bluuebunny/crossref_metadata_2025 huggingface dataset:
In Vivo Pravastatin Treatment Reverses Hypercholesterolemia Induced Mitochondria-Associated Membranes Contact Sites, Foam Cell Formation, and Phagocytosis in Macrophages
Authors: Assis Leandro Henrique de Paula , Dorighello Gabriel de Gabriel , Rentz Thiago , Souza Jane Cristina de , Vercesi Aníbal Eugênio , Oliveira Helena Coutinho Franco de
Published: March 2022

Statins are successful drugs used to treat hypercholesterolemia, a primary cause of atherosclerosis. In this work, we investigated how hypercholesterolemia and pravastatin treatment impact macrophage and mitochondria functions, the key cell involved in atherogenesis. By comparing bone marrow-derived macrophages (BMDM) of wild-type (WT) and LDL receptor knockout (LDLr−/−) mice, we observed hypercholesterolemia increased the number of contact sites at mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs), enhanced mitochondrial hydrogen peroxide release, altered the gene expression of inflammatory markers, and increased oxidized LDL (ox-LDL) uptake and phagocytic activity. Three months ofin vivopravastatin treatment of LDLr−/−mice reversed the number of contact sites at the MAM, ox-LDL uptake, and phagocytosis in LDLr−/−BMDM. Additionally, pravastatin increased BMDM mitochondrial network branching. In peritoneal macrophages (PMs), hypercholesterolemia did not change MAM stability, but stimulated hydrogen peroxide production and modulated gene expression of pro- and anti-inflammatory markers. It also increased mitochondrial branching degree and had no effects on ox-LDL uptake and phagocytosis in PM. Pravastatin treatment increased superoxide anion production and changed inflammation-related gene expression in LDLr−/−PM. In addition, pravastatin increased markedly the expression of the mitochondrial dynamics-related genes Mfn2 and Fis1 in both macrophages. In summary, our results show that hypercholesterolemia and pravastatin treatment affect macrophage mitochondria network structure as well as their interaction with the endoplasmic reticulum (ER). These effects impact on macrophage conversion rates to foam cell and macrophage phagocytic capacity. These findings associate MAM stability changes with known mechanisms involved in atherosclerosis progression and resolution.
Sulforaphane Ameliorates Metabolic Changes Associated With Status Epilepticus in Immature Rats
Authors: Daněk Jan , Danačíková Šárka , Kala David , Svoboda Jan , Kapoor Sonam , Pošusta Antonín , Folbergrová Jaroslava , Tauchmannová Kateřina , Mráček Tomáš , Otáhal Jakub
Published: March 2022

Status epilepticus (SE) is a common paediatric emergency with the highest incidence in the neonatal period and is a well-known epileptogenic insult. As previously established in various experimental and human studies, SE induces long-term alterations to brain metabolism, alterations that directly contribute to the development of epilepsy. To influence these changes, organic isothiocyanate compound sulforaphane (SFN) has been used in the present study for its known effect of enhancing antioxidative, cytoprotective, and metabolic cellular propertiesviathe Nrf2 pathway. We have explored the effect of SFN in a model of acquired epilepsy induced by Li-Cl pilocarpine in immature rats (12 days old). Energy metabolites PCr, ATP, glucose, glycogen, and lactate were determined by enzymatic fluorimetric methods during the acute phase of SE. Protein expression was evaluated by Western blot (WB) analysis. Neuronal death was scored on the FluoroJadeB stained brain sections harvested 24 h after SE. To assess the effect of SFN on glucose metabolism we have performed a series of 18F-DG μCT/PET recordings 1 h, 1 day, and 3 weeks after the induction of SE. Responses of cerebral blood flow (CBF) to electrical stimulation and their influence by SFN were evaluated by laser Doppler flowmetry (LDF). We have demonstrated that the Nrf2 pathway is upregulated in the CNS of immature rats after SFN treatment. In the animals that had undergone SE, SFN was responsible for lowering glucose uptake in most regions 1 h after the induction of SE. Moreover, SFN partially reversed hypometabolism observed after 24 h and achieved full reversal at approximately 3 weeks after SE. Since no difference in cell death was observed in SFN treated group, these changes cannot be attributed to differences in neurodegeneration. SFNper sedid not affect the glucose uptake at any given time point suggesting that SFN improves endogenous CNS ability to adapt to the epileptogenic insult. Furthermore, we had discovered that SFN improves blood flow and accelerates CBF response to electrical stimulation. Our findings suggest that SFN improves metabolic changes induced by SE which have been identified during epileptogenesis in various animal models of acquired epilepsy.
Effects of Supplemental Oxygen on Cardiovascular and Respiratory Interactions by Extended Partial Directed Coherence in Idiopathic Pulmonary Fibrosis
Authors: Santiago-Fuentes Laura M. , Charleston-Villalobos Sonia , González-Camarena Ramón , Voss Andreas , Mejía-Avila Mayra E. , Buendía-Roldan Ivette , Reulecke Sina , Aljama-Corrales Tomás
Published: March 2022

