bluuebunny/crossref_metadata_2025 huggingface dataset:
Airborne Bacterial Community Composition According to Their Origin in Tenerife, Canary Islands
Authors: González-Martín Cristina , Pérez-González Carlos J. , González-Toril Elena , Expósito Francisco J. , Aguilera Ángeles , Díaz Juan P.
Published: October 2021

Microorganisms are ubiquitous in the environment, and the atmosphere is no exception. However, airborne bacterial communities are some of the least studied. Increasing our knowledge about these communities and how environmental factors shape them is key to understanding disease outbreaks and transmission routes. We describe airborne bacterial communities at two different sites in Tenerife, La Laguna (urban, 600 m.a.s.l.) and Izaña (high mountain, 2,400 m.a.s.l.), and how they change throughout the year. Illumina MiSeq sequencing was used to target 16S rRNA genes in 293 samples. Results indicated a predominance of Proteobacteria at both sites (>65%), followed by Bacteroidetes, Actinobacteria, and Firmicutes. Gammaproteobacteria were the most frequent within the Proteobacteria phylum during spring and winter, while Alphaproteobacteria dominated in the fall and summer. Within the 519 genera identified, Cellvibrio was the most frequent during spring (35.75%) and winter (30.73%); Limnobacter (24.49%) and Blastomonas (19.88%) dominated in the summer; and Sediminibacterium represented 10.26 and 12.41% of fall and winter samples, respectively. Sphingomonas was also identified in 17.15% of the fall samples. These five genera were more abundant at the high mountain site, while other common airborne bacteria were more frequent at the urban site (Kocuria, Delftia, Mesorhizobium, and Methylobacterium). Diversity values showed different patterns for both sites, with higher values during the cooler seasons in Izaña, whereas the opposite was observed in La Laguna. Regarding wind back trajectories, Tropical air masses were significantly different from African ones at both sites, showing the highest diversity and characterized by genera regularly associated with humans (Pseudomonas, Sphingomonas, and Cloacibacterium), as well as others related to extreme conditions (Alicyclobacillus) or typically associated with animals (Lachnospiraceae). Marine and African air masses were consistent and very similar in their microbial composition. By contrast, European trajectories were dominated by Cellvibrio, Pseudomonas, Pseudoxanthomonas, and Sediminibacterium. These data contribute to our current state of knowledge in the field of atmospheric microbiology. However, future studies are needed to increase our understanding of the influence of different environmental factors on atmospheric microbial dispersion and the potential impact of airborne microorganisms on ecosystems and public health.
Pyomelanin-Producing Brevundimonas vitisensis sp. nov., Isolated From Grape (Vitis vinifera L.)
Authors: Jiang Lingmin , Jeon Doeun , Kim Jueun , Lee Chul Won , Peng Yuxin , Seo Jiyoon , Lee Ju Huck , Paik Jin Hyub , Kim Cha Young , Lee Jiyoung
Published: October 2021

