bluuebunny/crossref_metadata_2025_split huggingface dataset:
Empagliflozin attenuates cardiac microvascular ischemia/reperfusion injury through improving mitochondrial homeostasis
Authors: Zou Rongjun , Shi Wanting , Qiu Junxiong , Zhou Na , Du Na , Zhou Hao , Chen Xinxin , Ma Li 
Published: June 2022

AbstractBackgroundEmpagliflozin has been reported to protect endothelial cell function, regardless of diabetes status. However, the role of empagliflozin in microvascular protection during myocardial ischemia reperfusion injury (I/R) has not been fully understood.MethodsElectron microscopy, western blots, immunofluorescence, qPCR, mutant plasmid transfection, co-immunoprecipitation were employed to explore whether empagliflozin could alleviate microvascular damage and endothelial injury during cardiac I/R injury.ResultsIn mice, empagliflozin attenuated I/R injury-induced microvascular occlusion and microthrombus formation. In human coronary artery endothelial cells, I/R injury led to adhesive factor upregulation, endothelial nitric oxide synthase inactivation, focal adhesion kinase downregulation, barrier dysfunction, cytoskeletal degradation and cellular apoptosis; however, empagliflozin treatment diminished these effects. Empagliflozin improved mitochondrial oxidative stress, mitochondrial respiration and adenosine triphosphate metabolism in I/R-treated human coronary artery endothelial cells by preventing the phosphorylation of dynamin-related protein 1 (Drp1) and mitochondrial fission 1 protein (Fis1), thus repressing mitochondrial fission. The protective effects of empagliflozin on mitochondrial homeostasis and endothelial function were abrogated by the re-introduction of phosphorylated Fis1, but not phosphorylated Drp1, suggesting that Fis1 dephosphorylation is the predominant mechanism whereby empagliflozin inhibits mitochondrial fission during I/R injury. Besides, I/R injury induced Fis1 phosphorylation primarily by activating the DNA-dependent protein kinase catalytic subunit (DNA-PKcs) pathway, while empagliflozin inactivated this pathway by exerting anti-oxidative effects.ConclusionsThese results demonstrated that empagliflozin can protect the microvasculature by inhibiting the DNA-PKcs/Fis1/mitochondrial fission pathway during myocardial I/R injury.
Cigarette smoke extract-mediated FABP4 upregulation suppresses viability and induces apoptosis, inflammation and oxidative stress of bronchial epithelial cells by activating p38 MAPK/MK2 signaling pathway
Authors: Zhang Wei , Zhang Yibin , Zhu Qi 
Published: June 2022

AbstractBackgroundLong-term inhalation of cigarette smoke is considered to be one of the main causes of bronchial epithelioid cell damage, but its underlying mechanism has to be further clarified.MethodsGene expression at mRNA level and protein levels were detected by qRT-PCR and western blot analysis respectively. CCK-8, TUNEL assays, ELISA, western blot analysis and commercial kits were utilized to test cell viability, apoptosis inflammatory response and oxidative stress. The correlation between fatty acid binding protein 4 (FABP4) and the p38 mitogen-activated protein kinase (MAPK)/MAPK activated kinase 2 (MK2) signaling pathway was verified by western blot analysis and rescue assays.ResultsCigarette smoke extract (CSE) exposure decreased viability, induced apoptosis and inflammatory response in 16HBE cells. Moreover, the expression of FABP4 in CSE-treated 16HBE cells was up-regulated in a time and dose-dependent manner. Ablation of FABP4 in 16HBE cells significantly protected against CSE-mediated cell viability decline and apoptosis. Further, FABP4 knockdown suppressed inflammatory response by down-regulating the elevated levels of cellular inflammatory factors including TNF-α, IL-1β, IL-6, Cyclooxygenase-2 (Cox-2) and inducible nitric oxide synthase (iNOS) in CSE-treated 16HBE cells. The oxidative stress induced by CSE in 16HBE cells was also inhibited by FABP4 silence as evidence by reduced ROS and MDA level but increased SOD activity caused by FABP4 silence. Finally, all the above effects of FABP4 silence on CSE-treated 16HBE cells were reversed by asiatic acid, an agonist of p38 mitogen-activated protein kinase (MAPK).ConclusionsThe up-regulation of FABP4 expression mediated by CSE exerted pro-inflammatory, pro-oxidative stress and pro-apoptotic effects on bronchial epithelial cells by activating the p38 MAPK/MK2 signaling pathway. Our findings help to further understand the underlying mechanism of cigarette smoke-induced bronchial inflammation.
Strategies to adapt and implement health system guidelines and recommendations: a scoping review
Authors: Breneol Sydney , Curran Janet A. , Marten Robert , Minocha Kirti , Johnson Catie , Wong Helen , Langlois Etienne V. , Wozney Lori , Vélez C. Marcela , Cassidy Christine , Juvekar Sanjay , Rothfus Melissa , Aziato Lydia , Keeping-Burke Lisa , Adjorlolo Samuel , Patiño-Lugo Daniel F. 
Published: June 2022

