bluuebunny/crossref_metadata_2025 huggingface dataset:
Sex and age differences in the Multiple Sclerosis prodrome
Authors: Yusuf Fardowsa L. A. , Wijnands José M. A. , Karim Mohammad Ehsanul , Kingwell Elaine , Zhu Feng , Evans Charity , Fisk John D. , Zhao Yinshan , Marrie Ruth Ann , Tremlett Helen
Published: November 2022

Background and objectives

Little is known of the potential sex and age differences in the MS prodrome. We investigated sex and age differences in healthcare utilization during the MS prodrome.

Methods

This was a population-based matched cohort study linking administrative and clinical data from British Columbia, Canada (population = 5 million). MS cases in the 5 years preceding a first demyelinating event (“administrative cohort;” n = 6,863) or MS symptom onset (“clinical cohort;” n = 966) were compared to age-, sex- and geographically-matched controls (n = 31,865/4,534). Negative binomial and modified Poisson models were used to compare the rates of physician visits and hospitalizations per international classification of diseases chapter, and prescriptions filled per drug class, between MS cases and controls across sex and age-groups (< 30, 30–49, ≥50 years).

Results

In the administrative cohort, males with MS had a higher relative rate for genitourinary-related visits (males: adjusted Rate Ratio (aRR) = 1.65, females: aRR = 1.19, likelihood ratio test P = 0.02) and antivertigo prescriptions (males: aRR = 4.72, females: aRR = 3.01 P < 0.01). Injury and infection-related hospitalizations were relatively more frequent for ≥50-year-olds (injuries < 30/30–49/≥50: aRR = 1.16/1.39/2.12, P < 0.01; infections 30–49/≥50: aRR = 1.43/2.72, P = 0.03), while sensory-related visits and cardiovascular prescriptions were relatively more common in younger persons (sensory 30–49/≥50: aRR = 1.67/1.45, P = 0.03; cardiovascular < 30/30–49/≥50: aRR = 1.56/1.39/1.18, P < 0.01). General practitioner visits were relatively more frequent in males (males: aRR = 1.63, females: aRR = 1.40, P < 0.01) and ≥50-year-olds (< 30/≥50: aRR = 1.32/1.55, P = 0.02), while differences in ophthalmologist visits were disproportionally larger among younger persons, < 50-years-old (< 30/30–49/≥50: aRR = 2.25/2.20/1.55, P < 0.01). None of the sex and age-related differences in the smaller clinical cohort reached significance (P ≥ 0.05).

Discussion

Sex and age-specific differences in healthcare use were observed in the 5 years before MS onset. Findings demonstrate fundamental heterogeneity in the MS prodromal presentation.
Early diagnosis of intracranial atherosclerotic large vascular occlusion: A prediction model based on DIRECT-MT data
Authors: Li He , Ma Hong-Yu , Zhang Lei , Liu Pei , Zhang Yong-Xin , Zhang Xiao-Xi , Li Zi-Fu , Xing Peng-Fei , Zhang Yong-Wei , Li Qiang , Yang Peng-Fei , Liu Jian-Min
Published: November 2022

Aims

This study aimed to build a prediction model to early diagnose intracranial atherosclerosis (ICAS)-related large vascular occlusion (LVO) in acute ischemic stroke patients before digital subtractive angiography.

Methods

Patients enrolled in the DIRECT-MT trial (NCT03469206) were included in our secondary analysis and distributed into ICAS-LVO and non-ICAS-LVO groups. We also retrieved demographic data, medical histories, clinical characteristics, and pre-operative imaging data. Hypothesis testing was used to compare data of the two groups, and univariate logistic regression was used to identify the predictors of ICAS-LVO primarily. Then, we used multivariate logistic regression to determine the independent predictors and formulate the prediction model. Model efficacy was estimated by the area under the receiver operating characteristic (ROC) curve (AUC) and diagnostic parameters generated from internal and external validations.

Results

The subgroup analysis included 45 cases in the ICAS-LVO group and 611 cases in the non-ICAS-LVO group. Variates with p < 0.1 in the comparative analysis were used as inputs in the univariate logistic regression. Next, variates with p < 0.1 in the univariate logistic regression were used as inputs in the multivariate logistic regression. The multivariate logistic regression indicated that the atrial fibrillation history, hypertension and smoking, occlusion located at the proximal M1 and M2, hyperdense artery sign, and clot burden score were related to the diagnosis of ICAS-LVO. Then, we constructed a prediction model based on multivariate logistics regression. The sensitivity and specificity of the model were 84.09 and 74.54% in internal validation and 73.11 and 71.53% in external validation.

Conclusion

Our current prediction model based on clinical data of patients from the DIRECT-MT trial might be a promising tool for predicting ICAS-LVO.
Meditative-based diaphragmatic breathing vs. vagus nerve stimulation in the treatment of fibromyalgia—A randomized controlled trial: Body vs. machine
Authors: Paccione Charles Ethan , Stubhaug Audun , Diep Lien My , Rosseland Leiv Arne , Jacobsen Henrik Børsting
Published: November 2022

Importance

Vagus nerve innervation via electrical stimulation and meditative-based diaphragmatic breathing may be promising treatment avenues for fibromyalgia.

Objective

Explore and compare the treatment effectiveness of active and sham transcutaneous vagus nerve stimulation (tVNS) and meditative-based diaphragmatic breathing (MDB) for fibromyalgia.

