bluuebunny/crossref_metadata_2025 huggingface dataset:
PlGF knockdown attenuates hypoxia-induced stimulation of cell proliferation and glycolysis of lung adenocarcinoma through inhibiting Wnt/β-catenin pathway
Authors: Zhang Wei , Zhang Yanwei , Zhou Wensheng , Qian Fangfei , Hu Minjuan , Chen Ya , Lu Jun , Lou Yuqing , Han Baohui
Published: January 2021

Background

Angiogenic placental growth factor (PlGF) plays a role in hypoxia-induced angiogenesis. Here, we aimed to investigate the biological roles of PlGF in cell proliferation and glycolysis of lung adenocarcinoma (LUAD) and the underlying molecular mechanisms.

Methods

PlGF was knocked down in H358 and H1975 cells by lentiviruses, which were then cultured under hypoxia (90% N2, 5%CO2 and 5%O2) for 24 h. PlGF was overexpressed in PC9 cells treated with XAV939, inhibitor of Wnt/β-catenin signaling pathway. PlGF-silencing H1975 cells were implanted into mice, and tumor xenografts were harvested and analyzed.

Results

Hypoxia treatment led to up-regulation of PlGF, C-myc, lactate dehydrogenase A (LDHA), and β-catenin, promotion of cell proliferation and glycolysis in H358 and H1975 cells, which were obviously reversed by knocking down PlGF. In tumors, PlGF knockdown significantly prohibited cell proliferation and glycolysis, and decreased expression of C-myc, LDHA, and β-catenin. PlGF overexpression markedly strengthened cell proliferation, which was inhibited by β-catenin knockdown. Consistently, XAV939, inhibitor of Wnt/β-catenin pathway, also inhibited PlGF-induced cell proliferation, glycolysis, and β-catenin expression in PC9 cells.

Conclusion

PlGF knockdown inhibited the stimulatory effect of hypoxia on cell proliferation and glycolysis of LUAD through deactivating Wnt/β-catenin pathway.
Plasma angiopoietin-2 is associated with age-related deficits in cognitive sub-scales in Ugandan children following severe malaria
Authors: Ouma Benson J. , Bangirana Paul , Ssenkusu John M. , Datta Dibyadyuti , Opoka Robert O. , Idro Richard , Kain Kevin C. , John Chandy C. , Conroy Andrea L.
Published: January 2021

Background

Elevated angiopoietin-2 (Angpt-2) concentrations are associated with worse overall neurocognitive function in severe malaria survivors, but the specific domains affected have not been elucidated.

Methods

Ugandan children with severe malaria underwent neurocognitive evaluation a week after hospital discharge and at 6, 12 and 24 months follow-up. The relationship between Angpt-2 concentrations and age-adjusted, cognitive sub-scale z-scores over time were evaluated using linear mixed effects models, adjusting for disease severity (coma, acute kidney injury, number of seizures in hospital) and sociodemographic factors (age, gender, height-for-age z-score, socio-economic status, enrichment in the home environment, parental education, and any preschool education of the child). The Mullen Scales of Early Learning was used in children < 5 years and the Kaufman Assessment Battery for Children 2nd edition was used in children ≥ 5 years of age. Angpt-2 levels were measured on admission plasma samples by enzyme-linked immunosorbent assay. Adjustment for multiple comparisons was conducted using the Benjamini–Hochberg Procedure of False Discovery Rate.

Results

Increased admission Angpt-2 concentration was associated with worse outcomes in all domains (fine and gross motor, visual reception, receptive and expressive language) in children < 5 years of age at the time of severe malaria episode, and worse simultaneous processing and learning in children < 5 years of age at the time of severe malaria who were tested when ≥ 5 years of age. No association was seen between Angpt-2 levels and cognitive outcomes in children ≥ 5 years at the time of severe malaria episode, but numbers of children and testing time points were lower for children ≥ 5 years at the time of severe malaria episode.

Conclusion

Elevated Angpt-2 concentration in children with severe malaria is associated with worse outcomes in multiple neurocognitive domains. The relationship between Angpt-2 and worse cognition is evident in children < 5 years of age at the time of severe malaria presentation and in selected domains in older years.
Effects of acquisition device, sampling rate, and record length on kinocardiography during position-induced haemodynamic changes
Authors: Hossein Amin , Rabineau Jérémy , Gorlier Damien , Pinki Farhana , van de Borne Philippe , Nonclercq Antoine , Migeotte Pierre-François
Published: January 2021

Background

Kinocardiography (KCG) is a promising new technique used to monitor cardiac mechanical function remotely. KCG is based on ballistocardiography (BCG) and seismocardiography (SCG), and measures 12 degrees-of-freedom (DOF) of body motion produced by myocardial contraction and blood flow through the cardiac chambers and major vessels.

Results

The integral of kinetic energy ($$ iK$$

iK

) obtained from the linear and rotational SCG/BCG signals was computed over each dimension over the cardiac cycle, and used as a marker of cardiac mechanical function. We tested the hypotheses that KCG metrics can be acquired using different sensors, and at 50 Hz. We also tested the effect of record length on the ensemble average on which the metrics were computed. Twelve healthy males were tested in the supine, head-down tilt, and head-up tilt positions to expand the haemodynamic states on which the validation was performed.