A novel endophytic bacterial strain, designated GR-TSA-9T, was isolated from surface-sterilized grape (Vitis vinifera L.). 16S rRNA gene sequence analyses showed that the isolate was grouped within the genus Brevundimonas, displaying the highest similarity with Brevundimonas lenta DS-18T (97.9%) and Brevundimonas kwangchunensis KSL-102T (97.8%) and less than 97.5% similarity with other members of Brevundimonas. The strain GR-TSA-9T was a gram negative, rod shaped, facultatively anaerobic, catalase and oxidase positive, and motile bacterium. Its growth occurred at 10–37°C (optimally 25–30°C), at pH 7.0–8.0, and in NaCl 0–1% (optimally 0%). It contained ubiquinone-10 as a respiratory quinone, and the major cellular fatty acids (>10% of the total) were C16:0 (14.2%) and summed feature 8 (C18:1ω7c and/or C18:1ω6c, 65.6%). The polar lipids present in the strain were phosphoglycolipids, phosphatidylglycerol, 1,2-di-O-acyl-3-O-[d-glucopyranosyl-(1→4)-α-d-glucopyranuronosyl]glycerol, and unidentified lipids (L1, L2, and L4). The strain had one 2,976,716bp circular chromosome with a G+C content of 66.4%. The digital DNA–DNA hybridization value between strain GR-TSA-9T and B. lenta DS-18T was 20.9%, while the average nucleotide identity value was 76.7%. In addition, the dDDH and ANI values to other members in this genus, whose genome sequences are available, are less than 21.1 and 77.6%. Genome annotation predicted the presence of some gene clusters related to tyrosine degradation and pyomelanin formation. Strain GR-TSA-9T produced a brown melanin-like pigment in the presence of L-tyrosine-containing media. The highest pigment production (0.19g/L) was observed in tryptic soy broth with 1.0mg/ml L-tyrosine at 25°C for 6days of culture. Biophysical characterization by ultraviolet (UV)–visible spectroscopy, Fourier-transform infrared spectroscopy, and electrospray ionization mass spectrometry confirmed that the pigment was pyomelanin. Additionally, melanized GR-TSA-9T cells could protect the cells against UVC exposure. The phylogenetic, genomic, phenotypic, and chemotaxonomic features indicated that strain GR-TSA-9T represents a novel melanin-producing species of Brevundimonas. The type strain was GR-TSA-9T (KCTC 82386T=CGMCC 1.18820T).
The SNARE Protein CfVam7 Is Required for Growth, Endoplasmic Reticulum Stress Response, and Pathogenicity of Colletotrichum fructicola
Authors: Li Sizheng , Zhang Shengpei , Li Bing , Li He
Published: October 2021

The tea-oil tree Camellia oleifera is native to China and is cultivated in many parts of southern China. This plant has been grown for over 2,000 years, mainly for its high-quality cooking oil. Anthracnose is the main disease of tea-oil tree and results in a huge loss annually. Colletotrichum fructicola is a major pathogen causing anthracnose on tea-oil tree. In a previous study, we characterized that the bZIP transcription factor CfHac1 controlled the development and pathogenicity of C. fructicola. Here, we identified and characterized the function of CfVAM7 gene, which was significantly downregulated at the transcriptional level in the ΔCfhac1 strain under dithiothreitol stress. Targeted gene deletion revealed that CfVam7 is important in growth, pathogenicity, and responses to endoplasmic reticulum-related stresses. Further analysis revealed that CfVam7 is required for appressorium formation and homotypic vacuole fusion, which are important for fungal pathogen invasion. Cytological examinations revealed that CfVam7 is localized to vacuole membranes in the hyphal stage. The Phox homology (PX) and SNARE domains of CfVam7 were indispensable for normal cellular localization and biological function. Taken together, our results suggested that CfVam7-mediated vacuole membrane fusion promotes growth, stress response, and pathogenicity of C. fructicola.
Induction of Apoptotic Cell Death by Oral Streptococci in Human Periodontal Ligament Cells
Authors: Park Ok-Jin , Kim A Reum , So Yoon Ju , Im Jintaek , Ji Hyun Jung , Ahn Ki Bum , Seo Ho Seong , Yun Cheol-Heui , Han Seung Hyun
Published: October 2021

Initiation and progression of oral infectious diseases are associated with streptococcal species. Bacterial infection induces inflammatory responses together with reactive oxygen species (ROS), often causing cell death and tissue damage in the host. In the present study, we investigated the effects of oral streptococci on cytotoxicity and ROS production in human periodontal ligament (PDL) cells. Streptococcus gordonii showed cell cytotoxicity in a dose- and time-dependent manner. The cytotoxicity might be due to apoptosis since S. gordonii increased annexin V-positive cells, and the cytotoxicity was reduced by an apoptosis inhibitor, Z-VAD-FMK. Other oral streptococci such as Streptococcus mitis, Streptococcus sanguinis, and Streptococcus sobrinus also induced apoptosis, whereas Streptococcus mutans did not. All streptococci tested except S. mutans triggered ROS production in human PDL cells. Interestingly, however, streptococci-induced apoptosis appears to be ROS-independent, as the cell death induced by S. gordonii was not recovered by the ROS inhibitor, resveratrol or n-acetylcysteine. Instead, hydrogen peroxide (H2O2) appears to be important for the cytotoxic effects of streptococci since most oral streptococci except S. mutans generated H2O2, and the cytotoxicity was dramatically reduced by catalase. Furthermore, streptococcal lipoproteins are involved in cytotoxicity, as we observed that cytotoxicity induced by the lipoprotein-deficient S. gordonii mutant was less potent than that by the wild-type and was attenuated by anti-TLR2-neutralizing antibody. Indeed, lipoproteins purified from S. gordonii alone were sufficient to induce cytotoxicity. Notably, S. gordonii lipoproteins did not induce H2O2 or ROS but cooperatively induced cell death when co-treated with H2O2. Taken together, these results suggest that most oral streptococci except S. mutans efficiently induce damage to human PDL cells by inducing apoptotic cell death with bacterial H2O2 and lipoproteins, which might contribute to the progression of oral infectious diseases such as apical periodontitis.
Lactococcus lactis Mutants Obtained From Laboratory Evolution Showed Elevated Vitamin K2 Content and Enhanced Resistance to Oxidative Stress
Authors: Liu Yue , de Groot Anteun , Boeren Sjef , Abee Tjakko , Smid Eddy J.
Published: October 2021

