bluuebunny/crossref_metadata_2025 huggingface dataset:
Expression of substance P, calcitonin gene-related peptide and vascular endothelial growth factor in human dental pulp under different clinical stimuli
Authors: Caviedes-Bucheli Javier , Lopez-Moncayo Luis Fernando , Muñoz-Alvear Hernan Dario , Gomez-Sosa Jose Francisco , Diaz-Barrera Luis Eduardo , Curtidor Hernando , Munoz Hugo Roberto
Published: March 2021

Background

The aim of this study was to measure the dental pulp inflammatory response through neuropeptides (SP and CGRP) as a response to occlusal trauma, orthodontic movements and a combination of both, as well as the angiogenic defense mechanism through VEGF expression, which could be the initial step to mineralized tissue formation.

Methods

Forty human dental pulp samples were collected from healthy first premolars with extraction indicated due to orthodontic reasons from a sample of 20 patients. Patients were divided into four groups with 10 premolars each (1 mandibular and 1 maxillary premolar from each patient): healthy pulp control group, occlusal trauma group, moderate orthodontic forces group; and occlusal trauma plus moderate orthodontic forces group. Stimuli were applied for 24 h before tooth extraction in all experimental groups. All samples were processed, and SP, CGRP, and VEGF were measured by radioimmunoassay. The Kruskal–Wallis test was performed to assess significant differences among groups and Mann–Whitney’s U post hoc pairwise comparisons were also performed.

Results

The highest increase in SP, CGRP, and VEGF expressions was found in the occlusal trauma plus orthodontic forces group, followed by the moderate orthodontic forces, the occlusal trauma and the control groups, with statistically significant differences between all groups for each of the 3 peptides analyzed (Kruskal–Wallis p < 0.001). All possible pairwise post-hoc comparisons were also significant for each peptide analyzed (Mann–Whitney’s U p < 0.001).

Conclusion

SP, CGRP, and VEGF expressions significantly increase in human dental pulps when stimulated by occlusal trauma combined with moderate orthodontic forces, as compared with these two stimuli applied independently.

Name of the registry: Importance of Neurogenic Inflammation in the Angiogenic Response of the Dental Pulp as a Defensive Response.

Trial registration number: NCT03804034.

Date of registration: 01/15/2019 Retrospectively registered.

URL of trial registry record: https://clinicaltrials.gov/ct2/show/NCT03804034?term=NCT03804034&draw=2&rank=1.
Extracts of endophytic fungi from leaves of selected Nigerian ethnomedicinal plants exhibited antioxidant activity
Authors: Ibrahim Mutiat , Oyebanji Elizabeth , Fowora Muinah , Aiyeolemi Ayobami , Orabuchi Chiamaka , Akinnawo Babajide , Adekunle Adedotun A.
Published: March 2021

Background

Plants with an ethnobotanical history are known to harbor diverse group of endophytic fungi, which constitute major natural sources of bioactive compounds. In the present study, we evaluated the antioxidant activity of endophytic fungi from eight Nigerian ethnomedicinal plants. Endophytic fungi were isolated from the leaves of Acalypha ornata, Albizia zygia, Alchornea cordifolia, Chrysophyllum albidum, Ficus exasperata, Gomphrena celosioides, Millettia thonningii, and Newbouldia laevis.

Methods

Endophytic fungi were isolated from the leaves of selected plants via surface sterilization. Isolated fungi were identified by internal transcribed spacer (ITS-rDNA) sequence analysis. Pure fungal strains were subjected to fermentation process on solid rice medium and metabolites extracted using ethyl-acetate. Fungal crude extracts were screened for antioxidant activity using 2, 2- diphenyl-1-picrylhydrazyl (DPPH) radical scavenging and reduction of ferric ion assays. Gas chromatography/mass spectrometry (GC/MS) analysis was used to identify the major chemical constituents in active fungal extracts.

Results

A total of eighteen fungal endophytes with fungal codes CU (061 and 062); ZA (161, 162, 163, and 164); LO (261); CA (041, 042, and 043); FE (081, 082, and 084); GE (091); MO (211 and 212); and NA (021 and 022) were isolated from the eight ethnomedicinal plants A. ornata, A. zygia, A. cordifolia, C. albidum, F. exasperata, G. celosioides, M. thonningii, and N. laevis respectively. ZA 163 and MO 211 fungal extracts showed significant (p < 0.05) radical scavenging activity with IC50 values of 50.53 ± 0.01 and 86.69 ± 0.02 μg/ml respectively. Fungal extract CA 041 demonstrated significantly (p < 0.01) higher iron chelating activity than standard gallic acid with absorbance values of 0.803 and 1.107 at 250 and 500 μg/ml concentrations respectively. Pyrogallol, phenol, 2,6-dimethoxy-, phytol, dl-alpha-tocopherol, alpha-tocospiro, oleamide, methyl stearate, oleic acid, palmitic acid, campesterol, stigmasterol, β-sitosterol, urs-12-en-24-oic acid, 3-oxo-, methyl ester, lup-20(29)-en-3-one, and lupeol were detected in the selected active extracts.

Conclusion

These results showed that leaves of the selected Nigerian plants harbor diverse group of endophytic fungi, which can be potential antioxidant resource.

Graphical abstract
Evaluation and revision of core postoperative nursing outcomes for laryngeal carcinoma in China
Authors: Ding Yong-Xia , Yang Hui , Sun Ya-Xuan , Xu Jinxia , Jing Li , Ning Yan , Wang Bin-Quan
Published: March 2021

Background

The core nursing outcomes for laryngeal carcinoma in China needed further screening and revision. This study aimed to evaluate and revise a questionnaire according to the “Core Nursing Outcomes for Otorhinolaryngology Head-Neck” of the Nursing Outcomes Classification (NOC, 5th Edition), and determine suitable postoperative nursing outcomes for patients with laryngeal carcinoma in China.

