bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibition of Biogenic Amines Formation in Fermented Foods by the Addition of Cava Lees
Authors: Hernández-Macias Salvador , Martín-Garcia Alba , Ferrer-Bustins Núria , Comas-Basté Oriol , Riu-Aumatell Montserrat , López-Tamames Elvira , Jofré Anna , Latorre-Moratalla M. Luz , Bover-Cid Sara , Vidal-Carou M. Carmen
Published: January 2022

Food safety can be compromised by some bioactive compounds such as biogenic amines that can be specially found in fermented foods due to the bacterial decarboxylation of some amino acids by fermentative or spoilage bacteria. Cava lees are a winery by-product rich in fiber and phenolic compounds and previous works have raised their revalorization from a food safety point of view. The aim of the current work was to investigate whether the use of cava lees can help to control biogenic amine formation in bread and fermented sausages. In bread, only very low levels of biogenic amines (putrescine, cadaverine, and/or spermidine) were found, whose content did not vary with the addition of different amounts of lees. However, the addition of lees in fermented sausages significantly reduced the formation of tyramine and cadaverine. In sausages spontaneously fermented and inoculated with Salmonella spp., the presence of cadaverine and putrescine diminished by 62 and 78%, respectively, due to the addition of cava lees. The addition of cava lees phenolic extract also showed an anti-aminogenic effect (21% for cadaverine and 40% for putrescine), although in a lesser extent than cava lees. Cava lees and their phenolic extract were shown to be an effective strategy to control the undesirable accumulation of high levels of biogenic amines during the production of fermented products.
Metastatic Immune-Related Genes for Affecting Prognosis and Immune Response in Renal Clear Cell Carcinoma
Authors: Sun Si , Mao Weipu , Wan Lilin , Pan Kehao , Deng Liting , Zhang Lei , Zhang Guangyuan , Chen Ming
Published: January 2022

Background:In renal clear cell carcinoma, a common cancer of the urinary system, 25–30% patients are metastatic at initial diagnosis and 20–30% patients have a tendency of recurrence and metastasis after local surgery. With the rapid development of tumor immunology, immune agents have brought new directions to tumor therapy. However, no relevant studies have explored the role of immune-related genes in kidney cancer metastasis.

Methods:Co-expressed metastatic immune-related differentially expressed genes (mIR-DEGs) were screened by GSE12606, GSE47352, and immunorelated genes. Then, differential expression analysis, prognostic analysis, and univariate and multivariate Cox regression analysis in KIRC were performed to determine independent prognostic factors associated, and the risk prognostic model was established. The correlation of hub mIR-DEGs with clinicopathological factors, immune invasion, and immune checkpoints was analyzed, and the expression of hub mIR-DEGs and their effect on tumor were re-evaluated by OCLR scores in KIRC.

Results:By comprehensive bioassay, we found that FGF17, PRKCG, SSTR1, and SCTR were mIR-DEGs with independent prognostic values, which were significantly associated with clinicopathological factors and immune checkpoint–related genes. The risk prognostics model built on this basis had good predictive potential. In addition, targeted small molecule drugs, including calmidazolium and sulfasalazine, were predicted for mIR-DEGs. Further experimental results were consistent with the bioinformatics analysis.

Conclusion:This study preliminarily confirmed that FGF17, PRKCG, SSTR1, and SCTR were targeted genes affecting renal cancer metastasis and related immune responses and can be used as potential therapeutic targets and prognostic biomarkers for renal cancer. Preliminary validation found that PRKCG and SSTR1 were consistent with predictions.
The Interaction Between Intracellular Energy Metabolism and Signaling Pathways During Osteogenesis
Authors: Ye Jiapeng , Xiao Jirimutu , Wang Jianwei , Ma Yong , Zhang Yafeng , Zhang Qiang , Zhang Zongrui , Yin Heng
Published: January 2022

Osteoblasts primarily mediate bone formation, maintain bone structure, and regulate bone mineralization, which plays an important role in bone remodeling. In the past decades, the roles of cytokines, signaling proteins, and transcription factors in osteoblasts have been widely studied. However, whether the energy metabolism of cells can be regulated by these factors to affect the differentiation and functioning of osteoblasts has not been explored in depth. In addition, the signaling and energy metabolism pathways are not independent but closely connected. Although energy metabolism is mediated by signaling pathways, some intermediates of energy metabolism can participate in protein post-translational modification. The content of intermediates, such as acetyl coenzyme A (acetyl CoA) and uridine diphosphate N-acetylglucosamine (UDP-N-acetylglucosamine), determines the degree of acetylation and glycosylation in terms of the availability of energy-producing substrates. The utilization of intracellular metabolic resources and cell survival, proliferation, and differentiation are all related to the integration of metabolic and signaling pathways. In this paper, the interaction between the energy metabolism pathway and osteogenic signaling pathway in osteoblasts and bone marrow mesenchymal stem cells (BMSCs) will be discussed.
Dynamic Alterations of the Gut Microbial Pyrimidine and Purine Metabolism in the Development of Liver Cirrhosis
Authors: Xiong Yinghui , Wu Li , Shao Li , Wang Yang , Huang Zebing , Huang Xun , Li Chunhui , Wu Anhua , Liu Zhenguo , Fan Xuegong , Zhou Pengcheng
Published: January 2022

Background: Liver cirrhosis is the common end-stage of liver disease which lacks effective treatment, thus studies to determine prevention targets are an urgent need. The intestinal microbiota (IM) play important roles in modulating liver diseases which are mediated by microbial metabolites. Despite decades of growing microbial studies, whether IM contribute to the development of cirrhosis and the intimate metabolic link remain obscure. Here, we aimed to reveal the dynamic alterations of microbial composition and metabolic signatures in carbon tetrachloride (CCl4)-induced liver cirrhosis mice.

