bluuebunny/crossref_metadata_2025 huggingface dataset:
Reproductive health and the politics of abortion
Authors: Blystad Astrid , Haukanes Haldis , Tadele Getnet , Moland Karen Marie
Published: March 2020

This editorial provides an overview of a thematic series that brings attention to the persistently deficient and unequal access to sexual and reproductive health services for young women in sub-Saharan Africa. It represents an effort to analyze the multifaceted relationship between laws, policies and access to services in Ethiopia, Zambia and Tanzania. Using a comparative perspective and qualitative research methodology, the papers presented in this issue explore legal, political and social factors and circumstances that condition access to sexual and reproductive health services within and across the three countries. Through these examples we show the often inconsistent and even paradoxical relationship between the formal law and practices on the ground. Particular emphasis is placed on safe abortion services as an intensely politicized issue in global sexual and reproductive health. In addition to the presentation of the individual papers, this editorial comments on the global politics of abortion which represents a critical context for the regional and local developments in sexual and reproductive health policy and care provision in general, and for the contentious issue of abortion in particular.
Rationally assembled albumin/indocyanine green nanocomplex for enhanced tumor imaging to guide photothermal therapy
Authors: An Feifei , Yang Zhao , Zheng Meichen , Mei Ting , Deng Guowei , Guo Ping , Li Yanan , Sheng Ruilong
Published: March 2020

Herein, a novel phototheranostic nanocomplex that is self-assembled from bovine serum albumin (BSA) and indocyanine green (ICG) is developed for enhanced near-infrared (NIR) fluorescence imaging, which benefits the guidance on in vivo cancer photothermal therapy (PTT). The study confirms that the binding of ICG with the bind sits on the albumin will result in improved hydrolytic stability and high photoluminescence quantum yield (PLQY). The ICG loading ratio in the nanocomplex is optimized and confirms the loading ratio of 0.5% ICG to be the optimal content. The optimized ICG–BSA nanocomplex (ICG–BSA NC) possesses a higher PLQY of 16.8% than that of free ICG (2.7%). The high PLQY and efficient passive targeting ability of ICG–BSA NC help improve its in vivo tumor accumulation and NIR fluorescence imaging significantly. Under laser irradiation, efficient PTT with obvious tumor growth suppression on a triple negative breast tumor model can be observed in the ICG–BSA NC treated group.
Characterization of VDR and CYP27B1 expression in the endometrium during the menstrual cycle before embryo transfer: implications for endometrial receptivity
Authors: Guo Jing , Liu Shan , Wang Peng , Ren Haiying , Li Yuan
Published: March 2020

Background

Molecular analyses of vitamin D in a typical cycling endometrium has received minimal research attention in the reproductive field. This study was designed to assess how expression of the endometrial vitamin D receptor (VDR) and CYP27B1, a vitamin D metabolizing enzyme, change during the menstrual cycle in women of reproductive age. In addition, this study explores the association between expression of vitamin D-VDR system and endometrial receptivity during the implantation window.

Methods

Sixteen patients underwent standardized in vitro fertilization (IVF) treatment and freeze-all techniques. Before embryo transfer, total serum 25(OH) D levels were determined through blood samples and VDR, CYP27B1, HOXA10, and CYP19 expression were determined through endometrial samples. Endometrial receptivity was also assessed using an electron microscope.

Results

We found that VDR protein expression was significantly lower throughout the endometrial secretory phase compared to the proliferative phase, while CYP27B1 expression remained constant during the menstrual cycle. During the implantation window, ultrastructural evaluation showed that higher serum vitamin D levels were associated with more mature pinopodes; VDR and HOXA10 protein expression were substantially elevated in pregnant women compared to non-pregnant women; and VDR protein levels were positively correlated with HOXA10 levels. In addition, serum vitamin D levels were positively correlated with VDR and HOXA10 protein levels in the endometrium.

Conclusions

Women with increased VDR expression in the endometrium, especially during the implantation window of the menstrual cycle, were significantly more likely to be pregnant than women with decreased expression. Our results support the hypothesis that the Vitamin D-VDR system performs a role during the development of endometrial receptivity.
Glucose, insulin, insulin receptor subunits α and β in normal and spontaneously diabetic and obese ob/ob and db/db infertile mouse testis and hypophysis
Authors: Pelletier R.-Marc , Layeghkhavidaki Hamed , Vitale María L.
Published: March 2020

Background

Type 2 diabetes touches young subjects of reproductive age in epidemic proportion. This study assesses glucose, total InsulinT, Insulin2 and insulin receptor subunits α and β in testis during mouse development then, in the spontaneously type 2 diabetes models associated with infertilitydb/dbandob/obmice. IR-β and α were also assessed in spermatozoa (SPZ), anterior pituitary (AP) and serum.

Methods

Serum and tissue glucose were measured with enzymatic colorimetric assays and InsulinT and Insulin2 by ELISAs in serum, interstitial tissue- (ITf) and seminiferous tubule (STf) fractions in14- > 60-day-old normal anddb/db,ob/oband wild type (WT) mice. IR subunits were assessed by immunoblotting in tissues and by immunoprecipitation followed by immunoblotting in serum.

