bluuebunny/crossref_metadata_2025 huggingface dataset:
Antimicrobial Activity of Non-steroidal Anti-inflammatory Drugs on Biofilm: Current Evidence and Potential for Drug Repurposing
Authors: Paes Leme Rodrigo Cuiabano , da Silva Raquel Bandeira
Published: July 2021

It has been demonstrated that some non-steroidal anti-inflammatory drugs (NSAIDs), like acetylsalicylic acid, diclofenac, and ibuprofen, have anti-biofilm activity in concentrations found in human pharmacokinetic studies, which could fuel an interest in repurposing these well tolerated drugs as adjunctive therapies for biofilm-related infections. Here we sought to review the currently available data on the anti-biofilm activity of NSAIDs and its relevance in a clinical context. We performed a systematic literature review to identify the most commonly tested NSAIDs drugs in the last 5 years, the bacterial species that have demonstrated to be responsive to their actions, and the emergence of resistance to these molecules. We found that most studies investigating NSAIDs’ activity against biofilms were in vitro, and frequently tested non-clinical bacterial isolates, which may not adequately represent the bacterial populations that cause clinically-relevant biofilm-related infections. Furthermore, studies concerning NSAIDs and antibiotic resistance are scarce, with divergent outcomes. Although the potential to use NSAIDs to control biofilm-related infections seems to be an exciting avenue, there is a paucity of studies that tested these drugs using appropriate in vivo models of biofilm infections or in controlled human clinical trials to support their repurposing as anti-biofilm agents.
Genetic Diversity and Population Structure of Vibrio parahaemolyticus Isolated From Clinical and Food Sources
Authors: He Min , Lei Tao , Jiang Fufeng , Zhang Jumei , Zeng Haiyan , Wang Juan , Chen Moutong , Xue Liang , Wu Shi , Ye Qinghua , Pang Rui , Ding Yu , Wu Qingping
Published: July 2021

Vibrio parahaemolyticus is a common foodborne pathogen that causes gastroenteritis worldwide. Determining its prevalence and genetic diversity will minimize the risk of infection and the associated economic burden. Multilocus sequence typing (MLST) is an important tool for molecular epidemiology and population genetic studies of bacteria. Here, we analyzed the genetic and evolutionary relationships of 162 V. parahaemolyticus strains isolated in the Guangdong Province, China, using MLST. In the study, 120 strains were isolated from food samples, and 42 strains were isolated from clinical samples. All strains were categorized into 100 sequence types (STs), of which 58 were novel (48 from the food isolates and 10 from the clinical isolates). ST415 was the most prevalent ST among the food isolates, while ST3 was the most prevalent ST among the clinical isolates. Further, 12 clonal complexes, 14 doublets, and 73 singletons were identified in all ST clusters, indicating high genetic diversity of the analyzed strains. At the concatenated sequence level, non-synonymous sites in both, food and clinical isolates, were associated with purifying selection. Of note, the dN/dS ration was greater than 1 for some housekeeping genes in all isolates. This is the first time that some loci under positive selection were identified. These observations confirm frequent recombination events in V. parahaemolyticus. Recombination was much more important than mutation for genetic heterogeneity of the food isolates, but the probabilities of recombination and mutations were almost equal for the clinical isolates. Based on the phylogenetic analysis, the clinical isolates were concentrated in the maximum-likelihood tree, while the food isolates were heterogeneously distributed. In conclusion, the food and clinical isolates of V. parahaemolyticus from the Guangdong Province are similar, but show different evolutionary trends. This may help prevent large-scale spread of highly virulent strains and provides a genetic basis for the discovery of microevolutionary relationships in V. parahaemolyticus populations.
Mesenchymal Stromal Cell-Derived Tailored Exosomes Treat Bacteria-Associated Diabetes Foot Ulcers: A Customized Approach From Bench to Bed
Authors: Raghav Alok , Tripathi Prashant , Mishra Brijesh Kumar , Jeong Goo-Bo , Banday Shahid , Gautam Kirti Amresh , Mateen Qazi Noorul , Singh Prem , Singh Manish , Singla Akhil , Ahmad Jamal
Published: July 2021

Exosomes are nano-vesicles of endosomal origin inherited with characteristics of drug delivery and cargo loading. Exosomes offer a diverse range of opportunities that can be exploited in the treatment of various diseases post-functionalization. This membrane engineering is recently being used in the management of bacteria-associated diabetic foot ulcers (DFUs). Diabetes mellitus (DM) is among the most crippling disease of society with a large share of its imposing economic burden. DM in a chronic state is associated with the development of micro- and macrovascular complications. DFU is among the diabetic microvascular complications with the consequent occurrence of diabetic peripheral neuropathy. Mesenchymal stromal cell (MSC)-derived exosomes post-tailoring hold promise to accelerate the diabetic wound repair in DFU associated with bacterial inhabitant. These exosomes promote the antibacterial properties with regenerative activity by loading bioactive molecules like growth factors, nucleic acids, and proteins, and non-bioactive substances like antibiotics. Functionalization of MSC-derived exosomes is mediated by various physical, chemical, and biological processes that effectively load the desired cargo into the exosomes for targeted delivery at specific bacterial DFUs and wound. The present study focused on the application of the cargo-loaded exosomes in the treatment of DFU and also emphasizes the different approaches for loading the desired cargo/drug inside exosomes. However, more studies and clinical trials are needed in the domain to explore this membrane engineering.
Bacterial and Bacteriophage Antibiotic Resistance in Marine Bathing Waters in Relation to Rivers and Urban Streams
Authors: Sala-Comorera Laura , Nolan Tristan M. , Reynolds Liam J. , Venkatesh Anjan , Cheung Lily , Martin Niamh A. , Stephens Jayne H. , Gitto Aurora , O’Hare Gregory M. P. , O’Sullivan John J. , Meijer Wim G.
Published: July 2021

