bluuebunny/crossref_metadata_2025 huggingface dataset:
Antibiotics enhancing drug-induced liver injury assessed for causality using Roussel Uclaf Causality Assessment Method: Emerging role of gut microbiota dysbiosis
Authors: Fu Lihong , Qian Yihan , Shang Zhi , Sun Xuehua , Kong Xiaoni , Gao Yueqiu
Published: September 2022

Drug-induced liver injury (DILI) is a disease that remains difficult to predict and prevent from a clinical perspective, as its occurrence is hard to fully explain by the traditional mechanisms. In recent years, the risk of the DILI for microbiota dysbiosis has been recognized as a multifactorial process. Amoxicillin-clavulanate is the most commonly implicated drug in DILI worldwide with high causality gradings based on the use of RUCAM in different populations. Antibiotics directly affect the structure and diversity of gut microbiota (GM) and changes in metabolites. The depletion of probiotics after antibiotics interference can reduce the efficacy of hepatoprotective agents, also manifesting as liver injury. Follow-up with liver function examination is essential during the administration of drugs that affect intestinal microorganisms and their metabolic activities, such as antibiotics, especially in patients on a high-fat diet. In the meantime, altering the GM to reconstruct the hepatotoxicity of drugs by exhausting harmful bacteria and supplementing with probiotics/prebiotics are potential therapeutic approaches. This review will provide an overview of the current evidence between gut microbiota and DILI events, and discuss the potential mechanisms of gut microbiota-mediated drug interactions. Finally, this review also provides insights into the “double-edged sword” effect of antibiotics treatment against DILI and the potential prevention and therapeutic strategies.
Collaborative reliance in medicine safety and quality regulation: Investigation of experiences in handling N-nitrosamine impurities among ZaZiBoNa participating countries
Authors: Shabangu Patience P. , Kuwana Rutendo J. , Dube Admire
Published: September 2022

Introduction

The presence of N-nitrosamine impurities in medicines raised concerns globally as they are genotoxic and probable human carcinogens. A review of N-nitrosamine impurities in medicines provides an opportunity for National Regulatory Authorities (NRAs) to ensure that corrective and preventive actions are applied so that safe and good quality medicines are made available to the public. This study aimed to investigate the experiences on reviews conducted by NRAs from various Southern African Development Community countries which participate in the regional work-sharing forum, ZaZiBoNa, on the quality and safety data due to the presence of N-nitrosamine impurities in medicines.

Methods

A comparative, descriptive study using mixed methods was conducted. Purposive sampling was applied in selecting research participants based on their participation status in the ZaZiBoNa initiative. A standardized questionnaire structured into five parts was completed by ZaZiBoNa focal persons/nominated individuals to determine the experience of each NRA in addressing the safety and quality issues related to the presence of N-nitrosamine impurities in the affected medicines. Profiled medicines included sartans, ranitidine, metformin, rifampicin, and rifapentine.

Results

Sartan medicines had been reviewed by all countries participating in the ZaZiBoNa initiative. Although most NRAs have yet to conduct reviews on other profiled medicines, evaluations have been implemented to ensure access to safe and good quality medicines within the region. Most countries experienced challenges in communicating with applicants or marketing authorization holders (MAHs) on reviewing N-nitrosamine impurities in their medicines. The majority of NRAs agree that there is a need for further collaboration efforts to review N-nitrosamine impurities in medicines.

Conclusion

The review of N-nitrosamine impurities in the profiled medicines by NRAs within the region has demonstrated the importance of enhanced regulatory oversight to safeguard against the risks associated with medicines. Collaborative reliance on the review of the safety and quality of medicine, continuous monitoring, implementation and review of processes, testing methods, and regular engagements with stakeholders could be essential in ensuring adequate control of N-nitrosamine impurities in medicines.
Peripheral interleukin-6-associated microglial QUIN elevation in basolateral amygdala contributed to cognitive dysfunction in a mouse model of postoperative delirium
Authors: Mu Jing-Lan , Liu Xiao-Dong , Dong Ye-Hong , Fang Ying-Ying , Qiu Shi-Da , Zhang Fu , Liu Ke-Xuan
Published: September 2022

Background

Developing effective approaches for postoperative delirium has been hampered due to the lack of a pathophysiologically similar animal model to offer insights into the pathogenesis. The study, therefore, aimed to develop a delirium-like mouse model and explore the underlying mechanism.

Methods

The three cycles of 10-min clamp following 5-min reopening of the superior mesenteric artery (SMA) were performed in adult male C57BL/6 mice to induce a delirium-like phenotype. Composite Z score calculated based on the results of Open Field, Y Maze and Buried Food Tests was employed to assess the delirium phenotype in mice. Microglia activities were monitored by immunofluorescence staining and comprehensive morphological analysis. Systemic administration of minocycline (MINO), IL-6 antibody or IL-6 neutralizing antibody, was applied to manipulate microglia. The expressions of Indoleamine 2,3-dioxygenase-1 (IDO-1) and quinolinic acid (QUIN) were examined by RT-PCR and High-Performance Liquid Chromatography/Mass Spectrometry, respectively. Cytokines were measured using fluorescence activated cell sorting method.

