bluuebunny/crossref_metadata_2025_split huggingface dataset:
Curcumin-primed human BMSC-derived extracellular vesicles reverse IL-1β-induced catabolic responses of OA chondrocytes by upregulating miR-126-3p
Authors: Li Shushan , Stöckl Sabine , Lukas Christoph , Herrmann Marietta , Brochhausen Christoph , König Matthias A. , Johnstone Brian , Grässel Susanne 
Published: April 2021

AbstractBackgroundCurcumin has anti-inflammatory effects and qualifies as a potential candidate for the treatment of osteoarthritis (OA). However, curcumin has limited bioavailability. Extracellular vesicles (EVs) are released by multiple cell types and act as molecule carrier during intercellular communication. We assume that EVs can maintain bioavailability and stability of curcumin after encapsulation. Here, we evaluated modulatory effects of curcumin-primed human (h)BMSC-derived EVs (Cur-EVs) on IL-1β stimulated human osteoarthritic chondrocytes (OA-CH).MethodsCellTiter-Blue Viability- (CTB), Caspase 3/7-, and live/dead assays were used to determine range of cytotoxic curcumin concentrations for hBMSC and OA-CH. Cur-EVs and control EVs were harvested from cell culture supernatants of hBMSC by ultracentrifugation. Western blotting (WB), transmission electron microscopy, and nanoparticle tracking analysis were performed to characterize the EVs. The intracellular incorporation of EVs derived from PHK26 labeled and curcumin-primed or control hBMSC was tested by adding the labeled EVs to OA-CH cultures. OA-CH were pre-stimulated with IL-1β, followed by Cur-EV and control EV treatment for 24 h and subsequent analysis of viability, apoptosis, and migration (scratch assay). Relative expression of selected anabolic and catabolic genes was assessed with qRT-PCR. Furthermore, WB was performed to evaluate phosphorylation of Erk1/2, PI3K/Akt, and p38MAPK in OA-CH. The effect of hsa-miR-126-3p expression on IL-1β-induced OA-CH was determined using CTB-, Caspase 3/7-, live/dead assays, and WB.ResultsCur-EVs promoted viability and reduced apoptosis of IL-1β-stimulated OA-CH and attenuated IL-1β-induced inhibition of migration. Furthermore, Cur-EVs increased gene expression of BCL2, ACAN, SOX9, and COL2A1 and decreased gene expression of IL1B, IL6, MMP13, and COL10A1 in IL-1β-stimulated OA-CH. In addition, phosphorylation of Erk1/2, PI3K/Akt, and p38 MAPK, induced by IL-1β, is prevented by Cur-EVs. Cur-EVs increased IL-1β-reduced expression of hsa-miR-126-3p and hsa-miR-126-3p mimic reversed the effects of IL-1β.ConclusionCur-EVs alleviated IL-1β-induced catabolic effects on OA-CH by promoting viability and migration, reducing apoptosis and phosphorylation of Erk1/2, PI3K/Akt, and p38 MAPK thereby modulating pro-inflammatory signaling pathways. Treatment of OA-CH with Cur-EVs is followed by upregulation of expression of hsa-miR-126-3p which is involved in modulation of anabolic response of OA-CH. EVs may be considered as promising drug delivery vehicles of curcumin helping to alleviate OA.
Towards physiologically relevant human pluripotent stem cell (hPSC) models of Parkinson’s disease
Authors: Coccia Elena , Ahfeldt Tim 
Published: April 2021