Methods

The commonly used postoperative nursing outcomes for laryngeal carcinoma were screened using a questionnaire given to 93 nurses. An initial expert consultation questionnaire was constructed to discuss the indicators for each nursing outcome. A total of 20 experts were identified using the Delphi method, and their recommendations and revisions on the selected nursing outcomes were collected.

Results

A total of 14 postoperative core nursing outcomes and 69 indicators were identified for postoperative patients with laryngeal carcinoma, which are subordinate to 4 domains of the NOC: “Physiologic Health”, “Psychosocial Health”, “Health Knowledge & Behavior”, and “Perceived Health”.

Conclusions

The screening and revision of the NOC outcomes and indicators of the Delphi method could be applied to assess the effect of nursing intervention and the quality of the nursing service in China.
“Without the need for a second visit” initiative improves patient satisfaction with updated services of outpatient clinics in China
Authors: Shen Jian , Zhang Jun , He Qiang , Pan Haihui , Wu Zhiqiang , Nie Liangming , Zhang Hongfang , Liu Shuning , Sun Yan , Du Yaoqiang , Huang Dongsheng
Published: March 2021

Background

To implement the “without the need for a second visit” (WNASV) initiative in our hospital by optimizing the outpatient clinic services via an upgraded information system, in order to increase the quality of outpatient medical services and improve patients’ satisfaction.

Methods

An Internet-based care delivery approach was developed and applied to improve the delivery of health care services, simplify the treatment process, and reduce patient waiting time. The patient waiting time and consultation time in the outpatient clinics of our hospital during the peak service intervals and the proportions of various payment methods for outpatient services during the period from May 2017 to September 2019 were retrospectively analyzed. Also, the patients’ satisfaction with the outpatient process was surveyed.

Results

The waiting time for consultation was shortened from 32.25 min to 28.42 min; the consultation time was shortened from 6.52 min to 3.15 min; and the waiting time for payment decreased from 7.40 min to 4.31 min. The proportion of payment via a counter was reduced from 86.80 to 21.79%, the proportion of self-service payment increased from 9.99 to 16.05%, and the proportion of payment during a consultation increased from 3.21 to 61.91%. The scores of the patients’ satisfaction with the outpatient services increased from an average of 89.10 points in 2017 to an average of 90.26 points in 2019.

Conclusion

The continuous improvement of the service process markedly increases the efficiency of the outpatient services, and effectively improves patient’s satisfaction with the outpatient process, this initiative thus deserves further application.
Knockdown of GTF2E2 inhibits the growth and progression of lung adenocarcinoma via RPS4X in vitro and in vivo
Authors: Bi Guoshu , Zhu Donglin , Bian Yunyi , Huang Yiwei , Zhan Cheng , Yang Yong , Wang Qun
Published: March 2021

Background

Lung adenocarcinoma (LUAD) is one of the most common malignancies worldwide. However, the molecular mechanism of LUAD tumorigenesis and development remains unclear. The purpose of this study was to comprehensively illustrate the role of GTF2E2 in the growth and progression of LUAD.

Methods and materials

We obtained the mRNA expression data from The Cancer Genome Atlas, Gene Expression Omnibus database, and our institution. Systematic bioinformatical analyses were performed to investigate the expression and prognostic value of GTF2E2 in LUAD. The results were validated by immunohistochemistry and qPCR. The effect of knocking down GTF2E2 using two short hairpin RNAs was investigated by in vitro and in vivo assays. Subsequently, shotgun liquid chromatography coupled with tandem mass spectrometry (LC–MS/MS) analyses were applied to identified potential GTF2E2 interacting proteins, and the downstream molecular mechanisms of GTF2E2-signaling were further explored by a series of cellular functional assays.

Results

We found that GTF2E2 expression was significantly increased in LUAD tissue compared with adjacent normal tissue and was negatively associated with patients’ overall survival. Besides, we demonstrated that GTF2E2 knockdown inhibited LUAD cell proliferation, migration, invasion, and promote apoptosis in vitro, as well as attenuated tumor growth in vivo. Results from LC–MS/MS suggested that RPS4X might physically interact with GTF2E2 and mediated GTF2E2’s regulatory effect on LUAD development through the mTOR pathway.

Conclusion

Our findings indicate that GTF2E2 promotes LUAD development by activating RPS4X. Therefore, GTF2E2 might serve as a promising biomarker for the diagnosis and prognosis of LUAD patients, thus shedding light on the precise and personalized therapy for LUAD in the future.
Rolling out the radical cure for vivax malaria in Asia: a qualitative study among policy makers and stakeholders
Authors: Adhikari Bipin , Awab Ghulam Rhahim , von Seidlein Lorenz
Published: March 2021

Background

Wide-spread implementation of treatment regimens for the radical cure of vivax malaria is hindered by a range of factors. This has resulted in an increase in the relative proportion of vivax malaria and is an important obstacle in the achievement of global malaria elimination by 2030. The main objective of this study was to explore the current policies guiding the treatment plans on vivax malaria, and the factors affecting the implementation of radical cure in South/South East Asian and Asian Pacific countries.

Methods

This was a qualitative study among respondents who represented national malaria control programmes (NMCPs) or had a role and influence in the national malaria policies. 33 respondents from 17 countries in South/South East Asia and Asia Pacific participated in interviews between October 15 and December 15, 2020. Semi-structured interviews were conducted virtually except for two face to face interviews and audio-recorded. Transcribed audio-records underwent thematic analysis using QSR NVivo.