Vitamin K2 is an important vitamin for human health. Vitamin K2 enrichment in the human diet is possible by using vitamin K2-producing bacteria such as Lactococcus lactis in food fermentations. Based on previous observations that aerated cultivation conditions improved vitamin K2 content in L. lactis, we performed laboratory evolution on L. lactis MG1363 by cultivating this strain in a shake flask in a sequential propagation regime with transfers to a fresh medium every 72h. After 100 generations of propagation, we selected three evolved strains that showed improved stationary phase survival in oxygenated conditions. In comparison to the original strain MG1363, the evolved strains showed 50–110% increased vitamin K2 content and exhibited high resistance against hydrogen peroxide-induced oxidative stress. Genome sequencing of the evolved strains revealed common mutations in the genes ldh and gapB. Proteomics analysis revealed overproduction of glyceraldehyde 3-phosphate dehydrogenase (GapA), universal stress protein A2 (UspA2), and formamidopyrimidine-DNA glycosylase (MutM) under aerated conditions in evolved strains, proteins with putative functions in redox reactions, universal stress response, and DNA damage repair, all of which could contribute to the enhanced oxidative stress resistance. The mechanisms underlying elevated vitamin K2 content in the evolved strains remain to be elucidated. Two out of the three evolved strains performed similar to the original strain MG1363 in terms of growth and acidification of culture media. In conclusion, this study demonstrated a natural selection approach without genetic manipulations to obtain vitamin K2 overproducers that are highly relevant for food applications and contributed to the understanding of oxidative stress resistance in L. lactis.
Transcriptomic Profile and Probiotic Properties of Lactiplantibacillus pentosus Pre-adapted to Edible Oils
Authors: Alonso García Esther , de la Fuente Ordoñez Juan José , Lavilla Lerma Leyre , Estudillo-Martínez María D. , Castillo-Gutiérrez Sonia , Benomar Nabil , Knapp Charles W. , Abriouel Hikmate
Published: October 2021

In this study, we determined whether pre-adapting Lactiplantibacillus pentosus strains, isolated from Aloreña green table olives, to vegetable-based edible oils improved their robustness and functionality; this may have great importance on their stress response during fermentation, storage, and digestion. Pre-adapting the strains to the corresponding oils significantly increased their probiotic functionality (e.g., auto-aggregation, co-aggregation with pathogens, and mucin adhesion), although results depended on the strain and the oil used for pre-adaptation. As such, we selected olive-adapted (TO) L. pentosus AP2-16, which exhibited improved functionality, and subjected it to transcriptomic profiling with the aim to understand the molecular mechanisms involved in the adaptation and the increased functionality. Global transcriptomic analysis of oil-adapted (olive or almond) and non-adapted (control) L. pentosus AP2-16 realized that 3,259 genes were expressed, with 2,779 mapped to the reference database. Comparative transcriptomic analysis showed that 125 genes (olive vs. control) and 108 genes (olive vs. almond) became significantly differentially expressed. TO L. pentosus AP2-16 responded by rerouting its metabolic pathways to balance energy production and storage, cell growth and survivability, host interactions (glycoconjugates), and other physiological features. As such, the pre-adaptation of lactobacilli with olive oil switches their transcriptional network to regulate robustness and functionality, possibly representing a novel approach toward the design and manufacture of probiotic products with improved stability and functionality.
A Nanoparticle-Based Biosensor Combined With Multiple Cross Displacement Amplification for the Rapid and Visual Diagnosis of Neisseria gonorrhoeae in Clinical Application
Authors: Chen Xu , Huang Liming , Zhou Qingxue , Tan Yan , Tan Xuhong , Dong Shilei
Published: October 2021