Conclusions

KCG metrics computed on 50 Hz and 1 kHz SCG/BCG signals were very similar. Most of the metrics were highly similar when computed on different sensors, and with less than 5% of error when computed on record length longer than 60 s. These results suggest that KCG may be a robust and non-invasive method to monitor cardiac inotropic activity.

Trial registration Clinicaltrials.gov, NCT03107351. Registered 11 April 2017, https://clinicaltrials.gov/ct2/show/NCT03107351?term=NCT03107351&draw=2&rank=1.
What do you mean by engagement? – evaluating the use of community engagement in the design and implementation of chronic disease-based interventions for Indigenous populations – scoping review
Authors: Wali Sahr , Superina Stefan , Mashford-Pringle Angela , Ross Heather , Cafazzo Joseph A.
Published: January 2021

Background

Indigenous populations have remained strong and resilient in maintaining their unique culture and values, despite centuries of colonial oppression. Unfortunately, a consequential result of facing years of adversity has led Indigenous populations to experience a disproportionate level of poorer health outcomes compared to non-Indigenous populations. Specifically, the rate of Indigenous chronic disease prevalence has significantly increased in the last decade. Many of the unique issues Indigenous populations experience are deeply rooted in their colonial history and the intergenerational traumas that has subsequently impacted their physical, mental, emotional and spiritual well-being. With this, to better improve Indigenous health outcomes, understanding the local context of their challenges is key. Studies have begun to use modes of community engagement to initiate Indigenous partnerships and design chronic disease-based interventions. However, with the lack of a methodological guideline regarding the appropriate level of community engagement to be used, there is concern that many interventions will continue to fall short in meeting community needs.

Objective

The objective of this study was to investigate the how various community engagement strategies have been used to design and/or implement interventions for Indigenous populations with chronic disease.

Methods

A scoping review guided by the methods outlined by Arksey and O’Malley was conducted. A comprehensive search was completed by two reviewers in five electronic databases using keywords related to community engagement, Indigenous health and chronic disease. Studies were reviewed using a descriptive-analytical narrative method and data was categorized into thematic groups reflective of the main findings.

Results

We identified 23 articles that met the criteria for this scoping review. The majority of the studies included the use a participatory research model and the procurement of study approval. However, despite the claimed use of participatory research methods, only 6 studies had involved community members to identify the area of priority and only five had utilized Indigenous interview styles to promote meaningful feedback. Adapting for the local cultural context and the inclusion of community outreach were identified as the key themes from this review.

Conclusion

Many studies have begun to adopt community engagement strategies to better meet the needs of Indigenous Peoples. With the lack of a clear guideline to approach Indigenous-based participatory research, we recommend that researchers focus on 1) building partnerships, 2) obtaining study approval and 3) adapting interventions to the local context.
Epigenetic Effects of Nanomaterials and Nanoparticles
Authors: Pogribna Marta , Hammons George
Published: January 2021

The rise of nanotechnology and widespread use of engineered nanomaterials in everyday human life has led to concerns regarding their potential effect on human health. Adverse effects of nanomaterials and nanoparticles on various molecular and cellular alterations have been well-studied. In contrast, the role of epigenetic alterations in their toxicity remains relatively unexplored. This review summarizes current evidence of alterations in cytosine DNA methylation and histone modifications in response to nanomaterials and nanoparticles exposures in vivo and in vitro. This review also highlights existing knowledge gaps regarding the role of epigenetic alterations in nanomaterials and nanoparticles toxicity. Additionally, the role of epigenetic changes as potential translational biomarkers for detecting adverse effects of nanomaterials and nanoparticles is discussed.
Supervised consumption sites and crime: scrutinizing the methodological weaknesses and aberrant results of a government report in Alberta, Canada
Authors: Livingston James D.
Published: January 2021

To date, peer-reviewed research has found no evidence linking supervised consumptions sites (SCSs) to increased crime. Yet, in March 2020, a government Report released in the province of Alberta, Canada, presented the results of a review that reached a different conclusion. This commentary highlights the Report’s major methodological limitations with respect to its criminological components, including that crime was poorly operationalized and measured, change in crime was inadequately assessed, and the effect of SCSs on crime was not ascertained. It is argued that the magnitude of methodological flaws in the Report undermine the validity of its criminological claims and raise significant issues with the soundness of its conclusions.
What do we mean by individual capacity strengthening for primary health care in low- and middle-income countries? A systematic scoping review to improve conceptual clarity
Authors: Finn Mairéad , Gilmore Brynne , Sheaf Greg , Vallières Frédérique
Published: January 2021

Background

Capacity strengthening of primary health care workers is widely used as a means to strengthen health service delivery, particularly in low- and middle-income countries. Despite the widespread recognition of the importance of capacity strengthening to improve access to quality health care, how the term ‘capacity strengthening’ is both used and measured varies substantially across the literature. This scoping review sought to identify the most common domains of individual capacity strengthening, as well as their most common forms of measurement, to generate a better understanding of what is meant by the term ‘capacity strengthening’ for primary health care workers.

