring mesylate as outer sphere anions, cis,trans,cis-[PtCl2(OH2)2 (NH3)2](CH3SO3)2 (SPt-1) and cis,trans,cis-[PtCl2(OH2)2((1R,2R-DACH)](CH3SO3)2 (SPt-2) were synthesized, and characterized by elemental analysis, 1H- and 13C-NMR,IR, and ESI-MS. Both complexes have excellent water-solubility and high molar conductivity as well as good water-stability. They exhibit an irreversible two-electron reduction event with the peak potentials (Ep) for the processes being − 0.39 V and − 0.64 V for SPt-1 and 0.09 V and − 0.52 V for SPt-2. The biological tests reveal that SPt-2 possesses high in vitro anticancer activity against three human cancer cell lines and its overall anticancer activity is slightly greater than that of oxaliplatin, whereas SPt-1 is less active than cisplatin. Moreover, the antitumor efficacy of SPt-2 on human colon carcinoma HCT-116 xenografts in nude mice is also greater than that of oxaliplatin, suggesting SPt-2 deserves further evaluation as a prodrug for oxaliplatin.
Entomological Assessment of the Impact of Long-term Mass Administration of Ivermectin in Onchocerciasis – Endemic Communities in Kaduna State, Nigeria.
Authors: Isiyaku Sunday , Adamani William , Louise Hamill , Ndams Iliya Shehu , Ezekiel Kogi , Kal Alphonsus , Gazama James , Nock Ishaya Haruna 
Published: September 2021

Abstract
Background: Onchocerciasis constitutes a major public health burden in endemic communities and areas because of its dermal and ocular manifestations. Nigeria accounts for the highest burden of the disease globally. Long term mass distribution of ivermectin has been recommended by the World Health Organization as a potent strategy in halting the transmission of the disease in endemic communities.Aim: The aim of this study was to evaluate the prevalence of infective blackflies after 17 years of community-based treatment with ivermectin in two onchocerciasis foci in Kaduna State, Nigeria.Method: Blood seeking female flies were collected using human landing capture from two breeding sites (River Galma and Gurara) in Lere and Kagarko LGAs of Kaduna State in 2010 and 2011. The fly heads and bodies, in pools of 100, were analysed using Polymerase Chain Reaction (PCR)-ELISA specific for O. volvulus DNA. Results: A total of 24,937 blackflies were caught during two-year catching period. The prevalence of infective flies reduced from 0.15% to 0% at River Galma and 0.08% to 0.04% at river Gurara in 2010 and 2011 catching period. Some pools containing the bodies of the flies were also positive for Onchocerca volvulus. Conclusion: The presence of O. volvulus in the heads and bodies of the black flies collected confirmed that there was ongoing transmission of onchocerciasis in Kaduna State, Nigeria during the period of survey. There is continued need for mass distribution of ivermectin in Kaduna in order to halt the transmission.
Activation of the viral sensor oligoadenylate synthetase 2 (Oas2) prevents pregnancy-driven mammary cancer metastases
Authors: Ho Wing-Hong Jonathan , Law Andrew M. K. , Masle-Farquhar Etienne , Castillo Lesley E. , Mawson Amanda , O’Bryan Moira K. , Goodnow Christopher C. , Ortega David Gallego , Oakes Samantha R. , Ormandy Christopher 
Published: September 2021

Abstract
BackgroundThe interferon response can influence the primary and metastatic activity of breast cancers and can interact with checkpoint immunotherapy to modulate its effects. Using N-ethyl-N-nitrosourea mutagenesis we found a mouse with an activating mutation in oligoadenylate synthetase 2 ( Oas2 ), a sensor of viral double stranded RNA, that resulted in an interferon response and prevented lactation in otherwise healthy mice. MethodsTo determine if activation of Oas2 could alter the course of mammary cancer we combined the Oas2 mutation with the MMTV-PyMT oncogene model of breast cancer and examined disease progression and the effects of checkpoint immunotherapy using Kaplan-Meier survival analysis with immunohistochemistry and flow cytometry. ResultsOas2 mutation prevented pregnancy from increasing metastases to lung. Checkpoint immunotherapy with antibodies against programmed death-ligand 1 (PD-L1) was more effective when the Oas2 mutation was present. ConclusionsThese data establish OAS2 as a therapeutic target for agents designed to reduce metastases and increase the effectiveness of checkpoint immunotherapy in cases of pregnancy-associated breast cancer and outside of pregnancy in cases showing the lactation and involution-mimicry phenotypes.
Salidroside Alleviates Oxidative Stress and Apoptosis via AMPK/Nrf2 Pathway in DHT-induced Human Granulosa Cell Line KGN
Authors: Ji Rui , Jia Fang-yuan , Chen Xin , Wang Ze-hao , Jin Wen-yi , Yang Jing 
Published: September 2021