Design

Participants enrolled from March 2019–October 2020 and randomly assigned to active tVNS (n = 28), sham tVNS (n = 29), active MDB (n = 29), or sham MDB (n = 30). Treatments were self-delivered at home for 15 min/morning and 15 min/evening for 14 days. Follow-up was at 2 weeks.

Setting

Outpatient pain clinic in Oslo, Norway.

Participants

116 adults aged 18–65 years with severe fibromyalgia were consecutively enrolled and randomized. 86 participants (74%) had an 80% treatment adherence and 107 (92%) completed the study at 2 weeks; 1 participant dropped out due to adverse effects from active tVNS.

Interventions

Active tVNS is placed on the cymba conchae of the left ear; sham tVNS is placed on the left earlobe. Active MDB trains users in nondirective meditation with deep breathing; sham MDB trains users in open-awareness meditation with paced breathing.

Main outcomes and measures

Primary outcome was change from baseline in ultra short-term photoplethysmography-measured cardiac-vagal heart rate variability at 2 weeks. Prior to trial launch, we hypothesized that (1) those randomized to active MDB or active tVNS would display greater increases in heart rate variability compared to those randomized to sham MDB or sham tVNS after 2-weeks; (2) a change in heart rate variability would be correlated with a change in self-reported average pain intensity; and (3) active treatments would outperform sham treatments on all pain-related secondary outcome measures.

Results

No significant across-group changes in heart rate variability were found. Furthermore, no significant correlations were found between changes in heart rate variability and average pain intensity during treatment. Significant across group differences were found for overall FM severity yet were not found for average pain intensity.

Conclusions and relevance

These findings suggest that changes in cardiac-vagal heart rate variability when recorded with ultra short-term photoplethysmography in those with fibromyalgia may not be associated with treatment-specific changes in pain intensity. Further research should be conducted to evaluate potential changes in long-term cardiac-vagal heart rate variability in response to noninvasive vagus nerve innervation in those with fibromyalgia.

Clinical trial registration

https://clinicaltrials.gov/ct2/show/NCT03180554, Identifier: NCT03180554.
Wall characteristics of atherosclerotic middle cerebral arteries in patients with single or multiple infarcts: A high-resolution MRI Study
Authors: Ma Zelan , Huo Mengjuan , Xie Jiajun , Liu Guoqing , Li Guoming , Liu Qiang , Mao Liting , Huang Weikang , Liu Bo , Liu Xian
Published: November 2022

Background and purpose

Understanding the stroke mechanism of middle cerebral artery (MCA) atherosclerosis may inform secondary prevention. The aim of this study was to explore the relationship between vascular wall characteristics and infarction patterns using high-resolution magnetic resonance imaging (HRMRI) and diffusion-weighted imaging (DWI).

Methods

From November 2018 to March 2021, patients with acute ischemic stroke due to MCA atherosclerotic disease were retrospectively analyzed. The wall characteristics of atherosclerotic MCA, including conventional characteristics and histogram-defined characteristics, were evaluated using HRMRI. Patients were divided into single-infarction and multiple-infarction groups based on DWI, and wall characteristics were compared between the two groups.

Results

Of 92 patients with MCA plaques, 59 patients (64.1%) had multiple infarcts, and 33 (35.9%) had single infarcts. The histogram-defined characteristics showed no differences between the single-infarction and multiple-infarction groups (P>0.05). Plaque burden, degree of stenosis, and prevalence of intraplaque hemorrhage (IPH) were significantly greater in the multiple-infarction group than in the single-infarction group (plaque burden: P = 0.001; degree of stenosis: P = 0.010; IPH: P = 0.019). Multivariate analysis showed that plaque burden (odds ratio: 1.136; 95% confidence interval: 1.054–1.224, P = 0.001) and IPH (odds ratio: 5.248; 95% confidence interval: 1.573–17.512, P = 0.007) were independent predictors for multiple infarction.

Conclusion

IPH and plaque burden are independently associated with multiple infarcts. HRMRI may provide new insight into the mechanisms underlying the different MCA infarction patterns.
Case analysis of early-onset Alzheimer's disease associated with TBK1 p.Tyr235Phe gene mutation
Authors: Li Pan , Y Yuanyuan , Cai Hao , Zhang Huihong , Zhou Yuying
Published: November 2022

TANK1-binding kinase 1 (TBK1) is mainly involved in the regulation of various cellular pathways through the autophagic lysosomal system, and the loss of function or hypofunction caused by TBK1 gene mutation mainly leads to frontotemporal lobar degeneration (FTLD), amyotrophic lateral sclerosis (ALS), and ALS-FTLD. Alzheimer's disease (AD) due to TBK1 gene mutation is extremely rare, and only one case has been reported in China so far. In this report, we described a patient with early-onset AD (EOAD) in whom a new probable pathogenic variant c.704A>T (p.Tyr235Phe) in the TBK1 gene was identified by a whole-genome sequencing analysis. It is suggested that FTLD gene mutation may exist in patients with clinical manifestations of AD.
Interference of unilateral lower limb amputation on motor imagery rhythm and remodeling of sensorimotor areas
Authors: Liu Shaowen , Fu Wenjin , Wei Conghui , Ma Fengling , Cui Nanyi , Shan Xinying , Zhang Yan
Published: November 2022

Purpose

The effect of sensorimotor stripping on neuroplasticity and motor imagery capacity is unknown, and the physiological mechanisms of post-amputation phantom limb pain (PLP) illness remain to be investigated.