Gonorrhea is a sexually transmitted disease caused by the host-adapted human pathogen, Neisseria gonorrhoeae. The morbidity is increasing and poses a major public health concern, especially in resource-scarce regions. Therefore, a rapid, visual, sensitive, specific, cost-saving, and simple assay for N. gonorrhoeae detection is critical for prompt treatment and the prevention of further transmission. Here, for the first time, we report a novel assay called the multiple cross displacement amplification combined with gold nanoparticle-based lateral flow biosensor (MCDA-LFB), which we constructed for the rapid and visual identification of N. gonorrhoeae in clinical samples. We successfully devised a set of MCDA primers based on the N. gonorrhoeae-specific gene, orf1. Optimal assay conditions were determined at 67°C, including genomic DNA preparation (∼15 min), MCDA amplification (30 min), and LFB reading (∼2 min), which can be completed within 50 min. The limit of detection (LoD) of the assay was 20 copies/test (in a 25-μl reaction mixture). Assay specificity was 100%, with no cross-reactions with other pathogens. Thus, our N. gonorrhoeae-MCDA-LFB is a rapid, specific, visual, cost-saving, and easy-to-use assay for N. gonorrhoeae diagnostics, and may have great potential for point-of-care (POC) testing in clinical settings, especially in resource-limited regions.
The Contribution of the Predicted Sorting Platform Component HrcQ to Type III Secretion in Xanthomonas campestris pv. vesicatoria Depends on an Internal Translation Start Site
Authors: Otten Christian , Seifert Tanja , Hausner Jens , Büttner Daniela
Published: October 2021

Pathogenicity of the Gram-negative bacterium Xanthomonas campestris pv. vesicatoria depends on a type III secretion (T3S) system which translocates effector proteins into plant cells. T3S systems are conserved in plant- and animal-pathogenic bacteria and consist of at least nine structural core components, which are designated Sct (secretion and cellular translocation) in animal-pathogenic bacteria. Sct proteins are involved in the assembly of the membrane-spanning secretion apparatus which is associated with an extracellular needle structure and a cytoplasmic sorting platform. Components of the sorting platform include the ATPase SctN, its regulator SctL, and pod-like structures at the periphery of the sorting platform consisting of SctQ proteins. Members of the SctQ family form a complex with the C-terminal protein domain, SctQC, which is translated as separate protein and likely acts either as a structural component of the sorting platform or as a chaperone for SctQ. The sorting platform has been intensively studied in animal-pathogenic bacteria but has not yet been visualized in plant pathogens. We previously showed that the SctQ homolog HrcQ from X. campestris pv. vesicatoria assembles into complexes which associate with the T3S system and interact with components of the ATPase complex. Here, we report the presence of an internal alternative translation start site in hrcQ leading to the separate synthesis of the C-terminal protein region (HrcQC). The analysis of genomic hrcQ mutants showed that HrcQC is essential for pathogenicity and T3S. Increased expression levels of hrcQ or the T3S genes, however, compensated the lack of HrcQC. Interaction studies and protein analyses suggest that HrcQC forms a complex with HrcQ and promotes HrcQ stability. Furthermore, HrcQC colocalizes with HrcQ as was shown by fluorescence microscopy, suggesting that it is part of the predicted cytoplasmic sorting platform. In agreement with this finding, HrcQC interacts with the inner membrane ring protein HrcD and the SctK-like linker protein HrpB4 which contributes to the docking of the HrcQ complex to the membrane-spanning T3S apparatus. Taken together, our data suggest that HrcQC acts as a chaperone for HrcQ and as a structural component of the predicted sorting platform.
Roles of the Cell Surface Architecture of Bacteroides and Bifidobacterium in the Gut Colonization
Authors: Nishiyama Keita , Yokoi Tatsunari , Sugiyama Makoto , Osawa Ro , Mukai Takao , Okada Nobuhiko
Published: October 2021