Fecal pollution of surface water may introduce bacteria and bacteriophages harboring antibiotic resistance genes (ARGs) into the aquatic environment. Watercourses discharging into the marine environment, especially close to designated bathing waters, may expose recreational users to fecal pollution and therefore may increase the likelihood that they will be exposed to ARGs. This study compares the bacterial and bacteriophage ARG profiles of two rivers (River Tolka and Liffey) and two small urban streams (Elm Park and Trimleston Streams) that discharge close to two marine bathing waters in Dublin Bay. Despite the potential differences in pollution pressures experienced by these waterways, microbial source tracking analysis showed that the main source of pollution in both rivers and streams in the urban environment is human contamination. All ARGs included in this study, blaTEM, blaSHV, qnrS, and sul1, were present in all four waterways in both the bacterial and bacteriophage fractions, displaying a similar ARG profile. We show that nearshore marine bathing waters are strongly influenced by urban rivers and streams discharging into these, since they shared a similar ARG profile. In comparison to rivers and streams, the levels of bacterial ARGs were significantly reduced in the marine environment. In contrast, the bacteriophage ARG levels in freshwater and the marine were not significantly different. Nearshore marine bathing waters could therefore be a potential reservoir of bacteriophages carrying ARGs. In addition to being considered potential additional fecal indicators organism, bacteriophages may also be viewed as indicators of the spread of antimicrobial resistance.
Mutations in the Two-Component GluS-GluR Regulatory System Confer Resistance to β-Lactam Antibiotics in Burkholderia glumae
Authors: Marunga Joan , Goo Eunhye , Kang Yongsung , Hwang Ingyu
Published: July 2021

Bacteria have specific signaling systems to overcome selective pressure, such as exposure to antibiotics. The two-component system (TCS) plays an important role in the development of antibiotic resistance. Using the rice pathogen Burkholderia glumae BGR1 as a model organism, we showed that the GluS (BGLU_1G13350) – GluR (BGLU_1G13360) TCS, consisting of a sensor kinase and response regulator, respectively, contributes to β-lactam resistance through a distinct mechanism. Inactivation of gluS or gluR conferred resistance to β-lactam antibiotics in B. glumae, whereas wild-type (WT) B. glumae was susceptible to these antibiotics. In gluS and gluR mutants, the expression of genes encoding metallo-β-lactamases (MBLs) and penicillin-binding proteins (PBPs) was significantly higher than in the WT. GluR-His bound to the putative promoter regions of annotated genes encoding MBL (BGLU_1G21360) and PBPs (BGLU_1G13280 and BGLU_1G04560), functioning as a repressor. These results demonstrate that the potential to attain β-lactam resistance may be genetically concealed in the TCS, in contrast to the widely accepted view of the role of TCS in antibiotic resistance. Our findings provide a new perspective on antibiotic resistance mechanisms, and suggest a different therapeutic approach for successful control of bacterial pathogens.
Tissue Multiplex Analyte Detection in Anatomic Pathology – Pathways to Clinical Implementation
Authors: Wharton Keith A. , Wood Douglas , Manesse Mael , Maclean Kirsteen H. , Leiss Florian , Zuraw Aleksandra
Published: July 2021

Background:Multiplex tissue analysis has revolutionized our understanding of the tumor microenvironment (TME) with implications for biomarker development and diagnostic testing. Multiplex labeling is used for specific clinical situations, but there remain barriers to expanded use in anatomic pathology practice.

Methods:We review immunohistochemistry (IHC) and related assays used to localize molecules in tissues, with reference to United States regulatory and practice landscapes. We review multiplex methods and strategies used in clinical diagnosis and in research, particularly in immuno-oncology. Within the framework of assay design and testing phases, we examine the suitability of multiplex immunofluorescence (mIF) for clinical diagnostic workflows, considering its advantages and challenges to implementation.

Results:Multiplex labeling is poised to radically transform pathologic diagnosis because it can answer questions about tissue-level biology and single-cell phenotypes that cannot be addressed with traditional IHC biomarker panels. Widespread implementation will require improved detection chemistry, illustrated by InSituPlex technology (Ultivue, Inc., Cambridge, MA) that allows coregistration of hematoxylin and eosin (H&E) and mIF images, greater standardization and interoperability of workflow and data pipelines to facilitate consistent interpretation by pathologists, and integration of multichannel images into digital pathology whole slide imaging (WSI) systems, including interpretation aided by artificial intelligence (AI). Adoption will also be facilitated by evidence that justifies incorporation into clinical practice, an ability to navigate regulatory pathways, and adequate health care budgets and reimbursement. We expand the brightfield WSI system “pixel pathway” concept to multiplex workflows, suggesting that adoption might be accelerated by data standardization centered on cell phenotypes defined by coexpression of multiple molecules.

