bluuebunny/crossref_metadata_2025 huggingface dataset:
A rapid, parasite-dependent cellular response to Dirofilaria immitis in the Mongolian jird (Meriones unguiculatus)
Authors: Evans Christopher C. , Day Katherine M. , Chu Yi , Garner Bridget , Sakamoto Kaori , Moorhead Andrew R.
Published: January 2021

Background

The Mongolian jird (Meriones unguiculatus) has long been recognized as a permissive host for the filarial parasiteBrugia malayi; however, it is nonpermissive to another filarial parasite, canine heartworm (Dirofilaria immitis). By elucidating differences in the early response to infection, we sought to identify mechanisms involved in the species-specific clearance of these parasites. We hypothesized that the early clearance ofD. immitisin intraperitoneal infection of the jird is immune mediated and parasite species dependent.

Methods

Jird peritoneal exudate cells (PECs) were isolated and their attachment to parasite larvae assessed in vitro under various conditions:D. immitisandB. malayicultured separately, co-culture of both parasites, incubation before addition of cells, culture of heat-killed parasites, and culture with PECs isolated from jirds with matureB. malayiinfection. The cells attaching to larvae were identified by immunohistochemistry.

Results

In vitro cell attachment to liveD. immitiswas high (mean = 99.6%) while much lower forB. malayi(mean = 5.56%). This species-specific attachment was also observed when both filarial species were co-cultured, with no significant change from controls (U(9, 14)= 58.5,p= 0.999). When we replicated these experiments with PECs derived from jirds subcutaneously infected withB. malayi, the results were similar (99.4% and 4.72% ofD. immitisandB. malayi, respectively, exhibited cell attachment). Heat-killing the parasites significantly reduced cell attachment toD. immitis(mean = 71.9%;U(11, 14)= 7.5,p< 0.001) while increasing attachment toB. malayi(mean = 16.7%;U(9, 15)= 20,p= 0.002). Cell attachment to both species was reduced when larvae were allowed a 24-h pre-incubation period prior to the addition of cells. The attaching cells were identified as macrophages by immunohistochemistry.

Conclusions

These results suggest a strongly species-dependent response from whichB. malayicould not confer protection by proxy in co-culture. The changes in cell attachment following heat-killing and pre-incubation suggest a role for excretory/secretory products in host immune evasion and/or antigenicity. The nature of this attachment is the subject of ongoing study and may provide insight into filarial host specificity.

Graphical Abstract
Cytomegalovirus infection: friend or foe in rheumatoid arthritis?
Authors: Davignon Jean-Luc , Combe Bernard , Cantagrel Alain
Published: January 2021

Human cytomegalovirus (HCMV) is a β-herpesvirus that causes inflammation and remains for life in a latent state in their host. HCMV has been at the center of many hypotheses regarding RA.

We have recently shown that HCMV infection impairs bone erosion through the induction of the mRNA-binding protein QKI5. Latently infected RA patients display a slower progression of bone erosion in patients from a national cohort. Our observations question the possible association between HCMV and the pathophysiology of RA. In this review, we examine the possibility that HCMV may be an aggravating factor of inflammation in RA while protecting from bone erosion. We also assess its relationship with other pathogens such as bacteria causing periodontitis and responsible for ACPA production.

This review thus considers whether HCMV can be regarded as a friend or a foe in the pathogenesis and the course of RA.
Sleep quality and athletic performance according to chronotype
Authors: Lim Seung-Taek , Kim Do-Yoon , Kwon Hyeong-Tae , Lee Eunjae
Published: January 2021

Background

When studying the quality of sleep in relation to athletic performance, the athlete’s chronotype and habitual time consider important factors. We aim to investigate the sleep quality and athletes’ performance according to chronotype in elite athletes.

Methods

Three hundred forty elite athletes (males = 261, females = 79) were recruited for the present study. All participants were screening for chronotype by the Korean versions of the Morningness - Eveningness Questionnaire (MEQ-K). The Pittsburgh Sleep Quality Index (PSQI) and Wingate Anaerobic Test (WAnT) were measurement after screening.

Results

PSQI global score, PSQI sleep quality, PSQI sleep onset latency, PSQI sleep disturbance, and PSQI daytime dysfunction were significant differences among the groups. WAnT mean power (W), mean power (W/kg), peak power (W), and peak power (W/kg) were significant differences among the groups. A negative correlation coefficient was found between PSQI score and WAnT mean power (W) (r = − 0.256, p < 0.01), mean power (W/kg) (r = − 0.270, p < 0.01), peak power (W) (r = − 0.220, p < 0.01), and peak power (W/kg) (r = − 0.248, p < 0.01).

Conclusions

This study indicates that related poor sleep quality and late-type chronotype may reduce the athletes’ performance in elite athletes. In addition, the sleep quality is much higher in the early-type chronotype than in the late-type chronotype. Moreover, it also the athletic performance was better in the early-type chronotype than in the late-type chronotype.
Short tandem repeat near hypoxia response element (HRE) instead of HRE genetic variants in promoter calcitonin receptor-like receptor (CRLR) gene as risk factor in severe preeclampsia: a preliminary study
Authors: Herlambang  , Fitri Amelia Dwi , Syauqy Ahmad , Yuwono  , Puspasari Anggelia , Enis Rina Nofri , Faried Ahmad
Published: January 2021

Objective

Calcitonin receptor-like receptor (CRLR) regulates vasoconstriction and dilatation; the expression increases during hypoxia via activation of hypoxia response element (HRE) in CRLR gene promoter region. Variant in HRE, as well short tandem repeat (STR) variants near HRE in CRLR alters the gene expression. This study focused on a case–control study to investigate the expression of genetic typing CLRL promoter variant in pregnant women with severe preeclampsia and normal pregnancies, we also tried to describe interesting findings of the genetic expression in anemic patients in the severe preeclampsia group. Our aimed to observe the correlation of CRLR gene promoter variant and anemia in severe preeclampsia.