There are numerous bacteria reside within the mammalian gastrointestinal tract. Among the intestinal bacteria, Akkermansia, Bacteroides, Bifidobacterium, and Ruminococcus closely interact with the intestinal mucus layer and are, therefore, known as mucosal bacteria. Mucosal bacteria use host or dietary glycans for colonization via adhesion, allowing access to the carbon source that the host’s nutrients provide. Cell wall or membrane proteins, polysaccharides, and extracellular vesicles facilitate these mucosal bacteria-host interactions. Recent studies revealed that the physiological properties of Bacteroides and Bifidobacterium significantly change in the presence of co-existing symbiotic bacteria or markedly differ with the spatial distribution in the mucosal niche. These recently discovered strategic colonization processes are important for understanding the survival of bacteria in the gut. In this review, first, we introduce the experimental models used to study host-bacteria interactions, and then, we highlight the latest discoveries on the colonization properties of mucosal bacteria, focusing on the roles of the cell surface architecture regarding Bacteroides and Bifidobacterium.
The Visuospatial and Sensorimotor Functions of Posterior Parietal Cortex in Drawing Tasks: A Review
Authors: Bai Shuwei , Liu Wenyan , Guan Yangtai
Published: October 2021

Drawing is a comprehensive skill that primarily involves visuospatial processing, eye-hand coordination, and other higher-order cognitive functions. Various drawing tasks are widely used to assess brain function. The neuropsychological basis of drawing is extremely sophisticated. Previous work has addressed the critical role of the posterior parietal cortex (PPC) in drawing, but the specific functions of the PPC in drawing remain unclear. Functional magnetic resonance imaging and electrophysiological studies found that drawing activates the PPC. Lesion-symptom mapping studies have shown an association between PPC injury and drawing deficits in patients with global and focal cerebral pathology. These findings depicted a core framework of the fronto-parietal network in drawing tasks. Here, we review neuroimaging and electrophysiological studies applying drawing paradigms and discuss the specific functions of the PPC in visuospatial and sensorimotor aspects. Ultimately, we proposed a hypothetical model based on the dorsal stream. It demonstrates the organization of a PPC-centered network for drawing and provides systematic insights into drawing for future neuropsychological research.
High Blood Uric Acid Is Associated With Reduced Risks of Mild Cognitive Impairment Among Older Adults in China: A 9-Year Prospective Cohort Study
Authors: Chen Chen , Li Xueqin , Lv Yuebin , Yin Zhaoxue , Zhao Feng , Liu Yingchun , Li Chengcheng , Ji Saisai , Zhou Jinhui , Wei Yuan , Cao Xingqi , Wang Jiaonan , Gu Heng , Lu Feng , Liu Zuyun , Shi Xiaoming
Published: October 2021

Background: It remains unsolved that whether blood uric acid (UA) is a neuroprotective or neurotoxic agent. This study aimed to evaluate the longitudinal association of blood UA with mild cognitive impairment (MCI) among older adults in China.

Methods: A total of 3,103 older adults (aged 65+ years) free of MCI at baseline were included from the Healthy Aging and Biomarkers Cohort Study (HABCS). Blood UA level was determined by the uricase colorimetry assay and analyzed as both continuous and categorical (by quartile) variables. Global cognition was assessed using the Mini-Mental State Examination four times between 2008 and 2017, with a score below 24 being considered as MCI. Cox proportional hazards models were used to examine the associations.

Results: During a 9-year follow-up, 486 (15.7%) participants developed MCI. After adjustment for all covariates, higher UA had a dose-response association with a lower risk of MCI (all Pfor  trend < 0.05). Participants in the highest UA quartile group had a reduced risk [hazard ratio (HR), 0.73; 95% (CI): 0.55–0.96] of MCI, compared with those in the lowest quartile group. The associations were still robust even when considering death as a competing risk. Subgroup analyses revealed that these associations were statistically significant in younger older adults (65–79 years) and those without hyperuricemia. Similar significant associations were observed when treating UA as a continuous variable.

