bluuebunny/crossref_metadata_2025 huggingface dataset:
Natural history of carotid artery free-floating thrombus—A single center, consecutive cohort analysis
Authors: Müller Mandy D. , Raptis Nikolaos , Mordasini Pasquale , Z'Graggen Werner , Raabe Andreas , Schucht Philippe , Heldner Mirjam R. , Bervini David
Published: September 2022

Introduction

Carotid free-floating thrombus (CFFT) is a rare cause of stroke and is thought to be associated with a high risk of recurrent cerebrovascular ischaemic events. The existing data on the natural history and optimal treatment modalities of CFFT is scanty and no clear recommendations exist.

Objective

A retrospective analysis, single-center cohort of consecutive patients diagnosed with CFFT was conducted, investigating the risk for recurrent cerebrovascular ischaemic events.

Methods

We performed a single-center retrospective analysis including all patients presenting at our tertiary center between January 2005 and December 2020 with symptoms consistent with ischaemic stroke and/or transient ischaemic attack. Digital subtraction angiography (DSA), computed tomography angiography (CTA) or magnetic resonance angiography (MRA) were used to diagnose CFFT. In all included patients, CFFT was confirmed with a second imaging modality. CFFT was defined on imaging as a defect in contrast filling extending into the carotid lumen. We gathered information on vascular risk factors, diagnosis and follow-up methods, modality of treatment and neurological outcome. A survival analysis was performed, assessing the risk for recurrent cerebrovascular events.

Results

In total, N = 62 patients presenting with symptomatic CFFT were included. Mean age was 68 years, 69% (43/62) of patients were male, 52% (32/62) current or previous smokers, 76% (47/62) suffered from arterial hypertension, 68% (42/62) from dyslipidaemia, and 31% (19/62) from diabetes mellitus. Overall, 71% (44/62) of patients received any kind of intervention [endovascular or surgical carotid thrombo-endartectomy (CEA)] at any time point during follow-up. Sixteen percent of patients (10/62) received intervention within 48 h after diagnosis of CFFT. The survival analysis and Kaplan-Meier model censoring patients at the time of intervention or last follow-up showed that the risk for any recurrent ischaemic stroke was 19.7% within the first 7 days and 27.4% within 3 months after diagnosis. No patients experienced a new ischaemic stroke beyond 11 days after diagnosis of CFTT (n = 17).

Conclusion

The risk of recurrent ischaemic events in patients with CFFT is high, especially in the first week after diagnosis. Prospective studies are needed to further investigate the optimal management of these patients.
Psychiatric symptoms in adult patients with cerebral palsy: A cohort study
Authors: Pizzighello Silvia , Uliana Marianna , Michielotto Martina , Pellegri Alda , Vascello Matteo G. F. , Piccoli Sara , Martinuzzi Michela , Martinuzzi Andrea
Published: September 2022

Background

Patients with cerebral palsy (CP) have an increased risk of developing mental health disorders.

Aims

This paper is aimed to investigate the occurrence of psychiatric symptoms in adults with CP and to explore the relation between clinical and psychosocial variables.

Methods and procedures

We included 199 adults with a diagnosis of CP. The chi-square and the Mann-Whitney U tests were used to compare clinical and psychosocial variables, the level of perceived disability, and the type of observed parental style in patients with and without psychiatric symptoms. Logistic regression analysis was used to identify variables that could predict the occurrence of mental health disorders.

Outcome and results

Anxiety and psychosis were the most represented disorders. Age, living status, assumption of drugs, motor, manual, and global impairment were significantly different between patients with and without psychiatric symptoms. Similarly, a different parental style was observed between the two groups. Logistic regression indicated that living status, prescribed drugs, parental style, and the perceived disability in getting along with others predicted the occurrence of psychiatric symptoms.

Conclusions and implications

Results suggest that patients with and without psychiatric symptoms have different clinical and psychosocial characteristics. Some variables should be considered as potentially affecting the mental health of patients with CP.
The circadian stimulus-oscillator model: Improvements to Kronauer’s model of the human circadian pacemaker
Authors: Rea Mark S. , Nagare Rohan , Bierman Andrew , Figueiro Mariana G.
Published: September 2022

Modeling how patterns of light and dark affect circadian phase is important clinically and organizationally (e.g., the military) because circadian disruption can compromise health and performance. Limit-cycle oscillator models in various forms have been used to characterize phase changes to a limited set of light interventions. We approached the analysis of the van der Pol oscillator-based model proposed by Kronauer and colleagues in 1999 and 2000 (Kronauer99) using a well-established framework from experimental psychology whereby the stimulus (S) acts on the organism (O) to produce a response (R). Within that framework, using four independent data sets utilizing calibrated personal light measurements, we conducted a serial analysis of the factors in the Kronauer99 model that could affect prediction accuracy characterized by changes in dim-light melatonin onset. Prediction uncertainty was slightly greater than 1 h for the new data sets using the original Kronauer99 model. The revised model described here reduced prediction uncertainty for these same data sets by roughly half.
Anatomy imaging and hemodynamics research on the cerebral vein and venous sinus among individuals without cranial sinus and jugular vein diseases
Authors: Liu Lu , Wu Yan , Zhang Kaiyuan , Meng Ran , Duan Jiangang , Zhou Chen , Ji Xunming
Published: September 2022