Results

There was no nucleotide variant in HRE; CACA box prior to HRE varied in length (15–24); CACA box with length > 20 was used as cut off point. Hb was lower in CACA box length ≥ 21 (10.33 ± 1.57) vs. < 21 (11.01 ± 1.67; p = 0.391). CACA box polymorphism and anemia were correlated in severe preeclampsia (p = 0.005) OR 0.038 (CI 0.003–0.544); not in normal (p = 0.069).
Dysphagia and its impact on the quality of life of head and neck cancer patients: institution-based cross-sectional study
Authors: Yifru Tseganesh Asefa , Kisa Sezer , Dinegde Negalign Getahun , Atnafu Niguse Tadele
Published: January 2021

Objective

Impaired swallowing is a primary medical concern in head and neck cancer (HNC) patients. Swallowing therapy and supportive care to relieve swallowing problems among HNC patients are recommended. However, no data shows the effect of dysphagia on the quality of life (QoL) among Ethiopian patients. This cross-sectional study aimed to assess swallowing function and its impact on QoL.

Results

The sample included 102 HNC patients who visited oncology clinics at Tikur Anbessa Specialized Hospital. Majority were male (53.90%), employed (70.6%), single (57.80%), and completed some level of formal education (66.60%) with a mean age of 42.58 years (SD ± 14.08). More than half of the patients (69.6%) medical expenses were covered by the government. Most were suffering from advanced stage HNC (59.80%), squamous cell carcinoma (62.70%), and the most prevalent tumor location was nasopharynx (40.20%). The mean MDADI score was 53.29 (SD ± 15.85). Being female, low income, suffering from laryngeal cancer, advanced tumor, and undergoing a single modality therapy were crucial determinants of poor QoL related to swallowing problems. It is recommended to assess swallowing related QoL of patients using a validated tool and be included in treatment protocols.
Sperm DNA methylation epimutation biomarker for paternal offspring autism susceptibility
Authors: Garrido Nicolás , Cruz Fabio , Egea Rocio Rivera , Simon Carlos , Sadler-Riggleman Ingrid , Beck Daniel , Nilsson Eric , Ben Maamar Millissia , Skinner Michael K.
Published: January 2021

Background

Autism spectrum disorder (ASD) has increased over tenfold over the past several decades and appears predominantly associated with paternal transmission. Although genetics is anticipated to be a component of ASD etiology, environmental epigenetics is now also thought to be an important factor. Epigenetic alterations, such as DNA methylation, have been correlated with ASD. The current study was designed to identify a DNA methylation signature in sperm as a potential biomarker to identify paternal offspring autism susceptibility.

Methods and results

Sperm samples were obtained from fathers that have children with or without autism, and the sperm then assessed for alterations in DNA methylation. A genome-wide analysis (> 90%) for differential DNA methylation regions (DMRs) was used to identify DMRs in the sperm of fathers (n = 13) with autistic children in comparison with those (n = 13) without ASD children. The 805 DMR genomic features such as chromosomal location, CpG density and length of the DMRs were characterized. Genes associated with the DMRs were identified and found to be linked to previously known ASD genes, as well as other neurobiology-related genes. The potential sperm DMR biomarkers/diagnostic was validated with blinded test sets (n = 8–10) of individuals with an approximately 90% accuracy.

Conclusions

Observations demonstrate a highly significant set of 805 DMRs in sperm that can potentially act as a biomarker for paternal offspring autism susceptibility. Ancestral or early-life paternal exposures that alter germline epigenetics are anticipated to be a molecular component of ASD etiology.
Uncovering the secretome of mesenchymal stromal cells exposed to healthy, traumatic, and degenerative intervertebral discs: a proteomic analysis
Authors: Wangler Sebastian , Kamali Amir , Wapp Christina , Wuertz-Kozak Karin , Häckel Sonja , Fortes Claudia , Benneker Lorin M. , Haglund Lisbet , Richards R. Geoff , Alini Mauro , Peroglio Marianna , Grad Sibylle
Published: January 2021

Background

Mesenchymal stromal cells (MSCs) have been introduced as promising cell source for regenerative medicine. Besides their multilineage differentiation capacity, MSCs release a wide spectrum of bioactive factors. This secretome holds immunomodulatory and regenerative capacities. In intervertebral disc (IVD) cells, application of MSC secretome has been shown to decrease the apoptosis rate, induce proliferation, and promote production of extracellular matrix (ECM). For clinical translation of secretome-based treatment, characterization of the secretome composition is needed to better understand the induced biological processes and identify potentially effective secretomes.

Methods

This study aimed to investigate the proteome released by bone marrow-derived MSCs following exposure to a healthy, traumatic, or degenerative human IVD environment by mass spectroscopy and quantitative immunoassay analyses. Exposure of MSCs to the proinflammatory stimulus interleukin 1β (IL-1β) was used as control.