Abstract
Background: In the past few years, emerging evidence established persistent oxidative stress to be a key player in the pathogenesis of polycystic ovary syndrome (PCOS). Particularly, it damages the function of granulosa cells, and thus hinders the development of follicles. The present study aimed to explore and establish the protective effects of salidroside on dihydrotestosterone (DHT)‐induced Granulosa‐like tumor cell line (KGN), mediated via antioxidant mechanisms.Methods: KGN cells were treated with DHT as a PCOS cell model, and then incubated with salidroside in different concentrations. Apoptosis and reactive oxygen species (ROS) accumulation were assessed by flow cytometry, mitochondrial membrane potential depolarization and the nuclear translocation of Nrf2 were detected by immunofluorescence staining, and the level of apoptosis-related proteins and antioxidant proteins was assessed by western blotting.Results: Salidroside partly reversed DHT mediated effects, via stimulation of nuclear factor erythroid 2‐related factor 2 (Nrf2) signaling pathway and the downstream antioxidant proteins heme oxygenase‐1(HO‐1) and quinine oxidoreductase 1(NQO1). Additionally, knockdown of Nrf2 resulted in a deterioration in DHT‐induced oxidative stress and apoptosis. It partly moderated the protective effects of salidroside as well. Mechanistically, AMPK was identified to be the upstream signaling involved in salidroside‐induced Nrf2 activation, as silencing of AMPK partly prevented the upregulation of Nrf2 and the downstream proteins HO‐1 and NQO1. Conclusion: The present study is the first to effectively demonstrate the inhibitory effect of salidroside on DHT‐stimulated oxidative stress and apoptosis in KGN cells, which was dependent on Nrf2 activation that involved AMPK.
Dysregulated GLUT1 May Be Involved in the Pathogenesis of Preeclampsia by Impairing Decidualization
Authors: Yang Man , Li Hua , Rong Miaomiao , Zhang Hongya , Hou Linlin , Zhang Cong 
Published: September 2021

Abstract
Background: Preeclampsia (PE), a hypertensive complication in pregnancy, is a major contributor to maternal and fetal morbidity and mortality. Thus far, the molecular mechanism underlying PE has not been investigated thoroughly. Glucose transporter 1 (GLUT1) is a central rate-limiting pump for glucose uptake and subsequent utilization. Our previous RNA-seq results demonstrated it was significantly downregulated in deciduas from severe PE patients. Therefore, we aimed to explore the role of GLUT1 in the occurrence of PE.Methods: In this study, GLUT1 levels were evaluated by quantitative PCR, Western blotting and immunohistochemical staining in severe preeclamptic deciduas. The levels of GLUT1 during decidualization were also studied in human endometrial stromal cells (hESCs). Moreover, the role of GLUT1 during decidualization was studied by GLUT1-siRNA treatment. Furthermore, we explored the regulatory role of miRNA in GLUT1 expression.Results: The expression of GLUT1 was significantly downregulated in the deciduas from severe PE patients. Additionally, the level of GLUT1 was substantially induced in hESCs during in vitro decidualization. Moreover, GLUT1 knockdown significantly reduced the mRNA levels of decidualization markers (IGFBP1 and PRL) and aerobic glycolysis-related genes (LDHA and MCT4), and decreased glucose uptake and lactate production. Furthermore, the levels of apoptotic genes P53, P21 and BAX increased whereas the levels of BCL2 decreased after GLUT1 knockdown. Target prediction results and luciferase analysis showed GLUT1 is one of the targets of miR-140-5p, which is partly responsible for the impaired GLUT1 level. Conclusion: These results demonstrate that GLUT1 exerts pivotal role in human decidualization by participating in glycolysis, and its deficiency may trigger aberrant glycolysis and thus leads to destructive decidualization, which may be a pathogenetic mechanism of PE. These data suggest GLUT1 might be a promising target for PE therapy.
Association of ACE I/D Gene Polymorphism and Related Risk Factors in Impaired Fasting Glucose and Type 2 Diabetes: A Study Among Two Tribal Populations of North-East India.
Authors: RAJKUMARI SUNANDA , NINGOMBAM SOMORJIT SINGH , CHHUNGI VARHLUN , NEWMEI MASAN KAMBO , DEVI NAOREM KIRANMALA , MONDAL PRAKASH RANJAN , Saraswathy Kallur Nava 
Published: September 2021