Idiopathic pulmonary fibrosis (IPF) is a chronic and restrictive disease characterized by fibrosis and inflammatory changes in lung tissue producing a reduction in diffusion capacity and leading to exertional chronic arterial hypoxemia and dyspnea. Furthermore, clinically, supplemental oxygen (SupplO2) has been prescribed to IPF patients to improve symptoms. However, the evidence about the benefits or disadvantages of oxygen supplementation is not conclusive. In addition, the impact of SupplO2 on the autonomic nervous system (ANS) regulation in respiratory diseases needs to be evaluated. In this study the interactions between cardiovascular and respiratory systems in IPF patients, during ambient air (AA) and SupplO2 breathing, are compared to those from a matched healthy group. Interactions were estimated by time series of successive beat-to-beat intervals (BBI), respiratory amplitude (RESP) at BBI onset, arterial systolic (SYS) and diastolic (DIA) blood pressures. The paper explores the Granger causality (GC) between systems in the frequency domain by the extended partial directed coherence (ePDC), considering instantaneous effects. Also, traditional linear and nonlinear markers as power in low (LF) and high frequency (HF) bands, symbolic dynamic indices as well as arterial baroreflex, were calculated. The results showed that for IPF during AA phase: 1) mean BBI and power of BBI-HF band, as well as mean respiratory frequency were significantly lower (p < 0.05) and higher (p < 0.001), respectively, indicating a strong sympathetic influence, and 2) the RESP → SYS interaction was characterized by Mayer waves and diminished RESP → BBI, i.e., decreased respiratory sinus arrhythmia. In contrast, during short-term SupplO2 phase: 1) oxygen might produce a negative influence on the systolic blood pressure variability, 2) the arterial baroreflex reduced significantly (p < 0.01) and 3) reduction of RSA reflected by RESP → BBI with simultaneous increase of Traube-Hering waves in RESP → SYS (p < 0.001), reflected increased sympathetic modulation to the vessels. The results gathered in this study may be helpful in the management of the administration of SupplO2.
Misdiagnosis of HIV With Toxoplasmosis Encephalopathy With Progressive Memory Loss as the Initial Symptom: A Case Report
Authors: Wu Jingjing , Luo Xiumei , Huang Nanqu , Li Yuanyuan , Luo Yong
Published: March 2022

Toxoplasmosis encephalopathy (TE) is a kind of encephalopathy parasitic disease caused by Toxoplasma gondii. It is the most common opportunistic for central system infection in patients with acquired immunodeficiency syndrome (AIDS) or human immunodeficiency virus. Without early diagnosis and proper treatment, this opportunistic infection can be life-threatening. The common clinical manifestations of the disease include altered mental state, epilepsy, cranial nerve damage, paresthesia, cerebellar signs, meningitis, motor disorders, and neuropsychiatry. The most common presentation in about 75% of cases is a subacute episode of focal neurological abnormalities such as hemiplegia, personality changes, or aphasia. Imaging needs to be differentiated from multiple sclerosis, lymphoma, and metastases. We report a case of acquired immune deficiency syndrome complicated with toxoplasma encephalopathy with rapid progressive memory loss as the initial symptom and misdiagnosed as multiple sclerosis. Through the comprehensive analysis of the clinical symptoms and imaging examination of this disease, we hope to enhance the confidence of clinicians in the diagnosis of this disease.
Impact of Sarcopenia on Functional Outcomes Among Patients With Mild Acute Ischemic Stroke and Transient Ischemic Attack: A Retrospective Study
Authors: Lee Hyungwoo , Lee Il Hyung , Heo JoonNyung , Baik Minyoul , Park Hyungjong , Lee Hye Sun , Nam Hyo Suk , Kim Young Dae
Published: March 2022

Introduction

Sarcopenia, a age-related disease characterized by loss of muscle mass accompanied by loss of function, is associated with nutrition imbalance, physical inactivity, insulin resistance, inflammation, metabolic syndrome, and atherosclerosis which are risk factors for cardiovascular disease. However, its association with outcomes after ischemic stroke has not been well-established. This study investigated whether functional outcomes of patients with acute ischemic stroke is associated with sarcopenia.

Methods

Data were collected from 568 consecutive patients with acute ischemic stroke with National Institute of Health Stroke Scale 0–5 or transient ischemic attack who underwent bioelectrical impedance analysis between March 2018 and March 2021. Sarcopenia was defined, as low muscle mass, as measured by bioelectrical impedance analysis, and low muscle strength, as indicated by the Medical Research Council score. Unfavorable functional outcome was defined as mRS score of 2–6 at 90 days after discharge. The relationship between functional outcomes and the presence of sarcopenia or its components was determined.

Results

Of the 568 patients included (mean age 65.5 ± 12.6 years, 64.6% male), sarcopenia was detected in 48 (8.5%). After adjusting for potential confounders, sarcopenia was independently and significantly associated with unfavorable functional outcome (odds ratio 2.37, 95% confidence interval 1.15–4.73 for unfavorable functional outcome, odds ratio 2.10, 95% confidence interval 1.18–3.71 for an increase in the mRS score). Each component of sarcopenia was also independently associated with unfavorable functional outcome (odds ratio 1.76, 95% confidence interval 1.05–2.95 with low muscle mass, odds ratio 2.64, 95% confidence interval 1.64–4.23 with low muscle strength). The impact of low muscle mass was larger in men than in women, and in patients with lower muscle mass of the lower extremities than in those with lower muscle mass of the upper extremities.