Results

Development: Glucose increased in serum, ITf and STf. InsulinT and Insulin2 dropped in serum; both were higher in STf than in ITf. In > 60-day-old mouse ITf, insulinT rose whereas Insulin2 decreased; InsulinT and Insulin2 rose concurrently in STf. Glucose and insulin were high in > 60-day-old ITf; in STf high insulin2 accompanied low glucose. One hundred ten kDa IR-β peaked in 28-day-old ITf and 14-day-old STf. One hundred thirty five kDa IR-α was high in ITf but decreased in STf.

Glucose escalated indb/dbandob/obsera. Glucose doubled in ITf while being halved in STf indb/dbmice. Glucose significantly dropped indb/dbandob/obmice spermatozoa. InsulinT and Insulin2 rose significantly in the serum, ITf and STf indb/dbandob/obmice. One hundred ten kDa IR-β and 135 kDa IR-α decreased indb/dbandob/obITf. Only 110 kDa IR-β dropped indb/dbandob/obSTf and AP. One hundred ten kDa IR-β fell indb/dbandob/obSPZ. One hundred ten kDasIR-α rose in thedb/dbandob/obmouse sera.

Conclusion

Insulin regulates glucose in tubules not in the interstitium. The mouse interstitium contains InsulinT and Insulin2 whereas tubules contain Insulin2. Decreased 110 kDa IR-β and 135 kDa IR-α in thedb/dbandob/obinterstitial tissue suggest a loss of active receptor sites that could alter the testicular cell insulin binding and response to the hormone. Decreased IR-β levels were insufficient to stimulate downstream effectors in AP and tubules. IR-α shedding increased indb/dbandob/obmice.
Effectiveness of prescribing physical activity in parks to improve health and wellbeing - the park prescription randomized controlled trial
Authors: Müller-Riemenschneider Falk , Petrunoff Nicholas , Yao Jiali , Ng Alwyn , Sia Angelia , Ramiah Anbumalar , Wong Michael , Han Jane , Tai Bee Choo , Uijtdewilligen Léonie
Published: March 2020

Background

Programs promoting population health through physical activity (PA) and exposure to nature are popular, but few have been evaluated in randomized-controlled trials (RCTs).

Objective

To investigate the effectiveness of a park prescription intervention (PPI) for improving total moderate-to-vigorous PA (MVPA), other PA related behaviors, quality of life (QoL) and cardio-metabolic health among adults.

Methods

Healthy individuals aged 40 to 65 years were recruited through community health screenings and randomly assigned to 1) PPI: face-to-face Park Prescription + invitation to weekly exercise sessions in parks, or 2) control: standard PA materials. After the six-month intervention, participants completed accelerometer assessments, questionnaires on health behaviors and QoL, and health screenings. Independent sample t-tests were used to compare outcomes between groups, with secondary analysis adjusted for co-variates via multiple linear regression. A p-value <0.05 was considered statistically significant.

Results

Eighty participants were allocated to each group. Participants with mean age of 51.1 (Standard Deviation: 6.3) years were predominantly female (79%) and of Chinese ethnicity (81%). Participation in the group exercise started at 48% and declined to 24% by week 26. At six-months, 145 (91%) participants attended health screenings for outcome measure collection, and 126 (79%) provided valid accelerometer data. Time spent in MVPA favored the PPI group but this difference was not statistically significant (4.4 (− 43.8, 52.7) minutes/week; when removing 2 extreme outliers 26.8 (− 9.7, 63.4) minutes/week). Time spent in parks (147.5 (2.1, 292.9) minutes/month), PA in parks (192.5 (59.5, 325.5) minutes/month), and recreational PA (48.7 (1.4, 96.0) minutes/week) were significantly greater in the PPI group. PPI also significantly improved psychological QoL (4.0 (0.0, 8.0).

Discussion

PPI improved park use, PA in parks, recreational PA, and psychological QoL but not total MVPA. Future RCTs’ are warranted to investigate PPI in different target populations and to provide further evidence for improvements in health outcomes.

Trial registration

ClinicalTrials.gov NCT02615392, 26 November 2015.
Characteristics of the urinary microbiome in kidney stone patients with hypertension
Authors: Liu Fengping , Zhang Nan , Jiang Peng , Zhai Qixiao , Li Chen , Yu Deshui , Wu Yan , Zhang Yuwei , Lv Longxian , Xu Xinyu , Feng Ninghan
Published: March 2020

Background

Kidney stone disease (KSD) is more common in individuals with hypertension (HTN) than in individuals with normotension (NTN). Urinary dysbiosis is associated with urinary tract disease and systemic diseases. However, the role of the urinary microbiome in KSD complicated with HTN remains unclear.

Methods

This study investigated the relationship between the pelvis urinary microbiome and blood pressure (BP) in patients with KSD co-occurring with HTN (KSD-HTN) and healthy controls (HC) by conducting 16S rRNA gene sequencing of bacteria in urine samples. The urine samples were collected (after bladder disinfection) from 50 patients with unilateral kidney calcium stones and NTN (n = 12), prehypertension (pHTN; n = 11), or HTN (n = 27), along with 12 HCs.

Results

Principal coordinates analysis showed that there were significant differences in the urinary microbiomes not only between KSD patients and HCs but also between KSD-pHTN or KSD-HTN patients and KSD-NTN patients. Gardnerella dominated in HCs, Staphylococcus dominated in KSD-NTN patients and Sphingomonas dominated in both KSD-pHTN and KSD-HTN patients. The abundance of several genera including Acidovorax, Gardnerella and Lactobacillus was correlated with BP. Adherens junction and nitrogen and nucleotide metabolism pathways, among others, were associated with changes in BP.

