bluuebunny/crossref_metadata_2025 huggingface dataset:
Somatosensory Cortical Electrical Stimulation After Reperfusion Attenuates Ischemia/Reperfusion Injury of Rat Brain
Authors: Wang Liang-Chao , Wei Wei-Yen , Ho Pei-Chuan , Wu Pei-Yi , Chu Yuan-Ping , Tsai Kuen-Jer
Published: November 2021

Objective: Ischemic stroke is an important cause of death and disability worldwide. Early reperfusion by thrombolysis or thrombectomy has improved the outcome of acute ischemic stroke. However, the therapeutic window for reperfusion therapy is narrow, and adjuvant therapy for neuroprotection is demanded. Electrical stimulation (ES) has been reported to be neuroprotective in many neurological diseases. In this study, the neuroprotective effect of early somatosensory cortical ES in the acute stage of ischemia/reperfusion injury was evaluated.

Methods: In this study, the rat model of transient middle cerebral artery occlusion was used to explore the neuroprotective effect and underlying mechanisms of direct primary somatosensory (S1) cortex ES with an electric current of 20 Hz, 2 ms biphasic pulse, 100 μA for 30 min, starting at 30 min after reperfusion.

Results: These results showed that S1 cortical ES after reperfusion decreased infarction volume and improved functional outcome. The number of activated microglia, astrocytes, and cleaved caspase-3 positive neurons after ischemia/reperfusion injury were reduced, demonstrating that S1 cortical ES alleviates inflammation and apoptosis. Brain-derived neurotrophic factor (BDNF) and phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway were upregulated in the penumbra area, suggesting that BDNF/TrkB signals and their downstream PI3K/Akt signaling pathway play roles in ES-related neuroprotection.

Conclusion: This study demonstrates that somatosensory cortical ES soon after reperfusion can attenuate ischemia/reperfusion injury and is a promising adjuvant therapy for thrombolytic treatment after acute ischemic stroke. Advanced techniques and devices for high-definition transcranial direct current stimulation still deserve further development in this regard.
Ethanol Alleviates Amyloid-β-Induced Toxicity in an Alzheimer’s Disease Model of Caenorhabiditis elegans
Authors: Bai Shuju , Wang Wenbo , Zhang Zhiwei , Li Mengyao , Chen Zehan , Wang Jiuqiao , Zhao Yanlin , An Lu , Wang Yuxiang , Xing Shu , Fu Xueqi , Ma Junfeng
Published: November 2021

Amyloid-β, a hallmark of Alzheimer’s disease, forms toxic intracellular oligomers and extracellular senile plaques resulting in neuronal toxicity. Ethanol is widely consumed worldwide. Moderate ethanol consumption has numerous benefits in humans. We found that ethanol could significantly extend the lifespan of Caenorhabiditis elegans in a previous study. Based on that study, we tested the effect of ethanol on Alzheimer’s disease transgenic Caenorhabiditis elegans strain CL4176, which expresses amyloid-β1-42 peptide in body wall muscle cells. Ethanol delayed paralysis and reduced amyloid-β oligomers in Caenorhabiditis elegans worms of the CL4176 strain. Moreover, ethanol could induce the nuclear translocation of DAF-16 in the nematodes. However, in worms that were fed daf-16 RNAi bacteria, ethanol no longer delayed the paralysis. The qPCR assays showed that ethanol increases the expression of daf-16, hsf-1 and their common target genes- small heat shock protein genes. In addition, we also found that ethanol could increase lysosome mass in the CL4176 worms. In summary, our study indicated that ethanol attenuated amyloid-β toxicity in the Alzheimer’s disease model of Caenorhabiditis elegans via increasing the level of lysosomes to promote amyloid-β degradation and upregulating the levels of small heat shock protein genes to reduce amyloid-β aggregation.
The Potential Role of miRNAs in Cognitive Frailty
Authors: Carini Giulia , Musazzi Laura , Bolzetta Francesco , Cester Alberto , Fiorentini Chiara , Ieraci Alessandro , Maggi Stefania , Popoli Maurizio , Veronese Nicola , Barbon Alessandro
Published: November 2021

Frailty is an aging related condition, which has been defined as a state of enhanced vulnerability to stressors, leading to a limited capacity to meet homeostatic demands. Cognitive impairment is also frequent in older people, often accompanying frailty. Age is the main independent risk factor for both frailty and cognitive impairment, and compelling evidence suggests that similar age-associated mechanisms could underlie both clinical conditions. Accordingly, it has been suggested that frailty and cognitive impairment share common pathways, and some authors proposed “cognitive frailty” as a single complex phenotype. Nevertheless, so far, no clear common underlying pathways have been discovered for both conditions. microRNAs (miRNAs) have emerged as key fine-tuning regulators in most physiological processes, as well as pathological conditions. Importantly, miRNAs have been proposed as both peripheral biomarkers and potential molecular factors involved in physiological and pathological aging. In this review, we discuss the evidence linking changes of selected miRNAs expression with frailty and cognitive impairment. Overall, miR-92a-5p and miR-532-5p, as well as other miRNAs implicated in pathological aging, should be investigated as potential biomarkers (and putative molecular effectors) of cognitive frailty.
Expression Patterns of the Neuropeptide Urocortin 3 and Its Receptor CRFR2 in the Mouse Central Auditory System
Authors: Pagella Sara , Deussing Jan M. , Kopp-Scheinpflug Conny
Published: November 2021