Results

Compared to MSC baseline secretome, there were 224 significantly up- or downregulated proteins following healthy, 179 following traumatic, 223 following degenerative IVD, and 160 proteins following IL-1β stimulus. Stimulation of MSCs with IVD conditioned media induced a more complex MSC secretome, involving more biological processes, compared to stimulation with IL-1β. The MSC response to stimulation with IVD conditioned medium was dependent on their pathological status.

Conclusions

The MSC secretome seemed to match the primary need of the IVD: homeostasis maintenance in the case of healthy IVDs, versus immunomodulation, adjustment of ECM synthesis and degradation disbalance, and ECM (re) organization in the case of traumatic and degenerative IVDs. These findings highlight the importance of cell preconditioning in the development of tailored secretome therapies.

Graphical abstract

The secretome of human bone marrow-derived mesenchymal stromal cells (MSCs) stimulated with intervertebral disc (IVD) conditioned medium was analyzed by proteomic profiling. Depending on the pathological state of the IVD, the MSC secretome protein composition indicated immunomodulatory or anabolic activity of the secretome. These findings may have implications for tailored secretome therapy for the IVD and other tissues.
Human umbilical cord mesenchymal stem cell-derived exosomal miR-27b attenuates subretinal fibrosis via suppressing epithelial–mesenchymal transition by targeting HOXC6
Authors: Li Dongli , Zhang Junxiu , Liu Zijia , Gong Yuanyuan , Zheng Zhi
Published: January 2021

Background and aim

Subretinal fibrosis resulting from neovascular age-related macular degeneration (nAMD) is one of the major causes of serious and irreversible vision loss worldwide, and no definite and effective treatment exists currently. Retinal pigmented epithelium (RPE) cells are crucial in maintaining the visual function of normal eyes and its epithelial–mesenchymal transition (EMT) is associated with the pathogenesis of subretinal fibrosis. Stem cell-derived exosomes have been reported to play a crucial role in tissue fibrosis by transferring their molecular contents. This study aimed to explore the effects of human umbilical cord-derived mesenchymal stem cell exosomes (hucMSC-Exo) on subretinal fibrosis in vivo and in vitro and to investigate the anti-fibrotic mechanism of action of hucMSC-Exo.

Methods

In this study, human umbilical cord-derived mesenchymal stem cells (hucMSCs) were successfully cultured and identified, and exosomes were isolated from the supernatant by ultracentrifugation. A laser-induced choroidal neovascularization (CNV) and subretinal fibrosis model indicated that the intravitreal administration of hucMSC-Exo effectively alleviated subretinal fibrosis in vivo. Furthermore, hucMSC-Exo could efficaciously suppress the migration of retinal pigmented epithelial (RPE) cells and promote the mesenchymal–epithelial transition by delivering miR-27b-3p. The latent binding of miR-27b-3p to homeobox protein Hox-C6 (HOXC6) was analyzed by bioinformatics prediction and luciferase reporter assays.

Results

This study showed that the intravitreal injection of hucMSC-Exo effectively ameliorated laser-induced CNV and subretinal fibrosis via the suppression of epithelial–mesenchymal transition (EMT) process. In addition, hucMSC-Exo containing miR-27b repressed the EMT process in RPE cells induced by transforming growth factor-beta2 (TGF-β2) via inhibiting HOXC6 expression.

Conclusions

The present study showed that HucMSC-derived exosomal miR-27b could reverse the process of EMT induced by TGF-β2 via inhibiting HOXC6, indicating that the exosomal miR-27b/HOXC6 axis might play a vital role in ameliorating subretinal fibrosis. The present study proposed a promising therapeutic agent for treating ocular fibrotic diseases and provided insights into the mechanism of action of hucMSC-Exo on subretinal fibrosis.
CCR2 improves homing and engraftment of adipose-derived stem cells in dystrophic mice
Authors: Wang Liang , Li Huan , Lin Jinfu , He Ruojie , Chen Menglong , Zhang Yu , Liao Ziyu , Zhang Cheng
Published: January 2021

Background

Dystrophinopathy, a common neuromuscular disorder caused by the absence of dystrophin, currently lacks effective treatments. Systemic transplantation of adipose-derived stem cells (ADSCs) is a promising treatment approach, but its low efficacy remains a challenge. Chemokine system-mediated stem cell homing plays a critical role in systemic transplantation. Here, we investigated whether overexpression of a specific chemokine receptor could improve muscle homing and therapeutic effects of ADSC systemic transplantation in dystrophic mice.

Methods

We analysed multiple microarray datasets from the Gene Expression Omnibus to identify a candidate chemokine receptor and then evaluated the protein expression of target ligands in different tissues and organs of dystrophic mice. The candidate chemokine receptor was overexpressed using the lentiviral system in mouse ADSCs, which were used for systemic transplantation into the dystrophic mice, followed by evaluation of motor function, stem cell muscle homing, dystrophin expression, and muscle pathology.

Results

Chemokine-profile analysis identified C–C chemokine receptor (CCR)2 as the potential target for improving ADSC homing. We found that the levels of its ligands C–C chemokine ligand (CCL)2 and CCL7 were higher in muscles than in other tissues and organs of dystrophic mice. Additionally, CCR2 overexpression improved ADSC migration ability and maintained their multilineage-differentiation potentials. Compared with control ADSCs, transplantation of those overexpressing CCR2 displayed better muscle homing and further improved motor function, dystrophin expression, and muscle pathology in dystrophic mice.