Methods: CCl4-treated mice or normal control (NC) were sacrificed (n = 10 per group) after 5 and 15 weeks of intervention. The disease severity was confirmed by Masson’s trichrome or Sirius red staining. Metagenomics sequencing and fecal untargeted metabolomics were performed to evaluate the composition and metabolic function of IM in parallel with the development of cirrhosis.

Results: The CCl4-treated mice presented liver fibrosis at 5 weeks and liver cirrhosis at 15 weeks indicated by collagen deposition and pseudo-lobule formation, respectively. Mice with liver cirrhosis showed distinct microbial composition from NC, even in the earlier fibrosis stage. Importantly, both of the liver fibrosis and cirrhosis mice were characterized with the depletion of Deltaproteobacteria (p < 0.05) and enrichment of Akkermansia (p < 0.05). Furthermore, fecal metabolomics revealed distinguished metabolomics profiles of mice with liver fibrosis and cirrhosis from the NC. Notably, pathway enrichment analysis pointed to remarkable disturbance of purine (p < 0.001 at 5 weeks, p = 0.034 at 15 weeks) and pyrimidine metabolic pathways (p = 0.005 at 5 weeks, p = 0.006 at 15 weeks) during the development of liver cirrhosis. Interestingly, the disorders of pyrimidine and purine metabolites like the known microbial metabolites thymidine and 2′-deoxyuridine had already occurred in liver fibrosis and continued in cirrhosis.

Conclusion: These novel findings indicated the crucial role of IM-modulated pyrimidine and purine metabolites in the development of liver cirrhosis, which provides microbial targets for disease prevention.
Circadian Influences on the Habenula and Their Potential Contribution to Neuropsychiatric Disorders
Authors: Young Callum J. , Lyons David , Piggins Hugh D.
Published: January 2022

The neural circadian system consists of the master circadian clock in the hypothalamic suprachiasmatic nuclei (SCN) communicating time of day cues to the rest of the body including other brain areas that also rhythmically express circadian clock genes. Over the past 16 years, evidence has emerged to indicate that the habenula of the epithalamus is a candidate extra-SCN circadian oscillator. When isolated from the SCN, the habenula sustains rhythms in clock gene expression and neuronal activity, with the lateral habenula expressing more robust rhythms than the adjacent medial habenula. The lateral habenula is responsive to putative SCN output factors as well as light information conveyed to the perihabenula area. Neuronal activity in the lateral habenula is altered in depression and intriguingly disruptions in circadian rhythms can elevate risk of developing mental health disorders including depression. In this review, we will principally focus on how circadian and light signals affect the lateral habenula and evaluate the possibility that alteration in these influences contribute to mental health disorders.
Autophagy Contributes to the Rapamycin-Induced Improvement of Otitis Media
Authors: Xie Daoli , Zhao Tong , Zhang Xiaolin , Kui Lihong , Wang Qin , Wu Yuancheng , Zheng Tihua , Ma Peng , Zhang Yan , Molteni Helen , Geng Ruishuang , Yang Ying , Li Bo , Zheng Qing Yin
Published: January 2022

Otitis media (OM) is a pervasive disease that involves hearing loss and severe complications. In our previous study, we successfully established a mouse model of human OM using Tlr2tm1Kir (TLR2–/–) mice with middle ear (ME) inoculation of streptococcal peptidoglycan-polysaccharide (PGPS). In this study, we found that hearing loss and OM infections in OM mice were significantly alleviated after treatment with rapamycin (RPM), a widely used mechanistic target of RPM complex 1 (mTORC1) inhibitor and autophagy inducer. First of all, we tested the activity of mTORC1 by evaluating p-S6, Raptor, and mTOR protein expression. The data suggested that the protein expression level of p-S6, Raptor and mTOR are decreased in TLR2–/– mice after the injection of PGPS. Furthermore, our data showed that both the autophagosome protein LC3-II, Beclin-1, ATG7, and autophagy substrate protein p62 accumulated at higher levels in mice with OM than in OM-negative mice. The expression of lysosomal-associated proteins LAMP1, Cathepsin B, and Cathepsin D increased in the OM mice compared with OM-negative mice. Rab7 and Syntaxin 17, which is necessary for the fusion of autophagosomes with lysosomes, are reduced in the OM mice. In addition, data also described that the protein expression level of p-S6, mTOR and Raptor are lower than PGPS group after RPM treatment. The accumulation of LC3-II, Beclin-1, and ATG7 are decreased, and the expression of Rab7 and Syntaxin 17 are increased significantly after RPM treatment. Our results suggest that autophagy impairment is involved in PGPS-induced OM and that RPM improves OM at least partly by relieving autophagy impairment. Modulating autophagic activity by RPM may be a possible effective treatment strategy for OM.
Uncovering the Connectivity Logic of the Ventral Tegmental Area
Authors: Derdeyn Pieter , Hui May , Macchia Desiree , Beier Kevin T.
Published: January 2022