Conclusion:Multiplex labeling has the potential to complement next generation sequencing in cancer diagnosis by allowing pathologists to visualize and understand every cell in a tissue biopsy slide. Until mIF reagents, digital pathology systems including fluorescence scanners, and data pipelines are standardized, we propose that diagnostic labs will play a crucial role in driving adoption of multiplex tissue diagnostics by using retrospective data from tissue collections as a foundation for laboratory-developed test (LDT) implementation and use in prospective trials as companion diagnostics (CDx).
Noise-Induced Hearing Loss in Gerbil: Round Window Assays of Synapse Loss
Authors: Jeffers Penelope W. C. , Bourien Jérôme , Diuba Artem , Puel Jean-Luc , Kujawa Sharon G.
Published: July 2021

Previous work in animals with recovered hearing thresholds but permanent inner hair cell synapse loss after noise have suggested initial vulnerability of low spontaneous rate (SR) auditory nerve fibers (ANF). As these fibers have properties of response that facilitate robust sound coding in continuous noise backgrounds, their targeted loss would have important implications for function. To address the issue of relative ANF vulnerabilities after noise, we assessed cochlear physiologic and histologic consequences of temporary threshold shift-producing sound over-exposure in the gerbil, a species with well-characterized distributions of auditory neurons by SR category. The noise exposure targeted a cochlear region with distributed innervation (low-, medium- and high-SR neurons). It produced moderate elevations in outer hair cell-based distortion-product otoacoustic emission and whole nerve compound action potential thresholds in this region, with accompanying reductions in suprathreshold response amplitudes, quantified at 24 h. These parameters of response recovered well with post-exposure time. Chronic synapse loss was maximum in the frequency region initially targeted by the noise. Cochlear round window recorded mass potentials (spontaneous neural noise and sound-driven peri-stimulus time responses, PSTR) reflected parameters of the loss not detected by the conventional assays. Spontaneous activity was acutely reduced. Steady-state (PSTR plateau) activity was correlated with synapse loss in frequency regions with high concentrations of low-SR neurons, whereas the PSTR onset peak and spontaneous round window noise, both dominated by high-SR fiber activity, were relatively unaltered across frequency in chronic ears. Together, results suggest that acute targets of noise were of mixed SR subtypes, but chronic targets were predominantly low-SR neurons. PSTRs captured key properties of the auditory nerve response and vulnerability to injury that should yield important diagnostic information in hearing loss etiologies producing cochlear synaptic and neural loss.
Making the Invisible Visible: Advanced Neuroimaging Techniques in Focal Epilepsy
Authors: Sone Daichi
Published: July 2021

It has been a clinically important, long-standing challenge to accurately localize epileptogenic focus in drug-resistant focal epilepsy because more intensive intervention to the detected focus, including resection neurosurgery, can provide significant seizure reduction. In addition to neurophysiological examinations, neuroimaging plays a crucial role in the detection of focus by providing morphological and neuroanatomical information. On the other hand, epileptogenic lesions in the brain may sometimes show only subtle or even invisible abnormalities on conventional MRI sequences, and thus, efforts have been made for better visualization and improved detection of the focus lesions. Recent advance in neuroimaging has been attracting attention because of the potentials to better visualize the epileptogenic lesions as well as provide novel information about the pathophysiology of epilepsy. While the progress of newer neuroimaging techniques, including the non-Gaussian diffusion model and arterial spin labeling, could non-invasively detect decreased neurite parameters or hypoperfusion within the focus lesions, advances in analytic technology may also provide usefulness for both focus detection and understanding of epilepsy. There has been an increasing number of clinical and experimental applications of machine learning and network analysis in the field of epilepsy. This review article will shed light on recent advances in neuroimaging for focal epilepsy, including both technical progress of images and newer analytical methodologies and discuss about the potential usefulness in clinical practice.
Exosomal miR-125b Exerts Anti-Metastatic Properties and Predicts Early Metastasis of Hepatocellular Carcinoma
Authors: Kim Hye Seon , Kim Jin Seoub , Park Na Ri , Nam Heechul , Sung Pil Soo , Bae Si Hyun , Choi Jong Young , Yoon Seung Kew , Hur Wonhee , Jang Jeong Won
Published: July 2021

Background & Aims

Cancer metastasis is responsible for the majority of cancer-related deaths. Exosomal miRNAs have emerged as promising biomarkers for cancer, serving as signaling molecules that can regulate tumor growth and metastasis. This study examined circulating exosomal miRNAs that could predict hepatocellular carcinoma (HCC) metastasis.

Methods

Exosomal miRNA was measured by quantitative real-time PCR (qRT-PCR) in a large set of patients (n = 284). To investigate the role of exosomal miRNA in HCC, we performed a series of in vitro tests, such as exosome labeling, qRT-PCR, reverse transcription PCR, wound healing assay, transwell assay, and Western blot assay.

Results

Exosomal miR-125b was drastically downregulated in HCC patients with metastasis than in those without metastasis. In vitro, we observed the uptake of miR-125b by exosome in recipient cells. Exosome-mediated miR-125b significantly inhibited migration and invasion abilities and downregulated the mRNA expressions of MMP-2, MMP-9, and MMP-14 in recipient cells via intercellular communication. Further investigation revealed that miR-125b suppressed SMAD2 protein expression in recipient cells by binding to its 3′ untranslated regions. Exosome-mediated miR-125b transfer also disrupted TGF-β1–induced epithelial–mesenchymal transition and TGF-β1/SMAD signaling pathway in recipient cells by leading to a decrease of SMAD2 protein expression. Moreover, exosomal miR-125b was downregulated after metastasis compared with that at baseline in patients with serial measurements before and after metastasis.