Results

The repeated ischemia/reperfusion (I/R) surgery caused significant anxiety (P < 0.05) and cognition decline in working memory and orientation (P < 0.05) in mice at postoperative 24 h. The composite Z score, indicating an overall disturbance of brain function, fluctuated over 24 h after I/R surgery (P < 0.001). Immunofluorescent staining showed that the percentage of microglia in the basolateral amygdala (BLA) (P < 0.05) was reactivated after I/R surgery and was negatively correlated with dwell time at Y maze (R = −0.759, P = 0.035). Inhibiting microglia activities by MINO reduced QUIN productions (P < 0.01) that improved cognitive deficits (P < 0.05). The peripheral IL-6 might cause IL-6 elevation in the BLA. Systemic administration of IL-6 antibodies suppressed I/R-induced IL-6 elevations (P < 0.05), microglial reactivations (P < 0.05), IDO-1 expressions (P < 0.01), and neuroactive metabolite QUIN productions (P < 0.05) in the BLA, resulting in a recovery of cognitive deficits (P < 0.05). Injection of IL-6 exerted opposite effects.

Conclusion

The repeated intestinal I/R surgery-induced mouse model is a simple and reproducible one of postoperative delirium. Peripheral IL-6-associated microglial QUIN elevations in the BLA contributed to cognitive dysfunction in the model of postoperative delirium.
Exploring the mechanism of action of Sanzi formula in intervening colorectal adenoma by targeting intestinal flora and intestinal metabolism
Authors: Shang Jingyu , Guo Hong , Li Jie , Li Zhongyi , Yan Zhanpeng , Wei Lanfu , Hua Yongzhi , Lin Lin , Tian Yaozhou
Published: September 2022

Background

Sanzi formula (SZF) is a kind of Chinese herbal compound that has a certain effect on the prevention and treatment of colorectal adenoma (CRA), which can prevent and control the process of CRA-cancer transformation. In this study, we explored the mechanism of action of SZF in anti-CRA using 16S rRNA sequencing and metabolomics technology.

Methods

Mice were randomly divided into three groups: Control group, Apcmin/+ model group, and SZF treatment group. Except for the Control group, which used C57BL/6 J mice, the remaining two groups used Apcmin/+ mice. The Control group and Apcmin/+ model group were treated with ultrapure water by gavage, while the SZF treatment group was treated with SZF for 12 weeks. During this period, the physical changes of mice in each group were observed. The gut microbiota was determined by high-throughput sequencing of the 16S rRNA gene, and LC-ESI-MS/MS was used for colorectal metabolomics analysis.

Results

Sequencing of the 16S rRNA gut flora yielded 10,256 operational taxonomic units and metabolomic analysis obtained a total of 366 differential metabolites. The intestinal flora analysis showed that SZF could improve intestinal flora disorders in Apcmin/+ mice. For instance, beneficial bacteria such as Gastranaerophilales significantly increased and harmful bacteria such as Angelakisella, Dubosiella, Muribaculum, and Erysipelotrichaceae UCG-003 substantially decreased after the SZF intervention. In addition, metabolomic data analysis demonstrated that SZF also improved the colorectal metabolic profile of Apcmin/+ mice. In Apcmin/+ mice, metabolites such as Anserine and Ectoine were typically increased after SZF intervention; in contrast, metabolites such as Taurocholic acid, Taurochenodesoxycholic acid, Hyocholic acid, Cholic acid, and Tauro-alpha-muricholic acid showed noteworthy reductions. Metabolic flora association analysis indicated that 13 differential flora and 11 differential metabolites were associated.

Conclusion

SZF affects the abundance of specific intestinal flora and regulates intestinal flora disorders, improves colorectal-specific metabolites, and ameliorates intestinal metabolic disorders to prevent and treat CRA. Furthermore, the application of intestinal flora and colorectal metabolomics association analysis offers new strategies to reveal the mechanism of action of herbal medicines for the treatment of intestinal diseases.
Impacts of soybean agriculture on the resistome of the Amazonian soil
Authors: Cardenas Alegria Oscar , Pires Quaresma Marielle , Dias Dantas Carlos Willian , Silva Guedes Lobato Elaine Maria , de Oliveira Aragão Andressa , Patroca da Silva Sandro , Costa Barros da Silva Amanda , Ribeiro Cruz Ana Cecília , Ramos Rommel Thiago Jucá , Carneiro Adriana Ribeiro
Published: September 2022

The soils of the Amazon are complex environments with different organisms cohabiting in continuous adaptation processes; this changes significantly when these environments are modified for the development of agricultural activities that alter the chemical, macro, and microbiological compositions. The metagenomic variations and the levels of the environmental impact of four different soil samples from the Amazon region were evaluated, emphasizing the resistome. Soil samples from the organic phase from the different forest, pasture, and transgenic soybean monocultures of 2–14 years old were collected in triplicate at each site. The samples were divided into two groups, and one group was pre-treated to obtain genetic material to perform sequencing for metagenomic analysis; another group carried out the chemical characterization of the soil, determining the pH, the content of cations, and heavy metals; these were carried out in addition to identifying with different databases the components of the microbiological communities, functional genes, antibiotic and biocide resistance genes. A greater diversity of antibiotic resistance genes was observed in the forest soil. In contrast, in monoculture soils, a large number of biocide resistance genes were evidenced, highlighting the diversity and abundance of crop soils, which showed better resistance to heavy metals than other compounds, with a possible dominance of resistance to iron due to the presence of the acn gene. For up to 600 different genes for resistance to antibiotics and 256 genes for biocides were identified, most of which were for heavy metals. The most prevalent was resistance to tetracycline, cephalosporin, penam, fluoroquinolone, chloramphenicol, carbapenem, macrolide, and aminoglycoside, providing evidence for the co-selection of these resistance genes in different soils. Furthermore, the influence of vegetation cover on the forest floor was notable as a protective factor against the impact of human contamination. Regarding chemical characterization, the presence of heavy metals, different stress response mechanisms in monoculture soils, and the abundance of mobile genetic elements in crop and pasture soils stand out. The elimination of the forest increases the diversity of genes for resistance to biocides, favoring the selection of genes for resistance to antibiotics in soils.
High genomic differentiation and limited gene flow indicate recent cryptic speciation within the genus Laspinema (cyanobacteria)
Authors: Stanojković Aleksandar , Skoupý Svatopluk , Škaloud Pavel , Dvořák Petr
Published: September 2022

