bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gremlin‐1 promotes IL‐1β‐stimulated chondrocyte inflammation and extracellular matrix degradation via activation of the MAPK signaling pathway
Authors: Du Xiu‐fan , Huang Kai , Chen Xiao‐yan , Huang Chun‐hang , Cao Hui‐yuan , Wang Guang‐ji , Hu Yong 
Published: June 2023

AbstractThe role and mechanism of Gremlin‐1 in osteoarthritis (OA) were expected to be probed in this study. Firstly, an in vitro OA model was constructed by stimulating human chondrocyte cell line CHON‐001 with IL‐1β. Next, 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) and quantitative reverse transcriptase polymerase chain reaction (qRT‐PCR) were utilized for assessing the effect of IL‐1β with different concentrations (5, 10, and 20 ng/mL) on the activity and Gremlin‐1 messenger RNA of CHON‐001 cells, respectively. Besides, the influence of knocking down/over‐expressing Gremlin‐1 on the inflammatory factors (IL‐6, TNF‐α, IL‐18 and PGE2), oxidative stress‐related substances (malondialdehyde [MDA]; superoxide dismutase [SOD]; lactate dehydrogenase [LDH]), extracellular matrix (ECM) degradation‐related proteins, and mitogen‐activated protein kinase (MAPK) pathway proteins in IL‐1β‐stimulated CHON‐001 cells were tested by enzyme‐linked immunosorbent assay, related kits, qRT‐PCR, and western blot, respectively. IL‐1β inhibited CHON‐001 cell proliferation and upregulated Gremlin‐1 expression in a concentration‐dependent manner. Overexpression of Gremlin‐1 increased the IL‐6, TNF‐α, IL‐18, PGE2, and MDA levels, enhanced the LDH activity, and decreased the SOD activity in IL‐1β‐induced CHON‐001 cells; while the effect of Gremlin‐1 knockdown on the above factors was in contrast with that of the overexpression. Furthermore, overexpression of Gremlin‐1 upregulated protein expression of matrix metalloproteinase (MMP)‐3, MMP‐13, and ADAMTS4 while downregulated protein expression of collagen III, aggrecan, and SOX‐9 in IL‐1β‐stimulated CHON‐001 cells. Besides, overexpression of Gremlin‐1 increased the p‐p38/p38 value while decreased the p‐JNK/JNK value in L‐1β‐stimulated CHON‐001 cells; however, knockdown of Gremlin‐1 reversed the above results. Gremlin‐1 may promote IL‐1β‐stimulated CHON‐001 cell inflammation and ECM degradation by activating the MAPK signaling pathway.
Bisphenols as promoters of the dysregulation of cellular junction proteins of the blood‐testis barrier in experimental animals: A systematic review of the literature
Authors: Peña‐Corona Sheila I. , Vargas‐Estrada Dinorah , Juárez‐Rodríguez Ivan , Retana‐Márquez Socorro , Mendoza‐Rodríguez C. Adriana 
Published: June 2023

AbstractDaily, people are exposed to chemicals and environmental compounds such as bisphenols (BPs). These substances are present in more than 80% of human fluids. Human exposure to BPs is associated with male reproductive health disorders. Some of the main targets of BPs are intercellular junction proteins of the blood‐testis barrier (BTB) in Sertoli cells because BPs alter the expression or induce aberrant localization of these proteins. In this systematic review, we explore the effects of BP exposure on the expression of BTB junction proteins and the characteristics of in vivo studies to identify potential gaps and priorities for future research. To this end, we conducted a systematic review of articles. Thirteen studies met our inclusion criteria. In most studies, animals treated with bisphenol‐A (BPA) showed decreased occludin expression at all tested doses. However, bisphenol‐AF treatment did not alter occludin expression. Cx43, ZO‐1, β‐catenin, nectin‐3, cortactin, paladin, and claudin‐11 expression also decreased in some tested doses of BP, while N‐cadherin and FAK expression increased. BP treatment did not alter the expression of α and γ catenin, E‐cadherin, JAM‐A, and Arp 3. However, the expression of all these proteins was altered when BPA was administered to neonatal rodents in microgram doses. The results show significant heterogeneity between studies. Thus, it is necessary to perform more research to characterize the changes in BTB protein expression induced by BPs in animals to highlight future research directions that can inform the evaluation of risk of toxicity in humans.
Promising renoprotective effect of gold nanoparticles and dapagliflozin in diabetic nephropathy via targeting miR‐192 and miR‐21
Authors: Al‐Tantawy Samar M. , Eraky Salma M. , Eissa Laila A. 
Published: June 2023