Conclusions

The findings suggest that patients with KSD complicated with HTN have a unique urinary microbiome profile and that changes in the microbiome may reflect disease progression and may be useful to monitor response to treatments.
Transitional B cells involved in autoimmunity and their impact on neuroimmunological diseases
Authors: Zhou Yang , Zhang Ying , Han Jinming , Yang Mengge , Zhu Jie , Jin Tao
Published: March 2020

Transitional B cells (TrB cells) represent a crucial link between immature B cells in the bone marrow and mature peripheral B cells. Although TrB cells represent one of the regulatory B cell subpopulations in healthy individuals, the frequency of CD24hiCD38hi TrB cells in circulation may be altered in individuals with autoimmune diseases, such as multiple sclerosis, neuromyelitisoptica spectrum disorders, systemic lupus erythematosus, Sjögren’s syndrome, rheumatoid arthritis, systemic sclerosis, and juvenile dermatomyositis. Although TrB cells play regulatory roles under inflammatory conditions, consequences of their functional impairment vary across autoimmune diseases. Since the origin, development, and function of TrB cells, especially in humans, remain unclear and controversial, this review aimed to discuss the characteristics of TrB cells at steady state and explore their role in various immune diseases, including autoimmune rheumatic diseases and neuroimmunological diseases.
A case of rectal ulcers during aspirin therapy in acute Kawasaki disease
Authors: Han Yong , Hu Chenmin , Yu Yanping
Published: March 2020

Kawasaki disease (KD) is an acute febrile multisystem vasculitis and has been recognized to be one of the most common causes of acquired heart disease in children. Although gastrointestinal symptoms including vomiting, diarrhea, and abdominal pain are not uncommon in KD patients, KD with lower gastrointestinal bleeding is quite rare. Here, we describe a 3-year-old boy with typical KD who had lower gastrointestinal bleeding caused by rectal ulcers on the third day of aspirin therapy.
Distinct cortical activity patterns in Parkinson’s disease and essential tremor during a bimanual tapping task
Authors: Luft Frauke , Sharifi Sarvi , Mugge Winfred , Schouten Alfred C. , Bour Lo J. , van Rootselaar Anne Fleur , Veltink Peter H. , Heida Tijtske
Published: March 2020

Background

Parkinson’s disease (PD) and essential tremor (ET) are neurodegenerative diseases characterized by movement deficits. Especially in PD, maintaining cyclic movement can be significantly disturbed due to pathological changes in the basal ganglia and the cerebellum. Providing external cues improves timing of these movements in PD and also affects ET. The aim of this study is to determine differences in cortical activation patterns in PD and ET patients during externally and internally cued movements.

Methods

Eleven PD patients, twelve ET patients, OFF tremor suppressing medication, and nineteen age-matched healthy controls (HC) were included and asked to perform a bimanual tapping task at two predefined cue frequencies. The auditory cue, a metronome sound presented at 2 or 4 Hz, was alternately switched on and off every 30 s. Tapping at two different frequencies were used since it is expected that different brain networks are involved at different frequencies as has been shown in previous studies. Cortical activity was recorded using a 64-channel EEG cap. To establish the cortical activation pattern in each group, the task related power (TRP) was calculated for each subject. For inter-groups analysis, EEG electrodes for divided into 5 different areas.

Results

Inter-group analysis revealed significant differences in areas responsible for motor planning, organization and regulation and involved in initiation, maintenance, coordination and planning of complex sequences of movements. Within the area of the primary motor cortex the ET group showed a significantly lower TRP than the HC group. In the area responsible for combining somatosensory, auditory and visual information both patient groups had a higher TRP than the HC group.

Conclusions

Different neurological networks are involved during cued and non-cued movements in ET, PD and HC. Distinct cortical activation patterns were revealed using task related power calculations. Different activation patterns were revealed during the 2 and 4 Hz tapping task indicating different strategies to execute movements at these rates. The results suggest that a including a cued/non-cued tapping task during clinical decision making could be a valuable tool in an objective diagnostic protocol.
Prevalence of acquired drug resistance mutations in antiretroviral- experiencing subjects from 2012 to 2017 in Hunan Province of central South China
Authors: Zou Xiaobai , He Jianmei , Zheng Jun , Malmgren Roberta , Li Weisi , Wei Xiuqing , Zhang Guoqiang , Chen Xi
Published: March 2020

Background

There are few data on the prevalence of acquired drug resistance mutations (ADRs) in Hunan Province, China, that could affect the effectiveness of antiretroviral therapy (ART).

Objectives

The main objectives of this study were to determine the prevalence of acquired drug resistance (ADR) the epidemic characteristics of HIV-1-resistant strains among ART-failed HIV patients in Hunan Province, China.

Methods

ART-experienced and virus suppression failure subjects in Hunan between 2012 and 2017 were evaluated by genotyping analysis and mutations were scored using theHIVdb.stanford.edualgorithm to infer drug susceptibility.