Conclusions

In this study, the prevalence of sarcopenia in patients with stroke was lower than most of previous studies and patients with sarcopenia showed higher likelihood for unfavorable functional outcomes at 90 days after acute ischemic stroke or TIA. Further investigation of the interventions for treating sarcopenia and its impact on the outcome of ischemic stroke patients is needed.
Neuroprotective Mechanisms of Glucagon-Like Peptide-1-Based Therapies in Ischemic Stroke: An Update Based on Preclinical Research
Authors: Yang Xiaoyan , Qiang Qiang , Li Nan , Feng Peng , Wei Wenshi , Hölscher Christian
Published: March 2022

The public and social health burdens of ischemic stroke have been increasing worldwide. Hyperglycemia leads to a greater risk of stroke. This increased risk is commonly seen among patients with diabetes and is in connection with worsened clinical conditions and higher mortality in patients with acute ischemic stroke (AIS). Therapy for stroke focuses mainly on restoring cerebral blood flow (CBF) and ameliorating neurological impairment caused by stroke. Although choices of stroke treatment remain limited, much advance have been achieved in assisting patients in recovering from ischemic stroke, along with progress of recanalization therapy through pharmacological and mechanical thrombolysis. However, it is still necessary to develop neuroprotective therapies for AIS to protect the brain against injury before and during reperfusion, prolong the time window for intervention, and consequently improve neurological prognosis. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are broadly regarded as effective drugs in the treatment of type 2 diabetes mellitus (T2DM). Preclinical data on GLP-1 and GLP-1 RAs have displayed an impressive neuroprotective efficacy in stroke, Parkinson's disease (PD), Alzheimer's disease (AD), Amyotrophic lateral sclerosis (ALS), and other neurodegenerative diseases. Based on the preclinical studies in the past decade, we review recent progress in the biological roles of GLP-1 and GLP-1 RAs in ischemic stroke. Emphasis will be placed on their neuroprotective effects in experimental models of cerebral ischemia stroke at cellular and molecular levels.
Predicting Functional Connectivity From Observed and Latent Structural Connectivity via Eigenvalue Mapping
Authors: Cummings Jennifer A. , Sipes Benjamin , Mathalon Daniel H. , Raj Ashish
Published: March 2022

Understanding how complex dynamic activity propagates over a static structural network is an overarching question in the field of neuroscience. Previous work has demonstrated that linear graph-theoretic models perform as well as non-linear neural simulations in predicting functional connectivity with the added benefits of low dimensionality and a closed-form solution which make them far less computationally expensive. Here we show a simple model relating the eigenvalues of the structural connectivity and functional networks using the Gamma function, producing a reliable prediction of functional connectivity with a single model parameter. We also investigate the impact of local activity diffusion and long-range interhemispheric connectivity on the structure-function model and show an improvement in functional connectivity prediction when accounting for such latent variables which are often excluded from traditional diffusion tensor imaging (DTI) methods.
Key Disease Mechanisms Linked to Amyotrophic Lateral Sclerosis in Spinal Cord Motor Neurons
Authors: Bottero Virginie , Santiago Jose A. , Quinn James P. , Potashkin Judith A.
Published: March 2022

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with no modifying treatments available. The molecular mechanisms underpinning disease pathogenesis are not fully understood. Recent studies have employed co-expression networks to identify key genes, known as “switch genes”, responsible for dramatic transcriptional changes in the blood of ALS patients. In this study, we directly investigate the root cause of ALS by examining the changes in gene expression in motor neurons that degenerate in patients. Co-expression networks identified in ALS patients’ spinal cord motor neurons revealed 610 switch genes in seven independent microarrays. Switch genes were enriched in several pathways, including viral carcinogenesis, PI3K-Akt, focal adhesion, proteoglycans in cancer, colorectal cancer, and thyroid hormone signaling. Transcription factors ELK1 and GATA2 were identified as key master regulators of the switch genes. Protein-chemical network analysis identified valproic acid, cyclosporine, estradiol, acetaminophen, quercetin, and carbamazepine as potential therapeutics for ALS. Furthermore, the chemical analysis identified metals and organic compounds including, arsenic, copper, nickel, and benzo(a)pyrene as possible mediators of neurodegeneration. The identification of switch genes provides insights into previously unknown biological pathways associated with ALS.
Holographic Duality and the Physics of Consciousness
Authors: Awret Uziel
Published: March 2022

This paper introduces a novel dual-aspect theory of consciousness that is based on the principle of holographic-duality in modern physics and explores the prospects of making philosophically significant empirical discoveries about the physical correlates of consciousness. The theory is motivated by an approach that identifies certain anti-physicalist problem intuitions associated with representational content and spatial location and attempts to provide these with a consciousness-independent explanation, while suspending questions about the hard problem of consciousness and the more problematic “phenomenal character”. Providing such topic neutral explanations is “hard” enough to make a philosophical difference and yet “easy” enough to be approached scientifically. I will argue that abstract algorithms are not enough to solve this problem and that a more radical “computation” that is inspired by physics and that can be realized in “strange metals” may be needed. While speculative, this approach has the potential to both establish necessary connections between structural aspects of conscious mental states and the physical substrate “generating” them and explain why this representational content is “nowhere to be found”. I will end with a reconsideration of the conceivability of zombies.
Study on the Absorption and Immunity Regulation of Simulated Breast Milk Nutrients in Rats
Authors: Xie Qinggang , Zhang Jinlan , Liu Yang , Yang Yi , Wei Yanli , Jiang Shilong , Cui Dongying , Zhou Qile
Published: March 2022

Since infant formula (IF) manufacturers aim to produce a product as close to breast milk as possible, fortified nutrients are usually added. Generally, an IF is produced by adjusting the types and proportions of vitamins and minerals. This study comparatively examined the content of the six nutrients in different compound forms in vivo and evaluated the effect of different nutrient pack groups on immunity and growth. The results indicated that the simulated-human milk nutrients [minerals zinc (Zn), iron (Fe), calcium (Ca), and vitamins A, E, and B1] were more easily absorbed by the body while effectively regulating immunity. This study provides a scientific foundation for developing, manufacturing, and applying imitation-breast formula milk powder.
The Origins of Food Supplied to an Australian Public Hospital
Authors: Faulkner Kathy , Gilbertson Heather , Porter Judi , Collins Jorja
Published: March 2022