Methods

Six electronic databases were searched for studies published between January 2000 and October 2020. A total of 4474 articles were screened at title and abstract phase and 323 full-text articles were reviewed. 55 articles were ultimately identified for inclusion, covering various geographic settings and health topics.

Results

Capacity strengthening is predominantly conceptualised in relation to knowledge and skills, as either sole domains of capacity, or used in combination with other domains including self-efficacy, practices, ability, and competencies. Capacity strengthening is primarily measured using pre- and post-tests, practical evaluations, and observation. These occur along study-specific indicators, though some pre-existing, validated tools are also used.

Conclusion

The concept of capacity strengthening for primary health care workers reflected across a number of relevant frameworks and theories differs from what is commonly seen in practice. A framework of individual capacity strengthening across intra-personal, inter-personal, and technical domains is proposed, as an initial step towards building a common consensus of individual capacity strengthening for future work.
A systematic review of qualitative studies exploring the factors influencing the physical activity levels of Arab migrants
Authors: El Masri Aymen , Kolt Gregory S. , George Emma S.
Published: January 2021

Background

Evidence suggests that Arab migrant populations engage in low levels of physical activity. To our knowledge, there are no reviews that explore the perspectives of Arab migrant populations on the factors influencing physical activity. The aim of this systematic review was to thematically synthesise qualitative literature on the factors influencing physical activity among Arab migrant populations.

Methods

Five electronic databases (CINAHL, SPORTDiscus, PsychoInfo, MEDLINE, Embase) were searched in July 2018 and searched again in April 2020. A manual search in Google Scholar was also performed using keywords and the reference lists of included studies were also screened to identify further articles. The eligibility criteria for inclusion were studies that sampled adult (≥18 years) Arab migrant populations, used qualitative methodology, explored the factors influencing physical activity as a primary aim, and were published in English. The 10-item Critical Appraisal Skills Programme (CASP) checklist was used to assess methodological quality of individual studies. The results of the studies were thematically synthesised using the qualitative software Quirkos v1.6.

Results

A total of 15 studies were included, with the largest proportion of studies conducted in Australia, followed by the United States, Netherlands, Sweden, and then Canada. Five studies exclusively sampled Arab migrant populations in their study. A total of 7 major themes influencing physical activity among Arab migrants emerged from the synthesis: culture and religion, competing commitments and time, social factors, health-related influences, accessibility issues, outdoor environment, and the migratory experience.

Conclusions

The findings of this review highlighted the various factors influencing the physical activity levels of Arab migrant adults. While many of the factors influencing physical activity are shared with those experienced by other populations (e.g., time constraints), for Arab migrant populations there are other more unique factors closely associated with culture and religion that appear to influence their levels of physical activity. The findings of this review could be used to inform the design of physical activity interventions targeting Arab migrant populations.
Development of Australian physical activity and screen time guidelines for outside school hours care: an international Delphi study
Authors: Virgara Rosa , Phillips Anna , Lewis Lucy , Richardson Mandy , Maher Carol
Published: January 2021

Background

Children’s activity patterns in the periods before and after school make a key contribution to achieving 24-h movement guidelines. There are currently no national-level guidelines informing physical activity and screen time practices in Outside School Hours Care (OSHC) programs anywhere in the world. This study aimed to work with industry, government and academic stakeholders to develop draft physical activity and screen time guidelines for use in Australian OSHC.

Methods

A 4-round online Delphi survey was conducted from May 2019 to January 2020. The Delphi participants included national and international experts and stakeholders from academia, education, government, health and the OSHC sectors. Round 1 consisted of open-ended questions exploring physical activity, screen time and sedentary behaviour in various periods of OSHC (before school, after school and vacation care). In rounds 2 and 3, participants rated the importance of items generated from the first round for inclusion in national guidelines using a Likert scale (1–9). Consensus was defined a priori as ≥80% of respondents rating an item as “critically important” (score 7–9). Between rounds 3 and 4, the guideline development panel used the consensus items, systematic review evidence, and followed the GRADE process, to draft the guidelines. In round 4, participants were invited to provide feedback on the draft guidelines and comment on barriers and enablers to implementation.

Results

Sixty-seven stakeholders agreed to participate, with response rates 61, 81, 54 and 72% for the four rounds respectively. Of the 123 items generated across the three rounds, 48 statements achieved consensus agreement as critically important for inclusion in the guidelines. These included offering a variety of physical activities (free play, playground and equipment) and restriction of screen time. The final round provided feedback on the draft guidelines. The wording of the guidelines was found to be appropriate and preliminary enablers and barriers to implementation were identified.

Conclusions

This world-first expert and stakeholder consultation has underpinned the development of the draft Australian guidelines for physical activity and screen time in OSHC. Ongoing work is needed to further refine the guidelines, determine current rates of compliance with the guidelines and implement the guidelines into practice.
Exosomal LncRNA LINC00659 transferred from cancer-associated fibroblasts promotes colorectal cancer cell progression via miR-342-3p/ANXA2 axis
Authors: Zhou Lin , Li Jian , Tang Yaping , Yang Mei
Published: January 2021

Background

Cancer-associated fibroblasts (CAFs) play a pivotal role in regulating tumor progression by transferring exosomes to adjacent cells. Our aim was to clarify the role of LINC00659 encapsulated in CAFs-derived exosomes (CAFs-exo) in colorectal cancer (CRC).