Conclusions

The results imply that exosome-mediated miR-125b exerts anti-metastatic properties in HCC. These findings highlight that circulating exosomal miR-125b might represent a reliable biomarker with diagnostic and therapeutic implications for extrahepatic metastasis from HCC.
The COX10-AS1/miR-641/E2F6 Feedback Loop Is Involved in the Progression of Glioma
Authors: Liu Liang , Li Xiaojian , Wu Heming , Tang Yong , Li Xiang , Shi Yan
Published: July 2021

Glioma is the most common primary tumour of the central nervous system and is considered one of the greatest challenges for neurosurgery. Mounting evidence has shown that lncRNAs participate in various biological processes of tumours, including glioma. This study aimed to reveal the role and relevant mechanism of COX10-AS1 in glioma. The expression of COX10-AS1, miR-641 and E2F6 was measured by qRT-PCR and/or western blot. Clone formation assays, EdU assays, Transwell assays and tumour xenograft experiments were performed to evaluate the effects of COX10-AS1, miR-641 and E2F6 on glioma proliferation, migration and invasion. Luciferase reporter assays, RNA pull-down assays and ChIP assays were conducted to analyse the relationship among COX10-AS1, miR-641 and E2F6. We demonstrated that COX10-AS1 was upregulated in glioma tissues and cell lines, which was related to the grade of glioma and patient survival. Next, through functional assays, we found that COX10-AS1 influenced the proliferation, migration and invasion of glioma cell lines. Then, with the help of bioinformatics analysis, we confirmed that COX10-AS1 regulated glioma progress by acting as a sponge of miR-641 to regulate E2F6. Moreover, further study indicated that E2F6 could promote COX10-AS1 expression by binding to its promoter region. Taken together, the data indicated that COX10-AS1 acts as an oncogene in combination with COX10-AS1/miR-641/E2F6 in glioma, which may be beneficial to the diagnosis and treatment of glioma.
Decorin Suppresses Invasion and EMT Phenotype of Glioma by Inducing Autophagy via c-Met/Akt/mTOR Axis
Authors: Jia Yanfei , Feng Qian , Tang Bo , Luo Xiaodong , Yang Qiang , Yang Hu , Li Qiang
Published: July 2021

Decorin exhibits inhibitory effects in tumorigenesis in various types of cancers. The clinical characteristics of 42 patients with GBM were reviewed and analyzed. Lentiviral constructs for decorin overexpression and shRNA-mediated silencing were established for U87MG cells and T98G cells, respectively. The expressions of EMT- and autophagy-associated markers were detected in GBM cell lines. The migration and invasion of the glioma cells were assayed to reflect the malignant behavior of GBM. A mouse xenograft model was used to verify the effect of decorin on autophagy in vivo. Reduced expression of decorin in glioma tissues was associated with a poor survival of the patients. Decorin overexpression suppressed cell migration, invasion and attenuated EMT phenotype in glioma cell lines. Further study indicated that decorin inhibited EMT phenotype through the induction of autophagy. The mechanisms include inhibiting the activation of c-Met/Akt/mTOR signaling and regulating the expressions of mesenchymal markers including Slug, vimentin and Twist, and epithelial marker E-cadherin. In addition, decorin overexpression in a mice model can also suppress the GBM invasion and EMT phenotype. In conclusion, decorin suppresses invasion and EMT phenotype of glioma by inducing autophagy via c-Met/Akt/mTOR axis.
RETRACTED: A Novel Tumor Suppressor Gene, ZNF24, Inhibits the Development of NSCLC by Inhibiting the WNT Signaling Pathway to Induce Cell Senescence
Authors: Pang Bo , Wang Yong , Chang Xiaoyan
Published: July 2021

Objective

Understanding the characteristics of tumor suppressor genes (TSGs) is of great significance for the development of new targeted treatment strategies for non-small cell lung cancer (NSCLC). Therefore, this present article is to explore the underlying molecular mechanism of ZFN24 inhibiting the development of NSCLC.

Methods

We performed RT-PCR and Western blotting for evaluating associated RNA and protein expression. CCK8, colony forming and sphere-forming assays were used to evaluate the proliferation and stemness of NSCLC cells. NSCLC cell senescence was examined by β-galactosidase staining assay. Luciferase assay was performed to evaluate β-catenin transcriptional activity. The effect of ZNF24 on NSCLC cells in vivo was evaluated by the xenograft tumor experiment.

Results

Ectopic expression of ZNF24 significantly inhibited cell viability, colony forming ability, and stemness of NSCLC cells. WNT signaling pathway was inhibited by ZNF24 resulting in NSCLC cell senescence. β-catenin transcriptional activity was significantly inhibited by ZNF24 (P < 0.05). Ectopic expression of ZNF24 significantly inhibited xenotransplant tumors growth in vivo (P < 0.05).