Abstract
Background
Evidence-based health system guidelines are pivotal tools to help outline the important financial, policy and service components recommended to achieve a sustainable and resilient health system. However, not all guidelines are readily translatable into practice and/or policy without effective and tailored implementation and adaptation techniques. This scoping review mapped the evidence related to the adaptation and implementation of health system guidelines in low- and middle-income countries.

Methods
We conducted a scoping review following the Joanna Briggs Institute methodology for scoping reviews. A search strategy was implemented in MEDLINE (Ovid), Embase, CINAHL, LILACS (VHL Regional Portal), and Web of Science databases in late August 2020. We also searched sources of grey literature and reference lists of potentially relevant reviews. All findings were reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews.

Results
A total of 41 studies were included in the final set of papers. Common strategies were identified for adapting and implementing health system guidelines, related barriers and enablers, and indicators of success. The most common types of implementation strategies included education, clinical supervision, training and the formation of advisory groups. A paucity of reported information was also identified related to adaptation initiatives. Barriers to and enablers of implementation and adaptation were reported across studies, including the need for financial sustainability. Common approaches to evaluation were identified and included outcomes of interest at both the patient and health system level.

Conclusions
The findings from this review suggest several themes in the literature and identify a need for future research to strengthen the evidence base for improving the implementation and adaptation of health system guidelines in low- and middle-income countries. The findings can serve as a future resource for researchers seeking to evaluate implementation and adaptation of health system guidelines. Our findings also suggest that more effort may be required across research, policy and practice sectors to support the adaptation and implementation of health system guidelines to local contexts and health system arrangements in low- and middle-income countries.
Transforming growth factor-β1 negatively regulates SOCS7 via EGR1 during wound healing
Authors: Feng Xiao , Feng Wei , Ji Yu , Jin Tingting , Li Jingyu , Guo Jincai 
Published: June 2022

Abstract
Background
TGF-β1 promotes keratinocyte migration and re-epithelialization of cutaneous wounds during the wound healing process. Decreased SOCS7 expression has been associated with increased healing potential. However, the relationship between TGF-β1 and SOCS7 in wound re-epithelialization remains unclear.

Objectives
To investigate the relationship between TGF-β1 and SOCS7 in the re-epithelialization of keratinocytes during skin wound healing.

Methods
The expression of SOCS7 under different concentrations of TGF-β1 was detected by WB and qPCR. The migration ability of keratinocytes was detected by scratch and Transwell assay. Protein interactions were detected by ChIP and luciferase assay. The effect of SOCS7 on skin healing in mice was detected in animal model.

Results
In this study, we found that SOCS7 was downregulated by TGF-β1 and that overexpression of SOCS7 led to suppression of TGF-β1-induced keratinocyte migration through inhibition of the PI3K/AKT and MEK/ERK pathways. Also, TGF-β1 negatively regulated SOCS7 expression at the transcriptional level through the binding of EGR1 to the EGR1/SP1 overlapping binding sites in the SOCS7 promoter.

Conclusion
Taken together, our findings show that TGF-β1-induced EGR1 expression is required for repression of SOCS7, which promotes keratinocyte migration and re-epithelialization during wound healing. Finally, our study identifies the TGF-β1/EGR1/SOCS7 pathway as a potential therapeutic target to promote wound healing.
GDF-11 promotes human trophoblast cell invasion by increasing ID2-mediated MMP2 expression
Authors: Wu Ze , Fang Lanlan , Yang Sizhu , Gao Yibo , Wang Zhen , Meng Qingxue , Dang Xuan , Sun Ying-Pu , Cheng Jung-Chien 
Published: June 2022

Abstract
Background
Growth differentiation factor-11 (GDF-11), also known as bone morphogenetic protein-11, belongs to the transforming growth factor-beta superfamily. GDF-11 was first identified as an important regulator during embryonic development. Increasing evidence has demonstrated that GDF-11 regulates the development of various organs and its aberrant expressions are associated with the risk of cardiovascular diseases and cancers. Extravillous trophoblast (EVT) cells invasion is a critical event for placenta development and needs to be finely regulated. However, to date, the biological function of GDF-11 in the human EVT cells remains unknown.