The sympatric occurrence of closely related lineages displaying conserved morphological and ecological traits is often characteristic of free-living microbes. Gene flow, recombination, selection, and mutations govern the genetic variability between these cryptic lineages and drive their differentiation. However, sequencing conservative molecular markers (e.g., 16S rRNA) coupled with insufficient population-level sampling hindered the study of intra-species genetic diversity and speciation in cyanobacteria. We used phylogenomics and a population genomic approach to investigate the extent of local genomic diversity and the mechanisms underlying sympatric speciation of Laspinema thermale. We found two cryptic lineages of Laspinema. The lineages were highly genetically diverse, with recombination occurring more frequently within than between them. That suggests the existence of a barrier to gene flow, which further maintains divergence. Genomic regions of high population differentiation harbored genes associated with possible adaptations to high/low light conditions and stress stimuli, although with a weak diversifying selection. Overall, the diversification of Laspinema species might have been affected by both genomic and ecological processes.
Chicken IgY reduces the risk of Pseudomonas aeruginosa urinary tract infections in a murine model
Authors: Schwartz Franziska A. , Christophersen Lars , Thomsen Kim , Baekdal Sarah , Pals Bendixen Maria , Jørgensen Mette , Bull Rasmussen Ida Kirstine , Laulund Anne Sofie , Høiby Niels , Moser Claus
Published: September 2022

Introduction

Urinary tract infections (UTIs) withPseudomonas aeruginosaare a severe problem in disposed patients in modern healthcare.Pseudomonas aeruginosaestablishes recalcitrant biofilm infections and can develop antibiotic resistance. Gargling with avian egg yolk anti-Pseudomonasantibodies (IgY) has shown clinical effect in preventing onset of chronicP. aeruginosalung infections in patients with cystic fibrosis (CF). Therefore, we speculated whether passive intravesically administered IgY immunotherapy could be a novel strategy againstP. aeruginosaUTIs.

Aim

To evaluate if prophylactic repurposing of anti-PseudomonasIgY can prevent UTIs withP. aeruginosain a UTI mouse model.

Materials and methods

In vitro,P. aeruginosa(PAO1 and PAO3) was mixed with increasing concentrations of specific anti-PseudomonasIgY (sIgY) or non-specific control IgY (cIgY) and/or freshly isolated human neutrophils. Bacterial growth was evaluated by the optical density at 600 nm.In vivo,viaa temporary transurethral catheter, 10-week-old female Balb/c mice were intravesically infected with 50 ml of a bacterial suspension and sIgY, cIgY, or isotonic NaCl. IgY and NaCl were either co-instilled with the bacteria, or instilled prophylactically, 30 min prior to infection. The animals were euthanized 20 h after infection. Vesical bacteriology was quantified, and cytokine expression in the bladder homogenate was measured by multiplex cytokine assay.

Results

In vitro, sIgY concentrations above 2.5% reduced bacterial growth in a dose-dependent manner.In vivo, a UTI lasting for minimum 7 days was established by installing 5 × 106colony-forming units (CFU) ofP. aeruginosaPAO1. sIgY reduced vesical bacterial load if co-installed withP. aeruginosaPAO1. Prophylactic sIgY and cIgY reduced bacterial load when compared to isotonic NaCl. CXCL2 and G-CSF were both increased in infected bladders compared to non-infected controls which had non-detectable levels. Co-installation of sIgY and bacteria nearly completely inhibited the inflammatory response. However, the cytokine levels in the bladder did not change after prophylactic administration of sIgY or cIgY.

Conclusion

Prophylactic sIgY significantly reduces the amount of bacteria in the bladder in a mouse model ofP. aeruginosacystitis and may serve as a novel non-antibiotic strategy in preventingP. aeruginosaUTIs.
Torquetenovirus in pregnancy: Correlation with vaginal microbiome, metabolome and pro-inflammatory cytokines
Authors: Morselli Sara , Foschi Claudio , Laghi Luca , Zagonari Sara , Patuelli Giulia , Camboni Tania , Ceccarani Camilla , Consolandi Clarissa , Djusse Marielle Ezekielle , Pedna Maria Federica , Marangoni Antonella , Severgnini Marco , Sambri Vittorio
Published: September 2022