Results

The prevalence of HIV-1 ADR were 2.76, 2.30, 2.98, 2.62, 2.23and 2.17%, respectively, from 2012 to 2017. Overall 2295 sequences were completed from 2932 ART-failure patients, and 914 of these sequences were found to have drug resistance mutation. The most common subtype was AE (64.14%), followed by BC (17.91%) and B (11.50%). Among those 914 patients with drug resistance mutations,93.11% had NNRTI-associated drug resistance mutations, 74.40% had NRTI drug resistance mutations (DRMs) and 6.89% had PI DRMs. Dual-class mutations were observed in 591 (64.66%) cases, and triple-class mutations were observed in 43 (4.70%) cases. M184V (62.04%), K103N (41.90%) and I54L (3.83%) were the most common observed mutations, respectively, in NRTI-, NNRTI- and PI-associated drug resistance. 93.76% subjects who had DRMs received the ART first-line regimens. CD4 count, symptoms in the past 3 months, and ART adherence were found to be associated with HIV-1 DR.

Conclusions

This study showed that although the prevalence of HIV-acquired resistance in Hunan Province is at a low-level, the long-term and continuous surveillance of HIV ADR in antiretroviral drugs (ARVs) patients is necessary.
Effects of interoceptive training on decision making, anxiety, and somatic symptoms
Authors: Sugawara Ayako , Terasawa Yuri , Katsunuma Ruri , Sekiguchi Atsushi
Published: March 2020

Background

Interoception is the perception of afferent information that arises from any point within the body. Individual differences in interoception have been associated with affective processing and decision-making processing. The somatic marker hypothesis summarizes the potential effects of interoception on decision-making processes. According to this theory, individuals with interoceptive dysfunction exhibit disadvantageous decision making. Recently, enhancement of interoceptive accuracy, an element of interoception assessed by objective decision-making tasks, has been demonstrated using biofeedback. Garfinkle et al. developed an interoceptive training task, modified from the heartbeat perception task, which enhanced interoceptive accuracy and reduced anxiety symptoms. The purpose of this study was to determine the effects of interoceptive training on decision-making processes. Based on improvements in interoceptive accuracy, we hypothesized that decision-making scores would change in a manner indicative of increased rationality.

Methods

This longitudinal interventional study was performed with interoceptive training. Before and after the intervention, interoceptive accuracy and rationality of decision-making processes were assessed using a heartbeat perception task and rational decision-making tasks, respectively. Fourteen healthy volunteers (nine women; mean age, 21.9 ± 4.5 years) participated. The analysis included data from 12 participants. To detect individual differences in the effects of interoceptive accuracy on rationality of decision making, correlation analysis was conducted on change ratios of the indices of interoceptive accuracy and rationality of decision making.

Results

Interoceptive training resulted in significant enhancement of interoceptive accuracy scores and significant reductions in somatic symptom and state anxiety scores. In contrast, interoceptive training did not cause significant changes in decision-making indices. There was a significant positive correlation between change ratios of indices of interoceptive accuracy and rationality of decision making.

Conclusions

The results suggested a causal relation between interoception and rationality of decision making. These findings will enhance the understanding of mechanisms underlying alterations of decision-making related to psychotherapy by focusing on interoception.

Trial registration

Trial registration number: UMIN000037548.
Tumor burden is a potential marker of PARP inhibitor effects in ovarian cancer: a head-to-head observational series
Authors: Ni Jing , Zhou Rui , Cheng Xianzhong , Xu Xia , Guo Wenwen , Chen Xiaoxiang
Published: March 2020

Background

Olaparib, a poly ADP-ribose polymerase (PARP) inhibitor, has proven to be effective and safe as maintenance therapy and multiline therapy in ovarian cancer, especially in patients with BRCA mutations. This study intended to observe the influence of tumor load on the efficacy and safety of olaparib in recurrent ovarian cancer.

Cases presentation

Three patients harbored gBRCAwt with low tumor load (LTL), while two women harbored BRCAmt with high tumor load (HTL) were recruited. Two of the three LTL patients achieved partial response, and the other showed stable disease. Both HTL patients were assessed to have progressive disease in a short time. Olaparib appears to be effective and safe for LTL recurrent ovarian cancer patients even if it is gBRCAwt, while the response is poor in HTL patients.

Conclusions

Tumor load may be another potential marker to predict the effect of PARP inhibitors. The present head-to-head observational series provides new evidence on this issue for further research from bench to bedside in the future.
Benchmarking of computational error-correction methods for next-generation sequencing data
Authors: Mitchell Keith , Brito Jaqueline J. , Mandric Igor , Wu Qiaozhen , Knyazev Sergey , Chang Sei , Martin Lana S. , Karlsberg Aaron , Gerasimov Ekaterina , Littman Russell , Hill Brian L. , Wu Nicholas C. , Yang Harry Taegyun , Hsieh Kevin , Chen Linus , Littman Eli , Shabani Taylor , Enik German , Yao Douglas , Sun Ren , Schroeder Jan , Eskin Eleazar , Zelikovsky Alex , Skums Pavel , Pop Mihai , Mangul Serghei
Published: March 2020

Background

Recent advancements in next-generation sequencing have rapidly improved our ability to study genomic material at an unprecedented scale. Despite substantial improvements in sequencing technologies, errors present in the data still risk confounding downstream analysis and limiting the applicability of sequencing technologies in clinical tools. Computational error correction promises to eliminate sequencing errors, but the relative accuracy of error correction algorithms remains unknown.