Local food procurement by public institutions such as hospitals offers multiple benefits including stimulating the local economy, creating jobs, and building resilience within the food supply. Yet no published study has attempted to quantify the local food purchase by hospitals. This baseline is needed to identify gaps, set targets, and monitor change. The objective of this study was to investigate the origin of food supplied to a metro tertiary public hospital and to describe the proportion of food budget spent on items with ingredients grown in Australia and “locally” within the state of Victoria. Food procurement data were collected and analyzed during October 2020-April 2021. All items purchased by the cook fresh kitchen supplying meals to inpatients and two childcare centres during an 8-day menu cycle period were audited. Following an inspection of food packaging labels to determine country of origin, data on the proportion of Victorian content were collected from manufacturers and suppliers of foods containing Australian ingredient. Almost 80% of the food budget (AU $17,748 and 200 items) was spent on items containing significant (at least 75%) Australian content, while 11% was spent on entirely imported foods. The specific geographic origins of 55% of the budget spent on “Australian” food remain unknown as information from manufacturers and suppliers was not available. Where data were available, 3% of food budget was attributed to entirely Victorian grown foods, including fresh fruit, vegetables, and poultry. A considerable proportion of Australian grown foods are purchased by this hospital, but it is largely unknown whether these are local, from the state of Victoria, or not. Tracing and sharing of food origin data, a clear definition for “local” food, and an understanding of Victorian food growing industries are needed to progress the “local food to hospital” agenda.
The Design and Evaluation of Online Interactive Learning in an Undergraduate Nutrition Course
Authors: Livingstone Katherine M. , Milte Catherine M. , Macfarlane Susie , Woods Julie , Booth Alison
Published: March 2022

Understanding factors that promote student engagement with online learning environments is important for benchmarking and improving the quality of teaching in a digital era. This study aimed to describe the online interactive content created for delivery of an undergraduate nutrition course and to evaluate student engagement with the online interactive content. We collected online questionnaire data in 2018 and 2019 from two cohorts of students enrolled in a Deakin University undergraduate nutrition unit. Two-sample unpaired t-tests were used to examine differences in participant engagement with online topic guides between static text-based and interactive content. A total of 89 participants (19–56 years) were included. Sixty four of students reported always/usually reading static text-based topic guides most weeks and 64% perceived them as moderately/highly effective. While 60% of participants reported reading the online interactive topic guides most weeks and 93% perceived them as moderate/highly effective. Most participants indicated the interactive topic guides were more effective than static text-based topic guides they experienced in other courses (76%). Hours dedicated to the online interactive topic guide were higher (6.4 SD 2.9 vs. 1.7 SD 1.7 h; P < 0.001) as was the rating of how engaging the topic guides were (7.2 SD 1.6 vs. 6.7 SD 2.5; P = 0.008). These findings suggest that interactive content is more engaging. However, this content may not be accessible to all students, and so familiarization and training prior to engaging in an interactive online unit may be needed.
Relationship of Vitamin A and Thyroid Function in Individuals With Obesity and After Laparoscopic Sleeve Gastrectomy
Authors: Ma Bingwei , Yang Peng , Gao Jingyang , Du Lei , Sheng Chunjun , Usman Taofeek , Wang Xingchun , Qu Shen
Published: March 2022

Vitamin A deficiency (VAD) occurs in obesity and may be associated with thyroid dysfunction. We aimed to investigate the association of VA with thyroid function in obesity and after laparoscopic sleeve gastrectomy (LSG). Nine hundred and seventy-six obese subjects were enrolled for this study and were divided into VAD, marginal vitamin A deficiency (MVAD), and vitamin A normal (NVA) groups. VAD was defined as VA ≤ 200 ng/ml, MVAD was defined as VA > 200 but <300 ng/ml, and NVA was defined as VA ≥ 300 ng/ml. Thyroid function was compared among groups and the relationship of VA and thyroid function was analyzed. Two hundred and forty-four of the 976 obese subjects underwent LSG, and the change in thyroid function and VA at 3, 6, and 12 months after surgery was measured. Results showed that 37% of all the subjects had subclinical hypothyroidism (SH), and the SH group had lower VA levels than the non-SH group (P = 0.008). Forty-nine percent of all the subjects had MVAD, 9% had VAD, while the MVAD or VAD group had lower FT4 than the NVA group (P = 0.005 and P = 0.001). The VAD group also had higher TSH than NVA group (P = 0.037). VA was significantly negatively associated with TSH (r = −0.151, P = 0.006) and positively associated with FT4 (r = 0.228, P < 0.001). TSH was significantly decreased at 3, 6, and 12 months (3M: from 4.43 ± 2.70 to 2.63 ± 1.46 mU/l, P < 0.001; 6M: from 4.43 ± 2.70 to 3.84 ± 2.34 mU/l, P = 0.041; 12M: from 4.43 ± 2.70 to 2.85 ± 1.68 mU/l, P = 0.024). After LSG surgery, VA levels were slightly increased, when compared to pre-surgery levels, at 3, 6, and 12 months (3M: from 262.57 ± 68.19 to 410.33 ± 76.55 ng/ml, P = 0.065; 6M: from 262.57 ± 68.19 to 281.36 ± 93.23 ng/ml, P = 0.343; 12M: from 262.57 ± 68.19 to 300.37 ± 86.03 ng/ml, P = 0.083). SH group also had lower TSH and higher VA than the non-SH group at 3 months post-surgery [TSH: −1.4(−2.3, −0.3) vs. −0.2(−0.8, −0.2) mU/l, P < 0.001; VA: 163.99 ± 32.58 vs. 121.69 ± 27.59 ng/ml, P = 0.044]. In conclusion VA, which is related to thyroid hormone production, protects against thyroid dysfunction in obese subjects. The improvement of thyroid function in subjects with SH after LSG may be related to the increased VA levels observed post-surgery.