Decades of research have revealed the remarkable complexity of the midbrain dopamine (DA) system, which comprises cells principally located in the ventral tegmental area (VTA) and substantia nigra pars compacta (SNc). Neither homogenous nor serving a singular function, the midbrain DA system is instead composed of distinct cell populations that (1) receive different sets of inputs, (2) project to separate forebrain sites, and (3) are characterized by unique transcriptional and physiological signatures. To appreciate how these differences relate to circuit function, we first need to understand the anatomical connectivity of unique DA pathways and how this connectivity relates to DA-dependent motivated behavior. We and others have provided detailed maps of the input-output relationships of several subpopulations of midbrain DA cells and explored the roles of these different cell populations in directing behavioral output. In this study, we analyze VTA inputs and outputs as a high dimensional dataset (10 outputs, 22 inputs), deploying computational techniques well-suited to finding interpretable patterns in such data. In addition to reinforcing our previous conclusion that the connectivity in the VTA is dependent on spatial organization, our analysis also uncovered a set of inputs elevated onto each projection-defined VTADA cell type. For example, VTADA→NAcLat cells receive preferential innervation from inputs in the basal ganglia, while VTADA→Amygdala cells preferentially receive inputs from populations sending a distributed input across the VTA, which happen to be regions associated with the brain’s stress circuitry. In addition, VTADA→NAcMed cells receive ventromedially biased inputs including from the preoptic area, ventral pallidum, and laterodorsal tegmentum, while VTADA→mPFC cells are defined by dominant inputs from the habenula and dorsal raphe. We also go on to show that the biased input logic to the VTADA cells can be recapitulated using projection architecture in the ventral midbrain, reinforcing our finding that most input differences identified using rabies-based (RABV) circuit mapping reflect projection archetypes within the VTA.
Neuropsychological Impairment, Brain Injury Symptoms, and Health-Related Quality of Life After Pediatric TBI in Oslo
Authors: Holthe Ingvil Laberg , Dahl Hilde Margrete , Rohrer-Baumgartner Nina , Eichler Sandra , Elseth Marthe Fjellheim , Holthe Øyvor , Berntsen Torhild , Yeates Keith Owen , Andelic Nada , Løvstad Marianne
Published: January 2022

Descriptions of clinical outcomes in pediatric traumatic brain injury (pTBI) in Scandinavia are sparse. The Oslo site of the European CENTER-TBI study has performed a pTBI outcome study in a hospitalized population. The main objective was to investigate neuropsychological outcomes, self- and parent-reported symptoms associated with brain injury, and quality of life in children aged 1–15 years, 5–8 months after injury. Fifty-two children were included, and 45 completed the assessments. The sample consisted of 15.4% severe, 21.2% moderate, and 63.4% mild TBI. Subjectively experienced problems with concentration and fatigue were reported by the parents of nearly half of the children. Higher brain injury symptom load was associated with lower quality of life, but was unrelated to injury severity. Group average scores of the sample on neuropsychological testing appeared unimpaired relative to normative means aside from lower performance in working memory. However, based on an impairment index (i.e., 2 or more tests being >1.5 SD below the normative mean), the presence of weak cognitive performance was evident in as many as 45.4% of the sample. Two-thirds of the sample also showed abnormally large intraindividual variability in cognitive functioning (i.e., significant WISC-IV index discrepancies). The findings highlight the need to look beyond group averages on neuropsychological testing. Utilizing an impairment index and considering intraindividual performance variability conveyed deficits that may warrant clinical follow-up. The association of brain injury symptoms with quality of life but not injury severity emphasizes the need to consider symptoms after TBI within a biopsychosocial framework.

Clinical Trial Registration:ClinicalTrials.gov; identifier: NCT02210221.
Early Brain Volume Changes After Stroke: Subgroup Analysis From the AXIS-2 Trial
Authors: Bu Ning , Churilov Leonid , Khlif Mohamed Salah , Lemmens Robin , Wouters Anke , Fiebach Jochen B. , Chamorro Angel , Ringelstein E. Bernd , Norrving Bo , Laage Rico , Grond Martin , Wilms Guido , Brodtmann Amy , Thijs Vincent
Published: January 2022

Background and Purpose

The evolution of total brain volume early after stroke is not well understood. We investigated the associations between age and imaging features and brain volume change in the first month after stroke.

Methods

We retrospectively studied patients with acute ischemic stroke enrolled in the AXIS-2 trial. Total brain volume change from hyperacute MRI data to the first month after stroke was assessed using unified segmentation in SPM12. We hypothesized that age, ischemic brain lesion size, and white matter (WM) changes were associated with larger brain volume change. Enlarged perivascular spaces (EPVSs) and white matter hyperintensities (WMHs) were rated visually and the presence of lacunes was assessed.

Results

We enrolled 173 patients with a mean age of 67 ± 11 years, 44% were women. There was a median 6 ml decrease in volume (25th percentile −1 ml to 75th percentile 21 ml) over time, equivalent to a median 0.5% (interquartile range [IQR], −0.07%−1.4%), decrease in brain volume. Age was associated with larger brain volume loss (per 10 years of age, 5 ml 95% CI 2–8 ml). Baseline diffusion weighted imaging (DWI) lesion volume was not associated with greater volume loss per 10 ml of lesion volume, change by 0 ml (95% CI −0.1 to 0.1 ml). Increasing Fazekas scores of deep WMH were associated with greater tissue loss (5 ml, 95% CI 1–10 ml).

Conclusions

Total brain volume changes in a heterogenous fashion after stroke. Volume loss occurs over 1 month after stroke and is associated with age and deep WM disease. We did not find evidence that more severe strokes lead to increased early tissue loss.
Gut Microbiota Dysbiosis in Acute Ischemic Stroke Associated With 3-Month Unfavorable Outcome
Authors: Sun Huanhuan , Gu Mengmeng , Li Zhongyuan , Chen Xiangliang , Zhou Junshan
Published: January 2022

Background

Alterations in the gut microbiota after ischemic stroke have been demonstrated, whereas the effect on stroke outcome remains to be established.