In recent years, imaging technology has allowed the visualization of intracranial and extracranial vascular systems. However, compared with the cerebral arterial system, the relative lack of image information, individual differences in the anatomy of the cerebral veins and venous sinuses, and several unique structures often cause neurologists and radiologists to miss or over-diagnose. This increases the difficulty of the clinical diagnosis and treatment of cerebral venous system diseases. This review focuses on applying different imaging methods to the normal anatomical morphology of the cerebral venous system and special structural and physiological parameters, such as hemodynamics, in people without cranial sinus and jugular vein diseases and explores its clinical significance. We hope this study will reinforce the importance of studying the cerebral venous system anatomy and imaging data and will help diagnose and treat systemic diseases.
Protein quality of soy and the effect of processing: A quantitative review
Authors: van den Berg Lisa A. , Mes Jurriaan J. , Mensink Marco , Wanders Anne J.
Published: September 2022

There is a growing demand for plant-based protein-rich products for human consumption. During the production of plant-based protein-rich products, ingredients such as soy generally undergo several processing methods. However, little is known on the effect of processing methods on protein nutritional quality. To gain a better understanding of the effect of processing on the protein quality of soy, we performed a quantitative review of in-vivo and in-vitro studies that assessed the indispensable amino acid (IAA) composition and digestibility of varying soy products, to obtain digestibility indispensable amino acids scores (DIAAS) and protein digestibility corrected amino acid scores (PDCAAS). For all soy products combined, mean DIAAS was 84.5 ± 11.4 and mean PDCAAS was 85.6 ± 18.2. Data analyses showed different protein quality scores between soy product groups. DIAAS increased from tofu, soy flakes, soy hulls, soy flour, soy protein isolate, soybean, soybean meal, soy protein concentrate to soymilk with the highest DIAAS. In addition, we observed broad variations in protein quality scores within soy product groups, indicating that differences and variations in protein quality scores may also be attributed to various forms of post-processing (such as additional heat-treatment or moisture conditions), as well as study conditions. After excluding post-processed data points, for all soy products combined, mean DIAAS was 86.0 ± 10.8 and mean PDCAAS was 92.4 ± 11.9. This study confirms that the majority of soy products have high protein quality scores and we demonstrated that processing and post-processing conditions can increase or decrease protein quality. Additional experimental studies are needed to quantify to which extent processing and post-processing impact protein quality of plant-based protein-rich products relevant for human consumption.
Effects of drying strategies on sporulation and titer of microbial ecological agents with Bacillus subtilis
Authors: Li Chonglei , Zhao Kai , Ma Litong , Zhao Ji , Zhao Zhi-Min
Published: September 2022

Drying operation is beneficial to the preservation and transportation of microbial ecological agents. In this study, drying kinetics and water distribution variations in solid biomass medium during hot air drying (HAD) and vacuum freeze drying (VFD) were systematically investigated. Meanwhile, the effects of different drying strategies on the sporulation of Bacillus subtilis and the titer of microbial ecological agents were compared. The results showed that both HAD and VFD induced rapid water removal from the solid biomass medium. VFD retained bound water and maintained the porous structure of the solid medium. Both HAD and VFD induced sporulation. The expression level of sporulation-regulatory genes spo0A, sigF, and sigE followed the order 80°C-HAD > 60°C-HAD > VFD. The spore number in the medium after 80°C-HAD drying for 6 h was 0.72 × 1010/g dry medium, which was 9.1 and 12.5% larger than that of the medium with 60°C-HAD and VFD, respectively. Therefore, 80°C-HAD is an effective drying strategy for promoting sporulation, which improves the titer of microbial ecological agents with B. subtilis.
Association between vitamin D3 levels and frailty in the elderly: A large sample cross-sectional study
Authors: Zheng Zitian , Xu Wennan , Wang Fei , Qiu Yudian , Xue Qingyun
Published: September 2022

Background

Frailty is recognized as a cornerstone of geriatric medicine. Accurately screening and identifying frailty can promote better quality and personalized medical services for the elderly. Previous studies have shown that the association between vitamin D and frailty in the elderly population is still controversial. More research is needed to explore the association between them.

Materials and methods

We used three waves of data from the National Health and Nutrition Examination Survey (NHANES). Based on the widely accepted AAH FRAIL Scale, we measured and evaluated the participants’ frailty from five aspects: fatigue, resistance, ambulation, illness, and loss of weight. All possible relevant variables are included. Machine learning XGboost algorithm, the Least Absolute Shrinkage Selection Operator (LASSO) regression and univariate logistic regression were used to screen variables, and multivariate logistic regression and generalized additive model (GAM) were used to build the model. Finally, subgroup analysis and interaction test were performed to further confirm the association.

Results

In our study, XGboost machine learning algorithm explored the relative importance of all included variables, which confirmed the close association between vitamin D and frailty. After adjusting for all significant covariates, the result indicated that for each additional unit of 25-hydroxyvitamin D3, the risk of frailty was reduced by 1.3% with a statisticaldifference. A smooth curve was constructed based on the GAM. It was found that there was a significant negative correlation between 25-hydroxyvitamin D3 and the risk of frailty.