Clinical Trial Registration

ClinicalTrial.gov ID: NCT04548232.
The Association Between Frequent Sugar-Sweetened Beverage Intake and Sleep Duration in School Children: A Cross-Sectional Study
Authors: Shih Ya-Hui , Wu Hsin-Chuan , Pan Wen-Harn , Chang Hsing-Yi
Published: March 2022

Background

Higher consumption of sugar-sweetened beverages (SSBs) maybe association with children's sleep pattern. However, few studies have considered this association in Asia, especially in school children. This study investigated the relationship between children's consumption frequency of such beverages and their sleep duration.

Methods

Participants aged 6–12 years were analyzed from two survey data in 2012 and 2013–2016 Nutrition and Health Surveys in Taiwan. A total of 2,628 participants were included in the analysis (2012, N = 1,267; 2013–2016, N = 1,361). Beverages weekly consumption were divided into low and high intake groups by medians cut-off points. The sleep variables were the sleep duration at night (including school days and weekends) and sleep debt. After controlling the confounders, the correlation between sugar-sweetened beverage consumption and sleep duration was examined using multinomial logistic regression analysis.

Results

The students slept for an average of 8.8 h on school days and 9.7 h on weekends. Relative to the low SSB intake group, the high intake group exhibited shorter sleep durations on school days (P < 0.001), greater sleep debt (P = 0.049). In logistic regression, high intake group were more likely to sleep for <8.5 h on school days (OR = 1.67, P = 0.002) and exhibit >2 h of sleep debt than low intake group (OR = 1.41, P = 0.022).

Conclusions

Children who had consumed sugar-sweetened beverages frequently slept for shorter durations at night on school days and exhibited greater sleep debt. The causal relationship was not clear. Nonetheless, these two factors are important in promoting children health.
Characterization of Theabrownins Prepared From Tea Polyphenols by Enzymatic and Chemical Oxidation and Their Inhibitory Effect on Colon Cancer Cells
Authors: Chen Xiaoqiang , Hu Yuxi , Wang Bingjie , Chen Yin , Yuan Yao , Zhou Weilong , Song Wei , Wu Zhengqi , Li Xiuting
Published: March 2022

Theabrownins (TBs) are prepared from dark tea and contain a large number of complex heterogeneous components, such as carbohydrates, proteins, and flavonoids, which are difficult to remove. In addition, some toxic and harmful extraction solvents are used to purify TBs. These obstacles hinder the utilization and industrialization of TBs. In this study, tea polyphenols were used as substrates and polyphenol oxidase and sodium bicarbonate (NaHCO3) were used successively to prepare theabrownins (TBs-E). The UV-visible characteristic absorption peaks of the TBs-E were located at 203 and 270 nm and Fourier-transform IR analysis showed that they were polymerized phenolic substances containing the hydroxy and carboxyl groups. The TBs-E aqueous solution was negatively charged and the absolute values of the zeta potential increased with increasing pH. A storage experiment showed that TBs-E were more stable at pH 7.0 and in low-temperature environments around 25°C. HT-29 human colon cancer cells were used to evaluate the biological activity of TBs-E through 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di- phenytetrazoliumromide (MTT), H&E staining, propidium iodide immunofluorescent staining, flow cytometry, and real-time PCR assays. The TBs-E significantly inhibited cell growth and caused late apoptosis, particularly at the dose of 500 μg/ml. The TBs-E markedly reduced the expression of antioxidant enzyme genes and increased the generation of reactive oxygen species to break the redox balance, which may have led to cell damage and death. These results will promote research and industrialization of TBs.
Scientific Evidence of the Beneficial Effects of Tomato Products on Cardiovascular Disease and Platelet Aggregation
Authors: Cámara Montaña , Fernández-Ruiz Virginia , Sánchez-Mata María-Cortes , Cámara Rosa M. , Domínguez Laura , Sesso Howard D.
Published: March 2022

Cardiovascular disease (CVD) includes a group of disorders of the heart and blood vessels that includes numerous problems, many of which are related to the process called atherosclerosis. The present work is aimed to analyze the most relevant studies examining the potentially beneficial effects of tomato products on both CVD prevention and antiplatelet aggregation as well as an European Food Safety Authority health claims evaluation on tomato and tomato products. To date, only one health claim has been approved for a concentrated extract of tomato soluble in water (WSTC) marketed under the patented name of Fruitflow® with two forms of presentation: WSTC I and II, with the following claim “helping to maintain normal platelet aggregation, which contributes to healthy blood flow.” Other studies also demonstrate similar beneficial effects for fresh tomatoes, tomato products and tomato pomace extracts.
Commercial and Instant Coffees Effectively Lower Aβ1-40 and Aβ1-42 in N2a/APPswe Cells
Authors: Zhang Lifang , Cao Jessica , Yang Haiqiang , Pham Phillip , Khan Umer , Brown Breanna , Wang Yanhong , Zieneldien Tarek , Cao Chuanhai
Published: March 2022

Background

Alzheimer's disease (AD) is a multifactorial neurological disease with neurofibrillary tangles and neuritic plaques as histopathological markers. Due to this, although AD is the leading cause of dementia worldwide, clinical AD dementia cannot be certainly diagnosed until neuropathological post-mortem evaluation. Coffee has been reported to have neurologically protective factors, particularly against AD, but coffee brand and type have not been taken into consideration in previous studies. We examined the discrepancies among popular commercial and instant coffees in limiting the development and progression through Aβ1-40 and Aβ1-42 production, and hypothesized that coffee consumption, regardless of brand or type, is beneficial for stalling the progression and development of Aβ-related AD.