AbstractThe derivation of human embryonic stem cells followed by the discovery of induced pluripotent stem cells and leaps in genome editing approaches have continuously fueled enthusiasm for the development of new models of neurodegenerative diseases such as Parkinson’s disease (PD). PD is characterized by the relative selective loss of dopaminergic neurons (DNs) in specific areas of substantia nigra pars compacta (SNpc). While degeneration in late stages can be widespread, there is stereotypic early degeneration of these uniquely vulnerable neurons. Various causes of selective vulnerability have been investigated but much remains unclear. Most studies have sought to identify cell autonomous properties of the most vulnerable neurons. However, recent findings from genetic studies and model systems have added to our understanding of non-cell autonomous contributions including regional-specific neuro-immune interactions with astrocytes, resident or damage-activated microglia, neuro-glia cell metabolic interactions, involvement of endothelial cells, and damage to the vascular system. All of these contribute to specific vulnerability and, along with aging and environmental factors, might be integrated in a complex stressor-threshold model of neurodegeneration. In this forward-looking review, we synthesize recent advances in the field of PD modeling using human pluripotent stem cells, with an emphasis on organoid and complex co-culture models of the nigrostriatal niche, with emerging CRISPR applications to edit or perturb expression of causal PD genes and associated risk factors, such asGBA, to understand the impact of these genes on relevant phenotypes.
Fossilized leftover falls as sources of palaeoecological data: a ‘pabulite’ comprising a crustacean, a belemnite and a vertebrate from the Early Jurassic Posidonia Shale
Authors: Klug Christian , Schweigert Günter , Hoffmann René , Weis Robert , De Baets Kenneth 
Published: April 2021

AbstractEspecially in Lagerstätten with exceptionally preserved fossils, we can sometimes recognize fossilized remains of meals of animals. We suggest the term leftover fall for the event and the term pabulite for the fossilized meal when it never entered the digestive tract (difference to regurgitalites). Usually, pabulites are incomplete organismal remains and show traces of the predation. Pabulites have a great potential to inform about predation as well as anatomical detail, which is invisible otherwise. Here, we document a pabulite comprising the belemnitePassaloteuthis laevigatafrom the Toarcian of the Holzmaden region. Most of its soft parts are missing while the arm crown is one of the best preserved that is known. Its arms embrace an exuvia of a crustacean. We suggest that the belemnite represents the remnant of the food of a predatory fish such as the sharkHybodus.
Post-quantum Hermite–Hadamard type inequalities for interval-valued convex functions
Authors: Ali Muhammad Aamir , Budak Hüseyin , Murtaza Ghulam , Chu Yu-Ming 
Published: April 2021

AbstractIn this research, we introduce the notions of$(p,q)$(p,q)-derivative and integral for interval-valued functions and discuss their fundamental properties. After that, we prove some new inequalities of Hermite–Hadamard type for interval-valued convex functions employing the newly defined integral and derivative. Moreover, we find the estimates for the newly proved inequalities of Hermite–Hadamard type. It is also shown that the results proved in this study are the generalization of some already proved research in the field of Hermite–Hadamard inequalities.
An iterative scheme for split equality equilibrium problems and split equality hierarchical fixed point problem
Authors: Alansari Monairah 
Published: April 2021

AbstractThis paper deals with a split equality equilibrium problem for pseudomonotone bifunctions and a split equality hierarchical fixed point problem for nonexpansive and quasinonexpansive mappings. We suggest and analyze an iterative scheme where the stepsizes do not depend on the operator norms, the so-called simultaneous projected subgradient-proximal iterative scheme for approximating a common solution of the split equality equilibrium problem and the split equality hierarchical fixed point problem. Further, we prove a weak convergence theorem for the sequences generated by this scheme. Furthermore, we discuss some consequences of the weak convergence theorem. We present a numerical example to justify the main result.
Influence of physical activity and postural habits in schoolchildren with scoliosis
Authors: de Assis Sanderson José Costa , Sanchis Geronimo José Bouzas , de Souza Clécio Gabriel , Roncalli Angelo Giuseppe 
Published: April 2021

Abstract
Background
Scoliosis is considered one of the main musculoskeletal changes in childhood, and is characterized by three-dimensional changes in the spine. Schoolchildren is a group who are directly exposed to this condition because they go through a rapid growth phase in adolescence, added to other external factors such as school environment and daily living habits such as little physical activity. This study aimed to identify the risk factors associated with scoliosis in schoolchildren.

Methods
An observational, retrospective case control study with a quantitative approach was carried out in the city of Santa Cruz/RN. The presence of scoliosis was assessed using the Adams test and physical activity by the Daily Physical Activity Index (IPAQ) and by a questionnaire on competitive sports practice, in addition to a questionnaire on postural habits in childhood and adolescence. Conditional multiple logistic regression was performed for statistical analysis, and the adjusted Odds Ratios (OR) and the respective confidence intervals (95%) of the outcome variable were estimated.