Torquetenovirus (TTV) is a negative sense, single-stranded DNA virus present in many body fluids of apparently healthy individuals. At present, it is considered a non-pathogenic endogenous virus. TTV can be detected in the vagina of pregnant women, its abundance being modulated with the extent of immune system activation. Until now, there is only scarce information regarding the association between TTV and the composition of the vaginal environment. Therefore, this study aimed to assess the presence of TTV in the vaginal ecosystem of a cohort of white women with a normal pregnancy (n = 60) at different gestational stages (first, second and third trimester) and in 9 subjects suffering a first trimester miscarriage. For each woman, we determined (i) the presence and titer of TTV, (ii) the vaginal bacterial composition by means of Nugent score and 16S rRNA gene sequencing, (iii) the vaginal metabolic profiles through 1H-NMR spectroscopy, and (iv) the vaginal concentration of two pro-inflammatory cytokines (IL-6 and IL-8). More than one third of women were found negative for TTV at all gestational stages. Although not statistically significant, the positivity for TTV dropped from 53.3% in the first to 36.6% in the third trimester. TTV loads varied greatly among vaginal samples, ranging between 2 × 101 and 2 × 105 copies/reaction. No difference in TTV prevalence and loads was observed between women with normal pregnancies and miscarriages. The presence of TTV was more common in women with a higher vaginal leucocyte count (p = 0.02). The levels of IL-6 (p = 0.02), IL-8 (p = 0.03), propionate (p = 0.001) and cadaverine (p = 0.006) were significantly higher in TTV-positive samples. TTV titer was positively correlated with the concentrations of 4-hydroxyphenyllactate (p < 0.0001), isoleucine (p = 0.01) and phenylalanine (p = 0.04). TTV-positive samples were characterized by a higher relative abundance of Sneathia (p = 0.04) and Shuttleworthia (p = 0.0009). In addition, a trend toward a decrease of Lactobacillus crispatus and Lactobacillus jensenii, and an increase of Lactobacillus iners was observed for TTV-positive samples. In conclusion, we found that TTV is quite common in women with normal pregnancy outcomes, representing a possible predictor of local immune status.
Hizikia fusiforme functional oil (HFFO) prevents neuroinflammation and memory deficits evoked by lipopolysaccharide/aluminum trichloride in zebrafish
Authors: Nie Ying-Ying , Zhou Long-Jian , Li Yan-Mei , Yang Wen-Cong , Liu Ya-Yue , Yang Zhi-You , Ma Xiao-Xiang , Zhang Yong-Ping , Hong Peng-Zhi , Zhang Yi
Published: September 2022

Background

Oxidative stress, cholinergic deficiency, and neuroinflammation are hallmarks of most neurodegenerative disorders (NDs). Lipids play an important role in brain development and proper functioning. Marine-derived lipids have shown good memory-improving potentials, especially those from fish and microalgae. The cultivated macroalga Hizikia fusiforme is healthy food and shows benefits to memory, but the study is rare on the brain healthy value of its oil. Previously, we had reported that the Hizikia fusiforme functional oil (HFFO) contains arachidonic acid, 11,14,17-eicosatrienoic acid, phytol, and other molecules displaying in vitro acetylcholinesterase inhibitory and nitroxide scavenging activity; however, the in vivo effect remains unclear. In this study, we further investigated its potential effects against lipopolysaccharides (LPS)- or aluminum trichloride (AlCl3)-induced memory deficiency in zebrafish and its drug-related properties in silica.

Methods

We established memory deficit models in zebrafish by intraperitoneal (i.p.) injection of lipopolysaccharides (LPS) (75 ng) or aluminum trichloride (AlCl3) (21 μg), and assessed their behaviors in the T-maze test. The interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), acetylcholine (ACh), and malondialdehyde (MDA) levels were measured 24 h after the LPS/AlCl3 injection as markers of inflammation, cholinergic activity, and oxidative stress. Furthermore, the interaction of two main components, 11,14,17-eicosatrienoic acid and phytol, was investigated by molecular docking, with the important anti-inflammatory targets nuclear factor kappa B (NF-κB) and cyclooxygenase 2 (COX-2). Specifically, the absorption, distribution, metabolism, excretion, and toxicity (ADMET) and drug-likeness properties of HFFO were studied by ADMETlab.

Results

The results showed that HFFO reduced cognitive deficits in zebrafish T-maze induced by LPS/AlCl3. While the LPS/AlCl3 treatment increased MDA content, lowered ACh levels in the zebrafish brain, and elevated levels of central and peripheral proinflammatory cytokines, these effects were reversed by 100 mg/kg HFFO except for MDA. Moreover, 11,14,17-eicosatrienoic acid and phytol showed a good affinity with NF-κB, COX-2, and HFFO exhibited acceptable drug-likeness and ADMET profiles in general.

Conclusion

Collectively, this study's findings suggest HFFO as a potent neuroprotectant, potentially valuable for the prevention of memory impairment caused by cholinergic deficiency and neuroinflammation.
The neural stem cell properties of Pkd2l1+ cerebrospinal fluid-contacting neurons in vivo
Authors: Cao Liang , Huang Ming-Zhi , Zhang Qiang , Luo Zhang-Rong , Zhang Yi , An Ping-Jiang , Yang Lei-Luo , Tan Wei , Wang Chun-Qing , Dou Xiao-Wei , Li Qing
Published: September 2022

The neural stem cells (NSCs) in the ventricular-subventricular zone of the adult mammalian spinal cord may be of great benefit for repairing spinal cord injuries. However, the sources of NSCs remain unclear. Previously, we have confirmed that cerebrospinal fluid-contacting neurons (CSF-cNs) have NSC potential in vitro. In this study, we verified the NSC properties of CSF-cNs in vivo. In mouse spinal cords, Pkd2l1+ CSF-cNs localized around the central canal express NSC markers. In vitro, Pkd2l1+ CSF-cNs form a neurosphere and express NSC markers. Activation and proliferation of CSF-cNs can be induced by injection of the neurotrophic factors basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) into the lateral ventricle. Spinal cord injury (SCI) also induces NSC activation and proliferation of CSF-cNs. Collectively, our results demonstrate that Pkd2l1+ CSF-cNs have NSC properties in vivo and may be involved in SCI recovery.
Long- and short-term fluctuations compared for several organ systems across sleep stages
Authors: Zschocke Johannes , Bartsch Ronny P. , Glos Martin , Penzel Thomas , Mikolajczyk Rafael , Kantelhardt Jan W.
Published: September 2022