Conclusion

There may be a negative correlation between 25-hydroxyvitamin D3 and the risk of frailty. However, more well-designed studies are needed to verify this relationship.
PTEN loss promotes Warburg effect and prostate cancer cell growth by inducing FBP1 degradation
Authors: Song Changze , Zhang Jianong , Liu Xiao , Li Meilu , Wang Dejie , Kang Zhijian , Yu Jiaao , Chen Jiuwei , Pan Hongxin , Wang Honglei , Li Guangbin , Huang Haojie
Published: September 2022

Rationale

Fructose-1,6-bisphosphatase (FBP1) is a tumor suppressor and a key enzyme negatively regulating Warburg effect in cancer. However, regulation of FBP1 protein expression and its exact role in prostate cancer (PCa) is largely unclear. Phosphatase and tensin homolog (PTEN) is one of the most frequently deleted tumor suppressor genes in human PCa. However, the role of PTEN loss in aberrant Warburg effect in cancer remains poorly understood.

Methods

Expression of PTEN and FBP1 was analyzed in several PCa cell lines and prostate tumor tissues in mice. Western blot (WB) and RT-PCR approaches were used to examine how PTEN regulates FBP1 expression. Co-immunoprecipitation (co-IP) and in vivo ubiquitination assays were used to define the regulatory mechanisms. A PCa xenograft model was employed to determine the impact of PTEN regulation of FBP1 on PCa growth in vivo.

Result

We demonstrated that in a manner dependent of PI3K/AKT signal pathway PTEN regulated FBP1 expression in various PCa cell lines and tumors in mice. We confirmed that this regulation took place at the protein level and was mediated by SKP2 E3 ubiquitin ligase. Mechanistically, we showed that serine 271 phosphorylation of FBP1 by cyclin-dependent kinases (CDKs) was essential for SKP2-mediated degradation of FBP1 protein induced by PTEN loss. Most importantly, we further showed that loss of PTEN expression enhanced Warburg effect and PCa growth in mice in a manner dependent, at least partially on FBP1 protein degradation.

Conclusions

Our results reveal a novel tumor-suppressive feature of PTEN in restraining FBP1 degradation and the Warburg effect. These results also suggest that prohibiting FBP1 protein degradation could be a viable therapeutic strategy for PTEN-deficient PCa.
Analysis and prediction of relative survival trends in patients with non-Hodgkin lymphoma in the United States using a model-based period analysis method
Authors: Xie Shuping , Yu Zhong , Feng Aozi , Zheng Shuai , Li Yunmei , Zeng You , Lyu Jun
Published: September 2022

Background

Survival rates are usually used to evaluate the effect of cancer treatment and prevention. This study aims to analyze the 5-year relative survival of non-Hodgkin lymphoma (NHL) in United States using population-based cancer registry data.

Methods

A period analysis was used to evaluate the improvement in long-term prognosis of patients with NHL from 2004 to 2018, and a generalized linear model was developed to predict the 5-year relative survival rates of patients during 2019–2023 based on data from the SEER database stratified by age, sex, race and subtype.

Results

In this study, relative survival improved for all NHL, although the extent of improvement varied by sex, age group and lymphoma subtype. Survival improvement was also noted for NHL subtypes, although the extent varied, with marginal-zone lymphoma having the highest 5-year relative survival rate (92.5%) followed by follicular lymphoma (91.6%) and chronic lymphocytic leukemia/small lymphocytic lymphoma (87.3%). Across all subtypes, survival rates were slightly higher in females than in males. Survival rates are lower in the elderly than in the young. Furthermore, the study demonstrated that black patients had lower NHL survival rates than white patients. Survival rates for NHL were higher in rural areas than in urban areas. Patients with extra-nodal NHL had a higher survival rate than patients with nodal NHL.

Conclusion

Overall, patient survival rates for NHL gradually improved during 2004–2018. The trend continues with a survival rate of 75.2% for the period 2019–2023. Analysis by NHL subtype and subgroups indicating that etiology and risk factors may differ by subtype. Identification of population-specific prevention strategies and treatments for each subtype can be aided by understanding these variations.
bub1 as a potential oncogene and a prognostic biomarker for neuroblastoma
Authors: Song Jingjing , Ni Chao , Dong Xubin , Sheng Chenang , Qu Yue , Zhu Libin
Published: September 2022

Background

Neuroblastoma is the most common malignant extracranial tumor for children. Molecular mechanisms underpinning the pathogenesis of this disease are yet to be fully clarified. This study aimed to identify a novel oncogene that could be used as a biomarker informing the prognosis of neuroblastoma, and to predict its biological functions, using bioinformatics and molecular biology tools.

Methods

Three data sets from the TARGET, GSE62564, and GSE85047 databases were used for analysis. Survivals of patients with high or low expression of bub1 were compared, using the Kaplan-Meier curve and log-rank test. Immune infiltration was evaluated using ESTIMATE and MCP-counter algorithms. Synthetic small interfering RNAs (siRNAs) were employed to silence bub1 expression in neuroblastoma cell lines SH-SY5Y and SK-N-SH, in order to characterize its biological functions. Gene enrichment analyses of bub1 were carried out, using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses.

Results

Expression of bub1 was found to significantly affect overall survival and event-free survival of patients with neuroblastoma, positively correlate with the expressions of tpx2 and the ASPM gene, and negatively correlate with host immune infiltration. Expression of bub1 was elevated in patients with neuroblastoma. Silencing bub1 expression using siRNAs in SH-SY5Y and SK-N-SH resulted in decreased cell growth (p < 0.05), reduced migration (p < 0.05), and increased apoptosis (p < 0.05). Function analysis of bub1 revealed cancer-promoting effects, probably via regulating several important downstream molecules, including that related to the apoptosis process and epithelial-mesenchymal transition.