Conclusion

ZNF24 could notably inhibit the development of NSCLC by inhibiting the WNT signaling pathway.
Safety and Benefit Of Sentinel Lymph Nodes Biopsy Compared to Regional Lymph Node Dissection in Primary Vulvar Cancer Patients Without Distant Metastasis and Adjacent Organ Invasion: A Retrospective Population Study
Authors: Zhou Weili , Bai Yang , Yue Yangyang
Published: July 2021

Background

The safety and benefit of sentinel lymph node biopsy (SLNB) compared with regional lymph node dissection (RLND) and no lymph nodes removed (NA) in patients with vulvar squamous cell cancer (VSCC) was not well studied.

Methods

A retrospective analysis on VSCC patients without distant metastasis and adjacent organ invasion from the Surveillance, Epidemiology, and End Results Program database between 2004 and 2016 was carried out. Within subgroups stratified by negative (LN−) or positive (LN+) regional lymph node findings, inverse probability weighting (IPW) adjusted multivariate Fine-Gray compete risk (CR) model and accelerated failure time (AFT) model was used to investigate the factors associated with and cancer-specific survival (CSS) and overall survival (OS).

Results

Of the 3,161 VSCC patients treated with surgery, 287 (9.1%) underwent SLNB, 1,716 (54.3%) underwent RLND, and 1,158 (36.6%) had no regional lymph nodes removed. As illustrated by IPW adjusted multivariate regressions, SLNB was significantly associated with prolonged CSS (LN−, adjusted sub-proportional hazard ratio [sHR] = 0.42; 95% confidence interval [CI], 0.19–0.93; P=0.032; LN+, adjusted sHR = 0.29; 95% CI, 0.16–0.54, P<0.001) and OS (LN−, adjusted time ratio [TR] = 1.38; 95% CI, 0.82–2.32; P=0.226; LN+, adjusted TR = 2.68; 95% CI, 1.73–4.14; P<0.001), although the effect of SLNB on OS was not significant within the LN− cohort. Moreover, SLNB led to improved CSS (adjusted sHR = 0.40; 95% CI, 0.23–0.70; P = 0.001) and OS (adjusted TR=1.15, 95% CI 0.76-1.73, P=0.279) compared with NA. Age was a significant prognostic factor of CSS and OS, whereas tumor size, surgery type, and invasion depth were not.

Conclusions

SLNB leads to significantly prolonged CSS and OS in VSCC surgery patients without distant metastasis and adjacent organ invasion than RLND, except for the similar OS in the LN− cohort. SLNB could be carried out preferentially for VSCC surgery patients without distant metastasis and adjacent organ invasion, irrespective of tumor size, surgery type, invasion depth, and regional lymph nodes metastasis. Further prospective clinical trials are warranted to confirm the findings of this study.
Nomograms of Combining Apparent Diffusion Coefficient Value and Radiomics for Preoperative Risk Evaluation in Endometrial Carcinoma
Authors: Zhang Kaiyue , Zhang Yu , Fang Xin , Fang Mengshi , Shi Bin , Dong Jiangning , Qian Liting
Published: July 2021

Objectives

To evaluate the value of nomogram models combining apparent diffusion coefficient (ADC) value and radiomic features on magnetic resonance imaging (MRI) in predicting the type, grade, deep myometrial invasion (DMI), lymphovascular space invasion (LVSI), and lymph node metastasis (LNM) of endometrial carcinoma (EC) preoperatively.

Methods

This study included 210 EC patients. ADC value was calculated, and radiomic features were measured on T2-weighted images. The univariate and multivariate logistic regressions and cross-validations were performed to reduce valueless features, then radiomics signatures were developed. Nomogram models using ADC combined with radiomic features were developed in the training cohort. The receiver operating characteristic (ROC) curve was performed to estimate the diagnostic efficiency of nomogram models by the area under the curve (AUC) in the training and validation cohorts.

Results

The ADC value was significantly different between each subgroup. Radiomic features were ultimately limited to four features for type, six features for grade, six features for DMI, four features for LVSI, and eight features for LNM for the nomogram models. The AUC of the nomogram model combining ADC value and radiomic features in the training and validation cohorts was 0.851 and 0.867 for type, 0.959 and 0.880 for grade, 0.839 and 0.766 for DMI, 0.816 and 0.746 for LVSI, and 0.910 and 0.897 for LNM.

Conclusions

The nomogram models of ADC value combined with radiomic features were associated with the type, grade, DMI, LVSI, and LNM of EC, and provide an effective, non-invasive method to evaluate preoperative risk stratification for EC.
Helicobacter pylori Infection–Related Long Non-Coding RNA Signatures Predict the Prognostic Status for Gastric Cancer Patients
Authors: Xin Zhuoyuan , Zhang Luping , Liu Mingqing , Wang Yachen , Zhang Yingli , Zhao Weidan , Sun Yongxiao , Shi Lei , Xu Na , Zhang Nan , Xu Hong
Published: July 2021

Background

Helicobacter pylori (H. pylori) is a type I biological carcinogen, which may cause about 75% of the total incidence of gastric cancer worldwide. H. pylori infection can induce and activate the cancer-promoting signaling pathway and affect the occurrence and outcome of gastric cancer through controlling the regulatory functions of long non-coding RNAs (lncRNAs). However, we have no understanding of the prognostic worth of lncRNAs for gastric cancer patients infected with H. pylori.

Method

We screened differentially expressed lncRNAs using DESeq2 method among TCGA database. And we built the H. pylori infection-related lncRNAs regulatory patterns. Then, we constructed H. pylori infection-based lncRNAs prognostic signatures for gastric cancer patients together with H. pylori infection, via uni-variable and multi-variable COX regression analyses. Based on receiver operator characteristic curve (ROC) analysis, we evaluated the prediction effectiveness for this model.