Conclusions

These results demonstrated that CCR2 improved ADSC muscle homing and therapeutic effects following systemic transplantation in dystrophic mice.
Mesenchymal stem cell-secreted prostaglandin E2 ameliorates acute liver failure via attenuation of cell death and regulation of macrophage polarization
Authors: Wang Jinglin , Liu Yang , Ding Haoran , Shi Xiaolei , Ren Haozhen
Published: January 2021

Background

Acute liver failure (ALF) is an acute inflammatory liver disease with high mortality. Previous preclinical and clinical trials have confirmed that mesenchymal stem cell (MSC) is a promising therapeutic approach; however, the effect is not satisfied as the underlying molecular mechanisms of MSC in treating ALF remain unclear.

Methods

MSC isolated from 4- to 6-week-old C57BL/6 mice were used to treat ALF. Histological and serological parameters were analyzed to evaluate the efficacy of MSC. We explored the molecular mechanism of MSC in the treatment of ALF by detecting liver inflammatory response and hepatocyte death.

Results

In this study, we found that the therapeutic potential of MSC on ALF is dependent on the secretion of prostaglandin E2 (PGE2), a bioactive lipid. MSC-derived PGE2 inhibited TGF-β-activated kinase 1 (TAK1) signaling and NLRP3 inflammasome activation in liver macrophages to decrease the production of inflammatory cytokines. Meanwhile, macrophages in the liver could be induced to anti-inflammatory (M2) macrophages by MSC-derived PGE2 via STAT6 and mechanistic target of rapamycin (mTOR) signaling, which then promote inflammatory resolution and limit liver injury. Finally, administrating EP4 antagonist significantly ameliorated the therapeutic ability of MSC, which promoted liver inflammation and decreased M2 macrophages.

Conclusions

Our results indicate that PGE2 might be a novel important mediator of MSC in treating ALF, which is through inhibiting the liver inflammatory response and hepatocyte death.
Intramuscular injection of Botox causes tendon atrophy by induction of senescence of tendon-derived stem cells
Authors: Chen Peilin , Chen Ziming , Mitchell Christopher , Gao Junjie , Chen Lianzhi , Wang Allan , Leys Toby , Landao-Bassonga Euphemie , Zheng Qiujian , Wang Tao , Zheng Minghao
Published: January 2021

Background

Botulinum toxin (Botox) injection is in widespread clinical use for the treatment of muscle spasms and tendinopathy but the mechanism of action is poorly understood.

Hypothesis

We hypothesised that the reduction of patellar-tendon mechanical-loading following intra-muscular injection of Botox results in tendon atrophy that is at least in part mediated by the induction of senescence of tendon-derived stem cells (TDSCs).

Study design

Controlled laboratory study

Methods

A total of 36 mice were randomly divided into 2 groups (18 Botox-injected and 18 vehicle-only control). Mice were injected into the rightvastus lateralisof quadriceps muscles either with Botox (to induce mechanical stress deprivation of the patellar tendon) or with normal saline as a control. At 2 weeks post-injection, animals were euthanized prior to tissues being harvested for either evaluation of tendon morphology or in vitro studies. TDSCs were isolated by cell-sorting prior to determination of viability, differentiation capacity or the presence of senescence markers, as well as assessing their response to mechanical loading in a bioreactor. Finally, to examine the mechanism of tendon atrophy in vitro, the PTEN/AKT-mediated cell senescence pathway was evaluated in TDSCs from both groups.

Results

Two weeks after Botox injection, patellar tendons displayed several atrophic features including tissue volume reduction, collagen fibre misalignment and increased degradation. A colony formation assay revealed a significantly reduced number of colony forming units of TDSCs in the Botox-injected group compared to controls. Multipotent differentiation capacities of TDSCs were also diminished after Botox injection. To examine if mechanically deprived TDSC are capable of forming tendon tissue, we used an isolated bioreactor system to culture tendon constructs using TDSC. These results showed that TDSCs from the Botox-treated group failed to restore tenogenic differentiation after appropriate mechanical loading. Examination of the signalling pathway revealed that injection of Botox into quadriceps muscles causes PTEN/AKT-mediated cell senescence of TDSCs.

Conclusion

Intramuscular injection of Botox interferes with tendon homeostasis by inducing tendon atrophy and senescence of TDSCs. Botox injection may have long-term adverse consequences for the treatment of tendinopathy.

Clinical relevance

Intramuscular Botox injection for tendinopathy or tendon injury could result in adverse effects in human tendons and evaluation of its long-term efficacy is warranted.
Dental pulp stem cells overexpressing hepatocyte growth factor facilitate the repair of DSS-induced ulcerative colitis
Authors: Li Ning , Zhang Yichi , Nepal Narayan , Li Guoqing , Yang Ningning , Chen Haoyuan , Lin Qiuchi , Ji Xuechun , Zhang Sijia , Jin Shizhu
Published: January 2021

Background

Ulcerative colitis (UC) is a chronic and recurrent disease without satisfactory treatment strategies. Dental pulp stem cell (DPSC) transplantation has been proposed as a potential therapy for UC. This study aimed to investigate the therapeutic effects of the rat hepatocyte growth factor (HGF) gene transduced into DPSCs for UC.