AbstractDiabetic nephropathy (DN) is a worldwide issue that eventually leads to end‐stage renal failure, with limited therapeutic options. Prior research has revealed that gold nanoparticles (AuNPs) have a substantial antidiabetic impact. In addition, sodium‐glucose cotransporter2 (SGLT2) inhibitors, including dapagliflozin (DAPA), had renoprotective impact on DN. Therefore, this research attempted to determine the potential AuNPs and DAPA impacts in ameliorating experimentally DN induction and the underlying mechanisms focusing on miR‐192 and miR‐21, correlating them with autophagy, apoptosis, fibrosis, and oxidative stress. Diabetes induction was through a single intraperitoneal streptozotocin (55 mg/kg) injection, and rats with diabetes received AuNPs (2.5 mg/kg/day) as well as DAPA (2 mg/kg/day) for 7 weeks as a treatment. AuNPs and DAPA treatment for 7 weeks substantially alleviated DN. AuNPs and DAPA significantly increased catalase (CAT) activity as well as serum total antioxidant capacity (TAC), along with a substantial decline in malondialdehyde (MDA). AuNPs and DAPA treatment alleviated renal fibrosis as they decreased transforming growth factorß1(TGF‐ß1) as well as matrix metalloproteinase‐2 (MMP‐2) renal expression, decreased apoptosis through alleviating the proapoptotic gene (caspase‐3) renal expression and increased the antiapoptotic gene (Bcl‐2) renal expression, and increased autophagy as they increased LC‐3 as well as Beclin‐1 renal expression. Autophagy activation, inhibition of apoptosis, and renal fibrosis could be due to their inhibitory impact on miR‐192 and miR‐21 renal expression. AuNPs and DAPA have a protective effect on DN in rats by targeting miR‐192 and miR‐21 and their downstream pathways, including fibrosis, apoptosis, autophagy, and oxidative stress.
Exosomes from hepatitis B virus‐infected hepatocytes activate hepatic stellate cells and aggravate liver fibrosis through the miR‐506‐3p/Nur77 pathway
Authors: Yin Ming , Ding Xiurong , Yin Song , Wang Longmei , Zhang Kaiguang , Chen Yuankun , Liu Rui , Zhu Chuanlong , Li Wenting 
Published: June 2023

AbstractCumulative evidence indicates the important role of Nur77 in organ fibrogenesis. However, the role of Nur77 in hepatitis B virus (HBV)‐related liver fibrosis (LF) remains unclear. Cells were transfected with the microRNA mimic miRNA‐506‐3p or inhibitor, and pcDNA3.1‐Nur77 or Nur77 guide RNA. Exosomes were isolated from HBV‐infected HepG2‐sodium taurocholate cotransporting polypeptide cells. The levels of miR‐506‐3p, Nur77, and LF‐related genes and proteins were detected by quantitative polymerase chain reaction (qPCR) and western blot analysis, respectively. The pathology of the liver from HBV‐infected patients was examined using hematoxylin‐eosin and Masson's staining. The expression of Nur77 in liver tissue was determined by immunohistochemistry, and the LF score was assessed using the METAVIR system. The relationship between miR‐506‐3p/Nur77 and LF score was analyzed by correlation analysis. HBV infection downregulated miR‐506‐3p expression and upregulated Nur77 levels in hepatocytes. Exosomes from HBV‐infected hepatocytes also displayed decreased gene expression of miR‐506‐3p and increased expressions of Nur77‐ and LF‐related genes in stellate cells compared with exosomes from hepatocytes with mock infection. These changes were reversed by Nur77 guide RNA. Nur77 expression in liver tissue was strongly correlated with LF, whereas serum miR‐506‐3p was strongly negatively correlated with LF. Exosomes from HBV‐infected hepatocytes activate stellate cells and aggravate LF through the miR‐506‐3p/Nur77 pathway. These exosomes may be the basis of a promising therapeutic strategy.
Neuroprotective potential of berberine against acetamiprid induced toxicity in rats: Implication of oxidative stress, mitochondrial alterations, and structural changes in brain regions
Authors: Phogat Annu , Singh Jagjeet , Malik Vinay , Kumar Vijay 
Published: June 2023