Methods
HTR-8/SVneo, a human EVT cell line, and primary cultures of human EVT cells were used to examine the effect of GDF-11 on matrix metalloproteinase 2 (MMP2) expression. Matrigel-coated transwell invasion assay was used to examine cell invasiveness. A series of in vitro experiments were applied to explore the underlying mechanisms that mediate the effect of GDF-11 on MMP2 expression and cell invasion.

Results
Treatment with GDF-11 stimulates MMP2 expression, in the HTR-8/SVneo and primary human EVT cells. Using a pharmacological inhibitor and siRNA-mediated knockdown approaches, our results demonstrated that the stimulatory effect of GDF-11 on MMP2 expression was mediated by the ALK4/5-SMAD2/3 signaling pathways. In addition, the expression of inhibitor of DNA-binding protein 2 (ID2) was upregulated by GDF-11 and that was required for the GDF-11-stimulated MMP2 expression and EVT cell invasion.

Conclusions
These findings discover a new biological function and underlying molecular mechanisms of GDF-11 in the regulation of human EVT cell invasion.
Sciatic nerve stimulation alleviates acute neuropathic pain via modulation of neuroinflammation and descending pain inhibition in a rodent model
Authors: Wong Chia-En , Hu Chia-Ying , Lee Po-Hsuan , Huang Chi-Chen , Huang Han-Wei , Huang Chih-Yuan , Lo Hsin-Tien , Liu Wentai , Lee Jung-Shun 
Published: June 2022

Abstract
Background
Neuropathic pain (NP) is characterized by abnormal activation of pain conducting pathways and manifests as mechanical allodynia and thermal hypersensitivity. Peripheral nerve stimulation is used for treatment of medically refractory chronic NP and has been shown to reduce neuroinflammation. However, whether sciatic nerve stimulation (SNS) is of therapeutic benefit to NP remains unclear. Moreover, the optimal frequency for SNS is unknown. To address this research gap, we investigated the effect of SNS in an acute NP rodent model.

Methods
Rats with right L5 nerve root ligation (NRL) or Sham surgery were used. Ipsilateral SNS was performed at 2 Hz, 20 Hz, and 60 Hz frequencies. Behavioral tests were performed to assess pain and thermal hypersensitivity before and after NRL and SNS. Expression of inflammatory proteins in the L5 spinal cord and the immunohistochemical alterations of spinal cord astrocytes and microglia were examined on post-injury day 7 (PID7) following NRL and SNS. The involvement of the descending pain modulatory pathway was also investigated.

Results
Following NRL, the rats showed a decreased pain threshold and latency on the von Frey and Hargreaves tests. The immunofluorescence results indicated hyperactivation of superficial spinal cord dorsal horn (SCDH) neurons. Both 2-Hz and 20-Hz SNS alleviated pain behavior and hyperactivation of SCDH neurons. On PID7, NRL resulted in elevated expression of spinal cord inflammatory proteins including NF-κB, TNF-α, IL-1β, and IL-6, which was mitigated by 2-Hz and 20-Hz SNS. Furthermore, 2-Hz and 20-Hz SNS suppressed the activation of spinal cord astrocytes and microglia following NRL on PID7. Activity of the descending serotoninergic pain modulation pathway showed an increase early on PID1 following 2-Hz and 20-Hz SNS.