Methods

The therapeutic effects of HGF-DPSCs transplanted intravenously into a rat model of UC induced by 5% dextran sulphate sodium (DSS) were compared with the other treatment groups (LV-HGF group, DPSCs group and GFP-DPSCs group). Immunofluorescence and immunohistochemistry were used to observe the localization and proliferation of HGF-DPSCs at the site of colon injury. The expression levels of inflammatory factors were detected by real-time quantitative PCR (RT-PCR) and western blotting. The oxidative stress markers were detected by ELISA. DAI scores and body weight changes were used to macroscopically evaluate the treatment of rats in each group.

Results

Immunofluorescence and immunohistochemistry assays showed that HGF-DPSCs homed to colon injury sites and colocalized with intestinal stem cell (ISC) markers (Bmi1, Musashi1 and Sox9) and significantly promoted protein expression (Bmi1, Musashi1, Sox9 and PCNA). Anti-inflammatory cytokine (TGF-β and IL-10) expression was the highest in the HGF-DPSCs group compared with the other treatment groups, while the expression of pro-inflammatory cytokines (TNF-α and INF-γ) was the lowest. Additionally, the oxidative stress response results showed that malondialdehyde (MDA) and myeloperoxidase (MPO) expression decreased while superoxide dismutase (SOD) expression increased, especially in the HGF-DPSCs group. The DAI scores showed a downward trend with time in the five treatment groups, whereas body weight increased, and the changes were most prominent in the HGF-DPSCs group.

Conclusions

The study indicated that HGF-DPSCs can alleviate injuries to the intestinal mucosa by transdifferentiating into ISC-like cells, promoting ISC-like cell proliferation, suppressing inflammatory responses and reducing oxidative stress damage, which provides new ideas for the clinical treatment of UC.
Infrapatellar fat pad-derived mesenchymal stem cell-based spheroids enhance their therapeutic efficacy to reverse synovitis and fat pad fibrosis
Authors: Kouroupis Dimitrios , Willman Melissa A. , Best Thomas M. , Kaplan Lee D. , Correa Diego
Published: January 2021

Background

To investigate the in vitro and in vivo anti-inflammatory/anti-fibrotic capacity of IFP-MSC manufactured as 3D spheroids. Our hypothesis is that IFP-MSC do not require prior cell priming to acquire a robust immunomodulatory phenotype in vitro in order to efficiently reverse synovitis and IFP fibrosis, and secondarily delay articular cartilage damage in vivo.

Methods

Human IFP-MSC immunophenotype, tripotentiality, and transcriptional profiles were assessed in 3D settings. Multiplex secretomes were assessed in IFP-MSC spheroids [Crude (non-immunoselected), CD146+or CD146−immunoselected cells] and compared with 2D cultures with and without prior inflammatory/fibrotic cell priming. Functionally, IFP-MSC spheroids were assessed for their immunopotency on human PBMC proliferation and their effect on stimulated synoviocytes with inflammation and fibrotic cues. The anti-inflammatory and anti-fibrotic spheroid properties were further evaluated in vivo in a rat model of acute synovitis/fat pad fibrosis.

Results

Spheroids enhanced IFP-MSC phenotypic, transcriptional, and secretory immunomodulatory profiles compared to 2D cultures. Further, CD146+IFP-MSC spheroids showed enhanced secretory and transcriptional profiles; however, these attributes were not reflected in a superior capacity to suppress activated PBMC. This suggests that 3D culturing settings are sufficient to induce an enhanced immunomodulatory phenotype in both Crude and CD146-immunoselected IFP-MSC. Crude IFP-MSC spheroids modulated the molecular response of synoviocytes previously exposed to inflammatory cues. Therapeutically, IFP-MSC spheroids retained substance P degradation potential in vivo, while effectively inducing resolution of inflammation/fibrosis of the synovium and fat pad. Furthermore, their presence resulted in arrest of articular cartilage degradation in a rat model of progressive synovitis and fat pad fibrosis.

Conclusions

3D spheroids confer IFP-MSC a reproducible and enhanced immunomodulatory effect in vitro and in vivo, circumventing the requirement of non-compliant cell priming or selection before administration and thereby streamlining cell products manufacturing protocols.
Administration of mesenchymal stem cells in diabetic kidney disease: a systematic review and meta-analysis
Authors: Lin Wenshan , Li Hong-Yan , Yang Qian , Chen Guangyong , Lin Shujun , Liao Chunling , Zhou Tianbiao
Published: January 2021

Background

Mesenchymal stem cell (MSC) therapy shows great promise for diabetic kidney disease (DKD) patients. Research has been carried out on this topic in recent years. The main goals of this paper are to evaluate the therapeutic effects of MSCs on DKD through a meta-analysis and address the mechanism through a systematic review of the literature.

Method

An electronic search of the Embase, Cochrane Library, ISI Web of Science, PubMed, and US National Library of Medicine (NLM) databases was performed for all articles about MSC therapy for DKD, without species limitations, up to January 2020. Data were pooled for analysis with Stata SE 12.