Sensory systems have to be malleable to context-dependent modulations occurring over different time scales, in order to serve their evolutionary function of informing about the external world while also eliciting survival-promoting behaviors. Stress is a major context-dependent signal that can have fast and delayed effects on sensory systems, especially on the auditory system. Urocortin 3 (UCN3) is a member of the corticotropin-releasing factor family. As a neuropeptide, UCN3 regulates synaptic activity much faster than the classic steroid hormones of the hypothalamic-pituitary-adrenal axis. Moreover, due to the lack of synaptic re-uptake mechanisms, UCN3 can have more long-lasting and far-reaching effects. To date, a modest number of studies have reported the presence of UCN3 or its receptor CRFR2 in the auditory system, particularly in the cochlea and the superior olivary complex, and have highlighted the importance of this stress neuropeptide for protecting auditory function. However, a comprehensive map of all neurons synthesizing UCN3 or CRFR2 within the auditory pathway is lacking. Here, we utilize two reporter mouse lines to elucidate the expression patterns of UCN3 and CRFR2 in the auditory system. Additional immunolabelling enables further characterization of the neurons that synthesize UCN3 or CRFR2. Surprisingly, our results indicate that within the auditory system, UCN3 is expressed predominantly in principal cells, whereas CRFR2 expression is strongest in non-principal, presumably multisensory, cell types. Based on the presence or absence of overlap between UCN3 and CRFR2 labeling, our data suggest unusual modes of neuromodulation by UCN3, involving volume transmission and autocrine signaling.
Impact of Chronic Obstructive Pulmonary Disease on Infectious Complications and Mortality in Patients With Aneurysmal Subarachnoid Hemorrhage
Authors: Yang Lan , Zhang Yu , Yao Wei , Fang Fang , Li Weimin
Published: November 2021

Background and Purpose:Chronic obstructive pulmonary disease (COPD) has been associated with several complications and mortality in acutely ill patients. For patients with aneurysmal subarachnoid hemorrhage (aSAH), the association between COPD and clinical outcomes remains unclear.

Methods:In this retrospective cohort study, we analyzed consecutive aSAH patients admitted to the West China Hospital between 2014 and 2019. Propensity score matching analysis and cox regression models was used to assess the association between COPD and mortality. The primary outcome was long-term mortality.

Results:Using a clinical database from a large university medical center, 2,925 patients with aSAH were identified, of whom 219 (7.5%) also had COPD. Patients were followed-up for a median of 3.8 years, and during follow-up 633 patients (21.6%) died. Long-term mortality was higher in patients with COPD compared to patients without COPD in the Cox regression models [adjusted hazard ratio (HR) 1.52, 95% confidence interval (CI) 1.14–2.02]. Propensity score matching analysis also showed similar associations between COPD and mortality in hospital, at 1 year, at 2 years, and at long-term. Similarly, patients with COPD had significantly higher incidence of infections, such as pneumonia [odds ratio (OR) 3.24, 95% CI 2.30–4.56], urinary tract infection (OR 1.81, 95% CI 1.20–2.73), bloodstream infection (OR 3.83, 95% CI 1.84–7.99), and hospital infection (OR 3.24, 95% CI 2.28–4.61).

Conclusions:Among aSAH patients, COPD is associated with increased mortality. COPD represents a significant risk factor for infections. Given that these are preventable complications, our findings are of clinical relevance.
Top 100 Most-Cited Papers in Neuropathic Pain From 2000 to 2020: A Bibliometric Study
Authors: Xiong Huan-Yu , Liu Hao , Wang Xue-Qiang
Published: November 2021

Background: Neuropathic pain research has grown impressively in the past two decades, as evidenced by improvements in research quality and increments in the number of research papers. In views of this situation, the use of quantitative measurements to analyze and characterize existing research has become imperative. The aim of this research is to identify and analyze the 100 most-cited papers in neuropathic pain research.

Methods: Neuropathic pain-related articles published between 2000 and 2020 were screened from Web of Science (WOS) by using the following subject terms: TI = (Neuralgia$ OR Neurodynia$ OR “Neuropathic pain” OR sciatica OR “Nerve pain$”). The publications were ranked in a descending order on the basis of citation counts, and the top 100 most-cited neuropathic pain papers were determined. Subsequently, we conducted a bibliometric study to determine the authors, journals, countries, and institutions that contributed the most to the top 100 neuropathic pain lists; describe the keywords and hotspots of the top 100 most-cited papers; and explore the factors associated with successful citations.

Results: The top 100 most-cited papers were published from 2000 to 2017, and 2003 had the largest number of published papers (n = 16). The mean number of citations per paper was 480.72, with a range of 262–1,569. Forty-four kinds of journals contributed to the top 100 most-cited papers, which were predominantly published in “Pain” (n = 23). The USA was determined to be the leader of neuropathic pain research in terms of quality and quantity.

Conclusion: This study provides a comprehensive list of the most influential papers on neuropathic pain and demonstrates the important advances in this field to help understand academic concerns and the directions of technological innovations in neuropathic pain worldwide.
Effects of Meditation on Structural Changes of the Brain in Patients With Mild Cognitive Impairment or Alzheimer’s Disease Dementia
Authors: Dwivedi Madhukar , Dubey Neha , Pansari Aditya Jain , Bapi Raju Surampudi , Das Meghoranjani , Guha Maushumi , Banerjee Rahul , Pramanick Gobinda , Basu Jayanti , Ghosh Amitabha
Published: November 2021