Abstract
AIMType 2 diabetes is a serious public health concern in India, even the indigenous tribal populations are not felt unaffected. The present study aims to understand the association of major risk factors i.e obesity, hypertension, dyslipidemia, ACE I/D polymorphism with impaired (IFG) and type 2 diabetes (T2D) among two different Mendelian populations of North East India. METHODDemographic, somatometric and physiological variables along with fasting blood samples were collected from 609 individuals. ACE I/D polymorphism was screened. RESULTACE I/D polymorphism was found to follow HWE among Liangmai tribe but not among Mizo tribe. Distribution of DD genotype/D allele was found to be significantly higher for T2D among Mizo (OR 2.10; 95% CI 1.10-4.39, OR 2.10;1.16-4.09 respectively ).Significant association between DD genotype/D allele of ACE I/D polymorphism and TC in both IFG (OR 2.22; 95% CI 1.14-4.32) and T2D (OR 2.53;95%CI 1.51-4.23) were observed . LDL was also found to posed significant risk for IFG (OR 2.10;95% CI 1.10-3.91) and T2D (OR 1.04; 95%CI 1.02-1.06). CONCLUSIONThe present study is an example of gene-environment interaction where DD genotype or D allele and dyslipidemia (high TC and high LDL) are posing risk for IFG and T2D both independently and in combination only among Mizo tribe with relatively less physical activity attributed to their residence in less hilly terrain, but Liangmai tribe which resides in high hilly terrain shows no such association.
Synergistic Sorafenib with Jianpi Huayu Decoction Resulted in Tumor Regression and Prevented Adverse Events in Hepatocellular Carcinoma by Remodeling the Gut Microbiota
Authors: Deng Xue , Xie Yingjie , Lu Yantong , Li Xueyan , Guo Xuan , Zhang Yuan , Lin Juze , Tan Wei , Wang Changjun , Huang Xuhui 
Published: September 2021

Abstract
Background: There is an urgent need for effective treatments for hepatocellular carcinoma (HCC). Sorafenib is first-line treatment for HCC, which has a modest efficacy due to severe adverse effects(AE), acquired resistance and others. Combination therapy may be able to overcome this limitation. Jianpi Huayu Decoction (JHD) is a traditional Chinese medicine formulation, which has been shown to be effective as an alternative and complementary therapy of HCC. We investigated the synergistic effect of JHD with sorafenib by a xenograft model.Methods: Growth of mouse-derived HCC cells and adverse events(AE) of treatment were evaluated in a subcutaneous model with JHD and clinical-dose sorafenib combination treatment. Diarrhea, the most frequently reported AE, was evaluated by diarrhea score. The gut microbiota(GM) composition of the mice was analyzed by Illumina NovaSeq. Results: JHD administration in mice synergistically enhanced the anti-tumor response, thereby suppressing HCC, and prevented occurrence of the most common AEs(diarrhea and body weight loss) of sorafenib. Sorafenib induced increased proinflammatory GM(Helicobacter) which promoted the progression of HCC and against anti-tumor treatment. JHD reduced the abundance of anti-inflammatory microbiota Muribaculum, Fusicatenibacter, and Dorea. Following the modulation of GM, the proinflammatory signaling interleukin 6/signal transducer and activator of transcription-3 pathway was downregulated by JHD.Conclusions: Our finding suggested that differences in the microbial gut flora may modulate resistance to sorafenib through IL-6/STAT3 signaling. JHD with microbiota modulation properties could potentiate sorafenib and provided a promising approach for HCC treatment.
Longitudinal Preclinical Evaluation of the Novel Radioligand [11C]CHDI-626 for PET Imaging of Mutant Huntingtin Aggregates in Huntington’s Disease
Authors: Bertoglio Daniele , Verhaeghe Jeroen , Miranda Alan , Wyffels Leonie , Stroobants Sigrid , Mrzljak Ladislav , Khetarpal Vinod , Skinbjerg Mette , Liu Longbin , Dominguez Celia , Munoz-Sanjuan Ignacio , Bard Jonathan , Staelens Steven 
Published: September 2021