Results

We identified 115 H. pylori infection–related genes were differentially expressed among H. pylori–infected gastric cancer tissues versus gastric cancer tissues. Functional enrichment analysis implies that H. pylori infection might interfere with the immune-related pathways among gastric cancer tissues. Then, we built H. pylori infection–related dys-regulated lncRNA regulatory networks. We also identified 13 differentially expressed lncRNAs were associated with prognosis for gastric cancer patients together with H. pylori infection. Kaplan-Meier analysis demonstrated that the lncRNA signatures were correlated with the poor prognosis. What is more, the AUC of the lncRNA signatures was 0.712. Also, this prognostic prediction model was superior to the traditional clinical characters.

Conclusion

We successfully constructed a H. pylori–related lncRNA risk signature and nomogram associated with H. pylori–infected gastric cancer patients prognosis, and the signature and nomogram can predict the prognosis of these patients.
Fractalkine/CX3CR1 Pathway in Neuropathic Pain: An Update
Authors: Silva Rita , Malcangio Marzia
Published: July 2021

Injuries to the nervous system can result in a debilitating neuropathic pain state that is often resistant to treatment with available analgesics, which are commonly associated with several side-effects. Growing pre-clinical and clinical evidence over the last two decades indicates that immune cell-mediated mechanisms both in the periphery and in the Central Nervous System (CNS) play significant roles in the establishment and maintenance of neuropathic pain. Specifically, following peripheral nerve injury, microglia, which are CNS resident immune cells, respond to the activity of the first pain synapse in the dorsal horn of spinal cord and also to neuronal activity in higher centres in the brain. This microglial response leads to the production and release of several proinflammatory mediators which contribute to neuronal sensitisation under neuropathic pain states. In this review, we collect evidence demonstrating the critical role played by the Fractalkine/CX3CR1 signalling pathway in neuron-to-microglia communication in neuropathic pain states and explore how strategies that include components of this pathway offer opportunities for innovative targets for neuropathic pain.
Anti-inflammatory and Pro-apoptotic Effects of 18beta-Glycyrrhetinic Acid In Vitro and In Vivo Models of Rheumatoid Arthritis
Authors: Feng Yunhui , Mei Liyan , Wang Maojie , Huang Qingchun , Huang Runyue
Published: July 2021

18β-Glycyrrhetinic acid (18β-GA), an active component from Glycyrrhiza glabra L. root (licorice), has been demonstrated to be able to protect against inflammatory response and reduce methotrexate (MTX)-derived toxicity. This study was therefore designed to test the therapeutic possibility of 18β-GA on rheumatoid arthritis (RA) and to explore the underlying mechanism. LPS or TNF-α-induced inflammatory cell models and collagen-induced arthritis (CIA) animal models were applied in this study. Real-time quantitative PCR (RT-qPCR) was used to measure the mRNA levels of various cytokines and FOXO family members. The protein levels of molecules in the MAPK/NF-κB signaling pathway were analyzed using western blot. The cell proliferation assay and colony-forming assay were used to test the influence of 18β-GA on cell viability. The cell apoptosis assay and cell cycle assay were performed to detect the effect of 18β-GA on cell proliferative capacity by using flow cytometry. Hematoxylin and eosin (H&E) staining was performed to evaluate pathological changes after drug administration. The enzyme-linked immunosorbent assay (ELISA) was carried out for the detection of cytokines in serum. In vitro, we found that 18β-GA decreased the mRNA levels of IL-1β, IL-6, and COX-2 by inhibiting the MAPK/NF-κB signaling pathway in MH7A and RAW264.7 cell lines. Moreover, 18β-GA was able to suppress cell viability, trigger cell apoptosis, and G1 phase cell cycle arrest in our in vitro studies. 18β-GA dramatically enhanced the mRNA level of FOXO3 in both TNF-α- and LPS-induced inflammation models in vitro. Interestingly, after analyzing GEO datasets, we found that the FOXO3 gene was significantly decreased in the RA synovial tissue as compared to healthy donors in multiple microarray studies. In vivo, 18β-GA exhibited a promising therapeutic effect in a collagen-induced arthritis mouse model by alleviating joint pathological changes and declining serum levels of TNF-α, IL-1β, and IL-6. Finally, we observed that 18β-GA administration could mitigate liver damage caused by collagen or MTX. Collectively, the current study demonstrates for the first time that 18β-GA can inhibit inflammation and proliferation of synovial cells, and the underlying mechanism may be associated with its inhibition of MAPK/NF-κB signaling and promotion of FOXO3 signaling. Therefore, 18β-GA is expected to be a new drug candidate for RA therapy.
Circular RNAs in the Regulation of Oxidative Stress
Authors: Zhang Yao , Chen Yu , Wan Yue , Zhao Yueshui , Wen Qinglian , Tang Xiaolong , Shen Jing , Wu Xu , Li Mingxing , Li Xiang , Li Jing , Li Wanping , Xiao Zhangang , Du Fukuan
Published: July 2021