Materials and methods

In this study, an electroencephalogram (EEG)-based event-related (de)synchronization (ERD/ERS) analysis was conducted using a bilateral lower limb motor imagery (MI) paradigm. The differences in the execution of motor imagery tasks between left lower limb amputations and healthy controls were explored, and a correlation analysis was calculated between level of phantom limb pain and ERD/ERS.

Results

The multiple frequency bands showed a significant ERD phenomenon when the healthy control group performed the motor imagery task, whereas amputees showed significant ERS phenomena in mu band. Phantom limb pain in amputees was negatively correlated with bilateral sensorimotor areas electrode powers.

Conclusion

Sensorimotor abnormalities reduce neural activity in the sensorimotor cortex, while the motor imagination of the intact limb is diminished. In addition, phantom limb pain may lead to over-activation of sensorimotor areas, affecting bilateral sensorimotor area remodeling.
Leber’s hereditary optic neuropathy companied with multiple-related diseases
Authors: Sun Ming-ming , Zhou Huan-fen , Sun Qiao , Li Hong-en , Liu Hong-juan , Song Hong-lu , Yang Mo , Teng Da , Wei Shi-hui , Xu Quan-gang
Published: November 2022

Objective

To elucidate the clinical, radiologic characteristics of Leber’s hereditary optic neuropathy (LHON) associated with the other diseases.

Materials and methods

Clinical data were retrospectively collected from hospitalized patients with LHON associated with the other diseases at the Neuro-Ophthalmology Department at the Chinese People’s Liberation Army General Hospital (PLAGH) from December 2014 to October 2018.

Results

A total of 13 patients, 24 eyes (10 men and 3 women; mean age, 30.69 ± 12.76 years) with LHON mitochondrial DNA (mtDNA) mutations, were included in the cohort. 14502(5)11778(4)11778 &11696(1)12811(1)11696(1)3460(1). One patient was positive for aquaporin-4 antibody (AQP4-Ab), and two were positive for myelin oligodendrocyte glycoprotein antibody (MOG-Ab). Three patients were associated with idiopathic optic neuritis (ON). Two patients were with compression optic neuropathy. Three patients were with the central nervous system (CNS) diseases. One patient was with proliferative diabetic retinopathy (PDR) and one with idiopathic orbital inflammatory syndrome (IOIS). At the onset, visual acuity (VA) in eighteen eyes was below 0.1, one eye was 0.5, five eyes were above 0.5, while VA in sixteen eyes was below a 0.1 outcome, three eyes experienced moderate vision loss. MRI images showed T2 lesions and enhancement in nine patients who received corticosteroids treatment; additional immune modulators treatment was performed on two patients. None of the patients had relapse during the follow-up time.

Conclusion

Leber’s hereditary optic neuropathy can be accompanied with multiple-related diseases, especially different subtypes of ON, which were also exhibited with IOIS and compression optic neuropathy for the first time in this cohort. This condition may be a distinct entity with an unusual clinical and therapeutic profile.
The relationship between electrophysiological and hemodynamic measures of neural activity varies across picture naming tasks: A multimodal magnetoencephalography-functional magnetic resonance imaging study
Authors: Mononen Tommi , Kujala Jan , Liljeström Mia , Leppäaho Eemeli , Kaski Samuel , Salmelin Riitta
Published: November 2022

Different neuroimaging methods can yield different views of task-dependent neural engagement. Studies examining the relationship between electromagnetic and hemodynamic measures have revealed correlated patterns across brain regions but the role of the applied stimulation or experimental tasks in these correlation patterns is still poorly understood. Here, we evaluated the across-tasks variability of MEG-fMRI relationship using data recorded during three distinct naming tasks (naming objects and actions from action images, and objects from object images), from the same set of participants. Our results demonstrate that the MEG-fMRI correlation pattern varies according to the performed task, and that this variability shows distinct spectral profiles across brain regions. Notably, analysis of the MEG data alone did not reveal modulations across the examined tasks in the time-frequency windows emerging from the MEG-fMRI correlation analysis. Our results suggest that the electromagnetic-hemodynamic correlation could serve as a more sensitive proxy for task-dependent neural engagement in cognitive tasks than isolated within-modality measures.
Neurons and glial cells acquire a senescent signature after repeated mild traumatic brain injury in a sex-dependent manner
Authors: Schwab Nicole , Taskina Daria , Leung Emily , Innes Brendan T. , Bader Gary D. , Hazrati Lili-Naz
Published: November 2022

Mild traumatic brain injury (mTBI) is an important public health issue, as it can lead to long-term neurological symptoms and risk of neurodegenerative disease. The pathophysiological mechanisms driving this remain unclear, and currently there are no effective therapies for mTBI. In this study on repeated mTBI (rmTBI), we have induced three mild closed-skull injuries or sham procedures, separated by 24 h, in C57BL/6 mice. We show that rmTBI mice have prolonged righting reflexes and astrogliosis, with neurological impairment in the Morris water maze (MWM) and the light dark test. Cortical and hippocampal tissue analysis revealed DNA damage in the form of double-strand breaks, oxidative damage, and R-loops, markers of cellular senescence including p16 and p21, and signaling mediated by the cGAS-STING pathway. This study identified novel sex differences after rmTBI in mice. Although these markers were all increased by rmTBI in both sexes, females had higher levels of DNA damage, lower levels of the senescence protein p16, and lower levels of cGAS-STING signaling proteins compared to their male counterparts. Single-cell RNA sequencing of the male rmTBI mouse brain revealed activation of the DNA damage response, evidence of cellular senescence, and pro-inflammatory markers reminiscent of the senescence-associated secretory phenotype (SASP) in neurons and glial cells. Cell-type specific changes were also present with evidence of brain immune activation, neurotransmission alterations in both excitatory and inhibitory neurons, and vascular dysfunction. Treatment of injured mice with the senolytic drug ABT263 significantly reduced markers of senescence only in males, but was not therapeutic in females. The reduction of senescence by ABT263 in male mice was accompanied by significantly improved performance in the MWM. This study provides compelling evidence that senescence contributes to brain dysfunction after rmTBI, but may do so in a sex-dependent manner.
Fmrp regulates neuronal balance in embryonic motor circuit formation
Authors: Barker Chase M. , Miles Kaleb D. , Doll Caleb A.
Published: November 2022