Previous cross-sectional studies reported positive effects of meditation on the brain areas related to attention and executive function in the healthy elderly population. Effects of long-term regular meditation in persons with mild cognitive impairment (MCI) and Alzheimer’s disease dementia (AD) have rarely been studied. In this study, we explored changes in cortical thickness and gray matter volume in meditation-naïve persons with MCI or mild AD after long-term meditation intervention. MCI or mild AD patients underwent detailed clinical and neuropsychological assessment and were assigned into meditation or non-meditation groups. High resolution T1-weighted magnetic resonance images (MRI) were acquired at baseline and after 6 months. Longitudinal symmetrized percentage changes (SPC) in cortical thickness and gray matter volume were estimated. Left caudal middle frontal, left rostral middle frontal, left superior parietal, right lateral orbitofrontal, and right superior frontal cortices showed changes in both cortical thickness and gray matter volume; the left paracentral cortex showed changes in cortical thickness; the left lateral occipital, left superior frontal, left banks of the superior temporal sulcus (bankssts), and left medial orbitofrontal cortices showed changes in gray matter volume. All these areas exhibited significantly higher SPC values in meditators as compared to non-meditators. Conversely, the left lateral occipital, and right posterior cingulate cortices showed significantly lower SPC values for cortical thickness in the meditators. In hippocampal subfields analysis, we observed significantly higher SPC in gray matter volume of the left CA1, molecular layer HP, and CA3 with a trend for increased gray matter volume in most other areas. No significant changes were found for the hippocampal subfields in the right hemisphere. Analysis of the subcortical structures revealed significantly increased volume in the right thalamus in the meditation group. The results of the study point out that long-term meditation practice in persons with MCI or mild AD leads to salutary changes in cortical thickness and gray matter volumes. Most of these changes were observed in the brain areas related to executive control and memory that are prominently at risk in neurodegenerative diseases.
Is Fecal Calprotectin an Applicable Biomarker of Gut Immune System Activation in Chronic Inflammatory Demyelinating Polyneuropathy? – A Pilot Study
Authors: Koszewicz Magdalena , Mulak Agata , Dziadkowiak Edyta , Budrewicz Sławomir
Published: November 2021

Introduction:Chronic inflammatory demyelinating polyneuropathy (CIDP) is a complex autoimmune disease caused by dysregulated response to not fully recognized antigens. Some association between CIDP and inflammatory bowel disease (IBD) has been reported, but the exact pathophysiological links of these disorders are not well understood.

Aim of the Study:To evaluate fecal calprotectin as a biomarker of gut inflammation in CIDP patients without IBD.

Methods:Fifteen patients with CIDP and 15 healthy controls were included in the study. The CIDP diagnosis was based on the EFNS/PNS criteria. The occurrence of bowel symptoms was assessed based on a questionnaire. The quantitative evaluation of fecal calprotectin level was performed by the ELISA test.

Results:The fecal calprotectin level (μg/g) expressed as median along with the lower and upper quartiles [25Q–75Q] was significantly higher in CIDP patients compared to the controls: 26.6 [17.5–109.0] vs 15.6 [7.1–24.1],p= 0.0066. Abnormal fecal calprotectin level (>50 μg/g) was found in 33% of all CIDP patients and in none of the control subjects. The patients with abnormal fecal calprotectin level did not differ from the rest of the study group regarding the neurological status. The most common bowel symptoms reported by CIDP patients included constipation (33%), feeling of incomplete evacuation (33%), bloating (27%), and alternating bowel movement pattern (27%).

Conclusion:In one-third of CIDP patients the signs of gut immune system activation have been observed. This finding may be associated with CIDP pathogenesis and induction of autoimmune response as well as concomitant dysautonomia with gastrointestinal symptoms.
The Immediate Effects of Intermittent Theta Burst Stimulation of the Cerebellar Vermis on Cerebral Cortical Excitability During a Balance Task in Healthy Individuals: A Pilot Study
Authors: Tan Hui-Xin , Wei Qing-Chuan , Chen Yi , Xie Yun-Juan , Guo Qi-Fan , He Lin , Gao Qiang
Published: November 2021

Objective:This pilot study aimed to investigate the immediate effects of single-session intermittent theta-burst stimulation (iTBS) on the cerebellar vermis during a balance task, which could unveil the changes of cerebral cortical excitability in healthy individuals.

Subjects:A total of seven right-handed healthy subjects (26.86 ± 5.30 years) were included in this study.

Interventions:Each subject received single-session iTBS on cerebellar vermis in a sitting position.

Main Measures:Before and after the intervention, all subjects were asked to repeat the balance task of standing on the left leg three times. Each task consisted of 15 s of standing and 20 s of resting. Real-time changes in cerebral cortex oxygen concentrations were monitored with functional near-infrared spectroscopy (fNIRS). During the task, changes in blood oxygen concentration were recorded and converted into the mean HbO2for statistical analysis.

Results:After stimulation, the mean HbO2in the left SMA (P= 0.029) and right SMA (P= 0.043) significantly increased compared with baseline. However, no significant changes of mean HbO2were found in the bilateral dorsolateral prefrontal lobe (P> 0.05).

Conclusion:Single-session iTBS on the cerebellar vermis in healthy adults can increase the excitability of the cerebral cortex in the bilateral supplementary motor areas during balance tasks.