Methods

CAFs and normal fibroblasts (NFs) were isolated and cultured. CAFs-exo and NFs-derived exosomes (NFs-exo) were characterized by transmission electron microscope and Western blot. The mRNA level of LINC00659 in CAFs-exo and NFs-exo were measured. Then we analyzed cell proliferation by CCK-8 and clone formation assay, cell migration by cell scratch, and cell invasion by Transwell. Epithelial mesenchymal transformation (EMT) related markers E-cadherin, N-cadherin, Vimentin and Snail-1 expressions were assessed by Western blot. The binding of LINC00659 and miR-342-3p, miR-342-3p and ANXA2 were analyzed by dual-luciferase reporter gene assay.

Results

CAFs and NFs showed a spindle-like morphology. CAFs-exo promoted CRC cell proliferation, migration, invasion and EMT progression. The expression of LINC00659 in CAF-derived exosomes was significantly increased, and fibroblasts could transfer exosomal LINC00659 to CRC cells. We further revealed that transfection of miR-342-3p mimic or sh-ANXA2 could obviously reverse the promotion effect of exosomal LINC00659 on CRC progression. Functional studies reveal that LINC00659 is transferred from CAFs to the cancer cells via exosomes, where it promotes CRC cell proliferation, invasion, migration and EMT progression in vitro. Mechanistically, LINC00659 interacts directly with miR-342-3p to increase ANXA2 expression in CRC cells.

Conclusion

Collected evidence supported that CAFs-derived exosomal LINC00659 promotes CRC cell proliferation, invasion and migration via miR-342-3p/ANXA2axis.
Gastrointestinal perforation in anti-NXP2 antibody-associated juvenile dermatomyositis: case reports and a review of the literature
Authors: Xu Yingjie , Ma Xiaolin , Zhou Zhixuan , Li Jianguo , Hou Jun , Zhu Jia , Kang Min , Lai Jianming , Li Xiaohui
Published: January 2021

Background

To summarize the characteristics of gastrointestinal (GI) perforation in anti-nuclear matrix protein 2 (NXP2) antibody-associated juvenile dermatomyositis (JDM).

Methods

Five patients with GI perforation from a JDM cohort of 120 cases are described. Relevant literature was reviewed.

Results

Five patients, including four females and one male, were included in the study. The age of onset of these patients ranged from 3.3 to 9.5 years with the median age of 5.0 years. When these patients were complicated by GI perforation, childhood myositis assessment score (CMAS) ranged from 1 to 5 with the median score of 2. Myositis-specific antibody (MSA) spectrum analysis indicated that the five patients were anti-NXP2 antibody positive. The initial symptoms of GI perforation were progressive abdominal pain and intermittent fever. Two patients also presented with ureteral calculus with hydronephrosis and ureteral stricture. Surgery was performed in four patients. One patient failed to undergo a repair as the perforation was high in position. For the other three patients, perforation repair was successful, of which two patients failed due to recurrent perforation. At 24 months postoperative follow-up, one patient was in complete remission on prednisone (Pred) and methotrexate (MTX) treatment, and her ureteral stricture had disappeared. The other four patients died. Adding these cases with 16 other patients described in the literature, the symptom at onset was progressive abdominal pain, which often occurred within 10 months after JDM was diagnosed. Perforation most commonly occurred in the duodenum, although it also occurred at multiple sites or was recurrent. The mortality rate of GI perforation in JDM was 38% (8/21).

Conclusions

All the five perforation cases in our study subjected to MSA analysis were anti-NXP2 antibody positive. The symptom at onset was abdominal pain. The most common site of perforation was the duodenum in the retroperitoneum, and the lack of acute abdominal manifestations prevented early diagnosis. GI perforation may be a fatal complication in JDM, and early diagnosis is very important. More research is needed to determine the pathogenesis and predictive factors of GI perforation in JDM.
Type I interferonopathies with novel compound heterozygous TREX1 mutations in two siblings with different symptoms responded to tofacitinib
Authors: Zhang Shiyu , Song Jiaxing , Yang Yuyan , Miao Huilei , Yang Lu , Liu Yuehua , Zhang Xue , Liu Yaping , Wang Tao
Published: January 2021

Background

Type I interferonopathies are a group of rare autoimmune diseases characterised by excessive activation of type I interferon that leads to disturbances in immune function. Three prime repair exonuclease 1 (TREX1) is an important exonuclease and plays an important role in DNA damage repair. TREX1 mutations are associated with many type I interferonopathies. Studies have been published on the effectiveness of tofacitinib in the treatment of type I interferonopathies. The aim of this study is to identify the pathogenic variation in a Chinese family with type I interferonopathies and to observe the therapeutic effects of tofacitinib.

Methods

A Chinese family with two members with type I interferonopathies was investigated. Whole exome sequencing and Sanger sequencing were applied for mutation screening using peripheral blood DNA of the patient and her family members. Sequencing results were analysed using bioinformatics software tools including VarCards and PolyPhen-2. Close clinical follow-up and observation were used to record changes in the disease before and after treatment with tofacitinib.