Motor behavior requires the balanced production and integration of a variety of neural cell types. Motor neurons are positioned in discrete locations in the spinal cord, targeting specific muscles to drive locomotive contractions. Specialized spinal interneurons modulate and synchronize motor neuron activity to achieve coordinated motor output. Changes in the ratios and connectivity of spinal interneurons could drastically alter motor output by tipping the balance of inhibition and excitation onto target motor neurons. Importantly, individuals with Fragile X syndrome (FXS) and associated autism spectrum disorders often have significant motor challenges, including repetitive behaviors and epilepsy. FXS stems from the transcriptional silencing of the gene Fragile X Messenger Ribonucleoprotein 1 (FMR1), which encodes an RNA binding protein that is implicated in a multitude of crucial neurodevelopmental processes, including cell specification. Our work shows that Fmrp regulates the formation of specific interneurons and motor neurons that comprise early embryonic motor circuits. We find that zebrafish fmr1 mutants generate surplus ventral lateral descending (VeLD) interneurons, an early-born cell derived from the motor neuron progenitor domain (pMN). As VeLD interneurons are hypothesized to act as central pattern generators driving the earliest spontaneous movements, this imbalance could influence the formation and long-term function of motor circuits driving locomotion. fmr1 embryos also show reduced expression of proteins associated with inhibitory synapses, including the presynaptic transporter vGAT and the postsynaptic scaffold Gephyrin. Taken together, we show changes in embryonic motor circuit formation in fmr1 mutants that could underlie persistent hyperexcitability.
Decoding continuous variables from event-related potential (ERP) data with linear support vector regression using the Decision Decoding Toolbox (DDTBOX)
Authors: Bode Stefan , Schubert Elektra , Hogendoorn Hinze , Feuerriegel Daniel
Published: November 2022

Multivariate classification analysis for event-related potential (ERP) data is a powerful tool for predicting cognitive variables. However, classification is often restricted to categorical variables and under-utilises continuous data, such as response times, response force, or subjective ratings. An alternative approach is support vector regression (SVR), which uses single-trial data to predict continuous variables of interest. In this tutorial-style paper, we demonstrate how SVR is implemented in the Decision Decoding Toolbox (DDTBOX). To illustrate in more detail how results depend on specific toolbox settings and data features, we report results from two simulation studies resembling real EEG data, and one real ERP-data set, in which we predicted continuous variables across a range of analysis parameters. Across all studies, we demonstrate that SVR is effective for analysis windows ranging from 2 to 100 ms, and relatively unaffected by temporal averaging. Prediction is still successful when only a small number of channels encode true information, and the analysis is robust to temporal jittering of the relevant information in the signal. Our results show that SVR as implemented in DDTBOX can reliably predict continuous, more nuanced variables, which may not be well-captured by classification analysis. In sum, we demonstrate that linear SVR is a powerful tool for the investigation of single-trial EEG data in relation to continuous variables, and we provide practical guidance for users.
Association between circadian rhythm and sleep quality among nursing interns: A latent profile and moderation analysis
Authors: Wu Xiaona , Lu Yingzi , Xie Xian , Chen Rongjie , Zhang Ningning , Zhou Chen , Ye Zengjie
Published: November 2022

Background

Disturbances in circadian rhythms are common among night-shift workers and result in poor sleep quality. Nevertheless, the heterogeneity of circadian rhythms and their relationship with sleep quality is less explored in nursing interns. Therefore, we aimed to identify the latent subtypes of circadian rhythm, explore their relationship with sleep quality, and evaluate their moderating role between perceived stress and sleep quality in nursing interns.

Materials and methods

In all, 452 nursing interns were recruited between October 2020 and January 2021 from Be Resilient to Nursing Career (BRNC), which is a multicenter, prospective cohort of a career growth program for nursing students. They were assessed using the 10-item Chinese Perceived Stress Scale, Circadian Type Inventory, and Pittsburgh Sleep Quality Index. Latent profile analysis and moderation analysis were performed.

Results

Overall, 72.3% of the nursing interns reported poor sleep quality. We identified three latent subtypes of circadian rhythms, namely, Vigorousness (40.1%), Inadaptability (18.6%), and Flexibility (41.1%). Females (OR = 1.97, 95% Cl: 1.01–3.83, P = 0.047) with normal body mass index (OR = 1.62, 95% CI: 0.95–2.76, P = 0.078) were prone to Flexibility. Circadian rhythm types significantly moderated the association between perceived stress and sleep quality (P < 0.05).