Results

Policies against vivax malaria were underprioritized, compared with the focus on falciparum malaria and, in particular, drug resistant Plasmodium falciparum strains. Despite the familiarity with primaquine (PQ) as the essential treatment to achieve the radical cure, the respondents contested the need for G6PD testing. Optional G6PD testing was reported to have poor adherence. The fear of adverse events led health workers to hesitate prescribing PQ. In countries where G6PD was mandatory, respondents experienced frequent stockouts of G6PD rapid diagnostic kits in peripheral health facilities, which was compounded by a short shelf life of these tests. These challenges were echoed across participating countries to various degrees. Most respondents agreed that a shorter treatment regimen, such as single dose tafenoquine could resolve these problems but mandatory G6PD testing will be needed. The recommendation of shorter regimens including tafenoquine or high dose PQ requires operational evidence demonstrating the robust performance of point of care G6PD tests (biosensors).

Conclusion

There was sparse implementation and low adherence to the radical cure in South/South East Asian and Asian pacific countries. Shorter treatment regimens with appropriate point of care quantitative G6PD tests may resolve the current challenges. Operational evidence on point of care quantitative G6PD tests that includes the feasibility of integrating such tests into the radical cure regimen are critical to ensure its implementation.
Evaluation of lung involvement in COVID-19 pneumonia based on ultrasound images
Authors: Hu Zhaoyu , Liu Zhenhua , Dong Yijie , Liu Jianjian , Huang Bin , Liu Aihua , Huang Jingjing , Pu Xujuan , Shi Xia , Yu Jinhua , Xiao Yang , Zhang Hui , Zhou Jianqiao
Published: March 2021

Background

Lung ultrasound (LUS) can be an important imaging tool for the diagnosis and assessment of lung involvement. Ultrasound sonograms have been confirmed to illustrate damage to a person’s lungs, which means that the correct classification and scoring of a patient’s sonogram can be used to assess lung involvement.

Methods

The purpose of this study was to establish a lung involvement assessment model based on deep learning. A novel multimodal channel and receptive field attention network combined with ResNeXt (MCRFNet) was proposed to classify sonograms, and the network can automatically fuse shallow features and determine the importance of different channels and respective fields. Finally, sonogram classes were transformed into scores to evaluate lung involvement from the initial diagnosis to rehabilitation.

Results and conclusion

Using multicenter and multimodal ultrasound data from 104 patients, the diagnostic model achieved 94.39% accuracy, 82.28% precision, 76.27% sensitivity, and 96.44% specificity. The lung involvement severity and the trend of COVID-19 pneumonia were evaluated quantitatively.
How home anterior self-collected nasal swab simplifies SARS-CoV-2 testing: new surveillance horizons in public health and beyond
Authors: Ricci Silvia , Lodi Lorenzo , Citera Francesco , Nieddu Francesco , Moriondo Maria , Guarnieri Valentina , Giovannini Mattia , Indolfi Giuseppe , Resti Massimo , Zanobini Alberto , Azzari Chiara
Published: March 2021

The sample collection procedure for SARS-CoV-2 has a strong impact on diagnostic capability, contact tracing approach, ultimately affecting the infection containment performance. This study demonstrates that self-collected nasal-swab has shown to be a valid and well tolerated procedure to SARS-CoV-2 surveillance in a healthcare system. More significantly, no performance adequacy difference was detected in self-administered swabs between healthcare worker (HCW) and non-HCW which allows to speculate that this procedure could be successfully extended to the entire population for mass screening.
Neural crest cell-derived pericytes act as pro-angiogenic cells in human neocortex development and gliomas
Authors: Girolamo Francesco , de Trizio Ignazio , Errede Mariella , Longo Giovanna , d’Amati Antonio , Virgintino Daniela
Published: March 2021

Central nervous system diseases involving the parenchymal microvessels are frequently associated with a ‘microvasculopathy’, which includes different levels of neurovascular unit (NVU) dysfunction, including blood–brain barrier alterations. To contribute to the understanding of NVU responses to pathological noxae, we have focused on one of its cellular components, the microvascular pericytes, highlighting unique features of brain pericytes with the aid of the analyses carried out during vascularization of human developing neocortex and in human gliomas. Thanks to their position, centred within the endothelial/glial partition of the vessel basal lamina and therefore inserted between endothelial cells and the perivascular and vessel-associated components (astrocytes, oligodendrocyte precursor cells (OPCs)/NG2-glia, microglia, macrophages, nerve terminals), pericytes fulfil a central role within the microvessel NVU. Indeed, at this critical site, pericytes have a number of direct and extracellular matrix molecule- and soluble factor-mediated functions, displaying marked phenotypical and functional heterogeneity and carrying out multitasking services. This pericytes heterogeneity is primarily linked to their position in specific tissue and organ microenvironments and, most importantly, to their ontogeny. During ontogenesis, pericyte subtypes belong to two main embryonic germ layers, mesoderm and (neuro)ectoderm, and are therefore expected to be found in organs ontogenetically different, nonetheless, pericytes of different origin may converge and colonize neighbouring areas of the same organ/apparatus. Here, we provide a brief overview of the unusual roles played by forebrain pericytes in the processes of angiogenesis and barriergenesis by virtue of their origin from midbrain neural crest stem cells. A better knowledge of the ontogenetic subpopulations may support the understanding of specific interactions and mechanisms involved in pericyte function/dysfunction, including normal and pathological angiogenesis, thereby offering an alternative perspective on cell subtype-specific therapeutic approaches.
Ethnozoological and commercial drivers of the pangolin trade in Benin
Authors: Zanvo Stanislas , Djagoun Sylvestre C. A. M. , Azihou Fortuné A. , Djossa Bruno , Sinsin Brice , Gaubert Philippe
Published: March 2021

Background

Pangolins are trafficked in unsustainable volumes to feed both local and global trade networks for their meat and the medicinal properties of their derivatives, including scales. We focus on a West African country (Benin) to assess the medicinal and spiritual values of pangolins among different ethnic groups and identify the cohort of buyers involved in the pangolin trade and related economic values along the chain, notably from local diasporas.