Methods

A total of 132 consecutive patients with acute ischemic stroke were prospectively enrolled. Their gut microbiomes within 24 h of admission were profiled using 16S ribosomal RNA (rRNA) gene (V3–V4 region) sequencing. Microbiota comparisons were made between groups with good outcome (n = 105) and poor outcome (n = 27) based on 3-month modified Rankin Scale scores of 0–2 and 3–6. Propensity score-matching (PSM) analysis was conducted to assess the robustness of our findings. The functional potential was predicted using the Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt).

Results

Patients in the poor outcome group were characterized by a significant reduction in the alpha diversity (Shannon index, p = 0.025; Simpson index, p = 0.010), an increase in the pathogenic bacteria (e.g., Enterococcaceae and Enterococcus), and a decrease in the short-chain fatty acids (SCFAs)-producing bacteria (e.g., Bacteroidaceae, Ruminococcaceae, and Faecalibacterium) to those with good outcome group (all p < 0.05). Similar results of microbial composition were obtained after PSM. The PICRUSt revealed that the pathway for membrane transport was relatively dominant in patients with poor outcome (p < 0.05).

Conclusion

This study demonstrated that stroke patients with 3-month poor outcome had baseline gut microbiota dysbiosis featured by increased pathogenic bacteria and decreased SCFAs-producing bacteria.
Case Report: Need for Caution in the Diagnosis of GFAP Astrocytopathy—A Case of GFAP Astrocytopathy Coexistent With Primary Central Nervous System Lymphoma
Authors: Fang Jia , Tong Zhongyi , Lu Wei
Published: January 2022

We reported a case of primary central nervous system lymphoma (PCNSL) coexistent with glial fibrillary acidic protein (GFAP) astrocytopathy, and discussed the problems needing attention in the diagnosis and differential diagnosis of GFAP astrocytopathy. Our patient was a 51-year-old female who presented with somnolence for a month, and memory declination for 10 days. Brain magnetic resonance imaging (MRI) demonstrated multiple abnormal enhancement lesions in bilateral basal ganglia and around the third ventricle, as well as transient T2-weighted hyper-intensity lesions at the splenium of the corpus callosum during the course of the disease. The cerebrospinal fluid (CSF) was positive for anti-GFAP antibodies by antigen-transfected HEK293 cell-based assay (indirect immunofluorescence assay). She was initially diagnosed with autoimmune GFAP astrocytopathy. After treatment with corticosteroids for about 2 months, she displayed poor response and even worsened clinical manifestations when the dose of prednisone reduced to 45 mg. Stereotactic brain biopsy was adopted and the diagnosis of large B-cell lymphoma, non-germinal center type was established on pathological examination. The results of brain biopsy also showed perivascular inflammation and CD8+ T cell infiltration, which also accorded with GFAP astrocytopathy. After chemotherapy with rituximab and methotrexate, the patient showed clinical and radiological improvement significantly. Our findings suggest that positivity of GFAP antibody calls for cautious interpretation. Cancer screening appropriate for age, sex, and risk factors is recommended for GFAP antibody-positive patients, especially for patients with atypical clinical and radiologic manifestations.
Acupuncture Treatment Decreased Temporal Variability of Dynamic Functional Connectivity in Chronic Tinnitus
Authors: Wei Yarui , Zhang Wanlin , Li Yu , Liu Xiangwei , Zha Bixiang , Hu Sheng , Wang Yanming , Wang Xiaoxiao , Yu Xiaochun , Yang Jun , Qiu Bensheng
Published: January 2022

Acupuncture is recommended for the relief of chronic tinnitus in traditional Chinese medicine, but the underlying neural mechanism remains unclear. The human brain is a dynamic system, and it’s unclear about acupuncture’s effects on the dynamic functional connectivity (DFC) of chronic tinnitus. Therefore, this study based on resting-state functional magnetic resonance imaging (fMRI) investigates abnormal DFC in chronic tinnitus patients and the neural activity change evoked by acupuncture treatment for tinnitus. In this study, 17 chronic tinnitus patients and 22 age- and sex-matched normal subjects were recruited, and their tinnitus-related scales and hearing levels were collected. The fMRI data were measured before and after acupuncture, and then sliding-window and k-means clustering methods were used to calculate DFC and perform clustering analysis, respectively. We found that, compared with the normal subjects, chronic tinnitus patients had higher temporal variability of DFC between the supplementary motor area and medial part of the superior frontal gyrus, and it positively correlated with hearing loss. Clustering analysis showed higher transition probability (TP) between connection states in chronic tinnitus patients, and it was positively correlated with tinnitus severity. Furthermore, the findings showed that acupuncture treatment might improve tinnitus. DFC between the posterior cingulate gyrus and angular gyrus in chronic tinnitus patients after acupuncture showed significantly decreased, and it positively correlated with the improvement of tinnitus. Clustering analysis showed that acupuncture treatment might promote chronic tinnitus patients under lower DFC state, and it also positively correlated with the improvement of tinnitus. This study suggests that acupuncture as an alternative therapy method might decrease the tinnitus severity by decreasing the time variability of DFC in chronic tinnitus patients.
Gut Microbiome Composition Linked to Inflammatory Factors and Cognitive Functions in First-Episode, Drug-Naive Major Depressive Disorder Patients
Authors: Liu Penghong , Gao Mingxue , Liu Zhifen , Zhang Yanyan , Tu Hongwei , Lei Lei , Wu Peiyi , Zhang Aixia , Yang Chunxia , Li Gaizhi , Sun Ning , Zhang Kerang
Published: January 2022

Objective

The microbiota–gut–brain axis, especially the inflammatory pathway, may play a critical role in the pathogenesis of cognitive impairment in major depressive disorder (MDD). However, studies on the microbiota-inflammatory-cognitive function axis in MDD are lacking. The aim of the present study was to analyze the gut microbiota composition and explore the correlation between gut microbiota and inflammatory factors, cognitive function in MDD patients.