Conclusions: High blood UA level is associated with reduced risks of MCI among Chinese older adults, highlighting the potential of managing UA in daily life for maintaining late-life cognition.
Abnormal Functional Brain Network in Parkinson's Disease and the Effect of Acute Deep Brain Stimulation
Authors: Li Zhibao , Liu Chong , Wang Qiao , Liang Kun , Han Chunlei , Qiao Hui , Zhang Jianguo , Meng Fangang
Published: October 2021

Objective: The objective of this study was to use functional connectivity and graphic indicators to investigate the abnormal brain network topological characteristics caused by Parkinson's disease (PD) and the effect of acute deep brain stimulation (DBS) on those characteristics in patients with PD.

Methods: We recorded high-density EEG (256 channels) data from 21 healthy controls (HC) and 20 patients with PD who were in the DBS-OFF state and DBS-ON state during the resting state with eyes closed. A high-density EEG source connectivity method was used to identify functional brain networks. Power spectral density (PSD) analysis was compared between the groups. Functional connectivity was calculated for 68 brain regions in the theta (4–8 Hz), alpha (8–13 Hz), beta1 (13–20 Hz), and beta2 (20–30 Hz) frequency bands. Network estimates were measured at both the global (network topology) and local (inter-regional connection) levels.

Results: Compared with HC, PSD was significantly increased in the theta (p = 0.003) frequency band and was decreased in the beta1 (p = 0.009) and beta2 (p = 0.04) frequency bands in patients with PD. However, there were no differences in any frequency bands between patients with PD with DBS-OFF and DBS-ON. The clustering coefficient and local efficiency of patients with PD showed a significant decrease in the alpha, beta1, and beta2 frequency bands (p < 0.001). In addition, edgewise statistics showed a significant difference between the HC and patients with PD in all analyzed frequency bands (p < 0.005). However, there were no significant differences between the DBS-OFF state and DBS-ON state in the brain network, except for the functional connectivity in the beta2 frequency band (p < 0.05).

Conclusion: Compared with HC, patients with PD showed the following characteristics: slowed EEG background activity, decreased clustering coefficient and local efficiency of the brain network, as well as both increased and decreased functional connectivity between different brain areas. Acute DBS induces a local response of the brain network in patients with PD, mainly showing decreased functional connectivity in a few brain regions in the beta2 frequency band.
Cerebral Small Vessel Disease Burden Related to Carotid Intraplaque Hemorrhage Serves as an Imaging Marker for Clinical Symptoms in Carotid Stenosis
Authors: Fan Xiaoyuan , Zhang Xiaoqian , Lai Zhichao , Lin Tianye , You Hui , Liu Changwei , Feng Feng
Published: October 2021

Objectives: In patients with carotid stenosis, to investigate the relationship between carotid intraplaque hemorrhage (IPH) and total burden of cerebral small vessel disease (CSVD) and preliminarily explore whether the total CSVD burden as an imaging marker can distinguish the severity of clinical symptoms.

Methods: A total of 108 patients (the mean age was 66 ± 7 years, and 85.2% were male) with unilateral carotid stenosis ≥50% underwent brain MRI and high-resolution MRI for carotid plaque characterization. The total burden of CSVD was calculated by accumulating one point according to the presence or severity of each of the four MRI markers: white matter hyperintensities, lacunes, perivascular spaces, and cerebral microbleeds. Recent clinical symptoms including transient ischemic attack, amaurosis fugax, and ischemic stroke were recorded. The association between intraplaque hemorrhage (IPH) and total CSVD burden was examined adjusted for other risk factors. The symmetry of CSVD burdens between the ipsilateral and contralateral hemispheres of IPH was tested. Imaging features (CSVD score, IPH, degree of stenosis, and completeness of the circle of Willis) were correlated with clinical symptoms by Kruskal–Wallis H test, Chi-square test, and Fisher's exact test.

Results: Multivariable logistic regression analysis showed that IPH (OR = 2.98, 95% CI [1.39, 6.40], p = 0.005) was independently associated with a higher CSVD score. The presence of unilateral IPH was associated with the inter-hemispheric CSVD score difference (p = 0.004). Patients with stroke had a higher ipsilateral CSVD score than asymptomatic patients (p = 0.004) and those with transient ischemic attack/amaurosis fugax (p = 0.008). The statistical difference was marginally significant between symptoms and IPH (p = 0.057). No statistical difference was found between the symptoms and degree of stenosis and the completeness of the circle of Willis (p > 0.05).