Clinical Trial Registration:[www.ClinicalTrials.gov], identifier [ChiCTR2100048915].
Defining a Path Toward the Use of Fast-Scan Cyclic Voltammetry in Human Studies
Authors: Lucio Boschen Suelen , Trevathan James , Hara Seth A. , Asp Anders , Lujan J. Luis
Published: November 2021

Fast Scan Cyclic Voltammetry (FSCV) has been used for decades as a neurochemical tool for in vivo detection of phasic changes in electroactive neurotransmitters in animal models. Recently, multiple research groups have initiated human neurochemical studies using FSCV or demonstrated interest in bringing FSCV into clinical use. However, there remain technical challenges that limit clinical implementation of FSCV by creating barriers to appropriate scientific rigor and patient safety. In order to progress with clinical FSCV, these limitations must be first addressed through (1) appropriate pre-clinical studies to ensure accurate measurement of neurotransmitters and (2) the application of a risk management framework to assess patient safety. The intent of this work is to bring awareness of the current issues associated with FSCV to the scientific, engineering, and clinical communities and encourage them to seek solutions or alternatives that ensure data accuracy, rigor and reproducibility, and patient safety.
Quantitative Proteomic Analysis of Mouse Sciatic Nerve Reveals Post-injury Upregulation of ADP-Dependent Glucokinase Promoting Macrophage Phagocytosis
Authors: Zhang Kai , Wang Qingyao , Liang Yiyao , Yan Yu , Wang Haiqiong , Cao Xu , Shan Bing , Zhang Yaoyang , Li Ang , Fang Yanshan
Published: November 2021

Nerve injury induces profound and complex changes at molecular and cellular levels, leading to axonal self-destruction as well as immune and inflammatory responses that may further promote neurodegeneration. To better understand how neural injury changes the proteome within the injured nerve, we set up a mouse model of sciatic nerve injury (SNI) and conducted an unbiased, quantitative proteomic study followed by biochemical assays to confirm some of the changed proteins. Among them, the protein levels of ADP-dependent glucokinase (ADPGK) were significantly increased in the injured sciatic nerve. Further examination indicated that ADPGK was specifically expressed and upregulated in macrophages but not neurons or Schwann cells upon injury. Furthermore, culturing immortalized bone marrow-derived macrophages (iBMDMs) in vitro with the conditioned media from transected axons of mouse dorsal root ganglion (DRG) neurons induced ADPGK upregulation in iBMDMs, suggesting that injured axons could promote ADPGK expression in macrophages non-cell autonomously. Finally, we showed that overexpression of ADPGK per se did not activate macrophages but promoted the phagocytotic activity of lipopolysaccharides (LPS)-treated macrophages. Together, this proteomic analysis reveals interesting changes of many proteins within the injured nerve and our data identify ADPGK as an important in vivo booster of injury-induced macrophage phagocytosis.
Radiosynthesis of [11C]Ibrutinib via Pd-Mediated [11C]CO Carbonylation: Preliminary PET Imaging in Experimental Autoimmune Encephalomyelitis Mice
Authors: Lindberg Anton , Boyle Amanda J. , Tong Junchao , Harkness Michael B. , Garcia Armando , Tran Tritin , Zhai Dongxu , Liu Fang , Donnelly David J. , Vasdev Neil
Published: November 2021

Ibrutinib is a first-generation Bruton's tyrosine kinase (BTK) inhibitor that has shown efficacy in autoimmune diseases and has consequently been developed as a positron emission tomography (PET) radiotracer. Herein, we report the automated radiosynthesis of [11C]ibrutinib through 11C-carbonylation of the acrylamide functional group, by reaction of the secondary amine precursor with [11C]CO, iodoethylene, and palladium–NiXantphos. [11C]Ibrutinib was reliably formulated in radiochemical yields of 5.4% ± 2.5% (non-decay corrected; n = 9, relative to starting [11C]CO2), radiochemical purity >99%, and molar activity of 58.8 ± 30.8 GBq/μmol (1.55 ± 0.83 Ci/μmol). Preliminary PET/magnetic resonance imaging with [11C]ibrutinib in experimental autoimmune encephalomyelitis (EAE) mice showed a 49% higher radioactivity accumulation in the spinal cord of mice with EAE scores of 2.5 vs. sham mice.
Bornlisy Attenuates Colitis-Associated Colorectal Cancer via Inhibiting GPR43-Mediated Glycolysis
Authors: Lu Xia , Qiao Shuping , Peng Chen , Yan Wenyue , Xu Zhen , Qu Junxing , Hou Yayi , Zhao Shuli , Chen Ping , Wang Tingting
Published: November 2021

There is evidence that probiotics have a broad antitumor effect in colorectal cancer (CRC). However, the mechanism remains obscure. Here, we investigated the effect of Bornlisy (BO)-cocktails of three probiotics on colitis-associated colon cancer (CAC) and the underlying mechanism. The treatment of CAC mice with BO resulted in decreased tumor loads as compared with their counterparts. BO also inhibited the proliferation and metastasis of CRC cells in vitro. Furthermore, BO inhibited cell proliferation through downregulating glycolysis. Activating glycolysis reversed the protective role of BO in the CAC mice. Mechanically, BO administration promoted the activation of GPR43, followed by its downstream PLC-PKC-ERK pathway, which led to decreased glucose metabolism. These results suggest that BO may provide an intervention strategy for CRC therapy, while GPR43 is a potential targeting receptor during the BO treatment.
Effects of Antibacterial Peptide F1 on Bacterial Liposome Membrane Integrity
Authors: Wang Qun , Peng Bo , Song Mingyue , Abdullah  , Li Jun , Miao Jianyin , Feng Konglong , Chen Feilong , Zhai Xiaoxiang , Cao Yong
Published: November 2021