Conclusion

Nursing interns suffer from poor sleep. There exists heterogeneity of circadian rhythm subtypes in nursing interns, and attention should be paid to those with Inadaptability type. The association between perceived stress and sleep quality is significantly moderated by circadian rhythm subtypes.
Altered functional connectivity between primary motor cortex subregions and the whole brain in patients with incomplete cervical spinal cord injury
Authors: Wang Ling , Zheng Weimin , Yang Beining , Chen Qian , Li Xuejing , Chen Xin , Hu Yongsheng , Cao Lei , Ren Jian , Qin Wen , Yang Yanhui , Lu Jie , Chen Nan
Published: November 2022

To investigate the reorganizations of gray matter volume (GMV) in each subregion of primary motor cortex (M1) after incomplete cervical cord injury (ICCI) and to explore the differences in functional connectivity (FC) between the M1 subregions and the whole brain, and further to disclose the potential value of each M1 subregion in motor function rehabilitation of ICCI patients. Eighteen ICCI patients and eighteen age- and gender- matched healthy controls (HCs) were recruited in this study. The 3D high-resolution T1-weighted structural images and resting-state functional magnetic resonance imaging (rs-fMRI) of all subjects were obtained using a 3.0 Tesla MRI system. Based on the Human Brainnetome Atlas, the structural and functional changes of M1 subregions (including A4hf, A6cdl, A4ul, A4t, A4tl, A6cvl) in ICCI patients were analyzed by voxel-based morphometry (VBM) and seed-based FC, respectively. Compared with HCs, no structural changes in the M1 subregions of ICCI patients was detected. However, when compared with HCs, ICCI patients exhibited decreased FC in visual related areas (lingual gyrus, fusiform gyrus) and sensorimotor related areas (primary sensorimotor cortex) when the seeds were located in bilateral A4hf, A4ul, and decreased FC in visual related areas (lingual gyrus, fusiform gyrus) and cognitive related areas (temporal pole) when the seed was located in the left A4t. Moreover, when the seeds were located in the bilateral A6cdl, decreased FC in visual related areas (lingual gyrus, fusiform gyrus, calcarine gyrus) was also observed. Our findings demonstrated that each of the M1 regions had diverse FC reorganizations, which may provide a theoretical basis for the selection of precise stimulation targets, such as transcranial magnetic stimulation (TMS) or transcranial direct current stimulation (tCDS), meanwhile, our results may reveal the possible mechanism of visual feedback and cognitive training to promote motor rehabilitation.
The emerging power and promise of non-coding RNAs in chronic pain
Authors: Zhang Changteng , Gao Rui , Zhou Ruihao , Chen Hai , Liu Changliang , Zhu Tao , Chen Chan
Published: November 2022

Chronic pain (CP) is an unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage lasting longer than 3 months. CP is the main reason why people seek medical care and exerts an enormous economic burden. Genome-wide expression analysis has revealed that diverse essential genetic elements are altered in CP patients. Although many possible mechanisms of CP have been revealed, we are still unable to meet all the analgesic needs of patients. In recent years, non-coding RNAs (ncRNAs) have been shown to play essential roles in peripheral neuropathy and axon regeneration, which is associated with CP occurrence and development. Multiple key ncRNAs have been identified in animal models of CP, such as microRNA-30c-5p, ciRS-7, and lncRNA MRAK009713. This review highlights different kinds of ncRNAs in the regulation of CP, which provides a more comprehensive understanding of the pathogenesis of the disease. It mainly focuses on the contributions of miRNAs, circRNAs, and lncRNAs to CP, specifically peripheral neuropathic pain (NP), diabetic NP, central NP associated with spinal cord injury, complex regional pain syndrome, inflammatory pain, and cancer-induced pain. In addition, we summarize some potential ncRNAs as novel biomarkers for CP and its complications. With an in-depth understanding of the mechanism of CP, ncRNAs may provide novel insight into CP and could become new therapeutic targets in the future.
FruHis significantly increases the anti-benign prostatic hyperplasia effect of lycopene: A double-blinded randomized controlled clinical trial
Authors: Sadeghi Alireza , Saedisomeolia Ahmad , Jalili-Baleh Leili , Khoobi Mehdi , Soleimani Mohammad , Fakhr Yasseri Ali Mohammad , Yekaninejad Mir Saeed , Farzin Amirreza , Amini Erfan , Nowroozi Mohammad Reza
Published: November 2022

Background

For decades, lycopene was considered the main compound of tomato protecting benign prostatic hyperplasia (BPH). Recent animal studies suggest that a newly discovered compound “FruHis” boosts lycopene for its action. This study aimed to determine whether FruHis enhances the action of lycopene to modify the laboratory parameters and clinical outcomes of patients with BPH.

Materials and methods

Current study was conducted on 52 BPH patients, who were randomly assigned into four groups of treatments: lycopene plus FruHis (n = 11, 25 mg/day lycopene and 10 mg/day FruHis), lycopene (n = 12, 25 mg/day lycopene), FruHis (n = 12, 10 mg/day FruHis), and placebo (n = 13). Patients received these supplements for 8 weeks.

Results

FruHis intake strengthened the reducing effects of lycopene on insulin-like growth factor-1 (IGF-1) (−54.47 ± 28.36 ng/mL in the lycopene + FruHis group vs. −30.24 ± 46.69 ng/mL in the lycopene group), total prostate-specific antigen (TPSA) (−1.49 ± 4.78 ng/mL in the lycopene + FruHis group vs. −0.64 ± 2.02 ng/mL in the lycopene group), and symptom score (−4.45 ± 4.03 in the lycopene + FruHis group vs. −1.66 ± 5.41 in the lycopene group) in BPH patients. Such findings were also seen for body mass index (BMI) and waist circumference (WC). However, except for IGF-1, these reductions were not statistically significant compared with the placebo, and the intakes of lycopene and FruHis alone, however, were clinically important. Such effects of lycopene and FruHis were not seen for free PSA (FPSA) and FPSA/TPSA ratio.