Methods

We organised 54 focus groups in villages surrounding occurrence habitats of pangolins across Benin and conducted 35 individual interviews with vendors from five major traditional medicine markets (TMMs). Our questionnaire addressed the different uses of pangolins, the commercial value of pangolin items, the categories of clients and the related selling prices.

Results

Pangolin meat was strictly consumed as food. Scales, head, bones, tongue, blood, heart and xiphisternum were the items used by local communities as part of medicinal (65% of the focus groups) and spiritual (37%) practices. Scales were the most frequently used item (use value index = 1.56). A total of 42 medicinal and spiritual uses, covering 15 International Classification of Diseases (ICD) categories, were recorded among ethnic groups. The ICD and spiritual categories-based analyses of similarity showed a partial overlapping of ethnozoological knowledge across Benin, although knowledge was significantly influenced by ethnicity and geographic location. The pricing of pangolins both varied with the category of stakeholders (local communities vs. stakeholders of TMMs) and clients (local and West African clients vs. Chinese community) and the type of items sold. The Chinese community was reported to only buy pangolins alive, and average selling prices were 3–8 times higher than those to West African clients.

Conclusions

Our results confirm that pangolins in Africa are valuable and versatile resources for consumption and medicinal / spiritual practices. The pangolin trade in Benin is based on an endogenous and complex network of actors that now appears influenced by the specific, high-valued demand from the Chinese diaspora. Further investigations are required to assess the growing impact of the Chinese demand on the African wildlife trade.
Ethnobotanical study on herbal market at the Dragon Boat Festival of Chuanqing people in China
Authors: Wang Qinghe , Zhao Ling , Gao Chi , Zhao Jiawen , Ren Zixuan , Shen Yuxiang , Yao Ruyu , Yin Hongxiang
Published: March 2021

Background

The Chuanqing people (穿青人) are a linguistic group native to the Guizhou Province of China, with unique culture and rich knowledge of traditional medicinal plants. Herbal market at Dragon Boat Festival (DBF) plays an important role in the inheritance of traditional medicinal knowledge among the Chuanqing people. This study aims to record the profile of medicinal plants of the Chuanqing people, discuss the dilemmas faced by their inheritance, and propose some strategies for passing down information, which is critical for the inheritance and protection of the Chuanqing people’s traditional medical knowledge.

Methods

Data were collected through key informants and semi-structured interviews and free listing. Collected voucher specimens were identified using by botanical taxonomy method and deposited in the herbarium. Data were analyzed through use-value (UV) and cultural importance index (CI) values. Medicinal plants were compared with the Information System of Chinese Rare and Endangered Plants of the Chinese Academy of Sciences. Results were compared with the Pharmacopoeia of the People’s Republic of China (ChP), the Quality Standard of Traditional Chinese Medicine and National Medicine in Guizhou Province (QSG), and traditional medicines of Southeast Asian countries.

Results

A total of 102 species from 53 families and 92 genera were recorded, with Orchidaceae and Asparagaceae (six species each), and Berberidaceae and Asteraceae (five species each) as the predominant families. The whole plant (36%) was the most common medicinal part. Decoction (44%) was the most common preparation method. Seventy-one investigated human ailments were grouped into 12 categories. Diseases of the musculoskeletal system (34 mentions) were most frequently mentioned in this study. Moreover, the most frequently used taxon was Hedera sinensis (Tobler) Hand.-Mazz. (UV and CI = 0.29). The Chuanqing people’s medicine was highly similar to ChP and QSG. In comparison with Southeast Asian countries’ traditional medicines, except for the same preparation methods, the similarities in terms of medicinal ingredients, plants, and disease treatment were very low.

Conclusions

The herbal market at the DBF is an important platform for exchanging knowledge about the Chuanqing people’s traditional medicinal plants. The Chuanqing people’s traditional medicine is facing many challenges to its inheritance and development. To solve these problems, this study highlights the traditional medicinal knowledge of the Chuanqing people, providing basic data for further research and protection of minority medicine.
Atrio-aortic erosion caused by Amplatzer Atrial Septal Occluder – a case report
Authors: Kamla Christine E. , Buech Joscha , Doldi Philipp M. , Hagl Christian , Juchem Gerd , Dashkevich Alexey
Published: March 2021

Background

In specialized centers, percutaneous closure using specific occluders is the first-choice treatment in atrial septal defects (ASD). Late complications after this intervention, such as erosion of the aorta or the atria, are rare and have not been sufficiently approached and dealt with in literature. In our clinic we have been faced with the problematic situation of diagnosing and treating such cases. That is why, we have decided to share our experience with other colleagues.

Case presentation

We present two cases of severe late complications after percutaneous closure of atrial septal defects (ASD). In both cases, the atrial septal occluder (Amplatzer™ Atrial Septal Occluder Device, Abbott, Chicago USA) caused the erosion between the left atrium and the aortic root. The atrio-aortic erosion led to acute cardiac tamponade with upper venous congestion and shock. As the bleeding source remained undetectable for any imaging tools, a diagnostical sternotomy remained the only solution.