Results

In this paper, we evaluate the ability of error correction algorithms to fix errors across different types of datasets that contain various levels of heterogeneity. We highlight the advantages and limitations of computational error correction techniques across different domains of biology, including immunogenomics and virology. To demonstrate the efficacy of our technique, we apply the UMI-based high-fidelity sequencing protocol to eliminate sequencing errors from both simulated data and the raw reads. We then perform a realistic evaluation of error-correction methods.

Conclusions

In terms of accuracy, we find that method performance varies substantially across different types of datasets with no single method performing best on all types of examined data. Finally, we also identify the techniques that offer a good balance between precision and sensitivity.
Efficacy of Tuina in patients with chronic low back pain: study protocol for a randomized controlled trial
Authors: Zhang Shuaipan , Kong Lingjun , Zhu Qingguang , Wu Zhiwei , Li Jianhua , Fang Min , Sun Wuquan , Cheng Yanbin , Xu Shanda , Guo Guangxin , Zhou Xin , Lv Zhizhen
Published: March 2020

Background

Low back pain is a common reason for medical care and carries a heavy social burden. The efficacy of Tuina or health care education for low back pain has been evaluated in previous systematic reviews. However, there is no evidence to support the superiority of one form of treatment over another. The aim of this study is to compare the efficacy of Tuina with health care education in the management of low back pain.

Methods/design

This study is a randomized controlled trial with parallel-group design including two groups: a Tuina group and a health care education group. A total of 160 eligible participants will be randomly assigned to the groups in a 1:1 ratio. The interventions of both groups will last for 20 min and be carried out twice each week for a period of 12 weeks. The primary outcome is the Oswestry Disability Index. The secondary outcomes include a visual analogue scale and the 36-item Short Form Health Survey. They will be assessed at baseline, at the end of the intervention every month, and during 6 months and 9 months of follow-up by repeated measures analysis of variance. The significance level is 5%. The safety of Tuina and health care education will be evaluated after each treatment session. This study will focus on the value of Tuina and health care education for low back pain and will highlight any differences in the efficacy of the treatments.

Discussion

This study will evaluate the efficacy and safety of Tuina intervention for low back pain, which could provide reliable evidence for clinical decision making for patients with low back pain.

Trial registration

Chinese Clinical Trial Registry, ChiCTR1900022656. Registered on 23 April 2019.
Drosophila enabled promotes synapse morphogenesis and regulates active zone form and function
Authors: McNeill Elizabeth M. , Thompson Cheryl , Berke Brett , Chou Vivian T. , Rusch Jannette , Duckworth April , DeProto Jamin , Taylor Alicia , Gates Julie , Gertler Frank , Keshishian Haig , Van Vactor David
Published: March 2020

Background

Recent studies of synapse form and function highlight the importance of the actin cytoskeleton in regulating multiple aspects of morphogenesis, neurotransmission, and neural plasticity. The conserved actin-associated protein Enabled (Ena) is known to regulate development of the Drosophila larval neuromuscular junction through a postsynaptic mechanism. However, the functions and regulation of Ena within the presynaptic terminal has not been determined.

Methods

Here, we use a conditional genetic approach to address a presynaptic role for Ena on presynaptic morphology and ultrastructure, and also examine the pathway in which Ena functions through epistasis experiments.

Results

We find that Ena is required to promote the morphogenesis of presynaptic boutons and branches, in contrast to its inhibitory role in muscle. Moreover, while postsynaptic Ena is regulated by microRNA-mediated mechanisms, presynaptic Ena relays the output of the highly conserved receptor protein tyrosine phosphatase Dlar and associated proteins including the heparan sulfate proteoglycan Syndecan, and the non-receptor Abelson tyrosine kinase to regulate addition of presynaptic varicosities. Interestingly, Ena also influences active zones, where it restricts active zone size, regulates the recruitment of synaptic vesicles, and controls the amplitude and frequency of spontaneous glutamate release.

Conclusion

We thus show that Ena, under control of the Dlar pathway, is required for presynaptic terminal morphogenesis and bouton addition and that Ena has active zone and neurotransmission phenotypes. Notably, in contrast to Dlar, Ena appears to integrate multiple pathways that regulate synapse form and function.
The protective role of the 3-mercaptopyruvate sulfurtransferase (3-MST)-hydrogen sulfide (H2S) pathway against experimental osteoarthritis
Authors: Nasi Sonia , Ehirchiou Driss , Chatzianastasiou Athanasia , Nagahara Noriyuki , Papapetropoulos Andreas , Bertrand Jessica , Cirino Giuseppe , So Alexander , Busso Nathalie
Published: March 2020

Background

Osteoarthritis (OA) is characterized by the formation and deposition of calcium-containing crystals in joint tissues, but the underlying mechanisms are poorly understood. The gasotransmitter hydrogen sulfide (H2S) has been implicated in mineralization but has never been studied in OA. Here, we investigated the role of the H2S-producing enzyme 3-mercaptopyruvate sulfurtransferase (3-MST) in cartilage calcification and OA development.

Methods

3-MST expression was analyzed in cartilage from patients with different OA degrees, and in cartilage stimulated with hydroxyapatite (HA) crystals. The modulation of 3-MST expression in vivo was studied in the meniscectomy (MNX) model of murine OA, by comparing sham-operated to MNX knee cartilage. The role of 3-MST was investigated by quantifying joint calcification and cartilage degradation in WT and 3-MST−/−meniscectomized knees. Chondrocyte mineralization in vitro was measured in WT and 3-MST−/−cells. Finally, the effect of oxidative stress on 3-MST expression and chondrocyte mineralization was investigated.