Method

Study participants included 66 first-episode, drug naïve MDD patients as well as 43 healthy subjects (HCs). The composition of fecal microbiota was evaluated using16S rRNA sequencing and bioinformatics analysis. The cytokines such as hs-CRP, IL-1β, IL-6, IL-10, and TNF-α in peripheral blood were detected via enzyme linked immunosorbent assay (ELISA); assessment of cognitive functions was performed using the Color Trail Test (CTT), The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and the Stroop Color-Word Test (SCWT).

Results

We found that compared with HCs, MDD patients had cognitive impairments and showed different α-diversity and β-diversity of gut microbiota composition. LDA effect size (LEfSe) analysis found MDD have higher Deinococcaceae and lower Bacteroidaceae, Turicibacteraceae, Clostridiaceae and Barnesiellaceae at family level. Deinococcus and Odoribacter was higher in the MDD group, however, Bacteroides, Alistipes, Turicibacter, Clostridium, Roseburia, and Enterobacter were lower at genus level. Furthermore, In MDD patients, the Bacteroidaceae and Bacteroides were both positively correlated with hsCRP, CCT1, CCT2. Alistipes was positively correlated with IL-6, Word time, Color time, Word-Color time, Color-Word time and negatively correlated with Delayed Memory, Total score and Standardized score. Turicibacteraceae and Turicibacter were both negatively correlated with IL-1β and IL-6.

Conclusion

The present findings confirm that the gut microbiota in MDD patients have altered gut microbes that are closely associated with inflammatory factors and cognitive function in MDD patients.
Manual Therapy Research Methods in Animal Models, Focusing on Soft Tissues
Authors: Bove Geoffrey M. , Chapelle Susan L. , Barrigar Matthew J. S. , Barbe Mary F.
Published: January 2022

Manual therapies have been practiced for centuries, yet little research has been performed to understand their efficacy and almost no animal research has been performed to inform mechanisms of action. The methods of manual therapy practice are quite varied and present a challenge for scientists to model the treatments and perform research using rodents. In this perspective we present a descriptive analysis of the complexity of the treatments, highlighting the role of tissue mechanics and physics. With these complexities in mind, we compare using manual therapy as clinically practiced, to attempts to develop machinery to model or mimic manual therapy. We propose that because of the complexities of manual therapy as practiced, having therapists perform the treatments on research animals just as they would on humans is the most scientific approach. Our results using this approach have supported its practicality.
Modulatory Effects of Alpha-Mangostin Mediated by SIRT1/3-FOXO3a Pathway in Oxidative Stress-Induced Neuronal Cells
Authors: Ruankham Waralee , Suwanjang Wilasinee , Phopin Kamonrat , Songtawee Napat , Prachayasittikul Virapong , Prachayasittikul Supaluk
Published: January 2022

Background

alpha-Mangostin, a polyphenolic xanthone, is primarily found in the pericarp of mangosteen throughout Southeast Asia and is considered as the “Queen of Fruit” in Thailand. Nonetheless, it is not clarified how alpha-mangostin protects neuronal cells against oxidative stress.

Objective

In this study, molecular mechanisms underlying the neuroprotective effect of alpha-mangostin in defending hydrogen peroxide (H2O2)-induced neurotoxicity was explored.

Methods

cytotoxicity, reactive oxygen species (ROS) generation, apoptotic cascades, and protein expression profiles were performed incorporation of molecular docking.

Results

Human SH-SY5Y cells were pretreated with 1 μM alpha-mangostin for 3 h prior to exposure to 400 μM H2O2. alpha-Mangostin significantly inhibited oxidative stress-induced cell death in neuronal cells by reducing BAX protein, decreasing caspase-3/7 activation, and increasing anti-apoptotic BCL-2 protein. Collectively, alpha-mangostin was demonstrated to be a prominent ROS suppressor which reversed the reduction of antioxidant enzymes (CAT and SOD2). Surprisingly, alpha-mangostin significantly promoted the expression of the sirtuin family and the FOXO3a transcription factor exerting beneficial effects on cell survival and longevity. A molecular docking study predicted that alpha-mangostin is directly bound to the active site of SIRT1.