Conclusions: Carotid IPH is associated with an elevated total burden of CSVD in patients with carotid stenosis. Compared with the degree of stenosis, primary collaterals, and IPH, the total CSVD score might be a more effective imaging marker linked with clinical symptoms.
Porphyromonas gingivalis-Induced Neuroinflammation in Alzheimer’s Disease
Authors: Olsen Ingar
Published: October 2021

“Chronic” periodontitis and its keystone pathogen Porphyromonas gingivalis have repeatedly been associated with Alzheimer’s disease (AD). Pathological hallmarks in AD are brain accumulations of amyloid-beta and neurofibrillary tangles consisting of aggregated and hyperphosphorylated tau. In addition, neuroinflammation induced by P. gingivalis has increasingly been recognized as a factor in the pathogenesis of AD. The present mini-review discusses possible mechanisms for the induction of neuroinflammation by P. gingivalis in AD, involving factors such as pro-inflammatory mediators, amyloid-beta, tau, microglia, cathepsin B, and protein kinase R. Inflammagens of P. gingivalis such as lipopolysaccharide and gingipains are also discussed.
Sound-Evoked Responses in the Vestibulo-Ocular Reflex Pathways of Rats
Authors: Chen Tianwen , Huang Jun , Yu Yue , Tang Xuehui , Zhang Chunming , Xu Youguo , Arteaga Alberto , Allison Jerome , Mustain William , Donald Matthew C. , Rappai Tracy , Zhang Michael , Zhou Wu , Zhu Hong
Published: October 2021

Vestibular evoked myogenic potentials (VEMP) have been used to assess otolith function in clinics worldwide. However, there are accumulating evidence suggesting that the clinically used sound stimuli activate not only the otolith afferents, but also the canal afferents, indicating canal contributions to the VEMPs. To better understand the neural mechanisms underlying the VEMPs and develop discriminative VEMP protocols, we further examined sound-evoked responses of the vestibular nucleus neurons and the abducens neurons, which have the interneurons and motoneurons of the vestibulo-ocular reflex (VOR) pathways. Air-conducted clicks (50–80 dB SL re ABR threshold, 0.1 ms duration) or tone bursts (60–80 dB SL, 125–4,000 Hz, 8 ms plateau, 1 ms rise/fall) were delivered to the ears of Sprague-Dawley or Long-Evans rats. Among 425 vestibular nucleus neurons recorded in anesthetized rats and 18 abducens neurons recorded in awake rats, sound activated 35.9% of the vestibular neurons that increased discharge rates for ipsilateral head rotation (Type I neuron), 15.7% of the vestibular neurons that increased discharge rates for contralateral head rotation (Type II neuron), 57.2% of the vestibular neurons that did not change discharge rates during head rotation (non-canal neuron), and 38.9% of the abducens neurons. Sound sensitive vestibular nucleus neurons and abducens neurons exhibited characteristic tuning curves that reflected convergence of canal and otolith inputs in the VOR pathways. Tone bursts also evoked well-defined eye movements that increased with tone intensity and duration and exhibited peak frequency of ∼1,500 Hz. For the left eye, tone bursts evoked upward/rightward eye movements for ipsilateral stimulation, and downward/leftward eye movements for contralateral stimulation. These results demonstrate that sound stimulation results in activation of the canal and otolith VOR pathways that can be measured by eye tracking devices to develop discriminative tests of vestibular function in animal models and in humans.
Efficacy of the Suboccipital Paracondylar-Lateral Cervical Approach: The Series of 64 Jugular Foramen Tumors Along With Follow-Up Data
Authors: Wang Xiangyu , Yuan Jian , Liu Dingyang , Xie Yuanyang , Wu Ming , Xiao Qun , Qin Chaoying , Su Jun , Zeng Yu , Liu Qing
Published: October 2021

Objective

Complete resection of jugular foramen tumors with minimal cranial nerve complications remains challenging even for skilled neurosurgeons. Here, we introduce a modified paracondylar approach, named the suboccipital paracondylar-lateral cervical (SPCLC) approach for this purpose. We also share the follow-up data of our series and discuss the advantages and limitations of this modified paracondylar approach.