Some details of cardiovascular and cardio-respiratory regulation and their changes during different sleep stages remain still unknown. In this paper we compared the fluctuations of heart rate, pulse rate, respiration frequency, and pulse transit times as well as EEG alpha-band power on time scales from 6 to 200 s during different sleep stages in order to better understand regulatory pathways. The five considered time series were derived from ECG, photoplethysmogram, nasal air flow, and central electrode EEG measurements from full-night polysomnography recordings of 246 subjects with suspected sleep disorders. We applied detrended fluctuation analysis, distinguishing between short-term (6–16 s) and long-term (50–200 s) correlations, i.e., scaling behavior characterized by the fluctuation exponents α1 and α2 related with parasympathetic and sympathetic control, respectively. While heart rate (and pulse rate) are characterized by sex and age-dependent short-term correlations, their long-term correlations exhibit the well-known sleep stage dependence: weak long-term correlations during non-REM sleep and pronounced long-term correlations during REM sleep and wakefulness. In contrast, pulse transit times, which are believed to be mainly affected by blood pressure and arterial stiffness, do not show differences between short-term and long-term exponents. This is in constrast to previous results for blood pressure time series, where α1 was much larger than α2, and therefore questions a very close relation between pulse transit times and blood pressure values. Nevertheless, very similar sleep-stage dependent differences are observed for the long-term fluctuation exponent α2 in all considered signals including EEG alpha-band power. In conclusion, we found that the observed fluctuation exponents are very robust and hardly modified by body mass index, alcohol consumption, smoking, or sleep disorders. The long-term fluctuations of all observed systems seem to be modulated by patterns following sleep stages generated in the brain and thus regulated in a similar manner, while short-term regulations differ between the organ systems. Deviations from the reported dependence in any of the signals should be indicative of problems in the function of the particular organ system or its control mechanisms.
Safety and efficacy of low-dose and long-course tirofiban in large hemispheric infarction
Authors: Hu Yinqin , Xiao Qian , Shi Zhizhen , Hou Yangbo , Chen Zhen , Cheng Jiwei , Li Guoyi
Published: September 2022

Background

The clinical efficacy and safety of tirofiban in the treatment of large hemispheric infarction (LHI) remain controversial.

Methods

This study prospectively enrolled patients with acute LHI who were admitted to Putuo Hospital affiliated with Shanghai University of Traditional Chinese Medicine from June 2021 to December 2021. The patients were randomly assigned to the tirofiban group [3–4 μg/(kg·h)] or control group (clopidogrel 75 mg/d).

Results

A total of 71 patients with acute LHI were selected: 36 in the tirofiban group and 35 in the control group. The reduction of the NIHSS score in the tirofiban group was 2.92 ± 9.31 at discharge, and that of the control group was −3.23 ± 12.06 (p = 0.021, OR, 0.006; 95% CI, 0.004–0.008). Six patients (16.7%) in tirofiban group and 14 patients (40%) in control group died during hospitalization (p = 0.029, OR, 0.300; 95% CI, 0.099–0.908). There was significant difference in Modified Rankin Scale (mRS) 5–6 scores at 90 days between the two groups (p = 0.023, OR, 0.327; 95% CI, 0.124–0.867). However, there was no significant difference in mRS 0–1 (p = 0.321, OR, 0.972; 95% CI, 0.920–1.027), mRS 2 (p = 0.572, OR, 2.00; 95% CI, 0.173–23.109), mRS 3 (p = 0.225, OR, 2.214; 95% CI, 0.601–8.161), or mRS 4(p = 0.284, OR, 1.859; 95% CI, 0.593–5.825) scores between the two groups. There was no difference in symptomatic intracranial hemorrhage (p = 0.29, OR, 0.305; 95% CI, 0.030–3.081), asymptomatic intracranial hemorrhage (p = 0.123, OR, 0.284; 95% CI, 0.053–1.518). There was a significant difference in systemic bleeding events during hospitalization (p = 0.044, OR, 0.309; 95% CI, 0.096–1.000).

Conclusions

Low-dose and long-course tirofiban treatment may significantly improve the early neurological function and reduce the in-hospital mortality in LHI patients. Meanwhile, tirofiban does not increase the risk of any type of bleeding events.
Factors associated with artificial airway retention after skull base chordoma resection: A retrospective cohort study
Authors: Fu Yuxuan , Yu Yun , Cui Yidan , Wang Jing , Ma Bo , Jian Minyu , Yao Jingxin , Jing Longnian , Bai Jiwei , Han Ruquan
Published: September 2022

Background

Chordoma is a malignant bone and soft tissue tumor derived from embryonic notochord remnants, and skull base chordoma accounts for ~1/3 of all chordoma cases. Skull base chordoma is closely related to the brainstem and cranial nerves and has a high recurrence rate. The purpose of this study was to investigate the influence of the timing of tracheal extubation on perioperative pulmonary complications. We also aimed to explore predictors of postoperative artificial airway (AA) retention in patients with skull base chordoma.