Conclusion

We identified a potential tumor-promoting gene bub1 for neuroblastoma that could also serve as a prognostic biomarker.
Accurate classification of pain experiences using wearable electroencephalography in adolescents with and without chronic musculoskeletal pain
Authors: Teel Elizabeth F. , Ocay Don Daniel , Blain-Moraes Stefanie , Ferland Catherine E.
Published: September 2022

Objective

We assessed the potential of using EEG to detect cold thermal pain in adolescents with and without chronic musculoskeletal pain.

Methods

Thirty-nine healthy controls (15.2 ± 2.1 years, 18 females) and 121 chronic pain participants (15.0 ± 2.0 years, 100 females, 85 experiencing pain ≥12-months) had 19-channel EEG recorded at rest and throughout a cold-pressor task (CPT). Permutation entropy, directed phase lag index, peak frequency, and binary graph theory features were calculated across 10-second EEG epochs (Healthy: 292 baseline / 273 CPT epochs; Pain: 1039 baseline / 755 CPT epochs). Support vector machine (SVM) and logistic regression models were trained to classify between baseline and CPT conditions separately for control and pain participants.

Results

SVM models significantly distinguished between baseline and CPT conditions in chronic pain (75.2% accuracy, 95% CI: 71.4%–77.1%; p < 0.0001) and control (74.8% accuracy, 95% CI: 66.3%–77.6%; p < 0.0001) participants. Logistic regression models performed similar to the SVM (Pain: 75.8% accuracy, 95% CI: 69.5%–76.6%, p < 0.0001; Controls: 72.0% accuracy, 95% CI: 64.5%–78.5%, p < 0.0001). Permutation entropy features in the theta frequency band were the largest contributor to model accuracy for both groups.

Conclusions

Our results demonstrate that subjective pain experiences can accurately be detected from electrophysiological data, and represent the first step towards the development of a point-of-care system to detect pain in the absence of self-report.
Anti-oxidative and anti-inflammatory activities of the ethanol extract of edible flower from Chimonanthus praecox
Authors: Kang Yuan , Liu Zhuangzhuang , Li Wenjing , Li Ximeng , Zhang Xiaoyu , Xu Zhenlu , Gao Yuan , Qi Yun
Published: September 2022

Chimonanthi Praecocis Flos, namely wintersweet flower, is the edible flower or flower bud of Chimonanthus praecox (L.) Link which is a deciduous shrub plant originated from China and is widely cultivated as a garden or ornamental plant all over the world. However, few studies focused on its anti-inflammatory property. In the present study, we explored the anti-inflammatory and anti-oxidative activities of ethanol extract of Chimonanthi Praecocis Flos (CPE) which contained 7.980% ± 0.176% total flavonoids and 1.461% ± 0.041% total alkaloids. In LPS-stimulated RAW264.7 macrophages, CPE significantly decreased the production of NO and prostaglandin E2 (PGE2) through reducing the expressions of their synthases—inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). It also suppressed the transcription and translation of pro-inflammatory cytokines interleukin-1β (IL-1β) and interleukin-6 (IL-6). Further research revealed that CPE impeded the phosphorylation and degradation of IκBα, thus restraining the nuclear translocation of p65, and consequently dampening NF-κB signaling. In endotoxemia mice, several pro-inflammatory cytokines in serum were also decreased after CPE treatment. Besides anti-inflammatory activity, anti-oxidative activity is another important capacity of wintersweet flower. Indeed, CPE reduced LPS-elevated intracellular total reactive oxygen species (ROS) level by weakening NADPH oxidase activity in cell system. Moreover, it directly scavenged DPPH radical and superoxide anion, and exerted ferric reducing ability in cell-free system. Our findings demonstrate that wintersweet flower can be used as a beneficial natural product or an additive by virtue of its anti-oxidative and anti-inflammatory properties.
Advances in thiosemicarbazone metal complexes as anti-lung cancer agents
Authors: Bai Xian-Guang , Zheng Yunyun , Qi Jinxu
Published: September 2022

The great success of cisplatin as a chemotherapeutic agent considerably increased research efforts in inorganic biochemistry to identify more metallic drugs having the potential of treating lung cancer. Metal coordination centres, which exhibit a wide range of coordination numbers and geometries, various oxidised and reduced states and the inherent ligand properties offer pharmaceutical chemists a plethora of drug structures. Owing to the presence of C=N and C=S bonds in a thiosemicarbazone Schiff base, N and S atoms in its hybrid orbital has lone pair of electrons, which can generate metal complexes with different stabilities with most metal elements under certain conditions. Such ligands and complexes play key roles in the treatment of anti-lung cancer. Research regarding metallic anti-lung cancer has advanced considerably, but there remain several challenges. In this review, we discuss the potential of thiosemicarbazone Schiff base complexes as anti-lung cancer drugs, their anti-cancer activities and the most likely action mechanisms involving the recent families of copper, nickel, platinum, ruthenium and other complexes.
Analysing breast cancer survivors’ acceptance profiles for using an electronic pillbox connected to a smartphone application using Seintinelles, a French community-based research tool
Authors: Goetzinger Catherine , Alleaume Caroline , Schritz Anna , Vrijens Bernard , Préau Marie , Fagherazzi Guy , Huiart Laetitia
Published: September 2022

Introduction: Up to 50% of breast cancer (BC) survivors discontinue their adjuvant endocrine therapy (AET) before the recommended 5 years, raising the issue of medication non-adherence. eHealth technologies have the potential to support patients to enhance their medication adherence and may offer an effective way to complement the healthcare. In order for eHealth technologies to be successfully implemented into the healthcare system, end-users need to be willing and accepting to use these eHealth technologies.