Conclusion

Findings from this study suggest that alpha-mangostin potentially serves as a promising therapeutic compound against oxidative stress by activation of the SIRT1/3-FOXO3a pathway comparable to the effect of memantine, an anti-AD drug used for the treatment of moderate to severe dementia.
Grape Seed Proanthocyanidin Alleviates Intestinal Inflammation Through Gut Microbiota-Bile Acid Crosstalk in Mice
Authors: Wu Yi , Mo Ruixia , Zhang Mingrui , Zhou Weiwei , Li Defa
Published: January 2022

Regulation of gut microbiota and modulation of bile acid (BA) composition are potential strategies for the treatment of intestinal inflammation. This study aimed to investigate the effect of grape seed proanthocyanidin (GSP) on intestinal inflammation and to understand its mechanism. C57BL/6J male mice (7–8 weeks old) were used in experiments. Antibiotics were applied to deplete gut microbiota to evaluate the contribution of gut microbiota to the effect of dietary GSP. Intestinal-specific farnesoid X receptor (FXR) inhibitor was used to analyze the role of FXR signaling. In this study, GSP alleviated intestinal inflammation induced by LPS and altered the gut microbiota accompanied by increased abundance of hydroxysteroid dehydrogenase (HSD) producing microbes. GSP activated the intestinal FXR signaling pathway and increased gene expression of enzymes of the alternative BA synthetic pathway, which associated with elevated levels of chenodeoxycholic acid (CDCA) and lithocholic acid (LCA) in liver and feces. However, gut microbiota depletion by antibiotics removed those effects of GSP on mice injected with LPS. In addition, the protective effect of GSP on mice challenged with LPS was weakened by the inhibition of intestinal FXR signaling. Further, the mixture of CDCA and LCA mirrored the effects of GSP in mice injected with LPS, which might verify the efficiency of CDCA and LCA on intestinal inflammation. Taken together, our results indicated that GSP exerted an intestinal protection role in the inflammation induced by LPS, and these effects were mediated by regulating gut microbiota-BA crosstalk.
Gastrointestinal Tract and Dietary Fiber Driven Alterations of Gut Microbiota and Metabolites in Durco × Bamei Crossbred Pigs
Authors: Wu Guofang , Tang Xianjiang , Fan Chao , Wang Lei , Shen Wenjuan , Ren Shi'en , Zhang Liangzhi , Zhang Yanming
Published: January 2022

Gastrointestinal tract and dietary fiber (DF) are known to influence gut microbiome composition. However, the combined effect of gut segment and long-term intake of a high fiber diet on pig gut microbiota and metabolite profiles is unclear. Here, we applied 16S rRNA gene sequencing and untargeted metabolomics to investigate the effect of broad bean silage on the composition and metabolites of the cecal and jejunal microbiome in Durco × Bamei crossbred pigs. Twenty-four pigs were allotted to four graded levels of DF chow, and the content of jejunum and cecum were collected. Our results demonstrated that cecum possessed higher α-diversity and abundance of Bacteroidetes, unidentified Ruminococcaceae compared to jejunum, while jejunum possessed higher abundance of Lactobacillus, Streptococcus. DF intake significantly altered diversity of the bacterial community. The abundance of Bacteroidetes and Turicibacter increased with the increase of DF in cecum and jejunum respectively. Higher concentrations of amino acids and conjugated bile acids were detected in the jejunum, whereas free bile acids and fatty acids were enriched in the cecum. The concentrations of fatty acids, carbohydrate metabolites, organic acids, 2-oxoadipic acid, and succinate in cecum were higher in the high DF groups. Overall, the results indicate that the composition of bacteria and the microbiota metabolites were distinct in different gut segments. DF had a significant influence on the bacterial composition and structure in the cecum and jejunum, and that the cecal metabolites may further affect host health, growth, and slaughter performance.
Effects of Ball Milling Combined With Cellulase Treatment on Physicochemical Properties and in vitro Hypoglycemic Ability of Sea Buckthorn Seed Meal Insoluble Dietary Fiber
Authors: Zhu Yulian , Ji Xiaolong , Yuen Michael , Yuen Tina , Yuen Hywel , Wang Min , Smith Deandrae , Peng Qiang
Published: January 2022

To improve the rough texture and hypoglycemic ability of sea buckthorn insoluble dietary fiber (IDF), a novel combined modification method was developed in this study. The IDF was treated with ball milling and cellulase treatment to obtain co-modified insoluble dietary fiber (CIDF). The physicochemical and functional properties of IDF, milled insoluble dietary fiber (MIDF), and CIDF were studied. After treatments, MIDF had smaller particle sizes and a looser structure, and CIDF exhibited a wrinkled surface and sparse porous structure according to scanning electron microscopy (SEM) and X-ray diffraction. Compared to IDF, MIDF and CIDF showed improved water-holding, oil-binding, and swelling capacities, improved by 16.13, 14.29, and 15.38%, and 38.5, 22.2, and 25.0%, for MIDF and CIDF, respectively. The cation exchange ability of modified samples showed improvement as well. Treatments also changed the fluidity of MIDF and CIDF. Due to the smaller particles and increased stacking, the bulk density (BD) and angle of repose of MIDF improved by 33.3% and 4.1° compared to IDF, whereas CIDF had a looser structure and thus decreased by 7.1% and 13.3° with increased fluidity. Moreover, the modification also enhanced the effects of CIDF on glucose adsorption, glucose diffusion inhibition, starch digestion inhibition, starch pasting interference, and α-amylase activity inhibition. In summary, IDF modified by ball milling combined with cellulose treatment could be developed as a functional ingredient for regulating glucose content.
Effects of Alcohol Extracts From Ganoderma resinaceum on Sleep in Mice Using Combined Transcriptome and Metabolome Analysis
Authors: Chen Tianci , Zhang Fangyi , Chen Juanqin , Zhong Qiangui , Hu Yuxin , Wu Ruru , Xie Baogui , Jiang Yuji , Chen Bingzhi
Published: January 2022