Methods

This was a single-center, retrospective cohort study. The study population included all skull base chordoma patients undergoing surgical treatment between January 2019 and December 2021 at Beijing Tiantan Hospital. The primary outcome was the incidence of postoperative pulmonary complications. Several patient characteristics were evaluated for potential associations with AA retention.

Results

A total of 310 patients with skull base chordoma were enrolled. The frequency of AA retention after surgery for skull base chordoma was 30.97%. The incidence of postoperative pulmonary complications was much lower in those without AA retention (3.74 vs. 39.58%, P < 0.001). Factors with the highest point estimates for the odds of AA retention included body mass index, cranial nerve involvement, maximum tumor diameter, operative method, hemorrhage volume, operative duration and intraoperative mechanical ventilation duration.

Conclusions

In this retrospective cohort study, most of the factors associated with postoperative airway retention were closely related to the patient's tumor characteristics. These data demonstrate that respiratory management in patients with skull base chordoma remains an ongoing concern.
Membrane interaction to intercellular spread of pathology in Alzheimer’s disease
Authors: Valappil Deepak Kunhi , Mini Neeraj Jayakumar , Dilna Aysha , Nath Sangeeta
Published: September 2022

Progressive development of pathology is one of the major characteristic features of neurodegenerative diseases. Alzheimer’s disease (AD) is the most prevalent among them. Extracellular amyloid-β (Aβ) plaques and intracellular tau neurofibrillary tangles are the pathological phenotypes of AD. However, cellular and animal studies implicate tau as a secondary pathology in developing AD while Aβ aggregates is considered as a trigger point. Interaction of Aβ peptides with plasma membrane (PM) seems to be a promising site of involvement in the events that lead to AD. Aβ binding to the lipid membranes initiates formation of oligomers of Aβ species, and these oligomers are known as primary toxic agents for neuronal toxicities. Once initiated, neuropathological toxicities spread in a “prion-like” fashion probably through the mechanism of intercellular transfer of pathogenic aggregates. In the last two decades, several studies have demonstrated neuron-to-neuron transfer of neurodegenerative proteins including Aβ and tau via exosomes and tunneling nanotubes (TNTs), the two modes of long-range intercellular transfer. Emerging pieces of evidence indicate that molecular pathways related to the biogenesis of exosomes and TNTs interface with endo-lysosomal pathways and cellular signaling in connection to vesicle recycling-imposed PM and actin remodulation. In this review, we discuss interactions of Aβ aggregates at the membrane level and its implications in intercellular spread of pathogenic aggregates. Furthermore, we hypothesize how spread of pathogenic aggregates contributes to complex molecular events that could regulate pathological and synaptic changes related to AD.
Exploring neurometabolic alterations in bipolar disorder with suicidal ideation based on proton magnetic resonance spectroscopy and machine learning technology
Authors: Chen Jiayue , Zhang Xinxin , Qu Yuan , Peng Yanmin , Song Yingchao , Zhuo Chuanjun , Zou Shaohong , Tian Hongjun
Published: September 2022

Bipolar disorder (BD) is associated with a high risk of suicide. We used proton magnetic resonance spectroscopy (1H-MRS) to detect biochemical metabolite ratios in the bilateral prefrontal white matter (PWM) and hippocampus in 32 BD patients with suicidal ideation (SI) and 18 BD patients without SI, identified potential brain biochemical differences and used abnormal metabolite ratios to predict the severity of suicide risk based on the support vector machine (SVM) algorithm. Furthermore, we analyzed the correlations between biochemical metabolites and clinical variables in BD patients with SI. There were three main findings: (1) the highest classification accuracy of 88% and an area under the curve of 0.9 were achieved in distinguishing BD patients with and without SI, with N-acetyl aspartate (NAA)/creatine (Cr), myo-inositol (mI)/Cr values in the bilateral PWM, NAA/Cr and choline (Cho)/Cr values in the left hippocampus, and Cho/Cr values in the right hippocampus being the features contributing the most; (2) the above seven features could be used to predict Self-rating Idea of Suicide Scale scores (r = 0.4261, p = 0.0302); and (3) the level of neuronal function in the left hippocampus may be related to the duration of illness, the level of membrane phospholipid catabolism in the left hippocampus may be related to the severity of depression, and the level of inositol metabolism in the left PWM may be related to the age of onset in BD patients with SI. Our results showed that the combination of multiple brain biochemical metabolites could better predict the risk and severity of suicide in patients with BD and that there was a significant correlation between biochemical metabolic values and clinical variables in BD patients with SI.
Innate immune activation: Parallels in alcohol use disorder and Alzheimer’s disease
Authors: Ramos Adriana , Joshi Radhika S. , Szabo Gyongyi
Published: September 2022

Alcohol use disorder is associated with systemic inflammation and organ dysfunction especially in the liver and the brain. For more than a decade, studies have highlighted alcohol abuse-mediated impairment of brain function and acceleration of neurodegeneration through inflammatory mechanisms that directly involve innate immune cells. Furthermore, recent studies indicate overlapping genetic risk factors between alcohol use and neurodegenerative disorders, specifically regarding the role of innate immunity in the pathomechanisms of both areas. Considering the pressing need for a better understanding of the relevance of alcohol abuse in dementia progression, here we summarize the molecular mechanisms of neuroinflammation observed in alcohol abuse and Alzheimer’s disease, the most common cause of dementia. In addition, we highlight mechanisms that are already established in the field of Alzheimer’s disease that may be relevant to explore in alcoholism to better understand alcohol mediated neurodegeneration and dementia, including the relevance of the liver-brain axis.
Protective effects and regulatory pathways of melatonin in traumatic brain injury mice model: Transcriptomics and bioinformatics analysis
Authors: Fu Jiayuanyuan , Zhou Qiang , Wu Biying , Huang Xuekang , Tang Zhaohua , Tan Weilin , Zhu Ziyu , Du Mengran , Wu Chenrui , Ma Jun , Balawi Ehab , Liao Z. B.
Published: September 2022