Aim: This study aims to evaluate the current usability of eHealth technologiesin and to identify differences in BC SURVIVORS BC survivors accepting a medication adherence enhancing eHealth technology to support their AET to BC survivors that do not accept such a medication adherence enhancing eHealth technology.

Methods: This study was conducted in 2020 including volunteering BC survivors belonging to the Seintinelles Association. Eligible participants were women, diagnosed with BC within the last 10 years, and been exposed to, an AET. Univariable and multivariable logistic regression analyses were performed to investigate medication adherence enhancing eHealth technology acceptance profiles among BC survivors. The dependent variable was defined as acceptance of an electronic pillbox connected to a smartphone application (hereafter: medication adherence enhancing eHealth technology).

Results: Overall, 23% of the participants already use a connected device or health application on a regular basis. The mean age of the participants was 52.7 (SD 10.4) years. In total, 67% of 1268 BC survivors who participated in the survey declared that they would accept a medication adherence enhancing eHealth technology to improve their AET. BC survivors accepting a medication adherence enhancing eHealth technology for their AET, are younger (OR = 0.97, 95% CI [0.95; 0.98]), do take medication for other diseases (OR = 0.31, 95% CI [0.13; 0.68]), already use a medication adherence enhancing eHealth technology or technique (OR = 1.74, 95% CI [1.06; 2.94]) and are willing to possess or currently possess one or more connected devices or health applications (OR = 2.89, 95% CI [2.01; 4.19]).

Conclusion: Understanding acceptance profiles of BC survivors is fundamental for conceiving an effective eHealth technology enhancing AET among BC survivors. Hence, such profiling will foster the development of personalized medication adherence enhancing eHealth technology.
Gut microbiota-derived metabolites in inflammatory diseases based on targeted metabolomics
Authors: Xu Hui , Pan Li-Bin , Yu Hang , Han Pei , Fu Jie , Zhang Zheng-Wei , Hu Jia-Chun , Yang Xin-Yu , Keranmu Adili , Zhang Hao-Jian , Bu Meng-Meng , Jiang Jian-Dong , Wang Yan
Published: September 2022

The gut microbiota plays an important role in inflammatory diseases. Metabolites in the three metabolic pathways of tryptophan (Trp), histidine (His), and phenylalanine (Phe) can affect various inflammatory conditions, such as obesity, diabetes, arthritis, colitis, atherosclerosis, and neuroinflammation. We established an LC–MS/MS method to measure 17 metabolites—Trp, 3-indole-acetic acid (Iaa), 3-indole-lactate (Ila), 3-indole-propionic acid (Ipa), 3-indole formaldehyde (Iald), kynurenine (Kn), kynurenic acid (Kyna), 3-Hydroxyanthranilic acid (3-Haa), His, 3-methylhistidine (3-Mhis), histamine (Hist), imidazole propionic acid (Imp), 4-imidazoacetic acid (Imaa), urocanic acid (Ua), Phe, phenylethylamine (Pea), and hippuric acid (Ha)—in the three metabolic pathways. The method exhibited high sensitivity and good selectivity, linearity, accuracy, precision, stability; and recovery rate; all met the requirements of biological sample analysis. By establishing a rheumatoid arthritis (RA) model of Sprague–Dawley rats and performing 16S rRNA sequencing on their feces, it was found that there was dysbiosis, including changes in phylum level, genus level, and α biodiversity of gut bacteria. The contents of the microbiota metabolites Iaa and Ipa in the model group were significantly decreased, and those of Iald, Kn, Kyna, Ha, and Imp were significantly increased. The common therapeutic drugs Tripterygium glycosides, total glucosides of peony, and their main active ingredients were screened by in vitro incubation with gut bacteria: it was found that Tripterygium glycosides and their active ingredients could lead to a variation in metabolites in the Trp and Phe pathways. Total glucosides and active components of peony could lead to a variation in metabolites in the Phe pathway of the gut microbiota.
Efficacy and safety of Chinese herbal medicine for atopic dermatitis: Evidence from eight high-quality randomized placebo-controlled trials
Authors: Cai Xiaoce , Sun Xiaoying , Liu Liu , Zhou Yaqiong , Hong Seokgyeong , Wang Jiao , Chen Jiale , Zhang Miao , Wang Chunxiao , Lin Naixuan , Li Su , Xu Rong , Li Xin
Published: September 2022

Background: The use of Chinese herbal medicine (CHM) for the treatment of atopic dermatitis (AD) has gained attention. This quantitative study systematically evaluated the efficacy and safety of CHM for the treatment of AD in eight high-level clinical trials, resulting in a high level of clinical evidence.

Methods: Several databases were searched, including PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), the Chongqing VIP Chinese Science (VIP), and Wanfang Database. High-quality randomized controlled trials (RCTs) comparing CHM with placebo were included. The 95% confidence interval (CI) of the risk ratio (RR) was calculated using software (RevMan 5.3) and a meta-analysis was performed. Evidence level evaluation using GRADE Profiler 3.6.