Results

3-MST expression in human cartilage negatively correlated with calcification and OA severity, and diminished upon HA stimulation. In accordance, cartilage from menisectomized OA knees revealed decreased 3-MST if compared to sham-operated healthy knees. Moreover, 3-MST−/−mice showed exacerbated joint calcification and OA severity if compared to WT mice. In vitro,genetic or pharmacologic inhibition of 3-MST in chondrocytes resulted in enhanced mineralization and IL-6 secretion. Finally, oxidative stress decreased 3-MST expression and increased chondrocyte mineralization, maybe via induction of pro-mineralizing genes.

Conclusion

3-MST-generated H2S protects against joint calcification and experimental OA. Enhancing H2S production in chondrocytes may represent a potential disease modifier to treat OA.
Selection of human induced pluripotent stem cells lines optimization of cardiomyocytes differentiation in an integrated suspension microcarrier bioreactor
Authors: Laco Filip , Lam Alan Tin-Lun , Woo Tsung-Liang , Tong Gerine , Ho Valerie , Soong Poh-Loong , Grishina Elina , Lin Kun-Han , Reuveny Shaul , Oh Steve Kah-Weng
Published: March 2020

Background

The production of large quantities of cardiomyocyte is essential for the needs of cellular therapies. This study describes the selection of a human-induced pluripotent cell (hiPSC) line suitable for production of cardiomyocytes in a fully integrated bioprocess of stem cell expansion and differentiation in microcarrier stirred tank reactor.

Methods

Five hiPSC lines were evaluated first for their cardiac differentiation efficiency in monolayer cultures followed by their expansion and differentiation compatibility in microcarrier (MC) cultures under continuous stirring conditions.

Results

Three cell lines were highly cardiogenic but only one (FR202) of them was successfully expanded on continuous stirring MC cultures. FR202 was thus selected for cardiac differentiation in a 22-day integrated bioprocess under continuous stirring in a stirred tank bioreactor. In summary, we integrated a MC-based hiPSC expansion (phase 1), CHIR99021-induced cardiomyocyte differentiation step (phase 2), purification using the lactate-based treatment (phase 3) and cell recovery step (phase 4) into one process in one bioreactor, under restricted oxygen control (< 30% DO) and continuous stirring with periodic batch-type media exchanges. High density of undifferentiated hiPSC (2 ± 0.4 × 106 cells/mL) was achieved in the expansion phase. By controlling the stirring speed and DO levels in the bioreactor cultures, 7.36 ± 1.2 × 106 cells/mL cardiomyocytes with > 80% Troponin T were generated in the CHIR99021-induced differentiation phase. By adding lactate in glucose-free purification media, the purity of cardiomyocytes was enhanced (> 90% Troponin T), with minor cell loss as indicated by the increase in sub-G1 phase and the decrease of aggregate sizes. Lastly, we found that the recovery period is important for generating purer and functional cardiomyocytes (> 96% Troponin T). Three independent runs in a 300-ml working volume confirmed the robustness of this process.

Conclusion

A streamlined and controllable platform for large quantity manufacturing of pure functional atrial, ventricular and nodal cardiomyocytes on MCs in conventional-type stirred tank bioreactors was established, which can be further scaled up and translated to a good manufacturing practice-compliant production process, to fulfill the quantity requirements of the cellular therapeutic industry.
Adipose stem cells isolated from diabetic mice improve cutaneous wound healing in streptozotocin-induced diabetic mice
Authors: An Ran , Zhang Yong , Qiao Yu , Song Lili , Wang Hongjun , Dong Xiao
Published: March 2020

Background

Adipose-derived mesenchymal stem cells (ASCs) therapy is emerging as a novel therapeutic option for the treatment of a variety of diseases including diabetes and diabetic wound healing. Multiple studies indicate that ASCs could promote wound healing and reverse diabetes. However, whether ASCs from diabetic donors retain their therapeutic functions and the mechanisms of how ASCs contribute to wound healing remain largely unknown. In this study, we explored the cutaneous wound healing ability of ASCs collected from C57BL/6 mice that had been rendered diabetic with streptozotocin (STZ).

Methods

ASCs were harvested from adipose tissues of type 1 diabetic (T1D) or normal C57BL/6 mice. Cell phenotypes were evaluated by flow cytometry analysis, and cell differentiation into adipocytes, chondrocytes, and osteocytes was compared. Secretions of transforming growth factor β (TGF-β1), basic fibroblast growth factor (bFGF), and vascular endothelial growth factor (VEGF) by ASCs were assessed by ELISA. Migration and proliferation of fibroblasts co-cultured with T1D ASCs or control ASCs were also compared. The therapeutic effects of T1D and control ASCs in promoting wound closure were measured in vivo in a T1D wound mouse model. Granulation tissues were collected and stained with H&E at 14th day. CD34 and collagen I were detected by immunohistochemistry. Expressions of IL-6, α-SMA, CD31, collagen I, and collagen III were quantified by real-time PCR. GFP-expressing ASCs were used to trace in vivo cell differentiation.