Abstract
PurposeAs several therapies aimed at lowering mutant huntingtin (mHTT) brain levels in Huntington’s disease (HD) are currently being investigated, noninvasive positron emission tomography (PET) imaging of mHTT could be utilized to directly evaluate therapeutic efficacy and monitor disease progression. Here we characterized and longitudinally assessed the novel radioligand [11C]CHDI-626 for mHTT PET imaging in the zQ175DN mouse model of HD.MethodsAfter evaluating radiometabolites and radioligand kinetics, we conducted longitudinal dynamic PET imaging at 3, 6, 9, and 13 months of age (M) in wild-type (WT, n = 17) and heterozygous (HET, n = 23) zQ175DN mice. Statistical analysis was performed to evaluate temporal and genotypic differences. Cross-sectional cohorts at each longitudinal time point were included for post-mortem [3H]CHDI-626 autoradiography.ResultsDespite fast metabolism and kinetics, the radioligand was suitable for PET imaging of mHTT. Longitudinal quantification could discriminate between genotypes already at premanifest stage (3M), showing an age-associated increase in signal in HET mice in parallel with mHTT aggregate load progression, as supported by the post-mortem [3H]CHDI-626 autoradiography.Conclusion﻿With clinical evaluation underway, [11C]CHDI-626 PET imaging appears to be a suitable preclinical candidate marker to monitor natural HD progression and for the evaluation of mHTT-lowering therapies.
Specific Features of The Structure Formation of Aluminum Alloys During Rapid Crystallization-Deformation
Authors: Sidelnikov Sergey Borisovich , Lopatina Ekaterina Sergeevna , Voroshilov Denis Sergeevich , Dovzhenko Nikolay Nikolaevich , Konstantinov Igor Lazarevich , Mansurov Yulbarskhon Nabievich , Bespalov Vadim Mikhaylovich , Durnopyanov Aleksandr Vasilyevich , Galiev Roman Ilsurovich , Voroshilova Marina Vladimirovna , Bersenev Andrey Sergeevich 
Published: September 2021

Abstract
The results of studies of the structure and properties of semi-finished products from aluminum and its alloys, obtained with the use of cast-free rolling-extruding are presented. It has been found that the rods obtained by the high-speed crystallization-deformation technology by the direct rolling-extrusion method have a stable ultrafine subgrain structure, which makes it possible to use them as modifiers. Experimental studies have been carried out, which confirmed the assumption that the initial structure of the modifying rod affects the melt. It was revealed that the size and density of distribution of additional crystallization centers formed in the volume of the melt based on clusters are inherited from the original subgrain structure of the modifying rod made of aluminum or its alloys. Metallographic studies have also shown that the subsequent severe plastic deformation by equal-channel angular extruding of rods obtained by direct rolling-extruding from an experimental alloy of the composition Al-0.2Zr-0.2Fe-0.4Mg makes it possible to achieve additional strengthening of the metal, since even more refines its structure, while the average grain size is 647 μm.
Compound Dihuang Granule Protects against 6-OHDA Induced Toxicity in Parkinson’s Disease Rats by Suppressing the Phosphorylation of MAPK/ERK1/2
Authors: Wang Li , Zhang Jian-ying , Chen Long , Zhang Lei , He Zhu-qing , Huan Peng-fei , Yang Yu-fang , He Jian-cheng 
Published: September 2021