Previous studies from our lab have shown that the antimicrobial peptide F1 obtained from the milk fermentation by Lactobacillus paracasei FX-6 derived from Tibetan kefir was different from common antimicrobial peptides; specifically, F1 simultaneously inhibited the growth of Gram-negative and Gram-positive bacteria. Here, we present follow-on work demonstrating that after the antimicrobial peptide F1 acts on either Escherichia coli ATCC 25922 (E. coli) or Staphylococcus aureus ATCC 63589 (S. aureus), their respective bacterial membranes were severely deformed. This deformation allowed leakage of potassium and magnesium ions from the bacterial membrane. The interaction between the antimicrobial peptide F1 and the bacterial membrane was further explored by artificially simulating the bacterial phospholipid membranes and then extracting them. The study results indicated that after the antimicrobial peptide F1 interacted with the bacterial membranes caused significant calcein leakage that had been simulated by different liposomes. Furthermore, transmission electron microscopy observations revealed that the phospholipid membrane structure was destroyed and the liposomes presented aggregation and precipitation. Quartz Crystal Microbalance with Dissipation (QCM-D) results showed that the antimicrobial peptide F1 significantly reduced the quality of liposome membrane and increased their viscoelasticity. Based on the study's findings, the phospholipid membrane particle size was significantly increased, indicating that the antimicrobial peptide F1 had a direct effect on the phospholipid membrane. Conclusively, the antimicrobial peptide F1 destroyed the membrane structure of both Gram-negative and Gram-positive bacteria by destroying the shared components of their respective phospholipid membranes which resulted in leakage of cell contents and subsequently cell death.
MiR-489-3p Reduced Pancreatic Cancer Proliferation and Metastasis By Targeting PKM2 and LDHA Involving Glycolysis
Authors: Zhang Dan , He Zhiwei , Shen Yiyi , Wang Jie , Liu Tao , Jiang Jianxin
Published: November 2021

Introduction

Malignant proliferation and metastasis are some of the causes of high mortality in pancreatic cancer. MicroRNAs have been a hot spot in cancer research and are involved in tumor formation and metabolic stress responses. However, the biology function and underlying mechanism of miRNA regulating pancreatic cancer progress is remained uncleared.

Methods

RNA-seq analysis the glycolysis associated miRNAs and verified miRNA-489-3p was involving in glycolysis. We used RNA in situ hybridization (ISH) and qRT-PCR to analyze the differential expression of miR-489-3p in pancreatic cancer tissues and adjacent tissues and cell lines. Then the function assay of in vivo and in vitro were used to evaluated the role of miR-489-3p in the proliferation, metastasis and glucose metabolism of pancreatic cancer. Furthermore, dual luciferase reporter and rescue experiments were performed to explore the mechanism underlying in the role of miRNA-489-3p.

Results

We determined that glycolysis associated miRNA miR-489-3p was downregulated in pancreatic cancer tissues and cell lines. The gain and loos of function experiments confirmed that miR-489-3p could inhibit the proliferation, metastasis and glucose metabolism of pancreatic cancer. Further, we found that miR-489-3p could target regulating LDHA and PKM through the luciferase report experiment. Finally, in vivo experiment confirmed that highly expressed miR-489-3p inhibited the growth of pancreatic cancer.

Conclusion

In short, this study identified miR-489-3p as a novel therapy target for pancreatic cancer which was involving in the proliferation, metastasis and glycolysis, but its diagnostic value deserves further study.
MICAL2 Promotes Proliferation and Migration of Glioblastoma Cells Through TGF-β/p-Smad2/EMT-Like Signaling Pathway
Authors: Pu Bei , Zhang Xu , Yan Tengfeng , Li Yuntao , Liu Baohui , Jian Zhihong , Mahgoub Omer Kamal , Gu Lijuan , Xiong Xiaoxing , Zou Ning
Published: November 2021

Recent studies showed that molecule interacting with CasL2 (MICAL2) could be a novel tumor growth factor, and it is closely associated with tumor growth and invasion. However, the role it plays in glioblastoma (GBM) and its potential mechanisms are currently unknown. Our study is designed to identify the effect of MICAL2 on GBM cells and the potential mechanisms behind it. Here, we found that MICAL2 interacts with TGF receptor-type I (TGFRI) and promotes the proliferation and migration of glioblastoma through the TGF-β/p-Smad2/EMT-like signaling pathway. MICAL2-knockdown inhibited the proliferation of glioblastoma cells, which was related to cell cycle arrest and downregulation of DNA replication. The invasion abilities of U87 and U251 cells were reduced after the knockdown of MICAL2. MICAL2 promoted the growth of GBM in nude mice. High MICAL2 predicts poor outcome of GBM patients. MICAL2 could be identified as a novel promising therapeutic target for human GBM.
Lin28A/CENPE Promoting the Proliferation and Chemoresistance of Acute Myeloid Leukemia
Authors: Shi Mingyue , Niu Junwei , Niu Xiaona , Guo Honggang , Bai Yanliang , Shi Jie , Li Weiya , Sun Kai , Chen Yuqing , Shao Fengmin
Published: November 2021

The prognosis of chemoresistant acute myeloid leukemia (AML) is still poor, mainly owing to the sustained proliferation ability of leukemic cells, while the microtubules have a major role in sustaining the continuity of cell cycle. In the present study, we have identified CENPE, a microtubular kinesin-like motor protein that is highly expressed in the peripheral blood of patients with chemoresistant AML. In our in vitro studies, knockdown of CENPE expression resulted in the suppression of proliferation of myeloid leukemia cells and reversal of cytarabine (Ara-C) chemoresistance. Furthermore, Lin28A, one of the RNA-binding oncogene proteins that increase cell proliferation and invasion and contribute to unfavorable treatment responses in certain malignancies, was found to be remarkably correlated with CENPE expression in chemoresistance AML. Overexpression of LIN28A promoted the proliferation and Ara-C chemoresistance of leukemic cells. RIP assay, RNA pull-down, and dual luciferase reporter analyses indicated that LIN28A bound specifically to the promoter region GGAGA of CENPE. In addition, the impacts of LIN28A on cell growth, apoptosis, cell cycle progression, and Ara-C chemoresistance were reverted by the knockdown of CENPE. Hence, Lin28A/CENPE has enhanced the proliferation and chemoresistance of AML, and therefore, it could be a prospective candidate for AML treatment.
Explore the Predictive Value of Peripheral Blood Cell Parameters in Refractory Mycoplasma pneumoniae Pneumonia in Children Over 6 Years Old
Authors: Ling Yaoyao , Ning Jing , Xu Yongsheng
Published: November 2021

Background: To determine the predictive value of peripheral blood cell parameters for refractory Mycoplasma pneumoniae pneumonia (RMPP) in children over 6 years old.