The cause of the acute bleeding was discovered to be the erosion between the left atrium and the aortic root. The treatment consisted in the removal of the occluder, direct suturing of the perforated areas and the surgical closure of the remaining ASD. The patients fully recovered within the nine to fourteen days’ hospital stay. Six months after surgery both patients were well and able to recover their daily routine.

Conclusions

The atrio-aortic erosion after percutaneous closure of atrial septal defects is a surgical emergency. The more so, since it can be complicated by the absence of specific symptoms. A key-element in the diagnosis of this rare pathology remains the medical history of the patient, which the surgeon has to consider thoroughly and launch the diagnostic sternotomy without delay.
Increased detection of primary carnitine deficiency through second-tier newborn genetic screening
Authors: Lin Yiming , Zhang Weifeng , Huang Chenggang , Lin Chunmei , Lin Weihua , Peng Weilin , Fu Qingliu , Chen Dongmei
Published: March 2021

Background

Newborn screening for primary carnitine deficiency (NBS) is commonly implemented worldwide; however, it has poor sensitivity. This study aimed to evaluate the feasibility of improving screening by including a second-tier genetic assay.

Results

An Agena iPLEX assay was developed to identify 17 commonSLC22A5mutations in Chinese populations and was applied in NBS as a second-tier screening. From January 2017 to December 2018, 204,777 newborns were screened for PCD using tandem mass spectrometry. A total of 316 (0.15%) residual NBS-positive specimens with low free carnitine (C0) levels were subjected to this second-tier screening. The screening identified 20 screen-positive newborns who harboured biallelic mutations in theSLC22A5gene, 99 carriers with one mutation, and 197 screen-negative newborns with no mutations. Among the 99 carriers, four newborns were found to have a second disease-causingSLC22A5mutation by further genetic analysis. Among the 197 screen-negatives were four newborns with persistently low C0 levels, and further genetic analysis revealed that one newborn had two novelSLC22A5pathogenic variants. In total, 25 newborns were diagnosed with PCD, for a positive predictive value of 7.91% (25/316). Based on these data, we estimate the incidence of PCD in Quanzhou is estimated to be 1:8191.Thirteen distinctSLC22A5variants were identified, and the most common was c.760C > T, with an allelic frequency of 32% (16/50), followed by c.1400C > G (7/50, 14%), and c.51C > G (7/50, 14%).

Conclusion

Data from this study revealed that 24% (6/25) of PCD cases would have been missed by conventional NBS. This high-throughput iPLEX assay is a powerful tool for PCD genotyping. The addition of this second-tier genetic screening to the current NBS program could identify missed PCD cases, thereby increasing PCD detection. However, further studies are needed to optimise the workflow of the new screening algorithm and to evaluate the cost-effectiveness of this screening approach.
Reduction of RUNX1 transcription factor activity by a CBFA2T3-mimicking peptide: application to B cell precursor acute lymphoblastic leukemia
Authors: Jakobczyk Hélène , Debaize Lydie , Soubise Benoit , Avner Stéphane , Rouger-Gaudichon Jérémie , Commet Séverine , Jiang Yan , Sérandour Aurélien A. , Rio Anne-Gaëlle , Carroll Jason S. , Wichmann Christian , Lie-a-Ling Michael , Lacaud Georges , Corcos Laurent , Salbert Gilles , Galibert Marie-Dominique , Gandemer Virginie , Troadec Marie-Bérengère
Published: March 2021

Background

B Cell Precursor Acute Lymphoblastic Leukemia (BCP-ALL) is the most common pediatric cancer. Identifying key players involved in proliferation of BCP-ALL cells is crucial to propose new therapeutic targets. Runt Related Transcription Factor 1 (RUNX1) and Core-Binding Factor Runt Domain Alpha Subunit 2 Translocated To 3 (CBFA2T3, ETO2, MTG16) are master regulators of hematopoiesis and are implicated in leukemia.

Methods

We worked with BCP-ALL mononuclear bone marrow patients’ cells and BCP-ALL cell lines, and performed Chromatin Immunoprecipitations followed by Sequencing (ChIP-Seq), co-immunoprecipitations (co-IP), proximity ligation assays (PLA), luciferase reporter assays and mouse xenograft models.

Results

We demonstrated that CBFA2T3 transcript levels correlate with RUNX1 expression in the pediatric t(12;21) ETV6-RUNX1 BCP-ALL. By ChIP-Seq in BCP-ALL patients’ cells and cell lines, we found that RUNX1 is recruited on its promoter and on an enhancer of CBFA2T3 located − 2 kb upstream CBFA2T3 promoter and that, subsequently, the transcription factor RUNX1 drives both RUNX1 and CBFA2T3 expression. We demonstrated that, mechanistically, RUNX1 and CBFA2T3 can be part of the same complex allowing CBFA2T3 to strongly potentiate the activity of the transcription factor RUNX1. Finally, we characterized a CBFA2T3-mimicking peptide that inhibits the interaction between RUNX1 and CBFA2T3, abrogating the activity of this transcription complex and reducing BCP-ALL lymphoblast proliferation.