Results: In total, 662 patients (322 in the experimental group and 340 in the control group) were included. The response rate of the Eczema Area and Severity Index (EASI) −90 was higher in the CHM group than in the placebo group (RR, 3.72; 95% CI, 1.76 to7.83; p = 0.01). Furthermore, the scoring of atopic dermatitis (SCORAD) (RR, −10.20), body surface area (BSA) (RR, −2.01), surface damage score (RR, −2.25), visual analog scale (VAS) (RR, −1.90), and sleep score (RR, −2.16), improvement of investigator’s global assessment (IGA) (RR, 2.94) improved in the CHM group. The results showed no statistical difference between CHM and placebo (MD, −0.47; 95% CI, −1.30, 0.37; p = 0.27) in improving the Dermatology Life Quality Index (DLQI) or children’s DLQI (CDLQI). There was also no significant difference in the IgE level between the two groups (MD, −62.76; 95% CI, −809.58, 684.05; p = 0.87). However, the adverse events (AEs) rate was slightly higher in patients treated with CHM than in those treated with placebo (RR, 1.42; 95% CI, 1.06–1.90; p = 0.02).

Conclusion: CHM improved the size and severity of the skin lesions and sleep quality in patients with AD. Comparing the adverse effects between the two groups, CHM is safe. However, CHM does not improve the quality of life or the patient’s IgE levels.
Breviscapine remodels myocardial glucose and lipid metabolism by regulating serotonin to alleviate doxorubicin-induced cardiotoxicity
Authors: Li Meng-Jiao , Sun Wen-She , Yuan Yang , Zhang Yu-Kun , Lu Qi , Gao Yuan-Zhen , Ye Ting , Xing Dong-Ming
Published: September 2022

Aims: The broad-spectrum anticancer drug doxorubicin (Dox) is associated with a high incidence of cardiotoxicity, which severely affects the clinical application of the drug and patients’ quality of life. Here, we assess how Dox modulates myocardial energy and contractile function and this could aid the development of relevant protective drugs.

Methods: Mice were subjected to doxorubicin and breviscapine treatment. Cardiac function was analyzed by echocardiography, and Dox-mediated signaling was assessed in isolated cardiomyocytes. The dual cardio-protective and anti-tumor actions of breviscapine were assessed in mouse breast tumor models.

Results: We found that Dox disrupts myocardial energy metabolism by decreasing glucose uptake and increasing fatty acid oxidation, leading to a decrease in ATP production rate, an increase in oxygen consumption rate and oxidative stress, and further energy deficits to enhance myocardial fatty acid uptake and drive DIC development. Interestingly, breviscapine increases the efficiency of ATP production and restores myocardial energy homeostasis by modulating the serotonin-glucose-myocardial PI3K/AKT loop, increasing glucose utilization by the heart and reducing lipid oxidation. It enhances mitochondrial autophagy via the PINK1/Parkin pathway, eliminates damaged mitochondrial accumulation caused by Dox, reduces the degree of cardiac fibrosis and inflammation, and restores cardiac micro-environmental homeostasis. Importantly, its low inflammation levels reduce myeloid immunosuppressive cell infiltration, and this effect is synergistic with the anti-tumor effect of Dox.

Conclusion: Our findings suggest that disruption of the cardiac metabolic network by Dox is an important driver of its cardiotoxicity and that serotonin is an important regulator of myocardial glucose and lipid metabolism. Myocardial energy homeostasis and timely clearance of damaged mitochondria synergistically contribute to the prevention of anthracycline-induced cardiotoxicity and improve the efficiency of tumor treatment.
Optimizing thiopurine therapy in children with acute lymphoblastic leukemia: A promising “MINT” sequencing strategy and therapeutic “DNA-TG” monitoring
Authors: Guo Hong-Li , Zhao Yue-Tao , Wang Wei-Jun , Dong Na , Hu Ya-Hui , Zhang Yuan-Yuan , Chen Feng , Zhou Li , Li Tao
Published: September 2022

Thiopurines, including thioguanine (TG), 6-mercaptopurine (6-MP), and azathioprine (AZA), are extensively used in clinical practice in children with acute lymphoblastic leukemia (ALL) and inflammatory bowel diseases. However, the common adverse effects caused by myelosuppression and hepatotoxicity limit their application. Metabolizing enzymes such as thiopurine S-methyltransferase (TPMT), nudix hydrolase 15 (NUDT15), inosine triphosphate pyrophosphohydrolase (ITPA), and drug transporters like multidrug resistance-associated protein 4 (MRP4) have been reported to mediate the metabolism and transportation of thiopurine drugs. Hence, the single nucleotide polymorphisms (SNPs) in those genes could theoretically affect the pharmacokinetics and pharmacological effects of these drugs, and might also become one of the determinants of clinical efficacy and adverse effects. Moreover, long-term clinical practices have confirmed that thiopurine-related adverse reactions are associated with the systemic concentrations of their active metabolites. In this review, we mainly summarized the pharmacogenetic studies of thiopurine drugs. We also evaluated the therapeutic drug monitoring (TDM) research studies and focused on those active metabolites, hoping to continuously improve monitoring strategies for thiopurine therapy to maximize therapeutic efficacy and minimize the adverse effects or toxicity. We proposed that tailoring thiopurine dosing based on MRP4, ITPA, NUDT15, and TMPT genotypes, defined as “MINT” panel sequencing strategy, might contribute toward improving the efficacy and safety of thiopurines. Moreover, the DNA-incorporated thioguanine nucleotide (DNA-TG) metabolite level was more suitable for red cell 6-thioguanine nucleotide (6-TGNs) monitoring, which can better predict the efficacy and safety of thiopurines. Integrating the panel “MINT” sequencing strategy with therapeutic “DNA-TG” monitoring would offer a new insight into the precision thiopurine therapy for pediatric acute lymphoblastic leukemia patients.
Prescription medication use of United States military service members by therapeutic classification
Authors: Knapik Joseph J. , Trone Daniel W. , Steelman Ryan A. , Farina Emily K. , Lieberman Harris R.
Published: September 2022

Background: This cross-sectional study investigated the prevalence of, and factors associated with, filled prescription medications (FPMs) among United States (US) service members (SMs).