Methods

Coffee samples from four commercial coffee brands and four instant coffees were purchased or prepared following given instructions and filtered for the study. 5, 2.5, and 1.25% concentrations of each coffee were used to treat N2a/APPswe cell lines. MTT assay was used to assess cell viability for coffee concentrations, as well as pure caffeine concentrations. Sandwich ELISA assay was used to determine Aβ concentration for Aβ1-40 and Aβ1-42 peptides of coffee-treated cells.

Results

Caffeine concentrations were significantly varied among all coffees (DC vs. MDC, PC, SB, NIN, MIN p < 0.05). There was no correlation between caffeine concentration and cell toxicity among brands and types of coffee, with no toxicity at 0.5 mg/ml caffeine and lower. Most coffees were toxic to N2a/APPswe cells at 5% (p < 0.05), but not at 2.5%. Most coffees at a 2.5% concentration reduced Aβ1-40 and Aβ1-42 production, with comparable results between commercial and instant coffees.

Conclusion

All coffees tested have beneficial health effects for AD through lowering Aβ1-40 and Aβ1-42 production, with Dunkin' Donuts® medium roast coffee demonstrating the most consistent and optimal cell survival rates and Aβ concentration. On the other hand, Starbucks® coffee exhibited the highest cell toxicity rates among the tested coffees.
NCAPG Promotes Tumor Progression and Modulates Immune Cell Infiltration in Glioma
Authors: Zheng Guangrong , Han Tao , Hu Xiaomu , Yang Zhou , Wang Jin , Wen Zhenyi , Li Hengyu , Wang Hongjin
Published: March 2022

Glioma is one of the most deadly types of brain cancer. As it is highly invasive, the prognosis for glioma patients remains dismal, with median survival rarely exceeding 16 months. Thus, developing a new prognostic biomarker for glioma and investigating its molecular mechanisms is necessary for the development of an efficient treatment strategy. In this study, we analyzed a cohort of 1,131 glioma patients using RNA-seq data from The Cancer Genome Atlas (TCGA project) and Gene Expression Omnibus (GSE4290 and GSE16011 datasets), and validated the results using the RNA-seq data of 1,018 gliomas from the Chinese Glioma Genome Atlas (CGGA project). We used the R language as the main tool for statistical analysis and data visualization. We found that NCAPG, a mitosis-associated chromosomal condensing protein, is highly expressed in glioma tissues. Furthermore, the expression of NCAPG increased significantly with the increase in tumor grade, and high NCAPG expression was found to be a predictor of poor overall survival in glioma patients (P < 0.001). This result shows that NCAPG expression could be an independent prognostic factor. Importantly, when the expression of NCAPG was knocked down, the CCK-8 assay revealed that the proliferation of glioma cells (LN-229 and T98G cell lines) decreased significantly compared with the control group. In addition, the healing rates of these cells were significantly lower in the si-NCAPG group than in the control group (P < 0.001). We then used the CIBERSORT algorithm to analyze the expression levels of 22 subpopulations of immune cells and found that NCAPG was significantly negatively correlated with natural killer cell activation. In addition, it was positively correlated with MHC-I molecules and ADAM17. Our study is first in comprehensively describing the high expression of NCAPG in glioma. It also shows that NCAPG can function as an independent prognostic predictor of glioma, and that targeting NCAPG can be a new strategy for the treatment of glioma patients.
Mutation-Derived Long Noncoding RNA Signature Predicts Survival in Lung Adenocarcinoma
Authors: Yang Longjun , Guo Guangran , Yu Xiangyang , Wen Yingsheng , Lin Yongbin , Zhang Rusi , Zhao Dechang , Huang Zirui , Wang Gongming , Yan Yan , Zhang Xuewen , Chen Dongtai , Xing Wei , Wang Weidong , Zeng Weian , Zhang Lanjun
Published: March 2022

Background

Genomic instability is one of the representative features of cancer evolution. Recent research has revealed that long noncoding RNAs (lncRNAs) play a critical role in maintaining genomic instability. Our work proposed a gene signature (GILncSig) based on genomic instability-derived lncRNAs to probe the possibility of lncRNA signatures as an index of genomic instability, providing a potential new approach to identify genomic instability-related cancer biomarkers.

Methods

Lung adenocarcinoma (LUAD) gene expression data from an RNA-seq FPKM dataset, somatic mutation information and relevant clinical materials were downloaded from The Cancer Genome Atlas (TCGA). A prognostic model consisting of genomic instability-related lncRNAs was constructed, termed GILncSig, to calculate the risk score. We validated GILncSig using data from the Gene Expression Omnibus (GEO) database. In this study, we used R software for data analysis.

Results

Through univariate and multivariate Cox regression analyses, five genomic instability-associated lncRNAs (LINC01671, LINC01116, LINC01214, lncRNA PTCSC3, and LINC02555) were identified. We constructed a lncRNA signature (GILncSig) related to genomic instability. LUAD patients were classified into two risk groups by GILncSig. The results showed that the survival rate of LUAD patients in the low-risk group was higher than that of those in the high-risk group. Then, we verified GILncSig in the GEO database. GILncSig was associated with the genomic mutation rate of LUAD. We also used GILncSig to divide TP53 mutant-type patients and TP53 wild-type patients into two groups and performed prognostic analysis. The results suggested that compared with TP53 mutation status, GILncSig may have better prognostic significance.