Results
A total of 156 schoolchildren participated in the study, with an average age of 13.9 years, with 55.1% being female and 44.9% male, attending between the 6th grade of elementary school and the 3rd year of high school. Furthermore, 42.9% of these participants were considered irregularly active and only 33.3% practiced physical activity on a regular basis. After bivariate analysis and conditional logistic regression, little physical activity was shown to be a risk factor for scoliosis (p = 0.041; OR: 2.81; 95% CI: 1.04–7.57), while the postural habits evaluated in this study did not show a statistical association with scoliosis.

Conclusion
Low practice of physical activity and schoolchildren being classified as irregularly active were considered as risk factors for scoliosis, however postural habits do not seem to be associated with this condition.
Effectiveness and mechanisms of adipose-derived stem cell therapy in animal models of Parkinson’s disease: a systematic review and meta-analysis
Authors: Li Keya , Li Xinyue , Shi Guiying , Lei Xuepei , Huang Yiying , Bai Lin , Qin Chuan 
Published: April 2021

AbstractAnimal models provide an opportunity to assess the optimal treatment way and the underlying mechanisms of direct clinical application of adipose-derived stem cells (ADSCs). Previous studies have evaluated the effects of primitive and induced ADSCs in animal models of Parkinson’s disease (PD). Here, eight databases were systematically searched for studies on the effects and in vivo changes caused by ADSC intervention. Quality assessment was conducted using a 10-item risk of bias tool. For the subsequent meta-analysis, study characteristics were extracted and effect sizes were computed. Ten out of 2324 published articles (n = 169 animals) were selected for further meta-analysis. After ADSC therapy, the rotation behavior (10 experiments,n = 156 animals) and rotarod performance (3 experiments,n = 54 animals) were improved (P < 0.000 01 andP = 0.000 3, respectively). The rotation behavior test reflected functional recovery, which may be due to the neurogenesis from neuronally differentiated ADSCs, resulting in a higher pooled effect size of standard mean difference (SMD) (− 2.59; 95% CI, − 3.57 to − 1.61) when compared to that of primitive cells (− 2.18; 95% CI, − 3.29 to − 1.07). Stratified analyses by different time intervals indicated that ADSC intervention exhibited a long-term effect. Following the transplantation of ADSCs, tyrosine hydroxylase-positive neurons recovered in the lesion area with pooled SMD of 13.36 [6.85, 19.86]. Transplantation of ADSCs is a therapeutic option that shows long-lasting effects in animal models of PD. The potential mechanisms of ADSCs involve neurogenesis and neuroprotective effects. The standardized induction of neural form of transplanted ADSCs can lead to a future application in clinical practice.
Validation and standardization of DNA extraction and library construction methods for metagenomics-based human fecal microbiome measurements
Authors: Tourlousse Dieter M. , Narita Koji , Miura Takamasa , Sakamoto Mitsuo , Ohashi Akiko , Shiina Keita , Matsuda Masami , Miura Daisuke , Shimamura Mamiko , Ohyama Yoshifumi , Yamazoe Atsushi , Uchino Yoshihito , Kameyama Keishi , Arioka Shingo , Kataoka Jiro , Hisada Takayoshi , Fujii Kazuyuki , Takahashi Shunsuke , Kuroiwa Miho , Rokushima Masatomo , Nishiyama Mitsue , Tanaka Yoshiki , Fuchikami Takuya , Aoki Hitomi , Kira Satoshi , Koyanagi Ryo , Naito Takeshi , Nishiwaki Morie , Kumagai Hirotaka , Konda Mikiko , Kasahara Ken , Ohkuma Moriya , Kawasaki Hiroko , Sekiguchi Yuji , Terauchi Jun 
Published: April 2021