AbstractAcetamiprid (ACMP) is an extensively used neonicotinoid pesticide to control sucking and chewing insects and is known to cause nontarget toxicity. The present study aimed to evaluate the ameliorative potential of berberine (BBR)—a polyphenolic alkaloid‐ on ACMP‐induced oxidative stress, mitochondrial dysfunctioning, and structural changes in different rat brain regions. The male Wistar rats were divided into four groups, that is, control, BBR‐treated (150 mg/kg b.wt), ACMP‐exposed (21.7 mg/kg b.wt) and BBR + ACMP co‐treated; and were dosed intragastrically for 21 consecutive days. Results of the biochemical analysis showed that BBR significantly ameliorated ACMP‐induced oxidative stress by decreasing lipid peroxidation and protein oxidation along with a marked increase in endogenous antioxidants and lowered AChE activity in rat brain regions. Inside mitochondria, BBR significantly attenuated the toxic effects of ACMP by increasing the activity of mitochondrial complexes. Findings of polymerase chain reaction also demonstrated the modulatory effects of BBR against ACMP‐mediated downregulation of ND1, ND2, COX1, and COX4 subunits of mitochondrial complexes. The histopathological and ultrastructural examination also validated the biochemical and transcriptional alterations following toxicity of ACMP exposure and the protective potential of BBR against ACMP‐induced neurotoxicity. Thus, the present study indicates the promising ameliorative potential of BBR against ACMP‐induced neurotoxicity via its antioxidative and modulatory activities.
Probenecid ameliorates testosterone‐induced benign prostatic hyperplasia: Implications of PGE‐2 on ADAM‐17/EGFR/ERK1/2 signaling cascade
Authors: Abdel‐Fattah Maha M. , Abo‐El Fetoh Mohammed E. , Afify Hassan , Ramadan Laila A. A. , Mohamed Wafaa R. 
Published: June 2023

AbstractBenign prostatic hyperplasia (BPH) is one of the most prevalent clinical disorders in the elderly. Probenecid (Prob) is a well‐known FDA‐approved therapy for gout owing to its uricosuric effect. The present study evaluated the use of Prob for BPH as a COX‐2 inhibitor. Prob (100 and 200 mg/kg) was intraperitoneally injected into male Wistar rats daily for 3 weeks. In the second week, testosterone (3 mg/kg) was subcutaneously injected to induce BPH. Compared with BPH‐induced rats, Prob treatment reduced prostate weight and index and improved histopathological architecture. The protease activity of ADAM‐17/TACE and its ligands (TGF‐α and TNF‐α) were regulated by prob, which in turn abolished EGFR phosphorylation, and several inflammatory mediators (COX‐2, PGE2, NF‐κB (p65), and IL‐6) were suppressed. By reducing the nuclear import of extracellular regulated kinase protein 1/2 (ERK1/2), Prob helped re‐establish the usual equilibrium between antiapoptotic proteins like Bcl‐2 and cyclin D1 and proapoptotic proteins like Bax. All of these data point to Prob as a promising treatment for BPH because of its ability to inhibit COX‐2‐syntheiszed PGE2 and control the ADAM‐17/TGF‐α‐induced EGFR/ERK1/2 signaling cascade. These findings might help to repurpose Prob for the treatment of BPH.
Comparing the influence of explicit and implicit solvation models on site‐specific thermodynamic stability of proteins
Authors: Cho Myung Keun , Chong Song‐Ho , Ham Sihyun , Shin Seokmin 
Published: June 2023

AbstractUnderstanding the molecular basis for protein stability requires a thermodynamic analysis of protein folding. Thermodynamic analysis is often performed by sampling many atomistic conformations using molecular simulations that employ either explicit or implicit water models. However, it remains unclear to what extent thermodynamic results from different solvation models are reliable at the molecular level. In this study, we quantify the influence of both solvation models on folding stability at the individual backbone and side chain resolutions. We assess the residue‐specific folding free energy components of a β‐sheet protein and a helical protein using trajectories resulting from TIP3P explicit and generalized Born/surface area implicit solvent simulations of model proteins. We found that the thermodynamic discrepancy due to the implicit solvent mostly originates from charged side chains, followed by the under‐stabilized hydrophobic ones. In contrast, the contributions of backbone residue in both proteins were comparable for explicit and implicit water models. Our study lays out the foundation for detailed thermodynamic assessment of solvation models in the context of protein simulation.
A study of the relationship between brachial artery vasodilation and platelet/lymphocyte ratio in diabetic patients with coronary atherosclerosis
Authors: Wang Meiling , Liu Yanjie , Zhang Lei , Chen Li , Zhao Wei , Zhang Hebin , Wu Hao 
Published: June 2023