Conclusions

By combining the lncRNA expression profiles associated with somatic mutations and the corresponding clinical characteristics of LUAD, a lncRNA signature (GILncSig) related to genomic instability was established.
Challenging Diagnostic Process for a Malignant Peritoneal Mesothelioma Patient With Ascites and Pleural Effusion: A Case Report and Review of the Literature
Authors: Zeng Xiaofeng , Xu Ke , Zhang Liying , Huang Xiaoli
Published: March 2022

Malignant peritoneal mesothelioma (MPM) is a sporadic and fatal disease of the peritoneal lining. Its diagnosis has been known to be challenging, time-consuming, and money-consuming. In this paper, we report an MPM case of a 58-year-old man with severe abdominal distension. After he had received all kinds of auxiliary examination, including computed tomography scans of the chest and whole abdomen, examinations of peripheral and pleural fluid, positron emission tomography, and twice fine-needle peritoneal biopsies, his disease still could not be confirmed. Eventually, the patient was diagnosed with MPM through laparoscopic biopsy and IHC. From this case, we concluded that clinicians can gradually discover and diagnose the disease through 1) high platelet and CA125 levels and CT imaging results, 2) cytologic examinations of ascites and pleural fluid, 3) peritoneal biopsies (fine-needle biopsy, laparoscopy biopsy), and 4) histopathological examinations and immunohistochemistry findings. The diagnostic process involving this patient can be an example to demonstrate the effectiveness of various auxiliary examination methods in MPM diagnosis.
Exploration of the Potential Mechanism of Qi Yin San Liang San Decoction in the Treatment of EGFRI-Related Adverse Skin Reactions Using Network Pharmacology and In Vitro Experiments
Authors: Wang Yalei , Zhang Yali , Ding Chengcheng , Jia Caixia , Zhang Huawei , Peng Tiantian , Cheng Shuo , Chen Weihang , Tan Yan , Wang Xu , Liu Zhaoheng , Wei Peng , Wang Xue , Jiang Miao , Hua Qian
Published: March 2022

Background

Adverse skin reactions are the most common side effects of epidermal growth factor receptor inhibitors (EGFRIs) in the treatment of cancer, significantly affecting the survival rate and quality of life of patients. Qi Yin San Liang San Decoction (QYSLS) comes from folk prescription and is currently used in the clinical treatment of adverse skin reactions caused by EGFRIs. However, its therapeutic mechanism remains unclear.

Objectives

To explore the potential mechanism of QYSLS in the treatment of adverse skin reactions caused by EGFR inhibition using network pharmacology and experimental research.

Methods

First, we verified the effectiveness of QYSLS in vivo using model mice. Second, the related targets of adverse skin reactions associated with EGFR inhibition were predicted by the Gene Expression Omnibus (GEO) database, and effective components and predictive targets of QYSLS were analyzed by Traditional Chinese Medicine Systems Pharmacology (TCMSP) and Batman-TCM databases. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed via the Bioconductor (R) V3.8 bioinformatics software. Molecular docking studies verified the selected key ingredients and targets. Finally, the results of network pharmacology were verified by in vitro experiments.

Results

In the in vivo mouse model, QYSLS effectively reduced the occurrence of skin side effects. Network pharmacological results showed that the active ingredient luteolin, quercetin, licochalcone a, and kaempferol and the effective targets prostaglandin-endoperoxide synthase 2 (PTGS2), matrix metallopeptidase 9 (MMP9), and C–C motif chemokine ligand 2 (CCL2) were related to the interleukin-17 (IL-17) and tumor necrosis factor (TNF) pathway. Subsequently, the related active compounds and targets were verified using HaCaT cells as an in vitro adverse reaction model. The results showed that luteolin and quercetin increased the expression of PTGS2 and MMP9 and reduced the expression of CCL2 in HaCaT cells treated with gefitinib.

Conclusions

The results revealed that QYSLS effectively treats EGFRI-related adverse skin reactions through multi-target and multi-pathway mechanisms. Luteolin and quercetin may be the core active ingredients of QYSLS in the treatment of EGFRI-related adverse skin reactions, and their therapeutic effects are potentially mediated through PTGS2, CCL2, and MMP9 in the IL-17 and TNF signaling pathway.
An Update on the Immunotherapy for Oropharyngeal Squamous Cell Carcinoma
Authors: Huang Yaxuan , Lan Yunyun , Zhang Zhe , Xiao Xue , Huang Tingting
Published: March 2022

Oropharyngeal squamous cell carcinoma (OPSCC) is an uncommon malignancy worldwide. Remarkably, the rising incidence of OPSCC has been observed in many developed countries over the past few decades. On top of tobacco smoking and alcohol consumption, human papillomavirus (HPV) infection has become a major etiologic factor for OPSCC. The radiotherapy-based or surgery-based systemic therapies are recommended equally as first-line treatment, while chemotherapy-based strategy is applied to advanced diseases. Immunotherapy in head and neck squamous cell carcinoma (HNSCC) is currently under the spotlight, especially for patients with advanced diseases. Numerous researches on programmed death-1/programmed death-ligand 1 checkpoint inhibitors have proven beneficial to patients with metastatic HNSCC. In 2016, nivolumab and pembrolizumab were approved as the second-line treatment for advanced metastatic HNSCC by the USA Food and Drug Administration. Soon after, in 2019, the USA Food and Drug Administration approved pembrolizumab as the first-line treatment for patients with unresectable, recurrent, and metastatic HNSCC. It has been reported that HPV-positive HNSCC patients were associated with increased programmed death-ligand 1 expression; however, whether HPV status indicates different treatment outcomes among HNSCC patients treated with immunotherapy has contradicted. Notably, HPV-positive OPSCC exhibits a significantly better clinical response to primary treatment (i.e., radiotherapy, surgery, and chemotherapy) and a more desirable prognosis compared to the HPV-negative OPSCC. This review summarizes the current publications on immunotherapy in HNSCC/OPSCC patients and discusses the impact of HPV infection in immunotherapeutic efficacy, providing an update on the immune landscape and future perspectives in OPSCC.
Neurological Manifestations Related to Immune Checkpoint Inhibitors: Reverse Translational Research by Using the European Real-World Safety Data
Authors: Ruggiero Rosanna , Stelitano Barbara , Fraenza Federica , di Mauro Gabriella , Scavone Cristina , Sportiello Liberata , Rafaniello Concetta , Di Napoli Raffaella , Danesi Romano , Del Re Marzia , Rossi Francesco , Capuano Annalisa
Published: March 2022