Methods: A retrospective study was conducted in children with RMPP admitted to the respiratory department of Tianjin Children's Hospital from September 2017 to September 2019, and non-refractory Mycoplasma pneumoniae pneumonia (NRMPP) was selected by the propensity score method and matched according to the ratio of 1:1.5. We analyzed the differences in clinical characteristics, peripheral blood cell parameters, imaging findings, and treatments between the two groups, and further determined the predictive value of peripheral blood cell parameters on RMPP.

Results: There were 76 patients in the RMPP group and 114 patients in the NRMPP group. We found that the RMPP group has a longer clinical course and a higher incidence of intrapulmonary and extrapulmonary complications (p < 0.01). Moreover, the proportion of children in the RMPP group who received immunotherapy (such as glucocorticoid, gamma immunoglobulin) and fiberoptic bronchoscopy intervention was higher than that in the NRMPP group (p < 0.01). Meanwhile, the level of neutrophil, neutrophil/lymphocyte ratio (NLR), platelet count/lymphocyte ratio (PLR), mean platelet volume/lymphocyte ratio (MPVLR), C-reactive protein (CRP), lactic dehydrogenase (LDH), and interleukin (IL)-6 in the RMPP group was significantly higher (p < 0.01) than those in the NRMPP group. The incidence of pulmonary consolidation, atelectasis, and pleural effusion was also higher in the RMPP group (p < 0.05). ROC curve and binary logistic regression analysis showed that NLR > 3.92 (OR = 3.243; 95% CI = 1.485–7.081; p = 0.003), MPVLR > 5.29 (OR = 2.700; 95% CI = 1.258–5.795; p = 0.011), and pleural effusion (OR = 3.023; 95% CI = 1.424–6.420; p = 0.004) were significant factors in predicting RMPP. Our study showed that NLR had higher accuracy in predicting RMPP than CRP.

Conclusions: The parameters of peripheral blood cells might be a predictor of RMPP. NLR > 3.92, MPVLR > 5.29, and pleural effusion might have important predictive value for RMPP in children over 6 years old.
Case Report: Unusual Presentation of Myositis Ossificans of the Elbow in a Child Who Underwent Excessive Postoperative Rehabilitation Exercise
Authors: Cao Jin , Zheng Hua Jiang , Sun Jing Hua , Zhu Huan Ye , Gao Chao
Published: November 2021

Traumatic myositis ossificans (MO) is an unusual complication after muscle injury and is predominantly seen in young adults and adolescents. Pediatric MO cases are even rarer. We report an 8-year-old girl who was diagnosed with a lateral humeral condyle fracture. She was treated surgically, and her elbow joint was fixed with plaster. Rehabilitation exercise was administered 1 month after the operation. Due to the wrong exercise method, a palpable bony mass appeared around the elbow 1 month later. The clinical radiological diagnosis showed MO, and conservative treatment was administered. After 3 years of follow-up, the affected limb functioned well, with no sign of recurrence. Here, we report this long-term follow-up case of MO resulting from excessive rehabilitation exercise.
Understanding Stakeholder Views Regarding the Design of an Intervention Trial to Reduce Anticholinergic Burden: A Qualitative Study
Authors: Cunningham Yvonne , Wood Karen , Stewart Carrie , Nakham Athagran , Newlands Rumana , Gallacher Katie I. , Quinn Terence J. , Ellis Graham , Lowrie Richard , Myint Phyo Kyaw , Bond Christine , Mair Frances S.
Published: November 2021

Background: Anticholinergic burden (ACB), is defined as the cumulative effect of anticholinergic medication which are widely prescribed to older adults despite increasing ACB being associated with adverse effects such as: falls, dementia and increased mortality. This research explores the views of health care professionals (HCPs) and patients on a planned trial to reduce ACB by stopping or switching anticholinergic medications. The objectives were to explore the views of key stakeholders (patients, the public, and HCPs) regarding the potential acceptability, design and conduct of an ACB reduction trial.

Materials and Methods: We conducted qualitative interviews and focus groups with 25 HCPs involved in prescribing medication with anticholinergic properties and with 22 members of the public and patients who were prescribed with the medication. Topic guides for the interviews and focus groups explored aspects of feasibility including: 1) views of a trial of de-prescribing/medication switching; 2) how to best communicate information about such a trial; 3) views on who would be best placed and preferred to undertake such medication changes, e.g., pharmacists or General Practitioners (GPs)? 4) perceived barriers and facilitators to trial participation and the smooth conduct of such a trial; 5) HCP views on the future implementability of this approach to reducing ACB and 6) patients’ willingness to be contacted for participation in a future trial. Qualitative data analysis was underpinned by Normalization Process Theory.

Results: The public, patients and HCPs were supportive of an ACB reduction trial. There was consensus among the different groups that key points to consider with such a trial included: 1) ensuring patient engagement throughout to enable concerns/potential pitfalls to be addressed from the beginning; 2) ensuring clear communication to minimise potential misconceptions about the reasons for ACB reduction; and 3) provision of access to a point of contact for patients throughout the life of a trial to address concerns; The HCPs in particular suggested two more key points: 4) minimise the workload implications of any trial; and 5) pharmacists may be best placed to carry out ACB reviews, though overall responsibility for patient medication should remain with GPs.