Conclusion

Despite the non-significant effects of lycopene and FruHis, it seems that FruHis intake strengthens the beneficial effects of lycopene on IGF-1, TPSA, and symptom scores among BPH patients.

Clinical trial registration

[www.irct.ir], identifier [IRCT20190522043669N1].
Polysaccharides from Artocarpus heterophyllus Lam. (jackfruit) pulp improves intestinal barrier functions of high fat diet-induced obese rats
Authors: Zeng Shunjiang , Cao Jun , Chen Yuzi , Li Chuan , Wu Gang , Zhu Kexue , Chen Xiaoai , Xu Fei , Liu Qibing , Tan Lehe
Published: November 2022

Polysaccharides show protective effects on intestinal barrier function due to their effectiveness in mitigating oxidative damage, inflammation and probiotic effects. Little has been known about the effects of polysaccharides from Artocarpus heterophyllus Lam. pulp (jackfruit, JFP-Ps) on intestinal barrier function. This study aimed to investigate the effects of JFP-Ps on intestinal barrier function in high fat diet-induced obese rats. H&E staining and biochemical analysis were performed to measure the pathological and inflammatory state of the intestine as well as oxidative damage. Expression of the genes and proteins associated with intestinal health and inflammation were analyzed by RT-qPCR and western blots. Results showed that JFP-Ps promoted bowel movements and modified intestinal physiochemical environment by lowering fecal pH and increasing fecal water content. JFP-Ps also alleviated oxidative damage of the colon, relieved intestinal colonic inflammation, and regulated blood glucose transport in the small intestine. In addition, JFP-Ps modified intestinal physiological status through repairing intestinal mucosal damage and increasing the thickness of the mucus layer. Furthermore, JFP-Ps downregulated the inflammatory genes (TNF-α, IL-6) and up-regulated the free fatty acid receptors (GPR41 and GPR43) and tight junction protein (occludin). These results revealed that JFP-Ps showed a protective effect on intestinal function through enhancing the biological, mucosal, immune and mechanical barrier functions of the intestine, and activating SCFAs-GPR41/GPR43 related signaling pathways. JFP-Ps may be used as a promising phytochemical to improve human intestinal health.
Relationship between starch fine structure and simulated oral processing of cooked japonica rice
Authors: Liu Guodong , Wang Ruizhi , Liu Shaoqiang , Xu Man , Guo Lunan , Zhang Hongcheng , Wei Haiyan
Published: November 2022

Background

Simulated oral processing can be used to evaluate the palatability of cooked rice. Previously, we established a simulated oral processing method using a texture analyzer equipped with a multiple extrusion cell probe (TA/MEC). However, the relationship between oral processing and starch fine structure remains unknown.

Methods

In this study, we analyzed the oral processing properties using TA/MEC and characterized the starch fine structure of japonica rice by size-exclusion chromatography (SEC) and fluorophore-assisted capillary electrophoresis (FACE). The relationship between starch fine structure and oral processing of cooked japonica rice was further investigated.

Results

Cooked rice structure contains fast-breakdown (Type I structure), slow-breakdown (Type II structure) and unbreakable structures (Type III structure). Fast-breakdown and slow-breakdown structure were positively correlated with the content of amylose and shorter amylopectin branches. The content of longer amylopectin branches was positively correlated with the contribution of unbreakable structure.

Conclusion

The results indicated that cooked japonica rice varieties with more amylose and shorter amylopectin branches tend to form a harder texture and need more work to break down the fast and slow breakdown structures related to rice kernel fragmentation. Meanwhile, cooked japonica rice varieties possess stronger molecular entanglements due to their longer amylopectin branches and contribute more to the breakdown of unbreakable structures. These results can guide breeders to select rice varieties with desirable eating qualities for cultivation.
Effect of dietary protein content shift on aging in elderly rats by comprehensive quantitative score and metabolomics analysis
Authors: Zheng Wenxuan , Li Ruiding , Zhou Yang , Shi Fengcui , Song Yao , Liao Yanting , Zhou Fan , Zheng Xiaohua , Lv Jingwen , Li Quanyang
Published: November 2022

In the protein nutrition strategy of middle-aged and elderly people, some believe that low protein is good for health, while others believe high protein is good for health. Facing the contradictory situation, the following hypothesis is proposed. There is a process of change from lower to higher ratio of protein nutritional requirements that are good for health in the human body after about 50 years of age, and the age at which the switch occurs is around 65 years of age. Hence, in this study, 50, 25-month-old male rats were randomly divided into five groups: Control (basal diet), LP (low-protein diet with a 30% decrease in protein content compared to the basal diet), HP (high-protein diet with a 30% increase in protein content compared to the basal diet), Model 1 (switched from LP to HP feed at week 4), and Model 2 (switched from LP to HP feed at week 7). After a total of 10 weeks intervention, the liver and serum samples were examined for aging-related indicators, and a newly comprehensive quantitative score was generated using principal component analysis (PCA). The effects of the five protein nutritional modalities were quantified in descending order: Model 1 > HP > LP > Control > Model 2. Furthermore, the differential metabolites in serum and feces were determined by orthogonal partial least squares discriminant analysis, and 15 differential metabolites, significantly associated with protein intake, were identified by Spearman’s correlation analysis (p < 0.05). Among the fecal metabolites, 10 were positively correlated and 3 were negatively correlated. In the serum, tyrosine and lactate levels were positively correlated, and acetate levels were negatively correlated. MetaboAnalyst analysis identified that the metabolic pathways influenced by protein intake were mainly related to amino acid and carbohydrate metabolism. The results of metabolomic analysis elucidate the mechanisms underlying the preceding effects to some degree. These efforts not only contribute to a unified protein nutrition strategy but also positively impact the building of a wiser approach to protein nutrition, thereby helping middle-aged and older populations achieve healthy aging.
Mechanism of interactions between tripeptide NCW on cellular membrane using molecular dynamic simulation
Authors: Wu Sijia , Zhuang Hong , Yan Haiyang , Mao Chen , Wang Bing , Zhou Guangdong , Tian Ge
Published: November 2022