Result

The MSC-treated group showed a large and statistically significant hypoglycemic effect at 1 week, 2 weeks, 3 weeks, 1 month, 2 months, 3 months, and 6 months. Total hypoglycemic effect was observed (SMD = − 1.954, 95%CI − 2.389 to − 1.519, p < 0.001; I2 = 85.1%). The overall effects on serum creatinine (SCr) and blood urea nitrogen (BUN) were analyzed, suggesting that MSC decreased SCr and BUN and mitigated the impairment of renal function (SCr: SMD = − 4.838, 95%CI − 6.789 to − 2.887, p < 0.001; I2 = 90.8%; BUN: SMD = − 4.912, 95%CI − 6.402 to − 3.422, p < 0.001; I2 = 89.3%). Furthermore, MSC therapy decreased the excretion of urinary albumin. Fibrosis indicators were assessed, and the results showed that transforming growth factor-β, collagen I, fibronectin, and α-smooth muscle actin were significantly decreased in the MSC-treated group compared to the control group.

Conclusion

MSCs might improve glycemic control and reduce SCr, BUN, and urinary protein. MSCs can also alleviate renal fibrosis. MSC therapy might be a potential treatment for DKD.
Predicting invasion potential of Senna didymobotrya (Fresen.) Irwin & Barneby under the changing climate in Africa
Authors: Weldemariam Elias Ch. , Dejene Sintayehu W.
Published: January 2021

Background

Senna didymobotrya is a native African flowering shrub. It is suspected that climate change encourages the introduction and spread of invasive alien species. The possible invasion of S. didymobotrya across the continent is expected to increase in the future due to ongoing climate change. Nonetheless, there is still paucity of empirical evidence on the extent to which the changing climate contributes to the surge of the flowering shrub. This study, therefore, investigated the present and potential invasion of S. didymobotrya using the species distribution model under changing climate conditions. The two representative concentration pathways (RCP4.5 and RCP8.5) and eight bioclimatic variables and one topographic variable were used to simulate the current and future (2050s and 2070s) invasion of S. didymobotrya in Africa. The model performance was assessed using the area under the receiver operating characteristic curve (AUC) and true skill statistics (TSS).

Results

The results of the study showed that under the current climatic conditions, 18% of Africa is suitable for the establishment and invasion of S. didymobotrya. The most suitable hotspot for S. didymobotrya invasion is eastern Africa, followed by southern Africa. The predicted model showed that by 2050, 3.3% and 3.12% of the continent would be highly suitable areas for the invasion of the species under RCP4.5 and RCP8.5, respectively. In the 2070s, under RCP4.5 and RCP8.5, the highly suitable area would be 3.13% and 2.7%, respectively. In relation to the current suitability, the cumulative projected areas of the low and moderate suitability class under RCP4.5 and RCP8.5 will rise by the years 2050 and 2070. However, under both RCPs, the non-suitable area for S. didymobotrya invasion would gradually decrease.

Conclusions

From the findings, it can be concluded that the ecosystem’s vulnerability to S. didymobotrya invasion under future climatic conditions will proliferate significantly. Hence, to prevent the projected harm to biodiversity and ecosystem services, governments need to focus their future biodiversity management and policy directions on the means and strategies of minimizing the invasion and the distribution rate of S. didymobotrya across habitat types.
The effect of dolomite amendment on soil organic carbon mineralization is determined by the dolomite size
Authors: Wu Hongtao , Hu Jinli , Shaaban Muhammad , Xu Peng , Zhao Jinsong , Hu Ronggui
Published: January 2021

Background

The size of lime material is vital for the efficiency of ameliorating soil acidity, thereby influencing soil biochemical processes. However, the effects of different sized lime material application on soil organic carbon (SOC) mineralization are yet to be elucidated. Therefore, a 35-day incubation experiment was conducted to determine the effects of three particle size fractions (0.5 to 0.25, 0.25 to 0.15, and < 0.15 mm) of dolomite on SOC mineralization of two acidic paddy soils.

Results

CO2emission was increased by 3–7%, 11–21%, and 32–49% for coarse-, medium-, and fine-sized dolomite treatments, respectively, compared to the control in both soils. They also well conformed to a first-order model in all treatments, and the estimated decomposition rate constant was significantly higher in the fine-sized treatment than that of other treatments (P< 0.05), indicating that SOC turnover rate was dependent on the dolomite size. The finer particle sizes were characterized with higher efficiencies of modifying soil pH, consequently resulting in higher dissolved organic carbon contents and microbial biomass carbon, eventually leading to higher CO2emissions.

Conclusions

The results demonstrate that the size of dolomite is a key factor in regulating SOC mineralization in acidic paddy soils when dolomite is applied to manipulate soil pH.
Amyloid β and tau pathology in brains of aged pinniped species (sea lion, seal, and walrus)
Authors: Takaichi Yuta , Chambers James K. , Takahashi Kei , Soeda Yoshiyuki , Koike Riki , Katsumata Etsuko , Kita Chiaki , Matsuda Fuko , Haritani Makoto , Takashima Akihiko , Nakayama Hiroyuki , Uchida Kazuyuki
Published: January 2021