Conclusion: Patients, the public and HCPs are supportive of trials to reduce ACB. Good communication and patient engagement during design and delivery of a trial are essential as well as safety netting and minimising workload.
Chyawanprash, An Ancient Indian Ayurvedic Medicinal Food, Regulates Immune Response in Zebrafish Model of Inflammation by Moderating Inflammatory Biomarkers
Authors: Balkrishna Acharya , Tomer Meenu , Manik Moumita , Srivastava Jyotish , Dev Rishabh , Haldar Swati , Varshney Anurag
Published: November 2021

The time-tested Ayurvedic medicinal food, Chyawanprash, has been a part of the Indian diet since ancient times. It is an extremely concentrated mixture of extracts from medicinal herbs and processed minerals, known for its immunity boosting, rejuvenating, and anti-oxidative effects. In this study, we have evaluated the anti-inflammatory potential of Patanjali Special Chyawanprash (PSCP) using the zebrafish model of inflammation. Zebrafish were fed on PSCP-infused pellets at stipulated doses for 13 days before inducing inflammation through lipopolysaccharide (LPS) injection. The test subjects were monitored for inflammatory pathologies like behavioral fever, hyperventilation, skin hemorrhage, locomotory agility, and morphological anomaly. PSCP exerted a strong prophylactic effect on the zebrafish that efficiently protected them from inflammatory manifestations at a human equivalent dose. Expression levels of pro-inflammatory cytokines, like interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and interleukin-1 beta (IL-1β), were also reduced in the LPS-stimulated zebrafish fed on PSCP-infused pellets. Skin hemorrhage, hyperventilation, and loss of caudal fins are characteristics of LPS-induced inflammation in zebrafish. PSCP prophylactically ameliorated skin hemorrhage, restored normal respiration, and prevented loss of caudal fin in inflamed zebrafish. Under in vitro conditions, PSCP reduced IL-6 and TNF-α secretion by THP-1 macrophages in a dose-dependent manner by targeting NF-κB signaling, as evident from the secreted embryonic alkaline phosphatase (SEAP) reporter assay. These medicinal benefits of PSCP can be attributed to its constitutional bioactive components. Taken together, these observations provide in vivo validation of the anti-inflammatory property and in vitro insight into the mode-of-action of Chyawanprash, a traditionally described medicinal food.
Therapy for Pulmonary Arterial Hypertension: Glance on Nitric Oxide Pathway
Authors: Tettey Abraham , Jiang Yujie , Li Xiaohui , Li Ying
Published: November 2021

Pulmonary arterial hypertension (PAH) is a severe disease with a resultant increase of the mean pulmonary arterial pressure, right ventricular hypertrophy and eventual death. Research in recent years has produced various therapeutic options for its clinical management but the high mortality even under treatment remains a big challenge attributed to the complex pathophysiology. Studies from clinical and non-clinical experiments have revealed that the nitric oxide (NO) pathway is one of the key pathways underlying the pathophysiology of PAH. Many of the essential drugs used in the management of PAH act on this pathway highlighting its significant role in PAH. Meanwhile, several novel compounds targeting on NO pathway exhibits great potential to become future therapy medications. Furthermore, the NO pathway is found to interact with other crucial pathways. Understanding such interactions could be helpful in the discovery of new drug that provide better clinical outcomes.
Concurrent Validity of Power From Three On-Water Rowing Instrumentation Systems and a Concept2 Ergometer
Authors: Holt Ana C. , Hopkins William G. , Aughey Robert J. , Siegel Rodney , Rouillard Vincent , Ball Kevin
Published: November 2021

Purpose: Instrumentation systems are increasingly used in rowing to measure training intensity and performance but have not been validated for measures of power. In this study, the concurrent validity of Peach PowerLine (six units), Nielsen-Kellerman EmPower (five units), Weba OarPowerMeter (three units), Concept2 model D ergometer (one unit), and a custom-built reference instrumentation system (Reference System; one unit) were investigated.

Methods: Eight female and seven male rowers [age, 21 ± 2.5 years; rowing experience, 7.1 ± 2.6 years, mean ± standard deviation (SD)] performed a 30-s maximal test and a 7 × 4-min incremental test once per week for 5 weeks. Power per stroke was extracted concurrently from the Reference System (via chain force and velocity), the Concept2 itself, Weba (oar shaft-based), and either Peach or EmPower (oarlock-based). Differences from the Reference System in the mean (representing potential error) and the stroke-to-stroke variability (represented by its SD) of power per stroke for each stage and device, and between-unit differences, were estimated using general linear mixed modeling and interpreted using rejection of non-substantial and substantial hypotheses.

Results: Potential error in mean power was decisively substantial for all devices (Concept2, –11 to –15%; Peach, −7.9 to −17%; EmPower, −32 to −48%; and Weba, −7.9 to −16%). Between-unit differences (as SD) in mean power lacked statistical precision but were substantial and consistent across stages (Peach, ∼5%; EmPower, ∼7%; and Weba, ∼2%). Most differences from the Reference System in stroke-to-stroke variability of power were possibly or likely trivial or small for Peach (−3.0 to −16%), and likely or decisively substantial for EmPower (9.7–57%), and mostly decisively substantial for Weba (61–139%) and the Concept2 (−28 to 177%).