Tripeptide NCW identified in Mizuhopecten yessoensis has been shown to possess in vivo antihypertensive effect. However, the poor understanding of the absorption of NCW across the membrane limits its application. In this study, we have investigated the interaction of NCW with DPPC membrane via 400 ns all-atom molecular dynamic simulation using GROMACS software. The structural variations of NCW during absorption, the location and distribution of NCW in the membrane, and the effect of NCW on the properties of membranes during simulation were analyzed to understand the dynamic behavior of NCW in DPPC membrane system. The results suggested that the structures of NCW were stable during simulation. Further, NCW could bind on the surface of the DPPC membrane and enter the hydrophobic interior of the DPPC membrane. Residue Try played an important role in the absorption of NCW across the membrane. Hydrogen bonds and hydrophobic interactions stabilized the interaction of NCW with the membrane. All the above studies analyzed the interaction mechanism between NCW and DPPC membranes at the atomic level and laid the foundation for further transmembrane studies of NCW.
Association between chili pepper consumption and risk of gastrointestinal-tract cancers: A meta-analysis
Authors: Chen Changchang , Zhang Man , Zheng Xutong , Lang Hongjuan
Published: November 2022

Background

Stimulating food is emerging as an important modifiable factor in the development of gastrointestinal (GI) tract cancers, but the association between chili pepper consumption and the risk of GI cancers is unclear. We aimed to evaluate the direction and magnitude of the association between chili pepper consumption and the risk of GI cancers.

Methods

A literature search was performed in PubMed, Embase, and Web of Science databases from inception to 22 December 2021. Observational studies reporting the association between chili pepper consumption and the risk of gastric cancer (GC), esophageal cancer (EC), and/or colorectal cancer (CRC) in adults were eligible for inclusion. Data extraction and quality assessment were conducted independently by two reviewers for the included literature. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a random-effects model. Subgroup analyses were also performed based on the cancer type, study design, region of the study, study quality, and adjustments.

Results

A total of 11,421 studies were screened, and 14 case-control studies were included involving 5009 GI cancers among 11,310 participants. The summary OR showed that high consumption of chili pepper was positively related to the risk of GI cancers (OR = 1.64; 95% CI: 1.00–2.70). A stronger positive relationship was observed between chili pepper consumption and EC risk (OR = 2.71; 95% CI: 1.54–4.75), but there was no statistically significant association between GC and CRC risk. In analyses stratified by geographical location, a positive association was found between chili pepper consumption and the risk of GI cancers in Asian studies (OR = 2.50; 95% CI: 1.23–5.08), African studies (OR = 1.62; 95% CI: 1.04–2.52), and North American studies (OR = 2.61; 95% CI: 1.34–5.08), but an inverse association was seen in South American studies (OR = 0.50; 95% CI: 0.29–0.87) and European studies (OR = 0.30; 95% CI: 0.15–0.61).

Conclusion

This meta-analysis suggests that chili pepper is a risk factor for certain GI cancers (e.g., EC). Geographical regions influence the risk of GI cancers, especially in Asian, African, and North American populations, which require more attention during dietary guidance.

Systematic review registration

[https://www.crd.york.ac.uk/PROSPERO/], identifier [CRD42022320670].
Dietary metal intake and the prevalence of erectile dysfunction in US men: Results from National Health and Nutrition Examination Survey 2001–2004
Authors: Liu Rui-Ji , Li Shu-Ying , Xu Zhi-Peng , Yu Jun-Jie , Mao Wei-Pu , Sun Chao , Xu Bin , Chen Ming
Published: November 2022

Background

Erectile dysfunction (ED) mainly affects men over 40 years of age and is a common clinical condition. In addition to hypertension and diabetes, environment, and lifestyle are also significantly associated with erectile dysfunction. The relationship between dietary trace metal intake and ED has not been studied.

Materials and methods

Data on participants were obtained from the National Health and Nutrition Examination Survey for this study, and those with incomplete information on clinical variables were excluded. Dose-response curve analysis was used to investigate the relationship between dietary trace metal intake and ED prevalence. Multivariate logistic regression analysis was used to adjust for confounders to further investigate the relationship between dietary trace metal intake and ED prevalence. 1:1 propensity score matching (PSM) was performed to adjust for differences between clinical variables for data reanalysis to confirm the reliability of the results.

Results

A total of 3,745 individuals were included in the study, including 1096 ED patients and 2,649 participants without ED. Dietary intake of trace metals (Mg, Zn, Cu, and Se) was significantly higher in participants without ED than in ED patients (all P < 0.001). Dose-response curve analysis showed a significant negative association between these dietary metal intakes and ED prevalence (all P < 0.001). Multivariate logistic regression analysis adjusted for confounders (age, education, BMI, annual household income, hypertension, diabetes, marital status, race, and current health status) revealed that increased dietary metal intake reduced the odds ratio of ED. 1:1 PSM reanalysis further confirmed the validity of the results.