Conclusions
Our results support that both 2-Hz and 20-Hz SNS can alleviate NP behaviors and hyperactivation of pain conducting pathways. We showed that SNS regulates neuroinflammation and reduces inflammatory protein expression, astrocytic gliosis, and microglia activation. During the early post-injury period, SNS also facilitates the descending pain modulatory pathway. Taken together, these findings support the therapeutic potential of SNS for acute NP.
Early-life stress elicits peripheral and brain immune activation differently in wild type and 5xFAD mice in a sex-specific manner
Authors: Bachiller S. , Hidalgo I. , Garcia M. G. , Boza-Serrano A. , Paulus A. , Denis Q. , Haikal C. , Manouchehrian O. , Klementieva O. , Li J. Y. , Pronk C. J. , Gouras G. K. , Deierborg T. 
Published: June 2022

AbstractBackgroundThe risk of developing Alzheimer’s disease (AD) is modulated by genetic and environmental factors. Early-life stress (ELS) exposure during critical periods of brain development can impact later brain function and health, including increasing the risk of developing AD. Microglial dysfunction and neuroinflammation have been implicated as playing a role in AD pathology and may be modulated by ELS. To complicate matters further, sex-specific effects have been noted in response to ELS and in the incidence and progression of AD.MethodsHere, we subjected male and female mice with either a wild type or 5xFAD familial AD-model background to maternal separation (MS) from postnatal day 2 to 14 to induce ELS.ResultsWe detected hippocampal neuroinflammatory alterations already at postnatal day 15. By 4 months of age, MS mice presented increased immobility time in the forced swim test and a lower discrimination index in the novel object recognition memory test compared to controls. We found alteredBdnfandArcexpression in the hippocampus and increased microglial activation in the prefrontal cortex due to MS in a sex-dependent manner. In 5xFAD mice specifically, MS exacerbated amyloid-beta deposition, particularly in females. In the periphery, the immune cell population was altered by MS exposure.ConclusionOverall, our results demonstrate that MS has both short- and long-term effects on brain regions related to memory and on the inflammatory system, both in the brain and periphery. These ELS-related effects that are detectable even in adulthood may exacerbate pathology and increase the risk of developing AD via sex-specific mechanisms.
FKBP51 mediates resilience to inflammation-induced anxiety through regulation of glutamic acid decarboxylase 65 expression in mouse hippocampus
Authors: Gan Yu-Ling , Wang Chen-Yu , He Rong-Heng , Hsu Pei-Chien , Yeh Hsin-Hsien , Hsieh Tsung-Han , Lin Hui-Ching , Cheng Ming-Yen , Jeng Chung-Jiuan , Huang Ming-Chyi , Lee Yi-Hsuan 
Published: June 2022

AbstractBackgroundInflammation is a potential risk factor of mental disturbance.FKBP5that encodes FK506-binding protein 51 (FKBP51), a negative cochaperone of glucocorticoid receptor (GR), is a stress-inducible gene and has been linked to psychiatric disorders. Yet, the role of FKBP51 in the inflammatory stress-associated mental disturbance remained unclear.MethodsFkbp5-deficient (Fkbp5-KO) mice were used to study inflammatory stress by a single intraperitoneal injection of lipopolysaccharide (LPS). The anxiety-like behaviors, neuroimaging, immunofluorescence staining, immunohistochemistry, protein and mRNA expression analysis of inflammation- and neurotransmission-related mediators were evaluated. A dexamethasone drinking model was also applied to examine the effect ofFkbp5-KO in glucocorticoid-induced stress.ResultsLPS administration induced FKBP51 elevation in the liver and hippocampus accompanied with transient sickness. Notably,Fkbp5-KO but not wild-type (WT) mice showed anxiety-like behaviors 7 days after LPS injection (LPS-D7). LPS challenge rapidly increased peripheral and central immune responses and hippocampal microglial activation followed by a delayed GR upregulation on LPS-D7, and these effects were attenuated inFkbp5-KO mice. Whole-brain [18F]-FEPPA neuroimaging, which target translocator protein (TSPO) to indicate neuroinflammation, showed thatFkbp5-KO reduced LPS-induced neuroinflammation in various brain regions including hippocampus. Interestingly, LPS elevated glutamic acid decarboxylase 65 (GAD65), the membrane-associated GABA-synthesizing enzyme, in the hippocampus of WT but notFkbp5-KO mice on LPS-D7. This FKBP51-dependent GAD65 upregulation was observed in the ventral hippocampal CA1 accompanied by the reduction of c-Fos-indicated neuronal activity, whereas both GAD65 and neuronal activity were reduced in dorsal CA1 in a FKBP51-independent manner. GC-induced anxiety was also examined, which was attenuated inFkbp5-KO and hippocampal GAD65 expression was unaffected.ConclusionsThese results suggest that FKBP51/FKBP5is involved in the systemic inflammation-induced neuroinflammation and hippocampal GR activation, which may contribute to the enhancement of GAD65 expression for GABA synthesis in the ventral hippocampus, thereby facilitating resilience to inflammation-induced anxiety.
Mediating role of depression in the association between alexithymia and nonsuicidal self-injury in a representative sample of adolescents in Taiwan
Authors: Tang Wen-Ching , Lin Min-Pei , Wu Jo Yung-Wei , Lee Yueh-Ting , You Jianing 
Published: June 2022