Conclusion: Potential negative error in mean power was evident for all devices and units, particularly EmPower. Stroke-to-stroke variation in power showed a lack of measurement sensitivity (apparent smoothing) that was minor for Peach but larger for the Concept2, whereas EmPower and Weba added random error. Peach is therefore recommended for measurement of mean and stroke power.
Sexual and Apogamous Species of Woodferns Show Different Protein and Phytohormone Profiles
Authors: Fernández Helena , Grossmann Jonas , Gagliardini Valeria , Feito Isabel , Rivera Alejandro , Rodríguez Lucía , Quintanilla Luis G. , Quesada Víctor , Cañal Mª Jesús , Grossniklaus Ueli
Published: November 2021

The gametophyte of ferns reproduces either by sexual or asexual means. In the latter, apogamy represents a peculiar case of apomixis, in which an embryo is formed from somatic cells. A proteomic and physiological approach was applied to the apogamous fern Dryopteris affinis ssp. affinis and its sexual relative D. oreades. The proteomic analysis compared apogamous vs. female gametophytes, whereas the phytohormone study included, in addition to females, three apogamous stages (filamentous, spatulate, and cordate). The proteomic profiles revealed a total of 879 proteins and, after annotation, different regulation was found in 206 proteins of D. affinis and 166 of its sexual counterpart. The proteins upregulated in D. affinis are mostly associated to protein metabolism (including folding, transport, and proteolysis), ribosome biogenesis, gene expression and translation, while in the sexual counterpart, they account largely for starch and sucrose metabolism, generation of energy and photosynthesis. Likewise, ultra-performance liquid chromatography-tandem spectrometry (UHPLC-MS/MS) was used to assess the levels of indol-3-acetic acid (IAA); the cytokinins: 6-benzylaminopurine (BA), trans-Zeatine (Z), trans-Zeatin riboside (ZR), dyhidrozeatine (DHZ), dyhidrozeatin riboside (DHZR), isopentenyl adenine (iP), isopentenyl adenosine (iPR), abscisic acid (ABA), the gibberellins GA3 and GA4, salicylic acid (SA), and the brassinosteroids: brassinolide (BL) and castasterone (CS). IAA, the cytokinins Z, ZR, iPR, the gibberellin GA4, the brassinosteoids castasterone, and ABA accumulated more in the sexual gametophyte than in the apogamous one. When comparing the three apogamous stages, BA and SA peaked in filamentous, GA3 and BL in spatulate and DHRZ in cordate gametophytes. The results point to the existence of large metabolic differences between apogamous and sexual gametophytes, and invite to consider the fern gametophyte as a good experimental system to deepen our understanding of plant reproduction.
Biosynthesis and Transport of Nucleotide Sugars for Plant Hemicellulose
Authors: Zhang Wenjuan , Qin Wenqi , Li Huiling , Wu Ai-min
Published: November 2021

Hemicellulose is entangled with cellulose through hydrogen bonds and meanwhile acts as a bridge for the deposition of lignin monomer in the secondary wall. Therefore, hemicellulose plays a vital role in the utilization of cell wall biomass. Many advances in hemicellulose research have recently been made, and a large number of genes and their functions have been identified and verified. However, due to the diversity and complexity of hemicellulose, the biosynthesis and regulatory mechanisms are yet unknown. In this review, we summarized the types of plant hemicellulose, hemicellulose-specific nucleotide sugar substrates, key transporters, and biosynthesis pathways. This review will contribute to a better understanding of substrate-level regulation of hemicellulose synthesis.
Cell Wall Compositions of Sorghum bicolor Leaves and Roots Remain Relatively Constant Under Drought Conditions
Authors: Scavuzzo-Duggan Tess , Varoquaux Nelle , Madera Mary , Vogel John P. , Dahlberg Jeffery , Hutmacher Robert , Belcher Michael , Ortega Jasmine , Coleman-Derr Devin , Lemaux Peggy , Purdom Elizabeth , Scheller Henrik V.
Published: November 2021

Renewable fuels are needed to replace fossil fuels in the immediate future. Lignocellulosic bioenergy crops provide a renewable alternative that sequesters atmospheric carbon. To prevent displacement of food crops, it would be advantageous to grow biofuel crops on marginal lands. These lands will likely face more frequent and extreme drought conditions than conventional agricultural land, so it is crucial to see how proposed bioenergy crops fare under these conditions and how that may affect lignocellulosic biomass composition and saccharification properties. We found that while drought impacts the plant cell wall of Sorghum bicolor differently according to tissue and timing of drought induction, drought-induced cell wall compositional modifications are relatively minor and produce no negative effect on biomass conversion. This contrasts with the cell wall-related transcriptome, which had a varied range of highly variable genes (HVGs) within four cell wall-related GO categories, depending on the tissues surveyed and time of drought induction. Further, many HVGs had expression changes in which putative impacts were not seen in the physical cell wall or which were in opposition to their putative impacts. Interestingly, most pre-flowering drought-induced cell wall changes occurred in the leaf, with matrix and lignin compositional changes that did not persist after recovery from drought. Most measurable physical post-flowering cell wall changes occurred in the root, affecting mainly polysaccharide composition and cross-linking. This study couples transcriptomics to cell wall chemical analyses of a C4 grass experiencing progressive and differing drought stresses in the field. As such, we can analyze the cell wall-specific response to agriculturally relevant drought stresses on the transcriptomic level and see whether those changes translate to compositional or biomass conversion differences. Our results bolster the conclusion that drought stress does not substantially affect the cell wall composition of specific aerial and subterranean biomass nor impede enzymatic hydrolysis of leaf biomass, a positive result for biorefinery processes. Coupled with previously reported results on the root microbiome and rhizosphere and whole transcriptome analyses of this study, we can formulate and test hypotheses on individual gene candidates’ function in mediating drought stress in the grass cell wall, as demonstrated in sorghum.