Immune checkpoint inhibitors (ICIs) are widely used improving clinical outcomes in many cancer patients. However, they can induce serious consequences, like neurological immune-related adverse drug reactions (NirADRs). Although these are rare complications, they can be serious with important impact on patients’ quality of life. Our purpose is to describe these adverse events observed in the European clinical practice context. We carried out a descriptive analysis of individual case safety reports (ICSRs) related to ICIs collected until February 7, 2020, in the European spontaneous reporting database, EudraVigilance, and reported nervous disorders as suspect adverse drug reactions (ADRs). NirADRs were classified according to the Medical Dictionary for Regulatory Activities (MedDRA). In order to identify a hypothetical different reporting probability of the NirADR types between the ICI classes, we carried out a disproportionality analysis. The reporting odds ratio (ROR) with 95% CI was computed comparing the different ICI classes to each other based on their pharmacological target [the cytotoxic T-lymphocyte antigen-4 (CTLA-4), the programmed death-1 (PD-1) or its ligand (PD-L1)]. Finally, we researched in the literature the hypothesized mechanisms, which could explain the onset of these ICI-related neurological complications. Overall, we found 4,875 cases describing 6,429 ICI-related suspected NirADRs. ICI-related neurotoxicities include a wide range of central and peripheral events. These were mainly related to anti-PD-1 agents and occurred in male patients (59%). Our analysis confirmed a gender difference of NirADRs. Twenty-three percent of the events (comprising myasthenia gravis, neuropathy peripheral, and cerebral infarction) had unfavorable fallouts, including fatal outcome (7%). Majority of the NirADRs were categorized as “Neurological disorders NEC” HLGTs MedDRA (2,076; 32%). In 1,094 cases (22%), more NirADRs overlapped with other neurologic complications. An interesting overlapping of myasthenia gravis with myositis or myocarditis emerged. From our disproportionality analysis, an increased reporting probability of peripheral neuropathies and headaches emerged with ipilimumab when compared to anti-PD-1 and anti-PD-L1 agents. However, neuromuscular disorders were more probably reported with anti-PD-1. Several pathogenic mechanisms, including neuronal damage by T cells and autoantibodies and/or cytokine-mediated inflammation processes, have been hypothesized. However, the pathogenesis of these ICI-related complications is not completely understood. Considering the recent marketing authorizations of ICIs, further studies are strongly needed to monitor their neurologic safety profile.
The Metalloprotease-Disintegrin ADAM8 Alters the Tumor Suppressor miR-181a-5p Expression Profile in Glioblastoma Thereby Contributing to Its Aggressiveness
Authors: Schäfer Agnes , Evers Lara , Meier Lara , Schlomann Uwe , Bopp Miriam H. A. , Dreizner Gian-Luca , Lassmann Olivia , Ben Bacha Aaron , Benescu Andreea-Cristina , Pojskic Mirza , Preußer Christian , von Strandmann Elke Pogge , Carl Barbara , Nimsky Christopher , Bartsch Jörg W.
Published: March 2022

Glioblastoma (GBM) as the most common and aggressive brain tumor is characterized by genetic heterogeneity, invasiveness, radio-/chemoresistance, and occurrence of GBM stem-like cells. The metalloprotease-disintegrin ADAM8 is highly expressed in GBM tumor and immune cells and correlates with poor survival. In GBM, ADAM8 affects intracellular kinase signaling and increases expression levels of osteopontin/SPP1 and matrix metalloproteinase 9 (MMP9) by an unknown mechanism. Here we explored whether microRNA (miRNA) expression levels could be regulators of MMP9 expression in GBM cells expressing ADAM8. Initially, we identified several miRNAs as dysregulated in ADAM8-deficient U87 GBM cells. Among these, the tumor suppressor miR-181a-5p was significantly upregulated in ADAM8 knockout clones. By inhibiting kinase signaling, we found that ADAM8 downregulates expression of miR-181a-5p via activation of signal transducer and activator of transcription 3 (STAT3) and mitogen-activated protein kinase (MAPK) signaling suggesting an ADAM8-dependent silencing of miR-181a-5p. In turn, mimic miR-181a-5p transfection caused decreased cell proliferation and lower MMP9 expression in GBM cells. Furthermore, miR-181a-5p was detected in GBM cell-derived extracellular vesicles (EVs) as well as patient serum-derived EVs. We identified miR-181a-5p downregulating MMP9 expression via targeting the MAPK pathway. Analysis of patient tissue samples (n=22) revealed that in GBM, miR-181a-5p is strongly downregulated compared to ADAM8 and MMP9 mRNA expression, even in localized tumor areas. Taken together, we provide evidence for a functional axis involving ADAM8/miR-181a-5p/MAPK/MMP9 in GBM tumor cells.