Results

T1D ASCs and control ASCs showed similar expression of cell surface markers (CD29, CD34, CD105) and proliferation pattern. They can both differentiate into different cell types. T1D ASCs secreted similar amounts of VEGF and bFGF, but less TGF-β compared with control ASCs. Like control ASCs, T1D ASCs promoted the proliferation and migration of skin fibroblast cells. When injected in cutaneous wound of T1D mice, T1D ASCs increased wound closure and hair follicle regeneration at a comparable extent as ASCs. Mice receiving T1D ASCs or ASCs exhibited significantly higher expressions of collagen I, collagen III, and CD31 and reduced expression of IL-6 in wound tissues. Immunohistochemistry staining showed increased angiogenesis in mice receiving ASCs as was evident by increased CD34+ cells and collagen I staining. GFP+ ASCs injection showed that ASCs differentiated into fibroblasts and endothelial cells in vivo.

Conclusions

Our results suggest that T1D ASCs could accelerate cutaneous wound healing. Mechanisms may include increasing fibroblast growth and migration, skin angiogenesis, and differentiation into fibroblasts and endothelial cells. This study provides evidence that diabetic ASCs may be used as a therapeutic option in cutaneous wound healing in diabetic recipients.
Neocortical tissue recovery in severe congenital obstructive hydrocephalus after intraventricular administration of bone marrow-derived mesenchymal stem cells
Authors: García-Bonilla María , Ojeda-Pérez Betsaida , García-Martín María L. , Muñoz-Hernández M. Carmen , Vitorica Javier , Jiménez Sebastián , Cifuentes Manuel , Santos-Ruíz Leonor , Shumilov Kirill , Claros Silvia , Gutiérrez Antonia , Páez-González Patricia , Jiménez Antonio J.
Published: March 2020

Background

In obstructive congenital hydrocephalus, cerebrospinal fluid accumulation is associated with high intracranial pressure and the presence of periventricular edema, ischemia/hypoxia, damage of the white matter, and glial reactions in the neocortex. The viability and short time effects of a therapy based on bone marrow-derived mesenchymal stem cells (BM-MSC) have been evaluated in such pathological conditions in the hyh mouse model.

Methods

BM-MSC obtained from mice expressing fluorescent mRFP1 protein were injected into the lateral ventricle of hydrocephalic hyh mice at the moment they present a very severe form of the disease. The effect of transplantation in the neocortex was compared with hydrocephalic hyh mice injected with the vehicle and non-hydrocephalic littermates. Neural cell populations and the possibility of transdifferentiation were analyzed. The possibility of a tissue recovering was investigated using 1H High-Resolution Magic Angle Spinning Nuclear Magnetic Resonance (1H HR-MAS NMR) spectroscopy, thus allowing the detection of metabolites/osmolytes related with hydrocephalus severity and outcome in the neocortex. An in vitro assay to simulate the periventricular astrocyte reaction conditions was performed using BM-MSC under high TNFα level condition. The secretome in the culture medium was analyzed in this assay.

Results

Four days after transplantation, BM-MSC were found undifferentiated and scattered into the astrocyte reaction present in the damaged neocortex white matter. Tissue rejection to the integrated BM-MSC was not detected 4 days after transplantation. Hyh mice transplanted with BM-MSC showed a reduction in the apoptosis in the periventricular neocortex walls, suggesting a neuroprotector effect of the BM-MSC in these conditions. A decrease in the levels of metabolites/osmolytes in the neocortex, such as taurine and neuroexcytotoxic glutamate, also indicated a tissue recovering. Under high TNFα level condition in vitro, BM-MSC showed an upregulation of cytokine and protein secretion that may explain homing, immunomodulation, and vascular permeability, and therefore the tissue recovering.

Conclusions

BM-MSC treatment in severe congenital hydrocephalus is viable and leads to the recovery of the severe neurodegenerative conditions in the neocortex. NMR spectroscopy allows to follow-up the effects of stem cell therapy in hydrocephalus.
Targeting prostate cancer stem-like cells by an immunotherapeutic platform based on immunogenic peptide-sensitized dendritic cells-cytokine-induced killer cells
Authors: Wang Zhu , Li Youjia , Wang Yuliang , Wu Dinglan , Lau Alaster Hang Yung , Zhao Pan , Zou Chang , Dai Yong , Chan Franky Leung
Published: March 2020

Background

Autologous cellular immunotherapy or immune enhancement therapy has demonstrated some promising benefits for prostate cancer. T cell-based immunotherapy or sipuleucel-T therapy has yielded certain beneficial responses and a slight improvement on the overall survival of patients with metastatic castration-resistant prostate cancer (mCRPC) as shown in some clinical trials, suggesting that prostate cancer is immunoresponsive.

Methods

In this study, we developed an adaptive cytokine-induced killer cell (CIK)-based immunotherapeutic application targeting the prostate cancer stem-like cells (PCSCs). In this therapeutic platform, dendritic cells (DC) were isolated from the peripheral blood mononuclear cells (PBMCs) and preloaded or sensitized with immunogenic peptides derived from two PCSC-associated cell membrane molecules, CD44 and EpCAM, followed by co-culture with the expanded peripheral blood lymphocyte (PBL)-derived CIK cells. The in vitro cytotoxic activity of DC-activated CIK cells against PCSCs was determined by CCK8 and TUNEL assays, and the in vivo anti-tumor effect of DC-activated CIK cells on prostate cancer xenograft tumors was evaluated in subcutaneous and orthotopic xenograft models.