Conclusions

Altogether, our findings reveal a novel and important activation loop between the transcription regulator CBFA2T3 and the transcription factor RUNX1 that promotes BCP-ALL proliferation, supporting the development of an innovative therapeutic approach based on the NHR2 subdomain of CBFA2T3 protein.
Targeting chemokines for acute lymphoblastic leukemia therapy
Authors: Hong Zixi , Wei Zimeng , Xie Tian , Fu Lin , Sun Jiaxing , Zhou Fuling , Jamal Muhammad , Zhang Qiuping , Shao Liang
Published: March 2021

Acute lymphoblastic leukemia (ALL) is a hematological malignancy characterized by the malignant clonal expansion of lymphoid hematopoietic precursors. It is regulated by various signaling molecules such as cytokines and adhesion molecules in its microenvironment. Chemokines are chemotactic cytokines that regulate migration, positioning and interactions of cells. Many chemokine axes such as CXCL12/CXCR4 and CCL25/CCR9 have been proved to play important roles in leukemia microenvironment and further affect ALL outcomes. In this review, we summarize the chemokines that are involved in ALL progression and elaborate on their roles and mechanisms in leukemia cell proliferation, infiltration, drug resistance and disease relapse. We also discuss the potential of targeting chemokine axes for ALL treatments, since many related inhibitors have shown promising efficacy in preclinical trials, and some of them have entered clinical trials.
Erythropoietin therapy in a case of neonatal anemia after exposure to natalizumab throughout pregnancy
Authors: Godano Elisabetta , Barra Fabio , Allodi Alessandra , Ferraiolo Antonella , Laroni Alice , Novi Giovanni , Mancardi Giovanni Luigi , Gustavino Claudio , Arioni Cesare
Published: March 2021

Background

Natalizumab is a monoclonal antibody approved for the treatment of patients with relapsing-remitting multiple sclerosis. According to the current clinical recommendations, its use during pregnancy should be carefully evaluated only in women with highly active disease who plan a pregnancy or have an unplanned pregnancy, after accurate counseling about eventual maternal disease relapse due to therapy suspension.

Case presentation

This brief case report describes a case of documented anemia that we observed in a newborn whose mother with relapsing-remitting multiple sclerosis was treated with an extended dosing protocol of natalizumab throughout pregnancy. The newborn received the infusion of erythropoietin every seven days from the fortieth day of life; subsequently, the status of anemia underwent clinical resolution.

Conclusions

This case report confirmed that natalizumab can cause disorders of hematopoiesis, including anemia, thrombocytopenia, or pancytopenia, in newborns of patients treated during pregnancy. A multidisciplinary team, including experienced pediatricians and pediatric hematologists, has a critical role in managing newborns delivered by women, being treated with natalizumab for treating relapsing-remitting multiple sclerosis during pregnancy.
Expression of Ascaris lumbricoides putative virulence-associated genes when infecting a human host
Authors: Mohd-Shaharuddin Norashikin , Lim Yvonne Ai Lian , Ngui Romano , Nathan Sheila
Published: March 2021

Background

Ascaris lumbricoides is the most common causative agent of soil-transmitted helminth infections worldwide, with an estimated 450 million people infected with this nematode globally. It is suggested that helminths are capable of evading and manipulating the host immune system through the release of a spectrum of worm proteins which underpins their long-term survival in the host. We hypothesise that the worm overexpresses these proteins when infecting adults compared to children to cirvumvent the more robust defence mechanisms of adults. However, little is known about the parasite’s genes and encoded proteins involved during A. lumbricoides infection. Hence, this study was conducted to assess the expression profile of putative virulence-associated genes during an active infection of adults and children.

Methods

In this study, quantitative PCR was performed to evaluate the expression profile of putative virulence-associated genes in A. lumbricoides isolated from infected children and adults. The study was initiated by collecting adult worms expelled from adults and children following anthelminthic treatment. High-quality RNA was successfully extracted from each of six adult worms expelled by three adults and three children, respectively. Eleven putative homologues of helminth virulence-associated genes reported in previous studies were selected, primers were designed and specific amplicons of A. lumbricoides genes were noted. The expression profiles of these putative virulence-associated genes in A. lumbricoides from infected adults were compared to those in A. lumbricoides from infected children.

Results

The putative virulence-associated genes VENOM, CADHERIN and PEBP were significantly upregulated at 166-fold, 13-fold and fivefold, respectively, in adults compared to children. Conversely, the transcription of ABA-1 (fourfold), CATH-L (threefold) and INTEGRIN (twofold) was significantly suppressed in A. lumbricoides from infected adults.

Conclusions

On the basis of the expression profile of the putative virulence-associated genes, we
propose that the encoded proteins have potential roles in evasion mechanisms, which could guide the development of therapeutic interventions.

Graphical Abstract
A cookbook for DNase Hi-C
Authors: Gridina Maria , Mozheiko Evgeniy , Valeev Emil , Nazarenko Ludmila P. , Lopatkina Maria E. , Markova Zhanna G. , Yablonskaya Maria I. , Voinova Viktoria Yu , Shilova Nadezhda V. , Lebedev Igor N. , Fishman Veniamin
Published: March 2021

Background

The Hi-C technique is widely employed to study the 3-dimensional chromatin architecture and to assemble genomes. The conventional in situ Hi-C protocol employs restriction enzymes to digest chromatin, which results in nonuniform genomic coverage. Using sequence-agnostic restriction enzymes, such as DNAse I, could help to overcome this limitation.

Results

In this study, we compare different DNAse Hi-C protocols and identify the critical steps that significantly affect the efficiency of the protocol. In particular, we show that the SDS quenching strategy strongly affects subsequent chromatin digestion. The presence of biotinylated oligonucleotide adapters may lead to ligase reaction by-products, which can be avoided by rational design of the adapter sequences. Moreover, the use of nucleotide-exchange enzymes for biotin fill-in enables simultaneous labelling and repair of DNA ends, similar to the conventional Hi-C protocol. These improvements simplify the protocol, making it less expensive and time-consuming.