Methods: A stratified random sample of active duty SMs from the Air Force, Army, Marine Corps, and Navy was obtained from military workforce records. Participants (n = 26,680) completed a questionnaire on demographics, physical characteristics, and lifestyle factors and approved access to their FPM for the previous 6 months. FPMs were obtained from the military Pharmacy Data Transaction Service that included all prescription medications dispensed at military medical treatment facilities, abroad, at retail pharmacies in the US, and/or through mail-order programs.

Results: About two-thirds (65%) of SMs had ≥1 FPM in the 6 months surveillance period. Central nervous system (CNS) agents had the highest prevalence (41%), followed by anti-infective agents (20%), eye/ear/nose/throat preparations (20%), gastrointestinal drugs (18%), autonomic drugs (17%), skin and mucous membrane agents (13%), antihistamine drugs (12%), respiratory tract agents (12%) and cardiovascular drugs (9%). Among CNS agents, overall prevalence of dispensed non-steroidal anti-inflammatory drug (NSAIDs) was 30%. The odds of any FPM was independently associated with female gender, older age, higher body mass index, former tobacco use (smoking and smokeless tobacco), lower alcohol consumption, and was highest among Army, lowest among Marine Corps personnel.

Conclusion: In this sample of SMs, dispensing of prescription medication was high, especially NSAIDs, but dispensing of cardiovascular drugs was much lower compared to the general US population, likely because of the younger age and higher level of physical activity of SMs.
Reactivation of cocaine contextual memory engages mechanistic target of rapamycin/S6 kinase 1 signaling
Authors: Shi Xiangdang , von Weltin Eva , Fitzsimmons Emma , Do Chau , Caban Rivera Carolina , Chen Chongguang , Liu-Chen Lee-Yuan , Unterwald Ellen M.
Published: September 2022

Mechanistic target of rapamycin (mTOR) C1 and its downstream effectors have been implicated in synaptic plasticity and memory. Our prior work demonstrated that reactivation of cocaine memory engages a signaling pathway consisting of Akt, glycogen synthase kinase-3β (GSK3β), and mTORC1. The present study sought to identify other components of mTORC1 signaling involved in the reconsolidation of cocaine contextual memory, including eukaryotic translation initiation factor 4E (eIF4E)-eIF4G interactions, p70 S6 kinase polypeptide 1 (p70S6K, S6K1) activity, and activity-regulated cytoskeleton (Arc) expression. Cocaine contextual memory was established in adult CD-1 mice using conditioned place preference. After cocaine place preference was established, mice were briefly re-exposed to the cocaine-paired context to reactivate the cocaine memory and brains examined. Western blot analysis showed that phosphorylation of the mTORC1 target, p70S6K, in nucleus accumbens and hippocampus was enhanced 60 min following reactivation of cocaine memories. Inhibition of mTORC1 with systemic administration of rapamycin or inhibition of p70S6K with systemic PF-4708671 after reactivation of cocaine contextual memory abolished the established cocaine place preference. Immunoprecipitation assays showed that reactivation of cocaine memory did not affect eIF4E–eIF4G interactions in nucleus accumbens or hippocampus. Levels of Arc mRNA were significantly elevated 60 and 120 min after cocaine memory reactivation and returned to baseline 24 h later. These findings demonstrate that mTORC1 and p70S6K are required for reconsolidation of cocaine contextual memory.
Ginsenoside Rb1 improves intestinal aging via regulating the expression of sirtuins in the intestinal epithelium and modulating the gut microbiota of mice
Authors: Lei Zili , Chen Lei , Hu Qing , Yang Yanhong , Tong Fengxue , Li Keying , Lin Ting , Nie Ya , Rong Hedong , Yu Siping , Song Qi , Guo Jiao
Published: September 2022

Intestinal aging seriously affects the absorption of nutrients of the aged people. Ginsenoside Rb1 (GRb1) which has multiple functions on treating gastrointestinal disorders is one of the important ingredients from Ginseng, the famous herb in tradition Chinese medicine. However, it is still unclear if GRb1 could improve intestinal aging. To investigate the function and mechanism of GRb1 on improving intestinal aging, GRb1 was administrated to 104-week-old C57BL/6 mice for 6 weeks. The jejunum, colon and feces were collected for morphology, histology, gene expression and gut microbiota tests using H&E staining, X-gal staining, qPCR, Western blot, immunofluorescence staining, and 16S rDNA sequencing technologies. The numbers of cells reduced and the accumulation of senescent cells increased in the intestinal crypts of old mice, and administration of GRb1 could reverse them. The protein levels of CLDN 2, 3, 7, and 15 were all decreased in the jejunum of old mice, and administration of GRb1 could significantly increase them. The expression levels of Tert, Lgr5, mKi67, and c-Myc were all significantly reduced in the small intestines of old mice, and GRb1 significantly increased them at transcriptional or posttranscriptional levels. The protein levels of SIRT1, SIRT3, and SIRT6 were all reduced in the jejunum of old mice, and GRb1 could increase the protein levels of them. The 16S rDNA sequencing results demonstrated the dysbiosis of the gut microbiota of old mice, and GRb1 changed the composition and functions of the gut microbiota in the old mice. In conclusion, GRb1 could improve the intestinal aging via regulating the expression of Sirtuins family and modulating the gut microbiota in the aged mice.
Color fundus photograph registration based on feature and intensity for longitudinal evaluation of diabetic retinopathy progression
Authors: Zhou Jingxin , Jin Kai , Gu Renshu , Yan Yan , Zhang Yueyu , Sun Yiming , Ye Juan
Published: September 2022