Traumatic brain injury (TBI) is the leading cause of disability and mortality globally. Melatonin (Mel) is a neuroendocrine hormone synthesized from the pineal gland that protects against TBI. Yet, the precise mechanism of action is not fully understood. In this study, we examined the protective effect and regulatory pathways of melatonin in the TBI mice model using transcriptomics and bioinformatics analysis. The expression profiles of mRNA, long non-coding RNA (lncRNA), microRNA (miRNA), and circular RNA (circRNA) were constructed using the whole transcriptomes sequencing technique. In total, 93 differentially expressed (DE) mRNAs (DEmRNAs), 48 lncRNAs (DElncRNAs), 59 miRNAs (DEmiRNAs), and 59 circRNAs (DEcircRNAs) were identified by the TBI mice with Mel treatment compared to the group without drug intervention. The randomly selected coding RNAs and non-coding RNAs (ncRNAs) were identified by quantitative real-time polymerase chain reaction (qRT-PCR). To further detect the biological functions and potential pathways of those differentially expressed RNAs, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses were executed. In our research, the regulatory network was constructed to show the relationship of lncRNA-RBPs. The lncRNA-mRNA co-expression network was established based on the Pearson coefficient to indicate the expression correlations. Moreover, the DEcircRNA–DEmiRNA–DEmRNA and DElncRNA–DEmiRNA–DEmRNA regulatory networks were constructed to demonstrate the regulatory relationship between ncRNAs and mRNA. Finally, to further verify our predicted results, cytoHubba was used to find the hub gene in the synaptic vesicle cycle pathway, and the expression level of SNAP-25 and VAMP-2 after melatonin treatment were detected by Western blotting and immunofluorescence. To sum up, these data offer a new insight regarding the molecular effect of melatonin treatment after TBI and suggest that the high-throughput sequencing and analysis of transcriptomes are useful for studying the drug mechanisms in treatment after TBI.
Emerging roles of keratinocytes in nociceptive transduction and regulation
Authors: Xu Xiaohan , Yu Catherine , Xu Li , Xu Jijun
Published: September 2022

Keratinocytes are the predominant block-building cells in the epidermis. Emerging evidence has elucidated the roles of keratinocytes in a wide range of pathophysiological processes including cutaneous nociception, pruritus, and inflammation. Intraepidermal free nerve endings are entirely enwrapped within the gutters of keratinocyte cytoplasm and form en passant synaptic-like contacts with keratinocytes. Keratinocytes can detect thermal, mechanical, and chemical stimuli through transient receptor potential ion channels and other sensory receptors. The activated keratinocytes elicit calcium influx and release ATP, which binds to P2 receptors on free nerve endings and excites sensory neurons. This process is modulated by the endogenous opioid system and endothelin. Keratinocytes also express neurotransmitter receptors of adrenaline, acetylcholine, glutamate, and γ-aminobutyric acid, which are involved in regulating the activation and migration, of keratinocytes. Furthermore, keratinocytes serve as both sources and targets of neurotrophic factors, pro-inflammatory cytokines, and neuropeptides. The autocrine and/or paracrine mechanisms of these mediators create a bidirectional feedback loop that amplifies neuroinflammation and contributes to peripheral sensitization.
Misfolding at the synapse: A role in amyotrophic lateral sclerosis pathogenesis?
Authors: Lum Jeremy S. , Yerbury Justin J.
Published: September 2022

A growing wave of evidence has placed the concept of protein homeostasis at the center of the pathogenesis of amyotrophic lateral sclerosis (ALS). This is due primarily to the presence of pathological transactive response DNA-binding protein (TDP-43), fused in sarcoma (FUS) or superoxide dismutase-1 (SOD1) inclusions within motor neurons of ALS postmortem tissue. However, the earliest pathological alterations associated with ALS occur to the structure and function of the synapse, prior to motor neuron loss. Recent evidence demonstrates the pathological accumulation of ALS-associated proteins (TDP-43, FUS, C9orf72-associated di-peptide repeats and SOD1) within the axo-synaptic compartment of motor neurons. In this review, we discuss this recent evidence and how axo-synaptic proteome dyshomeostasis may contribute to synaptic dysfunction in ALS.
Recent advances in carrageenan-based films for food packaging applications
Authors: Cheng Cheng , Chen Shuai , Su Jiaqi , Zhu Ming , Zhou Mingrui , Chen Tianming , Han Yahong
Published: September 2022