Alzheimer’s disease (AD) is characterized by the accumulation of amyloid-β (Aβ) as senile plaques and cerebral amyloid angiopathy, and hyperphosphorylated tau (hp-tau) as neurofibrillary tangles in the brain. The AD-related pathology has been reported in several non-human animals, and most animals develop only the Aβ or tau pathology. We herein describe the Aβ and hp-tau pathology in the brains of aged pinniped species (seal, sea lion, and walrus). Molecular analyses revealed that the sequence of pinniped Aβ was identical to that of human Aβ. Histopathological examinations detected argyrophilic plaques composed of Aβ associated with dystrophic neurites in the cerebral cortex of aged pinnipeds. Astrogliosis and microglial infiltration were identified around Aβ plaques. Aβ deposits were observed in the blood vessel walls of the meninges and cerebrum. Pinniped tau protein was physiologically subjected to alternative splicing at exons 2, 3, and 10, and presented as five isoforms: two 3-repeat tau isoforms (1N3R, 2N3R) and three 4-repeat tau isoforms (0N4R, 1N4R, 2N4R); 0N3R tau isoform was absent. Histopathological examinations revealed argyrophilic fibrillar aggregates composed of hp-tau in the neuronal somata and neurites of aged pinniped brains. Few hp-tau aggregates were found in oligodendrocytes and microglia. Biochemically, hp-tau of the 3-repeat and 4-repeat isoforms was detected in brain sarkosyl-insoluble fractions. Aβ and hp-tau both predominantly accumulated in the neocortex, particularly the frontal cortex. Furthermore, the activation of GSK-3β was detected within cells containing hp-tau aggregates, and activated GSK-3β was strongly expressed in cases with severe hp-tau pathologies. The present results suggest that, in association with Aβ deposition, the activation of GSK-3β contributes to hp-tau accumulation in pinniped brains. Here, we report that pinniped species naturally accumulate Aβ and tau with aging, similar to the human AD pathology.
Loss of cholinergic innervation differentially affects eNOS-mediated blood flow, drainage of Aβ and cerebral amyloid angiopathy in the cortex and hippocampus of adult mice
Authors: Nizari Shereen , Wells Jack A. , Carare Roxana O. , Romero Ignacio A. , Hawkes Cheryl A.
Published: January 2021

Vascular dysregulation and cholinergic basal forebrain degeneration are both early pathological events in the development of Alzheimer’s disease (AD). Acetylcholine contributes to localised arterial dilatation and increased cerebral blood flow (CBF) during neurovascular coupling via activation of endothelial nitric oxide synthase (eNOS). Decreased vascular reactivity is suggested to contribute to impaired clearance of β-amyloid (Aβ) along intramural periarterial drainage (IPAD) pathways of the brain, leading to the development of cerebral amyloid angiopathy (CAA). However, the possible relationship between loss of cholinergic innervation, impaired vasoreactivity and reduced clearance of Aβ from the brain has not been previously investigated. In the present study, intracerebroventricular administration of mu-saporin resulted in significant death of cholinergic neurons and fibres in the medial septum, cortex and hippocampus of C57BL/6 mice. Arterial spin labelling MRI revealed a loss of CBF response to stimulation of eNOS by the Rho-kinase inhibitor fasudil hydrochloride in the cortex of denervated mice. By contrast, the hippocampus remained responsive to drug treatment, in association with altered eNOS expression. Fasudil hydrochloride significantly increased IPAD in the hippocampus of both control and saporin-treated mice, while increased clearance from the cortex was only observed in control animals. Administration of mu-saporin in the TetOAPPSweInd mouse model of AD was associated with a significant and selective increase in Aβ40-positive CAA. These findings support the importance of the interrelationship between cholinergic innervation and vascular function in the aetiology and/or progression of CAA and suggest that combined eNOS/cholinergic therapies may improve the efficiency of Aβ removal from the brain and reduce its deposition as CAA.
14-3-3 mitigates alpha-synuclein aggregation and toxicity in the in vivo preformed fibril model
Authors: Underwood Rachel , Gannon Mary , Pathak Aneesh , Kapa Navya , Chandra Sidhanth , Klop Alyssa , Yacoubian Talene A.
Published: January 2021

Alpha-synuclein (αsyn) is the key component of proteinaceous aggregates termed Lewy Bodies that pathologically define a group of disorders known as synucleinopathies, including Parkinson’s Disease (PD) and Dementia with Lewy Bodies. αSyn is hypothesized to misfold and spread throughout the brain in a prion-like fashion. Transmission of αsyn necessitates the release of misfolded αsyn from one cell and the uptake of that αsyn by another, in which it can template the misfolding of endogenous αsyn upon cell internalization. 14-3-3 proteins are a family of highly expressed brain proteins that are neuroprotective in multiple PD models. We have previously shown that 14-3-3θ acts as a chaperone to reduce αsyn aggregation, cell-to-cell transmission, and neurotoxicity in the in vitro pre-formed fibril (PFF) model. In this study, we expanded our studies to test the impact of 14-3-3s on αsyn toxicity in the in vivo αsyn PFF model. We used both transgenic expression models and adenovirus associated virus (AAV)-mediated expression to examine whether 14-3-3 manipulation impacts behavioral deficits, αsyn aggregation, and neuronal counts in the PFF model. 14-3-3θ transgene overexpression in cortical and amygdala regions rescued social dominance deficits induced by PFFs at 6 months post injection, whereas 14-3-3 inhibition by transgene expression of the competitive 14-3-3 peptide inhibitor difopein in the cortex and amygdala accelerated social dominance deficits. The behavioral rescue by 14-3-3θ overexpression was associated with delayed αsyn aggregation induced by PFFs in these brain regions. Conversely, 14-3-3 inhibition by difopein in the cortex and amygdala accelerated αsyn aggregation and reduction in NECAB1-positive neuron counts induced by PFFs. 14-3-3θ overexpression by AAV in the substantia nigra (SN) also delayed αsyn aggregation in the SN and partially rescued PFF-induced reduction in tyrosine hydroxylase (TH)-positive dopaminergic cells in the SN. 14-3-3 inhibition in the SN accelerated nigral αsyn aggregation and enhanced PFF-induced reduction in TH-positive dopaminergic cells. These data indicate a neuroprotective role for 14-3-3θ against αsyn toxicity in vivo.
The interaction of water with archaeological and ethnographic birch bark and its effects on swelling, shrinkage and deformations
Authors: Klügl Johanna , Di Pietro Giovanna
Published: January 2021