Longitudinal disease progression evaluation between follow-up examinations relies on precise registration of medical images. Compared to other medical imaging methods, color fundus photograph, a common retinal examination, is easily affected by eye movements while shooting, for which we think it is necessary to develop a reliable longitudinal registration method for this modality. Thus, the purpose of this study was to propose a robust registration method for longitudinal color fundus photographs and establish a longitudinal retinal registration dataset. In the proposed algorithm, radiation-variation insensitive feature transform (RIFT) feature points were calculated and aligned, followed by further refinement using a normalized total gradient (NTG). Experiments and ablation analyses were conducted on both public and private datasets, using the mean registration error and registration success plot as the main evaluation metrics. The results showed that our proposed method was comparable to other state-of-the-art registration algorithms and was particularly accurate for longitudinal images with disease progression. We believe the proposed method will be beneficial for the longitudinal evaluation of fundus images.
Chemosensory protein 4 is required for Bradysia odoriphaga to be olfactory attracted to sulfur compounds released from Chinese chives
Authors: Yang Yuting , Hua Dengke , Zhu Jiaqi , Wang Fu , Zhang Youjun
Published: September 2022

Bradysia odoriphaga (Diptera: Sciaridae) is a serious pest of Chinese chives cultivated in China. Chemosensory proteins (CSPs) are important components of insect olfactory systems that capture and bind environmental semiochemicals which are then transported to olfactory receptors. Despite their importance, the mechanism of olfaction and related behavioral processes in B. odoriphaga have not been characterized. Here, we found that BodoCSP4 has an important olfactory function. RT-qPCR indicated that BodoCSP4 expression was highest in the heads (antennae removed) of adult males, followed by the antennae of adult males. Competitive binding assays with 33 ligands indicated that BodoCSP4 binds well with methyl allyl disulfide, diallyl disulfide, and n-heptadecane; the corresponding dissolution constants (Ki) were as high as 5.71, 5.71, and 6.85 μM, respectively. 3D-structural and molecular docking indicated that BodoCSP4 has five α-helices and surrounds the ligand with certain hydrophobic residues including Leu60, Leu63, Leu64, Ala67, Val28, Ile30, Ile33, Leu34, and Val86, suggesting these residues help BodoCSP4 bind to ligands. Silencing of BodoCSP4 significantly decreased the attraction of B. odoriphaga males to diallyl disulfide and n-heptadecane but not to methyl allyl disulfide in Y-tube olfaction assays. These results increase our understanding of how BodoCSP4 contributes to host and female localization by B. odoriphaga males.
The thiol-reductase activity of YUCCA6 enhances nickel heavy metal stress tolerance in Arabidopsis
Authors: Cha Joon-Yung , Jeong Song Yi , Ahn Gyeongik , Shin Gyeong-Im , Ji Myung Geun , Lee Sang Cheol , Khakurel Dhruba , Macoy Donah Mary , Lee Yong Bok , Kim Min Gab , Lee Sang Yeol , Yun Dae-Jin , Kim Woe-Yeon
Published: September 2022

Anthropogenic activities cause the leaching of heavy metals into groundwater and their accumulation in soil. Excess levels of heavy metals cause toxicity in plants, inducing the production of reactive oxygen species (ROS) and possible death caused by the resulting oxidative stress. Heavy metal stresses repress auxin biosynthesis and transport, inhibiting plant growth. Here, we investigated whether nickel (Ni) heavy metal toxicity is reduced by exogenous auxin application and whether Ni stress tolerance in Arabidopsis thaliana is mediated by the bifunctional enzyme YUCCA6 (YUC6), which functions as an auxin biosynthetic enzyme and a thiol-reductase (TR). We found that an application of up to 1 µM exogenous indole-3-acetic acid (IAA) reduces Ni stress toxicity. yuc6-1D, a dominant mutant of YUC6 with high auxin levels, was more tolerant of Ni stress than wild-type (WT) plants, despite absorbing significantly more Ni. Treatments of WT plants with YUCASIN, a specific inhibitor of YUC-mediated auxin biosynthesis, increased Ni toxicity; however yuc6-1D was not affected by YUCASIN and remained tolerant of Ni stress. This suggests that rather than the elevated IAA levels in yuc6-1D, the TR activity of YUC6 might be critical for Ni stress tolerance. The loss of TR activity in YUC6 caused by the point-mutation of Cys85 abolished the YUC6-mediated Ni stress tolerance. We also found that the Ni stress–induced ROS accumulation was inhibited in yuc6-1D plants, which consequently also showed reduced oxidative damage. An enzymatic assay and transcriptional analysis revealed that the peroxidase activity and transcription of PEROXIREDOXIN Q were enhanced by Ni stress to a greater level in yuc6-1D than in the WT. These findings imply that despite the need to maintain endogenous IAA levels for basal Ni stress tolerance, the TR activity of YUC6, not the elevated IAA levels, plays the predominant role inNi stress tolerance by lowering Ni-induced oxidative stress.