AbstractBackgroundTo investigate the correlation between brachial artery flow‐mediated endothelium‐dependent dilation (FMD) and platelet–lymphocyte ratio (PLR) in peripheral blood and coronary atherosclerosis in diabetic patients.MethodsSeventy‐five diabetic patients aged 62 ± 9 years, 68% male and 32% female, who underwent brachial artery endothelial function test and coronary CT scan were collected. Coronary artery calcification (CAC) was observed to assess the presence of coronary atherosclerosis, and high‐resolution extravascular ultrasound was used to detect FMD. Platelet count and lymphocyte count were recorded by routine blood tests, and PLR was calculated for each study subject. Statistical methods were used to verify the association of FMD and PLR with CAC assessed by CT, respectively.ResultsPatients with coronary atherosclerosis had decreased FMD and increased PLR compared with patients with normal coronary arteries. Univariate logistic regression analysis showed that CAC score was significantly associated with both FMD (odds ratio: 0.167; 95% confidence interval: 0.049–0.565; p = 0.002) and PLR (odds ratio: 0.127; 95% confidence interval: 0.033–0.484; p = 0.001) at FMD < 5.1% or PLR > 130. The area under the ROC curve of FMD and PLR alone was 0.760 and 0.763, respectively. In addition, combined diagnosis of FMD and PLR showed the highest area under the ROC curve (0.830).ConclusionFMD combined with PLR is expected to be a precise diagnostic modality for coronary artery calcification in diabetic patients.
Detection of bacteria causing mastitis in cows with immunoelectric tool
Authors: Mohammad Khosravi , Meysam Makki , MohammadNasir Ghoudarzi , Darioush Gharibi 
Published: June 2023

AbstractBackgroundThis study has investigated designing, producing, and evaluating a newly developed immunoelectric device for the identification of the Staphylococcus aureus and Escherichia coli in experimentally or clinically polluted milk samples.MethodsThe design of the immunoelectric tool parts was carried out and produced by using a 3D printer. The animals were immunized against S. aureus and E. coli; purification of the specific IgG from hyperimmune serum was carried out by ion exchange and affinity chromatography methods. Coupling of the specific rabbit antibodies to the polystyrene filters was performed by DTPA linker. The purified rat antibodies were coupled to Fe nanoparticles and used as detector elements. The experimentally polluted milk and PBS samples were prepared. After optimization, the minimum traceable number of the bacteria was determined using immunoelectric tool. Also, the cow's milk samples with clinical mastitis were tested for bacterial detection by bacterial culture and immunoelectric methods.ResultsCoupling of the antibody to the filters and capturing of the target bacteria to the filters were successfully confirmed using enzyme immune assay and electron microscopy. The detection limit of the developed immunoelectric tool was equal to 15 cells/mL in PBS or milk samples for 30 min. Also, in agreement with bacterial cell culture, the clinically infected milk samples by S. aureus and E. coli were successfully detected using the immunoelectric device.ConclusionsThe developed immunoelectric device could be utilized for rapid and cost–benefit detection of the bacterial organism.
Simulator, machine learning, and artificial intelligence: Time has come to assist prenatal ultrasound diagnosis
Authors: Tonni Gabriele , Grisolia Gianpaolo 
Published: June 2023

AbstractIn this Commentary authors investigated and extended the role of simulator in assisting obstetric sonographers in training program. The interconnection of different digitalized technologies such as digital data, artificial neuronal and convolutional networks, machine and deep learning, telemedicine, and output are discussed and contribute to the generation of artificial intelligence.
First‐in‐human clinical trial of allogeneic, platelet‐derived extracellular vesicles as a potential therapeutic for delayed wound healing
Authors: Johnson Jancy , Law Sam Q. K. , Shojaee Mozhgan , Hall Alex S. , Bhuiyan Sadman , Lim Melissa B. L. , Silva Anabel , Kong Karmen J. W. , Schoppet Melanie , Blyth Chantelle , Ranasinghe Hansi N. , Sejic Nenad , Chuei Mun Joo , Tatford Owen C. , Cifuentes‐Rius Anna , James Patrick F. , Tester Angus , Dixon Ian , Lichtfuss Gregor 
Published: June 2023