The aim of this study is to gain specific information on the water vapour interaction with archaeological and ethnographic birch bark. Water is involved in a number of curative and preventive conservation measurements e.g. when re-shaping or drying objects and when defining climate directives for long-term storage. We measured the sorption isotherm of archaeological, ethnographic and contemporary birch bark at different temperatures and analysed the moisture-induced size and shape changes (swelling, shrinkage, deformation) during humidification and drying. The analysis revealed that, compared to other organic materials like wood, the moisture uptake of outer birch bark is modest. This can be attributed to the cell structure and composition: outer birch bark is composed of closed cells made to a large extent of hydrophobic components (suberin, lignin). The equilibrium moisture content is higher if lenticels or inner bark are present. The extent of brittleness and delamination of the sample influences the sorption behaviour: the less brittle and delaminated archaeological birch bark is, the lower the equilibrium moisture content (EMC). Since the moisture uptake is modest, the related swelling of the outer bark is also modest, but anisotropic due to the cellular arrangement. Swelling is largest in the radial direction, smaller in longitudinal and negligible in tangential direction. Water vapour can plasticize birch bark and as birch bark becomes flexible, it bends towards the outside of the bark. This deformation takes place at high moisture contents and the adsorption process is slow. Based on these results recommendations on how best to perform treatments involving moisture and on relative humidity ranges for birch bark objects are provided.
Author self-citation in orthodontics is associated with author origin and gender
Authors: Livas Christos , Delli Konstantina , Pandis Nikolaos
Published: January 2021

Background

The aims of this bibliometric study were to determine author self-citation trends in high-impact orthodontic literature and to investigate possible association between self-citation and publication characteristics.

Methods

Six orthodontic journals with the highest impact factor as ranked by 2017 Journal Citation Reports were screened for a full publication year (2018) for original research articles, reviews, and case reports. Eligible articles were scrutinized for article and author characteristics and citation metrics. Univariable and multivariable negative binomial regression was used to examine associations between self-citation incidence and publication characteristics.

Results

Medians for author self-citation rate of the most self-citing authors and self-citations were 3.03% (range 0–50) and 1 (range 0–19), respectively. In the univariable analysis, there was no association between self-citation counts and study type (P = 0.41), article topic (P = 0.61), number of authors (P = 0.62), and rank of authors (P = 0.56). Author origin (P = 0.001), gender (P = 0.001) and journal (P = 0.05) were associated with self-citation counts and in the multivariable analysis only origin and gender remained strong self-citation predictors. Asian authors and females self-cited significantly less often than all other regions and male authors.

Conclusions

Authors in orthodontics do not self-cite at a frequency that suggests potential citation manipulation. Author origin and gender were the only variables associated with citations counts. More bibliometric research is necessary to draw solid conclusions about author self-citation trends in orthodontic literature.
Brain monitoring using near-infrared spectroscopy to predict outcome after cardiac arrest: a novel phenotype in a rat model of cardiac arrest
Authors: Takegawa Ryosuke , Hayashida Kei , Choudhary Rishabh , Rolston Daniel M. , Becker Lance B.
Published: January 2021

Improving neurological outcomes after cardiac arrest (CA) is the most important patient-oriented outcome for CA research. Near-infrared spectroscopy (NIRS) enables a non-invasive, real-time measurement of regional cerebral oxygen saturation. Here, we demonstrate a novel, non-invasive measurement using NIRS, termed modified cerebral oximetry index (mCOx), to distinguish the severity of brain injury after CA. We aimed to test the feasibility of this method to predict neurological outcome after asphyxial CA in rats. Our results suggest that mCOx is feasible shortly after resuscitation and can provide a surrogate measure for the severity of brain injury in a rat asphyxia CA model.
Non-submodular model for group profit maximization problem in social networks
Authors: Zhu Jianming , Ghosh Smita , Wu Weili , Gao Chuangen
Published: January 2021

In social networks, there exist many kinds of groups in which people may have the same interests, hobbies, or political orientation. Sometimes, group decisions are made by simply majority, which means that most of the users in this group reach an agreement, such as US Presidential Elections. A group is calledactivatedif$$\beta$$βpercent of users are influenced in the group. Enterprise will gain income from all influenced groups. Simultaneously, to propagate influence, enterprise needs pay advertisement diffusion cost.Group profit maximization(GPM) problem aims to pickkseeds to maximize the expected profit that considers the benefit of influenced groups with the diffusion cost. GPM is proved to be NP-hard and the objective function is proved to be neither submodular nor supermodular. An upper bound and a lower bound which are difference of two submodular functions are designed. We propose a submodular–modular algorithm (SMA) to solve the difference of two submodular functions and SMA is shown to converge to a local optimal. We present an randomized algorithm based on weighted group coverage maximization for GPM and apply sandwich framework to get theoretical results. Our experiments verify the efficiency of our methods.