Ganoderma resinaceum is a valuable Chinese medicine. This study aimed to investigate whether a G. resinaceum alcohol extract (GRAE) improves sleep, and analyze the potential mechanism. After 30 days of continuous administration of GRAE at various doses, GRAE (1,000 mg/kg.bw) prolonged pentobarbital sodium-induced sleep, increased the rate of sleeping in mice treated with a subthreshold dose of pentobarbital sodium, and shortened sleep latency. The mice brain was analyzed using UPLC-MS/MS and RNA-sequencing. Metabolomics analysis revealed that 73 metabolites in the high-dose (HD) group had changed significantly, mainly in amino acids and their derivatives, especially the accumulation of L-glutamine and PGJ2 (11-oxo-15S-hydroxy-prosta-5Z, 9, 13E-trien-1-oic acid). Transcriptome analysis revealed 500 differential genes between HD and control groups, mainly enriched in neuroactive ligand-receptor interaction, amphetamine addiction, and cocaine addiction pathways. The conjoint analysis of the transcriptome and metabolome showed that the biosynthesis of L-glutamine might be regulated by Homer1, Homer3, and Grin3b. This suggests that GRAE may affect L-glutamine accumulation by regulating the expression of these genes. This study showed that GRAE may prolong the sleep time of mice by reducing the accumulation of L-glutamine and deepens our understanding of the regulatory network between certain genes and L-glutamine.
A County-Level Spatial Study of Serum Selenoprotein P and Keshan Disease
Authors: Jia Yuehui , Wang Ruixiang , Su Shengqi , Qi Lei , Wang Yuanyuan , Wang Yanan , Zou Yuanjie , Liu Xu , Zhang Yiyi , Hou Jie , Feng Hongqi , Li Qi , Wang Tong
Published: January 2022

Background

Keshan disease (KD) is strongly associated with selenium deficiency. Selenoprotein P (SELENOP) is a recognized molecular biomarker of selenoproteins and an important indicator of selenium nutrition. This study was aimed at providing geographically precisely visualized evidence of selenium nutrition at molecular level for assessing KD prevention, control, and elimination on the etiological perspective.

Methods

We used spatial ecological design for this study. The serum SELENOP levels of the residents were measured by ELISA. ArcGIS version 9.0 was used for spatial description, spatial autocorrelation analysis of SELENOP levels and spatial regression with per capita disposable income.

Results

The mean serum SELENOP levels of the 6,382 residents in 1,688 counties were 4.62 ± 1.82 μg/mL. The mean serum SELENOP levels of the residents living in the townships and rural areas of KD endemic counties were not statistically significantly lower than those of the KD non-endemic counties. The mean serum SELENOP levels were globally clustered (Moran's I = 0.03, z = 6.37, and P < 0.0001), and 99.3% (553/557) of the cold spots, identified by local autocorrelation analysis (Getis-Ord-Gi* analysis), were located in the KD endemic provinces of Shaanxi, Shanxi, Henan, Hebei, Shandong, Inner Mongolia, Gansu, Hubei, Chongqing, Yunnan, and Sichuan. The serum SELENOP level was positively correlated with per capita disposable income (t = 3.52, P = 0.0004).

Conclusions

The results of this study were the geographically precisely visualized evidence of selenium nutrition at molecular level for assessing KD elimination on the etiological perspective. The cold spot counties found by Getis-Ord-Gi* analysis in the KD endemic provinces should be the high priority of KD precision prevention and control.
Novel Insights From the Germline Landscape of Breast Cancer in Brazil
Authors: Barbalho Daniel , Sandoval Renata , Santos Erika , Pisani Janina , Quirino Carla , Garicochea Bernardo , Rossi Benedito , Achatz Maria Isabel
Published: January 2022

Introduction

Breast cancer patients with germline pathogenic variants may benefit from risk-reducing surgeries, intensive screening, and targeted cancer therapies. There is a paucity of data regarding prevalence and distribution of germline pathogenic variants in the Brazilian population. Our primary endpoint was the description of prevalence and distribution of germline pathogenic variants among breast cancer patients who underwent next-generation sequencing (NGS) panel testing. Secondary endpoint was the assessment of predictive factors of a positive test.

Methods

We analyzed NGS results, personal, and family history data from a prospectively collected cohort of breast cancer patients from August 2013 to May 2019. Exact logistic regression was used to perform multivariable analysis.

Results

Of 370 breast cancer patients, we found 59 pathogenic variants in 57 (15%) patients. Pathogenic variants were identified in BRCA1 (24%), ATM (14%), BRCA2 (10%), TP53 (8%), PALB2 (8%), CHEK2 (7%), CDH1 (3%), RAD51C (3%), MITF (2%), PMS2 (2%), RAD51D (2%), and TERT (2%). Monoallelic MUTYH pathogenic variants were found in 15%. After multivariable analysis, age of diagnosis (OR 0.89, 95% CI: 0.81–0.95, for each year increase), triple-negative subtype (OR 17.2, 95% CI: 3.74–114.72), and number of breast cancers in the family (OR 2.46, 95% CI 1.57–4.03, for each additional case) were associated with BRCA1 pathogenic variants. In the present study, a quarter of triple-negative breast cancer patients harbored a germline pathogenic variant and two-thirds of those were BRCA1 carriers.