Oxidative stress caused by an imbalance between the production and elimination of reactive metabolites and free radicals can lead to the development of a variety of diseases. Over the past years, with the development of science and technology, circular RNA (circRNA) has been found to be closely associated with oxidative stress, which plays an important role in the process of oxidative stress. Currently, the understanding of circRNAs in the mechanism of oxidative stress is limited. In this review, we described the relationship between oxidative stress and circRNAs, the circRNAs related to oxidative stress, and the role of circRNAs in promoting or inhibiting the occurrence and development of diseases associated with the oxidative stress system.
Herbal Medicine for Behavioral and Psychological Symptoms of Dementia: A Systematic Review and Meta-Analysis
Authors: Kwon Chan-Young , Lee Boram
Published: July 2021

Background: Dementia is a global health concern, causing serious health and socioeconomic burdens with population aging. The associated symptoms of dementia, called behavioral and psychological symptoms of dementia (BPSD), are factors contributing to the socioeconomic burden of dementia. Recently, herbal medicine (HM) has attracted attention as a potential complementary therapy for BPSD. Therefore, this systematic review was aimed at analyzing the effectiveness (or efficacy), safety, and research status of HM in BPSD management through a comprehensive review.

Methods: Thirteen electronic databases were searched comprehensively. Related clinical studies published until December 28, 2020, were collected. The methodological quality was evaluated using tools such as the Cochrane Collaboration’s risk of bias tool according to the study design. The effectiveness (or efficacy) was analyzed for randomized controlled trials (RCTs) only, and when sufficient homogeneity was assured, effect estimates were presented as mean difference (MD) and risk ratio (RR), with 95% confidence interval (CIs), through a meta-analysis.

Results: A total of 52 clinical studies, including 36 RCTs, were included in this review. As an adjunctive therapy, HM showed statistically significant benefits in BPSD severity assessed by the Behavior Pathology in Alzheimer’s Disease Rating Scale (combined with psychotropic drugs: MD = −3.48, 95% CI: −3.96 to −2.99; with anti-dementia drugs: MD = −2.81, 95% CI: −3.17 to −2.45) and Neuropsychiatric Inventory (with anti-dementia drugs: MD = −3.23, 95% CI: −4.06 to −2.40). Adverse events were significantly less frequent in the HM group (RR = 0.50; 95% CI: 0.28 to 0.88). However, the methodological quality of the RCTs included in this systematic review was not optimal overall.

Conclusion: According to the findings of this review, HM may be associated with additional benefits in BPSD treatment, particularly when used as an adjunct to conventional medications, including psychotropic and anti-dementia drugs. However, considering the methodological quality of the included RCTs, this clinical evidence is not robust. Nevertheless, dementia is a global health concern, and considering the limitations of conventional psychotropic drugs for BPSD, a major cause of the disease burden, HM appears to be a promising complementary therapy that warrants further research.
Assessment of Lentiviral Vector Mediated CFTR Correction in Mice Using an Improved Rapid in vivo Nasal Potential Difference Measurement Protocol
Authors: Cmielewski P. , Delhove J. , Donnelley M. , Parsons D.
Published: July 2021

Cystic Fibrosis (CF) is caused by a defect in the CF transmembrane conductance regulator (CFTR) gene responsible for epithelial ion transport. Nasal potential difference (PD) measurement is a well established diagnostic technique for assessing the efficacy of therapies in CF patients and animal models. The aim was to establish a rapid nasal PD protocol in mice and quantify the efficacy of lentiviral (LV) vector-based CFTR gene therapy. Anaesthetised wild-type (WT) and CF mice were non-surgically intubated and nasal PD measurements were made using a range of buffer flow rates. Addition of the cAMP agonist, isoproterenol, to the buffer sequence was then examined. The optimised rapid PD technique was then used to assess CFTR function produced by second and third generation LV-CFTR vectors. V5 epitope tagged-CFTR in nasal tissue was identified by immunohistochemistry. When intubated, mice tolerated higher flow rates. Isoproterenol could discriminate between WT and CF mice. Improved chloride transport was observed for the second and third generation LV-CFTR vectors, with up to 60% correction of the cAMP-driven chloride response towards WT. V5-CFTR was located in ciliated epithelial cells. The rapid PD technique enables improved functional assessment of the bioelectrical ion transport defect for both current and potential CF therapies.
Extracellular Fragmented Self-DNA Is Involved in Plant Responses to Biotic Stress
Authors: Barbero Francesca , Guglielmotto Michela , Islam Monirul , Maffei Massimo E.
Published: July 2021