Results

Compound heterozygous variants of TREX1 were observed in the patient’s genome. One was a missense variant (NM_016381; c.C227T; p.Ala76Val) from the patient’s father, and the other was a frameshift variant (NM_016381; c.458dupA; p.Gln153Glnfs*3) from the patient’s mother. One of the proband’s elder brothers with similar skin lesions also carried these two variants. This brother of the proband had more serious cutaneous involvement with the comorbidity of cerebral palsy. These TREX1 variants have not been reported in previous studies and are predicted to be highly pathogenic. The proband was given tofacitinib that led to a marked improvement.

Conclusions

We identified two novel complex heterozygous variants in the TREX1 gene, which may underlie the molecular pathogenesis of the type I interferonopathies observed in members of this family. Tofacitinib could be an alternative treatment for this disease.
Clinical characteristics and poor predictors of anti-NXP2 antibody-associated Chinese JDM children
Authors: Wang Xinning , Ding Yuchuan , Zhou Zhixuan , Hou Jun , Xu Yingjie , Li Jianguo
Published: January 2021

Background

Juvenile dermatomyositis (JDM) is a rare and sometimes fatal disease in children. The anti-NXP2 antibody is one of the most common antibodies and muscle ischaemia associated with NXP2 autoantibodies was a severe subtype of JDM. Further information is needed regarding clinical characteristics and factors associated with poor prognosis. But there are no reports about clinical characteristics and high risk factor of poor prognosis. For the first time, we introduced the clinical characteristics and poor predictors of anti-NXP2 antibody-associated juvenile dermatomyositis in Chinese children.

Methods

Twenty-six patients with anti-NXP2 antibody-related JDM from 85 JDM Chinese patients were diagnosed from January 2016 to November 2019. Logistic regression was used to analyze the risk factors for refractory cases and mortality.

Results

The ratio of male to female was 1:1.9. The median age of onset was 4.5 (1–13) years. Twenty-four cases (92.3%) had rash and muscle weakness. Treatments included glucocorticoids, immunosuppressive agents, biological agents (7 cases), plasma exchange, Janus kinase inhibitor (7 cases) and autologous stem cell transplant (1 case). Refractory JDM patients (11/26, 42.3%) were associated with edema, skin ulcer, muscle strength<=grade 3, CD4/CD8 ratio < 1.4 and ferritin > 200μg/ml. Among 6 cases (6/26, 23.1%) with severe gastrointestinal involvement, 5 cases died and 1 case survived after autologous stem cell transplant (ASCT). The risk factors for gastrointestinal involvement and mortality were edema, skin ulcer, severe muscle weakness (dysphagia/ hoarseness/ soft voice), BMI < 15 and ANA positive.

Conclusions

Edema, skin ulcer and severe muscle weakness predicted refractory disease, GI involvement, and mortality in anti-NXP2 antibody-positive JDM of Chinese children. Decreased CD4/CD8 ratio and high ferritin related with refractory cases, and very low BMI and ANA (+) are probably, associated with gastrointestinal involvement and mortality.

Trial registration

http://www.chictr.org.cn/showproj.aspx?proj=49846.
Comparisons of neuroinflammation, microglial activation, and degeneration of the locus coeruleus-norepinephrine system in APP/PS1 and aging mice
Authors: Cao Song , Fisher Daniel W. , Rodriguez Guadalupe , Yu Tian , Dong Hongxin
Published: January 2021

Background

The role of microglia in Alzheimer’s disease (AD) pathogenesis is becoming increasingly important, as activation of these cell types likely contributes to both pathological and protective processes associated with all phases of the disease. During early AD pathogenesis, one of the first areas of degeneration is the locus coeruleus (LC), which provides broad innervation of the central nervous system and facilitates norepinephrine (NE) transmission. Though the LC-NE is likely to influence microglial dynamics, it is unclear how these systems change with AD compared to otherwise healthy aging.

Methods

In this study, we evaluated the dynamic changes of neuroinflammation and neurodegeneration in the LC-NE system in the brain and spinal cord of APP/PS1 mice and aged WT mice using immunofluorescence and ELISA.

Results

Our results demonstrated increased expression of inflammatory cytokines and microglial activation observed in the cortex, hippocampus, and spinal cord of APP/PS1 compared to WT mice. LC-NE neuron and fiber loss as well as reduced norepinephrine transporter (NET) expression was more evident in APP/PS1 mice, although NE levels were similar between 12-month-old APP/PS1 and WT mice. Notably, the degree of microglial activation, LC-NE nerve fiber loss, and NET reduction in the brain and spinal cord were more severe in 12-month-old APP/PS1 compared to 12- and 24-month-old WT mice.