In order to solve the increasingly serious environmental problems caused by plastic-based packaging, carrageenan-based films are drawing much attentions in food packaging applications, due to low cost, biodegradability, compatibility, and film-forming property. The purpose of this article is to present a comprehensive review of recent developments in carrageenan-based films, including fabrication strategies, physical and chemical properties and novel food packaging applications. Carrageenan can be extracted from red algae mainly by hydrolysis, ultrasonic-assisted and microwave-assisted extraction, and the combination of multiple extraction methods will be future trends in carrageenan extraction methods. Carrageenan can form homogeneous film-forming solutions and fabricate films mainly by direct coating, solvent casting and electrospinning, and mechanism of film formation was discussed in detail. Due to the inherent limitations of the pure carrageenan film, physical and chemical properties of carrageenan films were enhanced by incorporation with other compounds. Therefore, carrageenan-based films can be widely used for extending the shelf life of food and monitoring the food freshness by inhibiting microbial growth, reducing moisture loss and the respiration, etc. This article will provide useful guidelines for further research on carrageenan-based films.
Higher Circulating Vitamin D Levels Are Associated With Decreased Migraine Risk: A Mendelian Randomization Study
Authors: Niu Peng-Peng , Wang Xue , Xu Yu-Ming
Published: September 2022

Background

Evidence showed the supplementation of vitamin D might have beneficial effects for migraine patients. We aimed to investigate the causal effects of serum vitamin D levels on migraine risk using two-sample Mendelian randomization (MR) method.

Methods

A total of 184 independent genetic instruments for serum vitamin D levels were selected from a study in 417,580 Europeans from UK biobank. Six variants from an independent study were obtained to perform replication analysis. Summary-level data for migraine were obtained from three studies with 48,975 migraine cases, 28,852 migraine cases and 10,536 migraine cases, respectively.

Results

The estimated odds ratios (ORs) per standard deviation increase in circulating vitamin D levels based on the three migraine datasets were 0.948 (95% CI = 0.883–1.016, p = 0.133), 0.902 (95% confidence intervals [CI] = 0.825–0.986, p = 0.023), and 0.880 (95% CI = 0.786–0.984, p = 0.025), respectively. Using pooled migraine summary data with no sample overlap, MR analysis showed per standard deviation increase in circulating vitamin D levels was significantly associated with a decreased migraine risk (OR = 0.916, 95% CI = 0.859–0.977, p = 0.008). Multivariable MR analyses, sensitivity analyses and replication analysis confirmed the association. MR analyses showed similar estimates for migraine with aura and migraine without aura but with wider 95% CIs. Mediation analysis showed the effect of vitamin D on migraine risk via pathway of serum calcium was corresponding to an OR of 1.003 (95% CI = 1.001–1.005) and a proportion mediated of 3.42%. The reverse MR analysis showed migraine might not affect vitamin D levels.

Conclusion

This two-sample MR study showed genetically determined increased circulating vitamin D levels are associated with decreased migraine risk. The effect seems consistent across different migraine subtypes. In addition, the role of serum calcium in mediating the association between vitamin D and migraine is negligible. Future large well-designed randomized trials are warranted to assess the effects of vitamin D supplementation for migraine patients, especially in those with vitamin D deficiency.
Non-alcoholic fatty liver disease and dairy products consumption: Results from FASA Persian cohort study
Authors: Keshavarz Zahra , Rahimlou Mehran , Farjam Mojtaba , Homayounfar Reza , Khodadost Mahmoud , Abdollahi Ashkan , Tabrizi Reza
Published: September 2022

Background/objectives

There are limited data on the association between dairy products consumption and nonalcoholic fatty liver disease (NAFLD). This study was conducted to evaluate the association between total intake of different dairy products and fatty liver index (FLI), a marker of subclinical fatty liver.

Methods

A total of 7,540 adults were included in this population-based cohort study. Dairy products consumption was evaluated by a validated interview questionnaire for food intake frequency. The FLI was calculated using the standard formula. Liver enzyme levels, lipid profiles, glycemic profiles and demographic characteristics were recorded for all participants. Univariate and multiple logistic regression models were used to respectively assess the mean percentage difference of mean FLI and odds ratios (ORs) for subclinical NAFLD across quantiles of dairy consumption.

Results

The mean age of all participants was 48.81 ± 9.631 years. FLI measurements for men and women were 26.71 ± 23.39 and 39.99 ± 26.64 respectively, which was significantly higher in women (P < 0.05). Multiple logistic regression analysis demonstrated that the amount of milk consumption was an independent preventive predictor of FLI (OR = 0.96; 95% CI: 0.94–0.99), conversely, it did not predict higher levels of liver enzymes. In term of cheese intake, participants in the third tertile of cheese intake had significantly lower FLI than lower tertiles (P = 0.01). However, there wasn't any significant association between cheese intake and the odds of FLI in the multivariate model (P > 0.05). We didn't find any significant association between yogurt consumption and NAFLD indicators (P > 0.05).

Conclusion

Higher milk consumption was inversely associated with FLI. However, there wasn't any significant association between other types of dairy products and NAFLD indicators.
Structural energy storage composites for aviation applications
Authors: Chan Kit-Ying , Demir Baris , Lau Kin-Tak , Shen Xi
Published: September 2022

Structural energy storage composites, which combine energy storage capability with load-carrying function, are receiving increasing attention for potential use in portable electronics, electric vehicles, and aircraft structures to store electrical energy in replace of traditional electrochemical energy storage devices. The integration of energy storage ability into mechanically strong carbon fibre reinforced polymer composite is promising in reducing the weight and volume while providing additional functions, ultimately leading to energy-efficient systems. In this review, the key designs and strategies to reconcile the trade-off between mechanical properties and energy storage performances of structural dielectric capacitors, a typical type of structural energy storage composites, are highlighted. Opportunities and challenges are also discussed for the further development of structural energy storage composites for aviation applications.