Conclusions

We propose a new robust protocol for the preparation of DNAse Hi-C libraries from cultured human cells and blood samples supplemented with experimental controls and computational tools for the evaluation of library quality.
Diarrhea in an infant due to Shigella flexneri 1 carrying multiple cephalosporinase-encoding genes
Authors: Albert M. John , Purohit Prashant , Poirel Laurent , Carter Glen , Bulach Dieter
Published: March 2021

Background

Infections caused by multidrug-resistant shigellae resistant to broad-spectrum cephalosporins are becoming more prevalent in the Middle East. We report a case of severe diarrhea due to a multiresistant Shigella flexneri 1 strain carrying four different ß-lactamase genes.

Case presentation

A one-year-old Syrian infant presented with severe acute diarrhea, vomiting and dehydration. She did not respond to empirical treatment with amoxicillin-clavulanic acid followed by cefotaxime. Later, stool culture revealed S. flexneri 1 resistant to both these drugs. The patient was successfully treated with meropenem to which S. flexneri 1 was susceptible. The isolate was resistant to eight classes of antibiotics, and the whole genome sequence (WGS) identified four ß-lactamase genes (blaCTX-M-15, blaEC-8, blaOXA-1, and blaTEM-1) along with genes mediating resistance to seven other antibiotic classes. The WGS also identified several virulence genes including senA that encodes ShET-2 which induces watery diarrhea. Phylogenetically, the isolate was closely related to isolates from South Asia.

Conclusions

This report highlights the emergence of extremely resistant Shigella that has acquired multiple resistance genes to cephalosporins rendering these drugs ineffective.
Whole genome mapping and identification of single nucleotide polymorphisms of four Bangladeshi individuals and their functional significance
Authors: Khan Salim , Akter Shahina , Goswami Barna , Habib Ahashan , Banu Tanjina Akhtar , Barton Carl , Osman Eshrar , Samir Samiruzzaman , Arjuman Farida , Hasan Saam , Hossain Maqsud
Published: March 2021

Objective

The major objective of the study was to sequence the whole genome of four Bangladeshi individuals and identify variants that are known to be associated with functional changes or disease states. We also carried out an ontology analysis to identify the functions and pathways most likely to be affected by these variants.

Results

We identified around 900,000 common variants and close to 5 million unique ones in all four of the individuals. This included over 11,500 variants that caused nonsynonymous changes in proteins. Heart function associated pathways were heavily implicated by the ontology analysis; corroborating previous studies that claimed the Bangladeshi population as highly susceptible to heart disorders. Two variants were found that have been previously identified as pathogenic factors in familial hypercholesteremia and structural disorders of the heart. Other pathogenic variants we found were associated with pseudoxanthoma elasticum, cancer progression, polyagglutinable erythrocyte syndrome, preeclampsia, and others.
Epigenetic evidence of an Ac/Dc axis by VPA and SAHA
Authors: Lunke Sebastian , Maxwell Scott , Khurana Ishant , K.N. Harikrishnan , Okabe Jun , Al-Hasani Keith , El-Osta Assam
Published: March 2021

Background

Valproic acid (VPA) is one of the most commonly used anti-epileptic drugs with pharmacological actions on GABA and blocking voltage-gated ion channels. VPA also inhibits histone deacetylase (HDAC) activity. Suberoylanilide hydroxamic acid is also a member of a larger class of compounds that inhibit HDACs. At the time of this article, there are 123 active international clinical trials for VPA (also known as valproate, convulex, divalproex, and depakote) and SAHA (vorinostat, zolinza). While it is well known that VPA and SAHA influence the accumulation of acetylated lysine residues on histones, their true epigenetic complexity remains poorly understood.

Results

Primary human cells were exposed to VPA and SAHA to understand the extent of histone acetylation (H3K9/14ac) using chromatin immunoprecipitation followed by sequencing (ChIP-seq). Because histone acetylation is often associated with modification of lysine methylation, we also examined H3K4me3 and H3K9me3. To assess the influence of the HDAC inhibitors on gene expression, we used RNA sequencing (RNA-seq). ChIP-seq reveals a distribution of histone modifications that is robust and more broadly regulated than previously anticipated by VPA and SAHA. Histone acetylation is a characteristic of the pharmacological inhibitors that influenced gene expression. Surprisingly, we observed histone deacetylation by VPA stimulation is a predominant signature following SAHA exposure and thus defines an acetylation/deacetylation (Ac/Dc) axis. ChIP-seq reveals regionalisation of histone acetylation by VPA and broader deacetylation by SAHA. Independent experiments confirm H3K9/14 deacetylation of NFκB target genes by SAHA.

Conclusions

The results provide an important framework for understanding the Ac/Dc axis by highlighting a broader complexity of histone modifications by the most established and efficacious anti-epileptic medication in this class, VPA and comparison with the broad spectrum HDAC inhibitor, SAHA.
The effect of Co-Q10 on allergic rhinitis and allergic asthma
Authors: Du Qixue , Meng Wei , Athari Seyyed Shamsadin , Wang Renzhong
Published: March 2021

Background

Allergic asthma is an inflammatory disease resulting from continued or intermittent allergen exposure, and allergic rhinitis can be trigger of asthma. The main mechanism of these disease is allergic reaction and immune response dysregulation. Co-Q10 is an enzyme cofactor in mitochondria can control asthma and allergic rhinitis symptoms. In the present study, we determined that the CoQ10-induced anti-allergic effects were mediated by up-regulation of Nrf2.