Conclusion

Increasing dietary intake of trace metals (magnesium, zinc, copper, and selenium) within the upper limit is beneficial in reducing the prevalence of ED.
Association of dietary n - 3 polyunsaturated fatty acids with breast cancer risk: Serial mediating roles of erythrocyte n - 3 polyunsaturated fatty acids
Authors: Zhang Zhuolin , Jiang Yiling , Li Xue , Shi Dandan , Ma Ting , Zhou Ruolin , Zhang Caixia
Published: November 2022

Background

Dietary n– 3 polyunsaturated fatty acids (PUFAs) were found to be inversely associated with breast cancer risk; however, the underlying pathways between them remain uncertain. We aimed to explore serial mediatory roles of erythrocyte n– 3 PUFAs in association between dietary n– 3 PUFAs and breast cancer risk.

Materials and methods

Using a case-control study, 850 cases and 861 controls completed structured questionnaires with dietary information. Erythrocyte n– 3 PUFAs were measured by gas chromatography. Odds ratios (ORs) and 95% confidence intervals (CIs) were obtained using multiple unconditional logistic regression models to examine association between dietary n– 3 PUFAs and breast cancer risk. Mediation analyses with bootstrapping were conducted to investigate indirect effects.

Results

Higher intake of dietary ALA, long-chain n– 3 PUFAs and total n– 3 PUFAs was associated with lower risk of breast cancer. The adjusted ORtertile 3 v.1 (95% CI) was 0.70 (0.55, 0.90) for ALA, 0.76 (0.60, 0.97) for long-chain n– 3 PUFAs and 0.74 (0.58, 0.94) for total n– 3 PUFAs, respectively. Mediation analysis showed that erythrocyte long-chain n– 3 PUFAs served as sequential mediators in the relationship between dietary long-chain or total n– 3 PUFAs and breast cancer risk. In particular, erythrocyte long-chain n– 3 PUFAs completely mediated the association between dietary long-chain n– 3 PUFAs and breast cancer risk [indirect effect (95% CI) = –0.982 (–1.529, –0.508)]. The relationship between dietary total n– 3 PUFAs and breast cancer risk was partly mediated by erythrocyte long-chain n– 3 PUFAs [indirect effect (95% CI) = –0.107 (–0.216, –0.014)], accounting for 19.31%. However, the serial mediation model in dietary ALA and risk of breast cancer was not statistically significant [indirect effect (95% CI) = –0.042 (–0.144, 0.049)].

Conclusion

This study highlights the complexity and inaccuracy in using a simple analysis of individual dietary n– 3 PUFAs to examine their associations with breast cancer risk without considering the variety of metabolic processes. Interventions aimed at increasing erythrocyte long-chain n– 3 PUFAs may represent a promising strategy for breast cancer prevention.
Reversion of methionine addiction of osteosarcoma cells to methionine independence results in loss of malignancy, modulation of the epithelial-mesenchymal phenotype and alteration of histone-H3 lysine-methylation
Authors: Aoki Yusuke , Han Qinghong , Tome Yasunori , Yamamoto Jun , Kubota Yutaro , Masaki Noriyuki , Obara Koya , Hamada Kazuyuki , Wang Justin D. , Inubushi Sachiko , Bouvet Michael , Clarke Steven G. , Nishida Kotaro , Hoffman Robert M.
Published: November 2022

Methionine addiction, a fundamental and general hallmark of cancer, known as the Hoffman Effect, is due to altered use of methionine for increased and aberrant transmethylation reactions. However, the linkage of methionine addiction and malignancy of cancer cells is incompletely understood. An isogenic pair of methionine-addicted parental osteosarcoma cells and their rare methionine-independent revertant cells enabled us to compare them for malignancy, their epithelial-mesenchymal phenotype, and pattern of histone-H3 lysine-methylation. Methionine-independent revertant 143B osteosarcoma cells (143B-R) were selected from methionine-addicted parental cells (143B-P) by their chronic growth in low-methionine culture medium for 4 passages, which was depleted of methionine by recombinant methioninase (rMETase). Cell-migration capacity was compared with a wound-healing assay and invasion capability was compared with a transwell assay in 143B-P and 143B-R cells in vitro. Tumor growth and metastatic potential were compared after orthotopic cell-injection into the tibia bone of nude mice in vivo. Epithelial-mesenchymal phenotypic expression and the status of H3 lysine-methylation were determined with western immunoblotting. 143B-P cells had an IC50 of 0.20 U/ml and 143B-R cells had an IC50 of 0.68 U/ml for treatment with rMETase, demonstrating that 143B-R cells had regained the ability to grow in low methionine conditions. 143B-R cells had reduced cell migration and invasion capability in vitro, formed much smaller tumors than 143B-P cells and lost metastatic potential in vivo, indicating loss of malignancy in 143B-R cells. 143B-R cells showed gain of the epithelial marker, ZO-1 and loss of mesenchymal markers, vimentin, Snail, and Slug and, an increase of histone H3K9me3 and H3K27me3 methylation and a decrease of H3K4me3, H3K36me3, and H3K79me3 methylation, along with their loss of malignancy. These results suggest that shifting the balance in histone methylases might be a way to decrease the malignant potential of cells. The present results demonstrate the rationale to target methionine addiction for improved sarcoma therapy.