Conclusion

These results suggest that elevated neuroinflammation and microglial activation in the brain and spinal cord of APP/PS1 mice correlate with significant degeneration of the LC-NE system.
Protein disulfide isomerase-mediated S-nitrosylation facilitates surface expression of P2X7 receptor following status epilepticus
Authors: Lee Duk-Shin , Kim Ji-Eun
Published: January 2021

Background

P2X7 receptor (P2X7R) is an ATP-gated nonselective cationic channel playing important roles in a variety of physiological functions, including inflammation, and apoptotic or necrotic cell death. An extracellular domain has ten cysteine residues forming five intrasubunit disulfide bonds, which are needed for the P2X7R trafficking to the cell surface and the recognition of surface epitopes of apoptotic cells and bacteria. However, the underlying mechanisms of redox/S-nitrosylation of cysteine residues on P2X7R and its role in P2X7R-mediated post-status epilepticus (SE, a prolonged seizure activity) events remain to be answered.

Methods

Rats were given pilocarpine (380 mg/kg i.p.) to induce SE. Animals were intracerebroventricularly infused Nω-nitro-l-arginine methyl ester hydrochloride (L-NAME, a NOS inhibitor) 3 days before SE, or protein disulfide isomerase (PDI) siRNA 1 day after SE using an osmotic pump. Thereafter, we performed Western blot, co-immunoprecipitation, membrane fraction, measurement of S-nitrosylated (SNO)-thiol and total thiol, Fluoro-Jade B staining, immunohistochemistry, and TUNEL staining.

Results

SE increased S-nitrosylation ratio of P2X7R and the PDI-P2X7R bindings, which were abolished by L-NAME and PDI knockdown. In addition, both L-NAME and PDI siRNA attenuated SE-induced microglial activation and astroglial apoptosis. L-NAME and PDI siRNA also ameliorated the increased P2X7R surface expression induced by SE.

Conclusions

These findings suggest that PDI-mediated redox/S-nitrosylation may facilitate the trafficking of P2X7R, which promotes microglial activation and astroglial apoptosis following SE. Therefore, our findings suggest that PDI-mediated regulations of dynamic redox status and S-nitrosylation of P2X7R may be a critical mechanism in the neuroinflammation and astroglial death following SE.
Analysis of influencing factors of viral load in patients with high-risk human papillomavirus
Authors: Lu Xuerong , Wang Tiantian , Zhang Youzhong , Liu Yuzhen
Published: January 2021

Background

High-risk human papillomavirus (HR-HPV) load is thought to be influenced by many factors, and the relationship between viral load and the degree of cervical lesion is controversial. This study explored the possible influencing factors of HR-HPV viral load in the uterine cervix.

Methods

A total of 605 women who needed colposcopic evaluation for abnormal cervical screening at the Affiliated Hospital of Weifang Medical University, China, between November 2017 and September 2018 were enrolled. Cervical specimens were collected from the endo- and ectocervix separately using two different cervical brushes. The hybrid capture II test was used to measure HR-HPV load. Age, histological severity, number of viral types, and area and location of cervical lesions were recorded. The correlations between viral load and influencing factors were analysed using univariate and multivariate analyses.

Results

HR-HPV load was positively correlated with age, histological severity, multiple HPV types and area of cervical lesions (P < 0.05). Viral load with the combination of endo- and ectocervical sampling was significantly higher than simple endocervical sampling (P < 0.001). Multivariate analysis showed that age, multiple HPV types and area of cervical lesions were independent factors for HR-HPV load with a combination of endo- and ectocervical sampling (P < 0.05). However, only age and area of cervical lesions were independent factors for viral load with simple endocervical sampling (P < 0.05). No significant association was found between viral load and lesion severity in multivariate analysis (P > 0.05).

Conclusion

HR-HPV load is influenced by age, histological severity, multiple viral types, area of cervical lesion and sampling methods. Age and area of cervical lesions are independent factors for viral load.
Novel and traditional anthropometric indices for identifying metabolic syndrome in non-overweight/obese adults
Authors: Wu Lihong , Zhu Wenhua , Qiao Qiaohua , Huang Lijuan , Li Yiqi , Chen Liying
Published: January 2021

Background

Metabolic syndrome (MetS) in non-overweight/obese people is insidiously associated with cardiovascular disease. Novel anthropometric indices can reflect central obesity better than the traditional anthropometric indices. Therefore, we hypothesize that these newly developed anthropometric indices can better identify MetS in non-overweight/obese people than conventional indices.

Methods

Cross-sectional data of sociodemographic, biochemical and anthropometric indices were collected from 2916 non-overweight/obese Chinese people. A body shape index (ABSI), body roundness index (BRI), waist-to-height ratio (WHtR), weight-adjusted-waist index (WWI) and abdominal volume index (AVI) were calculated. Partial correlation analysis was used to clarify the correlation between anthropometric indices and MetS variables. Binary logistic regression analysis was applied to assess the association between anthropometric indices and MetS and its components. Receiver-operating characteristic curve was used to identify the diagnostic ability of anthropometric indices for MetS and its components. The area under curve (AUC) difference between WHtR and each new anthropometric index was compared in pairs.

Results

After adjusting for covariates, AVI had the optimal ability of identifying MetS (AUC: 0.743 for male, 0.819 for female) and the strongest correlation with high-density lipoprotein cholesterol (HDL-C) (coe: − 0.227 for male, − 0.207 for female) and the highest odds rations (OR) with low HDL-C group (male: OR = 1.37, female: OR = 1.55). The WHtR was comparable to BRI in assessing MetS (AUC: 0.739 for male, 0.817 for female). WHtR or BRI could also well identify hypertension (AUC: 0.602 for male, 0.688 for female) and dysglycemia (AUC: 0.669 for male, 0.713 for female) and female’s high triglyceride level (AUC 0.712). The recognition ability of the two was equivalent. The ability of ABSI and WWI to identify MetS was weak.