AbstractBackgroundValidation and standardization of methodologies for microbial community measurements by high-throughput sequencing are needed to support human microbiome research and its industrialization. This study set out to establish standards-based solutions to improve the accuracy and reproducibility of metagenomics-based microbiome profiling of human fecal samples.ResultsIn the first phase, we performed a head-to-head comparison of a wide range of protocols for DNA extraction and sequencing library construction using defined mock communities, to identify performant protocols and pinpoint sources of inaccuracy in quantification. In the second phase, we validated performant protocols with respect to their variability of measurement results within a single laboratory (that is, intermediate precision) as well as interlaboratory transferability and reproducibility through an industry-based collaborative study. We further ascertained the performance of our recommended protocols in the context of a community-wide interlaboratory study (that is, the MOSAIC Standards Challenge). Finally, we defined performance metrics to provide best practice guidance for improving measurement consistency across methods and laboratories.ConclusionsThe validated protocols and methodological guidance for DNA extraction and library construction provided in this study expand current best practices for metagenomic analyses of human fecal microbiota. Uptake of our protocols and guidelines will improve the accuracy and comparability of metagenomics-based studies of the human microbiome, thereby facilitating development and commercialization of human microbiome-based products.
TNF-α differentially modulates subunit levels of respiratory electron transport complexes of ER/PR +ve/−ve breast cancer cells to regulate mitochondrial complex activity and tumorigenic potential
Authors: Shinde Anjali , Jung Hyeryeon , Lee Hayun , Singh Kritarth , Roy Milton , Gohel Dhruv , Kim Han Byeol , Mane Minal , Vasiyani Hitesh , Currim Fatema , Seo Yu Ri , Yang Seojin , Cho Ara , Yi Eugene C. , Singh Rajesh 
Published: April 2021

Abstract
Background
Tumor necrosis factor-α (TNF-α) is an immunostimulatory cytokine that is consistently high in the breast tumor microenvironment (TME); however, its differential role in mitochondrial functions and cell survival in ER/PR +ve and ER/PR −ve breast cancer cells is not well understood.

Methods
In the current study, we investigated TNF-α modulated mitochondrial proteome using high-resolution mass spectrometry and identified the differentially expressed proteins in two different breast cancer cell lines, ER/PR positive cell line; luminal, MCF-7 and ER/PR negative cell line; basal-like, MDA-MB-231 and explored its implication in regulating the tumorigenic potential of breast cancer cells. We also compared the activity of mitochondrial complexes, ATP, and ROS levels between MCF-7 and MDA-MB-231 in the presence of TNF-α. We used Tumor Immune Estimation Resource (TIMER) webserver to analyze the correlation between TNF-α and mitochondrial proteins in basal and luminal breast cancer patients. Kaplan-Meier method was used to analyze the correlation between mitochondrial protein expression and survival of breast cancer patients.

Results
The proteome analysis revealed that TNF-α differentially altered the level of critical proteins of mitochondrial respiratory chain complexes both in MCF-7 and MDA-MB-231, which correlated with differential assembly and activity of mitochondrial ETC complexes. The inhibition of the glycolytic pathway in the presence of TNF-α showed that glycolysis is indispensable for the proliferation and clonogenic ability of MDA-MB-231 cells (ER/PR −ve) as compared to MCF-7 cells (ER/PR +ve). The TIMER database showed a negative correlation between the expressions of TNF-α and key regulators of mitochondrial OXPHOS complexes in basal breast vs lobular carcinoma. Conversely, patient survival analysis showed an improved relapse-free survival with increased expression of identified proteins of ETC complexes and survival of the breast cancer patients.

Conclusion
The evidence presented in our study convincingly demonstrates that TNF-α regulates the survival and proliferation of aggressive tumor cells by modulating the levels of critical assembly factors and subunits involved in mitochondrial respiratory chain supercomplexes organization and function. This favors the rewiring of mitochondrial metabolism towards anaplerosis to support the survival and proliferation of breast cancer cells. Collectively, the results strongly suggest that TNF-α differentially regulates metabolic adaptation in ER/PR +ve (MCF-7) and ER/PR −ve (MDA-MB-231) cells by modulating the mitochondrial supercomplex assembly and activity.
Vision loss, vision difficulty and psychological distress in South Africa: results from SANHANES-1
Authors: Akuffo Kwadwo Owusu , Sewpaul Ronel , Darrah Samson , Dukhi Natisha , Kumah David Ben , Agyei-Manu Eldad , Addo Emmanuel Kofi , Asare Akosua Kesewah , Osei Duah Isaiah , Reddy Priscilla 
Published: April 2021

Abstract
Background
Psychological distress in vision impairments and blindness is a complex issue and a major public health concern. Sudden adjustments in routine lifestyle and career aspirations in such persons culminate in and/or aggravate their level of stress. Yet, psychological distress in persons with visual difficulties and vision loss in South Africa is poorly understood. We investigated the association between psychological distress and self-reported vision difficulties as well as clinician-assessed vision loss using data from the South African National Health and Nutrition Examination Survey (SANHANES-1).