Methods

Animal models of allergic rhinitis and allergic asthma were produced and treated with Co-Q10, Co-Q10 and O-3, Co-Q10 and Mg-S. Bronchoalveolar lavage fluid was collected from animal models, and IL-4, 5, 13, INF-y, Eicosanoids, IgE, EPO, and histamine production were measured. Also, COX-2, CCL24, CCL11, Nrf2, Eotaxin, Cytb, COX1 and ND1 genes expressions and histopathology were studied. BALf's cells were collected by tracheostomy and used in slide producing by cytospine. Cytokines, Eicosanoids, IgE, EPO, and histamine were measured by ELISA method. Gene expression was done by Real-time PCR.

Results

Co-Q10 with two supplementation (Mg-S and O-3) modulate MRC, BALf eosinophils, eosinophilic inflammation related genes (eotaxin, CCL11 and CCL24), peribronchial and perivascular inflammation, EPO, type 2 cytokines (IL-4, 5 and 13), IgE, histamine, Cyc-LT and LTB4 as main allergic bio-factors. Importantly, Co-Q10 treatment increased Nrf2 expression and Nrf2 induced antioxidant genes, glutathione redox and inhibited inflammation, oxidative stress injury, Th2 cytokines production and attenuated allergic inflammatory responses.

Conclusion

Nrf2 is activated in response to allergen, induces resistance against the rhinitis and asthma development and plays an essential role in broncho-protection. Co-Q10 increases the Nrf2 expression and the Nrf2 over-expression has strong effect in control of type2 cytokines, allergic mediators and inflammatory factors that lead to harnessing of allergy and asthma.

Graphic abstract
Optimization of contrast medium volume for abdominal CT in oncologic patients: prospective comparison between fixed and lean body weight-adapted dosing protocols
Authors: Caruso Damiano , Rosati Elisa , Panvini Nicola , Rengo Marco , Bellini Davide , Moltoni Giulia , Bracci Benedetta , Lucertini Elena , Zerunian Marta , Polici Michela , De Santis Domenico , Iannicelli Elsa , Anibaldi Paolo , Carbone Iacopo , Laghi Andrea
Published: March 2021

Background

Patient body size represents the main determinant of parenchymal enhancement and by adjusting the contrast media (CM) dose to patient weight may be a more appropriate approach to avoid a patient over dosage of CM. To compare the performance of fixed-dose and lean body weight (LBW)-adapted contrast media dosing protocols, in terms of image quality and parenchymal enhancement.

Results

One-hundred cancer patients undergoing multiphasic abdominal CT were prospectively enrolled in this multicentric study and randomly divided in two groups: patients in fixed-dose group (n = 50) received 120 mL of CM while in LBW group (n = 50) the amount of CM was computed according to the patient’s LBW. LBW protocol group received a significantly lower amount of CM (103.47 ± 17.65 mL vs. 120.00 ± 0.00 mL, p < 0.001). Arterial kidney signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) and pancreatic CNR were significantly higher in LBW group (all p ≤ 0.004). LBW group provided significantly higher arterial liver, kidney, and pancreatic contrast enhancement index (CEI) and portal venous phase kidney CEI (all p ≤ 0.002). Significantly lower portal vein SNR and CNR were observed in LBW-Group (all p ≤ 0.020).

Conclusions

LBW-adapted CM administration for abdominal CT reduces the volume of injected CM and improves both image quality and parenchymal enhancement.
Chitosan hydrogel-loaded MSC-derived extracellular vesicles promote skin rejuvenation by ameliorating the senescence of dermal fibroblasts
Authors: Zhao Xiangnan , Liu Yue , Jia Pingping , Cheng Hui , Wang Chen , Chen Shang , Huang Haoyan , Han Zhibo , Han Zhong-Chao , Marycz Krzysztof , Chen Xiaoniao , Li Zongjin
Published: March 2021

Background

The senescence of dermal fibroblasts (DFLs) leads to an imbalance in the synthesis and degradation of extracellular matrix (ECM) proteins, presenting so-called senescence-associated secretory phenotype (SASP), which ultimately leads to skin aging. Recently, mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) have been recognized as a promising cell-free therapy for degenerative diseases, which opens a new avenue for skin aging treatment.

Methods

In this study, we utilized chitosan (CS) hydrogel for effective loading and sustained release of EVs. In vitro, we explored the rejuvenation effects of CS hydrogel-incorporated EVs (CS-EVs) on replicative senescence DFLs through a series of experiments such as senescence-associated β-galactosidase (SA-β-gal) staining, RT-PCR, and Western blot analysis. Besides, we employed local multi-site subcutaneous injection to treat skin aging of naturally aged mice with CS-EVs and DiI fluorescent dye was used to label EVs to achieve in vivo real-time tracking.

Results

CS-EVs can significantly improve the biological functions of senescent fibroblasts, including promoting their proliferation, enhancing the synthesis of ECM proteins, and inhibiting the overexpression of matrix metalloproteinases (MMPs). Moreover, CS hydrogel could prolong the release of EVs and significantly increase the retention of EVs in vivo. After CS-EVs subcutaneous injection treatment, the aging skin tissues showed a rejuvenation state, manifested explicitly as the enhanced expression of collagen, the decreased expression of SASP-related factors, and the restoration of tissue structures.

Conclusions

CS hydrogel-encapsulated EVs could delay the skin aging processes by ameliorating the function of aging DFLs. Our results also highlight the potential of CS hydrogel-encapsulated EVs as a novel therapeutic strategy for improving aging skin to rejuvenation.