Conclusions

AVI is the optimal anthropometric indices to identify MetS in non-overweight/obese Chinese adults. BRI and WHtR can also be considered as discriminators, while ABSI and WWI are weak discriminators. WHtR is easy to measure. So, it is recommended as an early preliminary screening method for the MetS in non-overweight/obese people.
A method for experimental warming of developing tree seeds with a common garden demonstration of seedling responses
Authors: Moler E. R. V. , Page G. , Flores-Rentería L. , Garms C. G. , Hull J. B. , Cooper H. F. , Swenson J. , Perks S. , Waring K. M. , Whipple A. V.
Published: January 2021

Background

Forest dieback driven by rapid climate warming threatens ecosystems worldwide. The health of forested ecosystems depends on how tree species respond to warming during all life history stages. While it is known that seed development is temperature-sensitive, little is known about possible effects of climate warming on seed development and subsequent seedling performance. Exposure of seeds to high air temperatures may influence subsequent seedling performance negatively, though conversely, warming during seed development may aid acclimation of seedlings to subsequent thermal stress. Technical challenges associated within-situwarming of developing tree seeds limit understanding of how tree species may respond to seed development in a warmer climate.

Results

We developed and validated a simple method for passively warming seeds as they develop in tree canopies to enable controlled study of climate warming on seedling performance. We quantified thermal effects of the cone-warming method across individual pine trees and stands by measuring the air temperature surrounding seed cones using thermal loggers and the temperature of seed cone tissue using thermocouples. We then investigated seedling phenotypes in relation to the warming method through a common garden study. We assessed seedling morphology, physiology, and mycorrhizal nodulation in response to experimental cone-warming in 20 seed-source-tree canopies on the San Francisco Peaks in northern Arizona, USA. The warming method increased air temperature surrounding developing seed cones by 2.1 °C, a plausible increase in mean air temperature by 2050 under current climate projections. Notable effect sizes of cone-warming were detected for seedling root length, shoot length, and diameter at root collar using Cohen’s Localf2. Root length was affected most by cone-warming, but effect sizes of cone-warming on root length and diameter at root collar became negligible after the first year of growth. Cone-warming had small but significant effects on mycorrhizal fungal richness and seedling multispectral near-infrared indices indicative of plant health.

Conclusions

The method was shown to reliably elevate the temperature surrounding seed cones and thereby facilitate experimentalin-situclimate warming research on forest trees. The method was furthermore shown to influence plant traits that may affect seedling performance under climate warming.
Quantitative visualization of photosynthetic pigments in tea leaves based on Raman spectroscopy and calibration model transfer
Authors: Zeng Jianjun , Ping Wen , Sanaeifar Alireza , Xu Xiao , Luo Wei , Sha Junjing , Huang Zhenxiong , Huang Yifeng , Liu Xuemei , Zhan Baishao , Zhang Hailiang , Li Xiaoli
Published: January 2021

Background

Photosynthetic pigments participating in the absorption, transformation and transfer of light energy play a very important role in plant growth. While, the spatial distribution of foliar pigments is an important indicator of environmental stress, such as pests, diseases and heavy metal stress.

Results

In this paper, in situ quantitative visualization of chlorophyll and carotenoid was realized by combining the Raman spectroscopy with calibration model transfer, and a laboratory Raman spectral model was successfully extended to a portable field spectral measurement. Firstly, a nondestructive and fast model for determination of chlorophyll and carotenoid in tea leaf was established based on confocal micro-Raman spectrometer in the laboratory. Then the spectral model was extended to a real-time foliar map scanning spectra of a field portable Raman spectrometer through calibration model transfer, and the spectral variation between the confocal micro-Raman spectrometer in the laboratory and the portable Raman spectrometer were effectively corrected by the direct standardization (DS) algorithm. The portable map scanning Raman spectra of the tea leaves after the model transfer were got into the established quantitative determination model to predict the concentration of photosynthetic pigments at each pixel of the tea leaves. The predicted photosynthetic pigments concentration of each pixel was imaged to illustrate the distribution map of foliar pigments. Statistical analysis showed that the predicted pigment contents were highly correlated with the real contents.

Conclusions

It can be concluded that the Raman spectroscopy was applicable for in situ, non-destructive and rapid quantitative detecting and imaging of photosynthetic pigment concentration in tea leaves, and the spectral detection model established based on the laboratory Raman spectrometer can be applied to a portable field spectrometer for quantitatively imaging of the foliar pigments.
Investigating the molecular control of deer antler extract on articular cartilage
Authors: Yao Baojin , Zhou Zhenwei , Zhang Mei , Leng Xiangyang , Zhao Daqing
Published: January 2021

Background

Deer antler is considered as a precious traditional Chinese medicinal material and has been widely used to reinforce kidney’s yang, nourish essence, and strengthen bone function. The most prominent bioactive components in deer antler are water-soluble proteins that play potential roles in bone formation and repair. The aim of this study was to explore the molecular control and therapeutic targets of deer antler extract (DAE) on articular cartilage.