Abstract
BackgroundParkinson’s disease (PD) is a multifactorial neurodegenerative disorder characterized by progressive loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc) and the presence of Lewy bodies (LBs) consisting of misfolded α-synuclein protein in the substantia nigra pars compacta (SNpc). Compound Dihuang Granule (CDG), a famous traditional Chinese medicine (TCM) has been clinically used in PD therapy with curative effects. However, the specific functions and the mechanism of action remained unclear. This study explored the therapeutic effects and potential mechanisms of CDG in the PD rats induced by 6-OHDA toxicity.MethodsThe PD rat model was induced by unilaterally stereotactic injection of 6-OHDA into the SNpc of midbrain. The behavioral performances of rats were evaluated by rotation test, muscle strength assessment and balance beam walking test. The striatal contents of neurotransmitters were detected by HPLC.The numbers of dopaminergic (DA) neurons were determined with immunohistochemistry (IHC) staining and Western blotting assay. Indicators of oxidative stress were determined with colorimetric method. Apoptotic cells were detected by TUNEL assay. The expression levels of neurotrophic factors were examined with IHC staining and real-time quantitative PCR. The related protein expression levels were determined with Western blotting assay.ResultsCDG significantly attenuated the 6-OHDA induced abnormal rotational behaviors and alleviated the loss of DA neurons in the nigrostriatal axis of PD rats with a 6-week treatment. Consistently, the striatal contents of DA and its metabolites including DOPAC and HVA of PD rats were all significantly increased with CDG treatment. The 6-OHDA induced oxidative stress indicated with decreased superoxide dismutase (SOD), glutathione (GSH), glutathione peroxidase (GSH-Px) and increased malondialdehyde (MDA) was also suppressed by CDG treatment. Moreover, CDG treatment increased the expression levels of neurotrophic factors including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and glial-derived neurotrophic factor (GDNF) in the nigrostriatal axis of PD rats. Consistently, the 6-OHDA induced cell apoptosis was inhibited by the 6-week CDG treatment. Further, the phosphorylation of MAPK/ERK1/2 and CREB proteins in the striatum of PD rats was suppressed by CDG treatment and CDG showed synergistic effects with the MAPK/ERK1/2 phosphorylation inhibitor SL327.Conclusion﻿CDG could ameliorate the 6-OHDA induced brain injuries and motor symptoms, and also inhibit the oxidative stress and cell apoptosis in the nigrostriatal axis, which was mainly mediated by enhancing the expression levels of the neurotrophic factors and suppressing the phosphorylation of MAPK/ERK1/2 pathway in the midbrain of rats.
The Diagnostic Efficacy of Three-Dimensional Reconstruction System-Based Methods for Predicting Axillary Lymph Node Metastasis in Breast Cancer Patients: An Exploratory Study
Authors: Qu Limeng , Yi Wenjun , Luo Na , Zhao Piao , Zou Qiongyan , Chen Qitong , Mei Xilong 
Published: September 2021

Abstract
Background: The status of axillary lymph node metastases determines the treatment and overall survival of breast cancer (BC) patients. Three-dimensional (3D) assessment methods have advantages for spatial localization and are more responsive to morphological changes in lymph nodes than two-dimensional (2D) assessment methods, and we speculate that methods developed using 3D reconstruction systems have high diagnostic efficacy.Methods: This exploratory study included 43 patients with histologically confirmed BC diagnosed at Second Xiangya Hospital of Central South University between July 2017 and August 2020, all of whom underwent preoperative CT scans. Patients were divided into a training cohort to train the model and a validation cohort to validate the model. A 3D axillary lymph node atlas was constructed on a 3D reconstruction system to create various methods of assessing lymph node metastases for a comparison of diagnostic efficacy. Receiver operating characteristic (ROC) curve analysis was performed to assess the diagnostic values of these methods.Results: A total of 43 patients (mean [SD] age, 47 [10] years) met the eligibility criteria and completed 3D reconstruction. An axillary lymph node atlas was established, and a correlation between lymph node sphericity and lymph node metastasis was revealed. By continuously fitting the size and characteristics of axillary lymph nodes on the 3D reconstruction system, formulas and models were established to determine the presence or absence of lymph node metastasis, and the 3D method had better sensitivity for axillary lymph node assessment than the 2D method, with a statistically significant difference in the correct classification rate. The combined diagnostic method was superior to a single diagnostic method, with a 92.3% correct classification rate for the 3D method combined with ultrasound. In addition, in patients who received neoadjuvant chemotherapy (NAC), the correct classification rate of the 3D method (72.7%) was significantly higher than that of ultrasound (45.5%) and CT (54.5%).Conclusion: By establishing an axillary lymph node atlas, the sphericity formula and model developed with the 3D reconstruction system achieve a high correct classification rate when combined with ultrasound or CT and can also be applied to patients receiving NAC.