AbstractThe release of growth factors, cytokines and extracellular matrix modifiers by activated platelets is an important step in the process of healthy wound healing. Extracellular vesicles (EVs) released by activated platelets carry this bioactive cargo in an enriched form, and may therefore represent a potential therapeutic for the treatment of delayed wound healing, such as chronic wounds. While EVs show great promise in regenerative medicine, their production at clinical scale remains a critical challenge and their tolerability in humans is still to be fully established. In this work, we demonstrate that Ligand‐based Exosome Affinity Purification (LEAP) chromatography can successfully isolate platelet EVs (pEVs) of clinical grade from activated platelets, which retain the regenerative properties of the parent cell. LEAP‐isolated pEVs display the expected biophysical features of EV populations and transport essential proteins in wound healing processes, including insulin growth factor (IGF) and transforming growth factor beta (TGF‐ß). In vitro studies show that pEVs induce proliferation and migration of dermal fibroblasts and increase dermal endothelial cells' angiogenic potential, demonstrating their wound healing potential. pEV treatment activates the ERK and Akt signalling pathways within recipient cells. In a first‐in‐human, double‐blind, placebo‐controlled, phase I clinical trial of healthy volunteer adults, designed primarily to assess safety in the context of wound healing, we demonstrate that injections of LEAP‐purified pEVs in formulation buffer are safe and well tolerated (Plexoval II study, ACTRN12620000944932). As a secondary objective, biological activity in the context of wound healing rate was assessed. In this cohort of healthy participants, in which the wound bed would not be expected to be deficient in the bioactive cargo that pEVs carry, all wounds healed rapidly and completely and no difference in time to wound closure of the treated and untreated wounds was observed at the single dose tested. The outcomes of this study evidence that pEVs manufactured through the LEAP process can be injected safely in humans as a potential wound healing treatment, and warrant further study in clinical trials designed expressly to assess therapeutic efficacy in patients with delayed or disrupted wound healing.
Gene therapy in cancer
Authors: Cesur‐Ergün Büşra , Demir‐Dora Devrim 
Published: June 2023

AbstractGene therapy, recently frequently investigated, is an alternative treatment method that introduces therapeutic genes into a cancer cell or tissue to cause cell death or slow down the growth of the cancer. This treatment has various strategies such as therapeutic gene activation or silencing of unwanted or defective genes; therefore a wide variety of genes and viral or nonviral vectors are being used in studies. Gene therapy strategies in cancer can be classified as inhibition of oncogene activation, activation of tumor suppressor gene, immunotherapy, suicide gene therapy and antiangiogenic gene therapy. In this review, we explain gene therapy, gene therapy strategies in cancer, approved gene medicines for cancer treatment and future of gene therapy in cancer. Today gene therapy has not yet reached the level of replacing conventional therapies. However, with a better understanding of the mechanism of cancer to determine the right treatment and target, in the future gene therapy, used as monotherapy or in combination with another existing treatment options, is likely to be used as a new medical procedure that will make cancer a controllable disease.
The crime and the place: Robbery in the night‐time economy
Authors: Wüllenweber Sarah , Burrell Amy 
Published: June 2023

AbstractThe night‐time economy (NTE) provides many opportunities for crime as there is an abundance of potential victims who are often intoxicated and clustered in a small geographical area. Previous research on NTE violence has primarily focused on assault. However, other offences are also common, such as robbery. This study focused on NTE‐related robbery using police recorded crime data relating to 1624 personal robberies (including attempts) from West Midlands Police, UK. The data was binary coded to identify and compare offence characteristics. Robbery offences in the NTE showed unique characteristics compared to robberies unrelated to this context. In particular, there were differences in alcohol, use of violence, injuries, approach style and crime locations. The findings of the current research align with theoretical frameworks from environmental criminology (e.g. crime generators and attractors), have implications for crime prevention and investigations and can feed into developing policing strategies that take into account the background context for offending.
Functional Magnetic Resonance Imaging of the Amygdala and Subregions at 3 Tesla: A Scoping Review
Authors: Foster Sheryl L. , Breukelaar Isabella A. , Ekanayake Kanchana , Lewis Sarah , Korgaonkar Mayuresh S. 
Published: June 2023

The amygdalae are a pair of small brain structures, each of which is composed of three main subregions and whose function is implicated in neuropsychiatric conditions. Functional Magnetic Resonance Imaging (fMRI) has been utilized extensively in investigation of amygdala activation and functional connectivity (FC) with most clinical research sites now utilizing 3 Tesla (3T) MR systems. However, accurate imaging and analysis remains challenging not just due to the small size of the amygdala, but also its location deep in the temporal lobe. Selection of imaging parameters can significantly impact data quality with implications for the accuracy of study results and validity of conclusions. Wide variation exists in acquisition protocols with spatial resolution of some protocols suboptimal for accurate assessment of the amygdala as a whole, and for measuring activation and FC of the three main subregions, each of which contains multiple nuclei with specialized roles. The primary objective of this scoping review is to provide a broad overview of 3T fMRI protocols in use to image the activation and FC of the amygdala with particular reference to spatial resolution. The secondary objective is to provide context for a discussion culminating in recommendations for a standardized protocol for imaging activation of the amygdala and its subregions. As the advantages of big data and protocol harmonization in imaging become more apparent so, too, do the disadvantages of data heterogeneity.Evidence Level3Technical EfficacyStage 2