Results

Our results showed that the peptide-sensitized DC-CIK cell preparation manifested significant in vitro cytotoxic activity against the PCSC-enriched prostatospheroids and also in vivo anti-tumor effect against prostate cancer xenografts derived from the PCSC-enriched prostatospheroids.

Conclusions

Together, our established immunogenic peptide-sensitized DC-CIK-based cell preparation platform manifests its potential immunotherapeutic application in targeting the PCSCs and also prostate cancer.
Screening for efficient nitrogen sources for overproduction of the biomass of the functionally probiotic L. plantarum strain RPR42 in a cane molasses-based medium
Authors: Papizadeh Moslem , Rohani Mahdi , Hosseini Seyed Nezamedin , Shojaosadati Seyed Abbas , Nahrevanian Hossein , Talebi Malihe , Pourshafie Mohammad Reza
Published: March 2020

Nitrogen source has a vital role for the efficient growth of lactobacilli. The effects of cheese whey, corn steep liquor, and wheat germ extract on the growth of L. plantarum strain RPR42 in cane molasses-based media was evaluated using various approaches of design of experiments. Our results showed that such protein-rich agricultural by-products significantly increase the biomass production of the strain RPR42 in cane molasses-based media. The most affecting nitrogenous material was cheese whey followed by CSL and the minor effect was reported for wheat germ extract as revealed in factorial and Box–Behnken design experiments. The replacement of costly beef extract and yeast extract with a defined mixtures of the above nitrogenous agricultural by-products in cane molasses-based medium led to production of up to 12.64 g/L/24 h of dry biomass of strain RPR42. A detectable cell density of strain RPR42 (~ 9.81 × 109 CFU/mL 24 h) which was observed in such an economic medium showed that the large-scale production of the strain RPR42 tend to be feasible at significantly low costs.
Mapping evidence on the prevalence, incidence, risk factors and cost associated with chronic low back pain among adults in Sub-Saharan Africa: a systematic scoping review protocol
Authors: Kahere Morris , Ginindza Themba
Published: March 2020

Background

Globally, low back pain (LBP) is a major public health problem affecting mainly adults of the working class and is the leading cause of disability. The estimated lifetime prevalence of LBP is 50 to 80%. From 1990 to 2015, the years lived with disability caused by LBP have scaled up by 54% with the greatest increase observed in low-middle-income countries (LMICs). LBP poses a significant socio-economic burden to the society regardless of all the technological advancement in diagnosis and intervention approaches in recent years. Despite an increase in the literature of LBP in LMICs, chronic low back pain (CLBP) is poorly investigated yet it is responsible for the largest amount of burden. The purpose of this scoping review is to map the existing evidence on the prevalence, incidence, mortality, risk factors, and cost associated with CLBP among adults in Sub-Saharan Africa (SSA).

Methods

We will conduct a scoping review to explore, describe, and map literature on the prevalence, incidence, mortality, risk factors, and costs associated with CLBP among adults in SSA. The search will be performed using the EBSCOhost platform by searching the following databases within the platform: Academic search complete, health source: nursing/academic edition, CINAHL with full text, Embase, PubMed, MEDLINE, Science Direct databases, Google Scholar, and the World Health Organization library databases. The search will include peer-reviewed, review articles, and gray literature. The first (title and abstract) and the second (full text) screening phases will be performed by two independent reviewers, with the third reviewer employed to adjudicate discrepancies. The reference list of all included articles will also be searched for eligible articles. This scoping review will be reported in accordance to the MOOSE and PRISMA-ScR guidelines. The NVivo 12 data analysis software will be used to generate themes, and a thematic content analysis will be used to give the narrative account of the review.

Discussion

The study anticipates finding relevant literature on the prevalence, incidence, risk factors, mortality, and cost associated with CLBP among adults in SSA. The study outcomes will aid in identifying research gaps, planning, informing policy, commissioning of future research, and funding prioritization.
Sustainability indices for energy utilization using a multi-criteria decision model
Authors: Suganthi L.
Published: March 2020

Background

Energy and water availability are considered vital for a country’s development. An exhaustive review of literature has been undertaken on indicators for sustainable energy development. In addition to energy and water, the resources of the country namely land availability, human capital, and nation’s wealth were also found to be vital for sustainable energy development of any country. These resources have to be optimally used for sustainable energy development which is measured in terms of technical, economic, social, environmental, and institutional indices.

Methods

In this research, a multi-criteria decision model was used to measure sustainable energy development efficiency. The natural resource of the country was considered as the input criteria, while the indices were used as the output criteria. This research is unique in finding if the country’s resources are being utilized in an efficient manner for sustainable development using the multi-criteria fuzzy-analytical hierarchical processing—data envelopment analysis model.

Results

From the fuzzy analytical hierarchical processing, it was found that experts were of the opinion that water availability and energy reserves were the most important parameters among the input resources, while environmental and social indices were opined to be the most important parameters among the output indices. Data envelopment analysis model was carried out using assurance region Charnes, Cooper, and Rhodes output-oriented method. The results revealed that Togo was the most efficient country with maximum sustainable energy development efficiency. Sensitivity analysis was also carried out to find which among the resources were sensitive with respect to energy sustainability for a specific country.

Conclusion

The analysis can help countries to benchmark themselves against the country lying in the efficient frontier and draft policies to improve their energy sustainability indices. Similar analysis and comparison can be done for other countries, since this research analysis was carried out only for 48 developing countries.