Methods
Data was analysed on participants aged ≥ 15 years who participated in the SANHANES-1 clinical examinations and interviews. Data on demographic, socio-economic, and health status variables were gathered using a structured questionnaire. Psychological distress was assessed using the Kessler psychological distress scale (K10). Vision assessment was conducted by clinicians adhering to standard protocols as well as by participants’ subjective response to vision-related questions. Vision loss was defined as presenting visual acuity worse than Snellen 6/12 in the better eye. Bivariate and multiple logistic regressions were used to examine the association between vision parameters and psychological distress.

Results
The analytic sample comprised 6859 participants with mean age of 38.4 years (60.8% females). The prevalence of psychological distress was 19.9%. After adjusting for demographics, socioeconomic, health risk and eye care variables, self-reported myopia (mild adjusted odds ratio [AOR] = 1.9, 95% CI 1.3–2.7; moderate AOR = 2.4, 95% CI 1.6–3.7; severe AOR = 3.6, 95% CI 1.8–7.3) and self-reported hyperopia (mild AOR = 1.7, 95% CI 1.2–2.5; moderate AOR = 2.4, 95% CI 1.5–3.8; severe AOR = 3.5, 95% CI 1.8–6.8) were significantly associated with psychological distress. While psychological distress was higher in patients with clinician assessed vision loss than those with normal vision, the association was not statistically significant after adjusting for confounders (AOR: 1.0, 95% CI 0.7–1.4).

Conclusions
Persons who self-reported vision difficulty experienced a higher prevalence of psychological distress. Therefore, comprehensive psychological care is needed for patients with eye disease or vision difficulties as part of a governmental strategy to provide mental health care for all South Africans.
Improving salinity tolerance in Salvia officinalis L. by foliar application of salicylic acid
Authors: Es-sbihi Fatima Zohra , Hazzoumi Zakaria , Aasfar Abderrahim , Amrani Joutei Khalid 
Published: April 2021

Abstract
Background
Higher absorption and translocation of sodium (Na) and chlorine (Cl) ions in plant tissue can lead to serious physiological and biochemical changes. However, salicylic acid (SA) is a natural signaling molecule responsible for the induction of environmental stress tolerance in plants. Spraying SA could provide protection against several types of stress such as salinity. This study aimed to show the influence of SA spraying (0.5 and 1 mM) on the damaging effects of NaCl toxicity (150 mM) in Salvia officinalis L. plants.

Results
The results showed that salinity strongly inhibited the growth of aerial and root parts and this inhibition was accompanied by a significant decrease in the production of chlorophyll pigments (by 63%). There was also a significant accumulation of Na, mainly in the roots. This accumulation of Na+ ions was accompanied by a decrease of calcium (Ca), potassium (K) and phosphorus (P) concentrations. However, SA mainly at 0.5 mM, greatly improved plant growth, essential oils and chlorophyll pigments synthesis. Besides, SA led to a decrease in Na content and an improvement in Ca, K and P content in the leaves and roots. Salt stress decreased the essential oil yield from 1.2% (control) to 0.4% (NaCl). Furthermore, gas chromatography–mass spectrometry analysis of essential oils exhibited that the 1,8-cineol, α-thujone, and camphor were identified as the main components of essential oils under all treatments. However, we noted in stressed plant treated or not with SA the appearance of the new majority compound thujanone. Salt stress decreased the major compounds content. SA spray under stress condition increased the content of major compounds compared to stressed plants untreated with SA. The histological study in scanning electron microscopy showed the peltate glands density decreased strongly under NaCl toxicity. However, SA application on stressed plants increased peltate glands density. On the other hand, the glands of stressed plants often show certain anomalies in the morphology: the first anomaly observed was the presence of glandular structures characterized by deformations in the form of small protuberances located on the head of the gland. The second, a less common abnormality is the morphological change in certain glands that change from a spherical to an ovoid shape. On another hand, all these anomalies were not detected in stressed plants sprayed with SA. Therefore, the absence of these anomalies under the effect of SA showed the repairing effect of this growth regulator.

Conclusion
The findings of the present work suggest that spraying of SA may be useful for improving the plant growth in NaCl-contaminated areas.