Methods

DAE was prepared as previously described. All rats were randomly divided into Blank group and DAE group (10 rats per group) after 7-day adaptive feeding. The rats in DAE group were orally administrated with DAE at a dose of 0.2 g/kg per day for 3 weeks, and the rats in Blank group were fed with drinking water. Total RNA was isolated from the articular cartilage of knee joints. RNA sequencing (RNA-seq) experiment combined with quantitative real-time polymerase chain reaction (qRT-PCR) verification assay was carried out to explore the molecular control and therapeutic targets of DAE on articular cartilage.

Results

We demonstrated that DAE significantly increased the expression levels of functional genes involved in cartilage formation, growth, and repair and decreased the expression levels of susceptibility genes involved in the pathophysiology of osteoarthritis.

Conclusions

DAE might serve as a candidate supplement for maintaining cartilage homeostasis and preventing cartilage degeneration and inflammation. These effects were possibly achieved by accelerating the expression of functional genes involved in chondrocyte commitment, survival, proliferation, and differentiation and suppressing the expression of susceptibility genes involved in the pathophysiology of osteoarthritis. Thus, our findings will contribute towards deepening the knowledge about the molecular control and therapeutic targets of DAE on the treatment of cartilage-related diseases.
Factors affecting the incidence of postoperative periprosthetic fractures following primary and revision hip arthroplasty: a systematic review and meta-analysis
Authors: Bissias Christos , Kaspiris Angelos , Kalogeropoulos Athanasios , Papoutsis Konstantinos , Natsioulas Nikolaos , Barbagiannis Konstantinos , Papagelopoulos Panayiotis J. , Savvidou Olga D.
Published: January 2021

Objectives

The increasing number of hip arthroplasties (HA), due to the growing elderly population, is associated with the risk of femoral periprosthetic fractures (FPFs). The purpose of this study was to identify potential risk factors for the development of FPFs after HA.

Methods

A systematic review was conducted in five data bases (Medline, Embase, Cochrane, Cinahl, ICTRP) according to the Preferred Reporting Items for Systematic reviews and Meta-analysis (PRISMA) guidelines up to May 2019, using the key words “risk factor,” “periprosthetic fracture,” and “hip replacement or arthroplasty.” Meta-analysis of the clinical outcomes of HA and subgroup analysis based on the factors that were implicated in FPFs was performed.

Results

Sixteen studies were included (sample size: 599,551 HA patients, 4253 FPFs, incidence 0.71%). Risk factors statistically associated with increased incidence of FPFs were female gender (+ 40%), previous revision arthroplasty surgery (× 3 times), and the presence of rheumatoid arthritis (× 2.1 times), while osteoarthritis (− 57%), cement application (− 59%), and insertion of Biomet (− 68%) or Thompson’s prosthesis (− 75%) were correlated with low prevalence of FPFs. Obesity, cardiac diseases, advanced age, bad general health (ASA grade ≥ 3), and use of Exeter or Lubinus prosthesis were not linked to the appearance of FPFs.

Conclusion

This meta-analysis suggested that female gender, rheumatoid arthritis, and revision arthroplasty are major risk factors for the development of FPFs after a HA. In those patients, frequent follow-ups should be planned. Further prospective studies are necessary to clarify all the risk factors contributing to the appearance of FPFs after HA.
Direct comparison of 3D and 2D cultivation reveals higher osteogenic capacity of elderly osteoblasts in 3D
Authors: Payr Stephan , Rosado-Balmayor Elizabeth , Tiefenboeck Thomas , Schuseil Tim , Unger Marina , Seeliger Claudine , van Griensven Martijn
Published: January 2021

Background

The aim of this study was the investigation of the osteogenic potential of human osteoblasts of advanced donor age in 2D and 3D culture.

Methods

Osteoblasts were induced to osteogenic differentiation and cultivated, using the same polystyrene material in 2D and 3D culture for 2 weeks. Samples were taken to evaluate alkaline phosphatase (ALP) activity, mineralization and gene expression.

Results

Osteoprotegerin (OPG) levels were significantly increased (8.2-fold) on day 7 in 3D compared to day 0 (p < 0.0001) and 11.6-fold higher in 3D than in 2D (p < 0.0001). Both culture systems showed reduced osteocalcin (OC) levels (2D 85% and 3D 50% of basic value). Collagen type 1 (Col1) expression was elevated in 3D on day 7 (1.4-fold;p = 0.009). Osteopontin (OP) expression showed 6.5-fold higher levels on day 7 (p = 0.002) in 3D than in 2D. Mineralization was significantly higher in 3D on day 14 (p = 0.0002).

Conclusion

Advanced donor age human primary osteoblasts reveal significantly higher gene expression levels of OPG, Col1 and OP in 3D than in monolayer. Therefore, it seems that a relatively high potential of bone formation in a natural 3D arrangement is presumably still present in osteoblasts of elderly people.

Trial registration

5217/11on the 22nd of Dec. 2011.