A growing body of evidence indicates that extracellular fragmented self-DNA (eDNA), by acting as a signaling molecule, triggers inhibitory effects on conspecific plants and functions as a damage-associated molecular pattern (DAMP). To evaluate early and late events in DAMP-dependent responses to eDNA, we extracted, fragmented, and applied the tomato (Solanum lycopersicum) eDNA to tomato leaves. Non-sonicated, intact self-DNA (intact DNA) was used as control. Early event analyses included the evaluation of plasma transmembrane potentials (Vm), cytosolic calcium variations (Ca2+cyt), the activity and subcellular localization of both voltage-gated and ligand-gated rectified K+ channels, and the reactive oxygen species (ROS) subcellular localization and quantification. Late events included RNA-Seq transcriptomic analysis and qPCR validation of gene expression of tomato leaves exposed to tomato eDNA. Application of eDNA induced a concentration-dependent Vm depolarization which was correlated to an increase in (Ca2+)cyt; this event was associated to the opening of K+ channels, with particular action on ligand-gated rectified K+ channels. Both eDNA-dependent (Ca2+)cyt and K+ increases were correlated to ROS production. In contrast, application of intact DNA produced no effects. The plant response to eDNA was the modulation of the expression of genes involved in plant–biotic interactions including pathogenesis-related proteins (PRPs), calcium-dependent protein kinases (CPK1), heat shock transcription factors (Hsf), heat shock proteins (Hsp), receptor-like kinases (RLKs), and ethylene-responsive factors (ERFs). Several genes involved in calcium signaling, ROS scavenging and ion homeostasis were also modulated by application of eDNA. Shared elements among the transcriptional response to eDNA and to biotic stress indicate that eDNA might be a common DAMP that triggers plant responses to pathogens and herbivores, particularly to those that intensive plant cell disruption or cell death. Our results suggest the intriguing hypothesis that some of the plant reactions to pathogens and herbivores might be due to DNA degradation, especially when associated to the plant cell disruption. Fragmented DNA would then become an important and powerful elicitor able to trigger early and late responses to biotic stress.
Nitrogen Supply Alters Rice Defense Against the Striped Stem Borer Chilo suppressalis
Authors: Zheng Yueqin , Zhang Xiyong , Liu Xin , Qin Ningning , Xu Kaifang , Zeng Rensen , Liu Jian , Song Yuanyuan
Published: July 2021

Plant nutrition status is closely associated with plant defense against insect herbivores. However, the way nitrogen supply regulates rice anti-herbivore is not clear. This study investigated the effects of low (LN, 0.3 mM) and high (HN, 3 mM) nitrate levels on rice resistance against the striped stem borer Chilo suppressalis (SSB), one of the major destructive rice pests. Seven-day-old rice seedlings were cultured with different nitrate levels for 30 days and then inoculated with third instars of SSB. LN significantly enhanced rice anti-herbivore defense and lowered the total nitrogen content in the plants, but increased the content of free amino acids after SSB infestation. Additionally, LN significantly increased the accumulation of phenolic acids and flavonoids, especially lignin, resulting in enhanced constitutive defense in SSB-infested plants. SSB feeding led to a rapid accumulation of secondary metabolites. HN application led to the accumulation of metabolites derived from cinnamic acid, p-coumaric acid, p-coumaric CoA, feruloyl CoA, and apigenin, while LN led to the accumulation of metabolites derived from 3-dehydroquinic acid, phenylalanine, acetyl CoA, and aspartic acid. Collectively, our finding suggests that nitrogen deficiency enhances rice anti-herbivore defense via constitutive defense by the accumulation of phenolic acids and flavonoids.
Sequential Deposition and Remodeling of Cell Wall Polymers During Tomato Pollen Development
Authors: Jaffri Syeda Roop Fatima , MacAlister Cora A.
Published: July 2021

The cell wall of a mature pollen grain is a highly specialized, multilayered structure. The outer, sporopollenin-based exine provides protection and support to the pollen grain, while the inner intine, composed primarily of cellulose, is important for pollen germination. The formation of the mature pollen grain wall takes place within the anther with contributions of cell wall material from both the developing pollen grain as well as the surrounding cells of the tapetum. The process of wall development is complex; multiple cell wall polymers are deposited, some transiently, in a controlled sequence of events. Tomato (Solanum lycopersicum) is an important agricultural crop, which requires successful fertilization for fruit production as do many other members of the Solanaceae family. Despite the importance of pollen development for tomato, little is known about the detailed pollen gain wall developmental process. Here, we describe the structure of the tomato pollen wall and establish a developmental timeline of its formation. Mature tomato pollen is released from the anther in a dehydrated state and is tricolpate, with three long apertures without overlaying exine from which the pollen tube may emerge. Using histology and immunostaining, we determined the order in which key cell wall polymers were deposited with respect to overall pollen and anther development. Pollen development began in young flower buds when the premeiotic microspore mother cells (MMCs) began losing their cellulose primary cell wall. Following meiosis, the still conjoined microspores progressed to the tetrad stage characterized by a temporary, thick callose wall. Breakdown of the callose wall released the individual early microspores. Exine deposition began with the secretion of the sporopollenin foot layer. At the late microspore stage, exine deposition was completed and the tapetum degenerated. The pollen underwent mitosis to produce bicellular pollen; at which point, intine formation began, continuing through to pollen maturation. The entire cell wall development process was also punctuated by dynamic changes in pectin composition, particularly changes in methyl-esterified and de-methyl-esterified homogalacturonan.
Differential Item Functioning Among English Language Learners on a Large-Scale Mathematics Assessment
Authors: Liu Ruixue , Bradley Kelly D.
Published: July 2021

The current study research showed the nature and potential sources of the gaps in mathematics achievement between English language learners (ELLs) and non-English language learners (non-ELLs). The nature of achievement gap was examined using three DIF methodologies: including Mantel-Haenszel procedure, Rasch model, and Hierarchical Generalized Linear Model (HGLM). These were conducted at the item level in contrast to total test level. Results revealed that the three DIF approaches identified 10 common items. These 10 items demonstrated in favor of non-ELLs. Findings from this study will help educational researchers, administrators, and policymakers understand the nature of the achievement gap in mathematics at item level so that United States can be competitive in middle school mathematics education. This study also suggested that item writers and test developers should construct assessments where language is equally accessible for ELL students.