Conclusions

Prevalence and distribution of germline pathogenic variants in this Brazilian sample of breast cancer patients are mostly similar to other populations. However, there is a trend to an overrepresentation of TP53 pathogenic variants that merits confirmation in further studies. Early-onset breast cancer patients should be offered genetic counseling, particularly those with triple-negative subtype.
Organoid: Next-Generation Modeling of Cancer Research and Drug Development
Authors: Liu Jungang , Huang Xiaoliang , Huang Lihaoyun , Huang Jinlian , Liang Dingyu , Liao Lixian , Deng Yuqing , Zhang Lihua , Zhang Beibei , Tang Weizhong
Published: January 2022

Colorectal carcinoma is a highly prevalent and heterogeneous gastrointestinal malignancy. The emergence of organoid technology has provided a new direction for colorectal cancer research. As a novel-type model, organoid has significant advantages compared with conventional tumor research models, characterized with the high success rate of construction and the high matching with the original tumor. These characteristics provide new possibilities to study the mechanism of colorectal carcinogenesis and improve the treatment effects. The present literature would mainly summarize the characteristics of tumor organoids and the up-to-date technique development of patient-derived organoids (PDOs) and application in colorectal cancer.
PFKFB3 Regulates Chemoresistance, Metastasis and Stemness via IAP Proteins and the NF-κB Signaling Pathway in Ovarian Cancer
Authors: Jiang Yu-xin , Siu Michelle K. Y. , Wang Jing-jing , Leung Thomas H. Y. , Chan David W. , Cheung Annie N. Y. , Ngan Hextan Y. S. , Chan Karen K. L.
Published: January 2022

Glycolysis has been reported to be critical for cancer stem cells (CSCs), which are associated with tumor chemoresistance, metastasis and recurrence. Thus, selectively targeting glycolytic enzymes may be a potential therapy for ovarian cancer. 6‐phosphofructo‐2‐kinase/fructose‐2,6‐biphosphatase 3 (PFKFB3), the main source of fructose-2,6-bisphosphate, controls the first committed step in glycolysis. We investigate the clinical significance and roles of PFKFB3 in ovarian cancer using in vitro and in vivo experiments. We demonstrate that PFKFB3 is widely overexpressed in ovarian cancer and correlates with advanced stage/grade and poor outcomes. Significant up-regulation of PFKFB3 was found in ascites and metastatic foci, as well as CSC-enriched tumorspheres and ALDH+CD44+ cells. 3PO, a PFKFB3 inhibitor, reduced lactate level and sensitized A2780CP cells to cisplatin treatment, along with the modulation of inhibitors of apoptosis proteins (c-IAP1, c-IAP2 and survivin) and an immune modulator CD70. Blockade of PFKFB3 by siRNA approach in the CSC-enriched subset led to decreases in glycolysis and CSC properties, and activation of the NF-κB cascade. PFK158, another potent inhibitor of PFKFB3, impaired the stemness of ALDH+CD44+ cells in vitro and in vivo, whereas ectopic expression of PFKFB3 had the opposite results. Overall, PFKFB3 was found to mediate metabolic reprogramming, chemoresistance, metastasis and stemness in ovarian cancer, possibly via the modulation of inhibitors of apoptosis proteins and the NF-κB signaling pathway; thus, suggesting that PFKFB3 may be a potential therapeutic target for ovarian cancer.
Emerging Roles of m6A RNA Methylation Regulators in Gynecological Cancer
Authors: Huang Wanjun , Kong Fanhua , Li Ruolan , Chen Xiang , Wang Kunpeng
Published: January 2022

Gynecological cancers seriously affect the reproductive system of females; diseases include ovarian tumors, uterine tumors, endometrial cancers, cervical cancers, and vulva and vaginal tumors. At present, the diagnosis methods of gynecological cancer are insufficiently sensitive and specific, leading to failure of early disease detection. N6-methyladenosine (m6A) plays various biological functions in RNA modification and is currently studied extensively. m6A modification controls the fate of transcripts and regulates RNA metabolism and biological processes through the interaction of m6A methyltransferase (“writer”) and demethylase (“erasers”) and the binding protein decoding m6A methylation (“readers”). In the field of epigenetics, m6A modification is a dynamic process of reversible regulation of target RNA through its regulatory factors. It plays an important role in many diseases, especially cancer. However, its role in gynecologic cancers has not been fully investigated. Thus, we review the regulatory mechanism, biological functions, and therapeutic prospects of m6A RNA methylation regulators in gynecological cancers.
Quantitative Sensory Testing Across Chronic Pain Conditions and Use in Special Populations
Authors: Weaver Kristen R. , Griffioen Mari A. , Klinedinst N. Jennifer , Galik Elizabeth , Duarte Ana C. , Colloca Luana , Resnick Barbara , Dorsey Susan G. , Renn Cynthia L.
Published: January 2022

Chronic pain imposes a significant burden to the healthcare system and adversely affects patients' quality of life. Traditional subjective assessments, however, do not adequately capture the complex phenomenon of pain, which is influenced by a multitude of factors including environmental, developmental, genetic, and psychological. Quantitative sensory testing (QST), established as a protocol to examine thermal and mechanical sensory function, offers insight on potential mechanisms contributing to an individual's experience of pain, by assessing their perceived response to standardized delivery of stimuli. Although the use of QST as a research methodology has been described in the literature in reference to specific pain populations, this manuscript details application of QST across a variety of chronic pain conditions. Specific conditions include lower extremity chronic pain, knee osteoarthritis, chronic low back pain, temporomandibular joint disorder, and irritable bowel syndrome. Furthermore, we describe the use of QST in placebo/nocebo research, and discuss the use of QST in vulnerable populations such as those with dementia. We illustrate how the evaluation of peripheral sensory nerve function holds clinical promise in targeting interventions, and how using QST can enhance patient education regarding prognostic outcomes with particular treatments. Incorporation of QST methodology in research investigations may facilitate the identification of common mechanisms underlying chronic pain conditions, guide the development of non-pharmacological behavioral interventions to reduce pain and pain-related morbidity, and enhance our efforts toward reducing the burden of chronic pain.