Abstract
Background
Nock’s (2009) integrated theoretical model suggests that specific intrapersonal vulnerability factors caused by distal risk factors contribute to the development of nonsuicidal self-injury (NSSI). Alexithymia and depression have been found to predict NSSI. Based on Nock’s model, alexithymia plays a distal risk factor role to increase the risk of depression—an intrapersonal vulnerability factor—and further increase the risk of NSSI. However, small or unrepresentative samples in past studies limit the generalizability of the results. This study examined the roles of depression and alexithymia in predicting NSSI, as well as the mediating effect of depression in the relation between alexithymia and NSSI in a large representative sample of adolescents in Taiwan.

Methods
Using a cross-sectional study design, a large representative sample of 2,170 senior high school students in Taiwan was assessed by self-report measures of alexithymia, depression, and NSSI. Mediation analyses were performed to examine whether the relation between alexithymia and NSSI was mediated by depression. The questionnaires were administered in classrooms.

Results
Results showed that alexithymia positively predicted NSSI (β = 0.23, p < .001) and depression can also positively predict NSSI (β = 0.41, p < .001). Additionally, the association between alexithymia and NSSI was fully mediated by depression.

Conclusions
This study data provided evidence for the mediating role of depression between alexithymia and NSSI, which can be explained by Nock’s (2009) integrated theoretical model. The implications of the findings for future research and intervention were discussed.
The development and validation of the Japanese version of job satisfaction scale: a cross-sectional study on home healthcare nurses
Authors: Mori Yoko , Sasaki Miki , Ogata Yasuko , Togari Taisuke 
Published: June 2022

Abstract
Objective
A reliable and valid tool is required to assess home healthcare nurses’ job satisfaction for evaluating and improving the work environment and clinical practice of home healthcare. This study aimed to develop and examine the Japanese version of the Home Healthcare Nurses’ Job Satisfaction Scale (HHNJS-J). The Home Healthcare Nurses’ Job Satisfaction Scale (HHNJS) was translated into Japanese; a backward translation was performed until equivalence between the original and the backward-translated HHNJS was confirmed. Subsequently, a mail survey was conducted among 409 home healthcare nurses from 154 home healthcare agencies in Japan. We evaluated construct validity through Confirmatory Factor Analysis (CFA), and criterion-related validity and internal consistency were also tested.

Results
The CFA revealed a second-order seven-factor structure and adequate internal consistency, although, the fit of the data to the factor structure was moderate. As per the goodness-of-fit indices of the final model of the CFA, the comparative fit index was 0.89 and root mean square error of approximation was 0.06. This newly translated scale can be used to assess the job satisfaction of home healthcare nurses within Japan. The HHNJS-J evaluated acceptable reliability and validity among Japanese home healthcare nurses and had application in clinical practice in Japan.
Comparison of decomposition algorithms for identification of single motor units in ultrafast ultrasound image sequences of low force voluntary skeletal muscle contractions
Authors: Rohlén Robin , Yu Jun , Grönlund Christer 
Published: June 2022

AbstractObjectiveIn this study, the aim was to compare the performance of four spatiotemporal decomposition algorithms (stICA, stJADE, stSOBI, and sPCA) and parameters for identifying single motor units in human skeletal muscle under voluntary isometric contractions in ultrafast ultrasound image sequences as an extension of a previous study. The performance was quantified using two measures: (1) the similarity of components’ temporal characteristics against gold standard needle electromyography recordings and (2) the agreement of detected sets of components between the different algorithms.ResultsWe found that out of these four algorithms, no algorithm significantly improved the motor unit identification success compared to stICA using spatial information, which was the best together with stSOBI using either spatial or temporal information. Moreover, there was a strong agreement of detected sets of components between the different algorithms. However, stJADE (using temporal information) provided with complementary successful detections. These results suggest that the choice of decomposition algorithm is not critical, but there may be a methodological improvement potential to detect more motor units.