Methods

We included 64 patients with jugular foramen tumors who underwent surgery by the same senior neurosurgeon between November 2011 and August 2020. All patients were treated with the SPCLC approach, which aimed for gross total tumor removal in a single-stage operation. The clinical characteristics, including preoperative and postoperative neurological status, the extent of surgical resection, and follow-up data were retrospectively acquired and evaluated.

Results

There were 48 schwannomas, nine meningiomas, three paragangliomas, one hemangiopericytoma, one chordoma, one endolymphatic sac tumor, and one Langerhans’ cell histiocytosis. The median age of our patients was 43 years (range: 21–77 years). Dysphagia, hoarseness, and tongue deviation were observed in 36, 26, and 28 patients, respectively. Thirty-two patients had hearing function impairments, including hearing loss or tinnitus. Gross total resection was achieved in 59 patients (59/64, 92.2%). Gamma Knife treatment was used to manage residual tumors in five patients. Postoperatively, new-onset or aggravative dysphagia and hoarseness occurred in 26 and 18 cases, respectively. Nine patients developed new-onset facial palsy, and one patient developed new-onset hearing loss. There were no cases of intracranial hematoma, re-operation, tracheostomy, or death. At the latest follow-up, hearing loss and tinnitus had improved in 20 cases (20/32, 62.5%), dysphagia alleviated in 20 cases (20/36, 55.6%), and hoarseness improved in 14 cases (14/26, 53.8%). Over a mean follow-up period of 27.8 ± 19.5 months (range: 3–68 months), tumor recurrence was observed in one patient.

Conclusion

The SPCLC approach, modified from the paracondylar approach, and was less invasive, safe, and efficient for certain jugular foramen tumors. Taking advantage of the anatomic understanding, clear operational vision, and appropriate surgical skills, it is possible to achieve gross total tumor removal and the preservation of neurological function.
Homologous Recombination Deficiency Assays in Epithelial Ovarian Cancer: Current Status and Future Direction
Authors: Chiang Ying-Cheng , Lin Po-Han , Cheng Wen-Fang
Published: October 2021

Epithelial ovarian cancer (EOC) patients are generally diagnosed at an advanced stage, usually relapse after initial treatments, which include debulking surgery and adjuvant platinum-based chemotherapy, and eventually have poor 5-year survival of less than 50%. In recent years, promising survival benefits from maintenance therapy with poly(ADP-ribose) polymerase (PARP) inhibitor (PARPi) has changed the management of EOC in newly diagnosed and recurrent disease. Identification of BRCA mutations and/or homologous recombination deficiency (HRD) is critical for selecting patients for PARPi treatment. However, the currently available HRD assays are not perfect predictors of the clinical response to PARPis in EOC patients. In this review, we introduce the concept of synthetic lethality, the rationale of using PARPi when HRD is present in tumor cells, the clinical trials of PARPi incorporating the HRD assays for EOC, the current HRD assays, and other HRD assays in development.
Long-Term Clinical Outcomes of Gastric MALT Lymphoma: A Nationwide Multicenter Study in Korea
Authors: Kim Joon Sung , Park Jun Chul , Lee Jong Yeul , Ahn Ji Yong , Kang Sun Hyung , Yang Hyo-Joon , Kim Su Jin , Joo Moon Kyung , Park Jae Myung
Published: October 2021

Background

Treatment recommendations for gastric mucosa-associated lymphoid tissue (MALT) lymphoma are based on case series and expert opinions. Only a few previous studies have focused on the long-term outcomes of gastric MALT lymphoma, especially according to stage.

Methods

Patients diagnosed with gastric MALT lymphoma from January 2000 to December 2018 at nine university hospitals in Korea were included. Clinical data of medical history, endoscopic features, histological diagnosis, results of Helicobacter pylori (H. pylori) testing, stage, treatment conditions, and outcomes were collected.

Results

A total of 1,163 patients was enrolled, and 97.6% (n=1,038) of patients were diagnosed as stage IE. 10-year overall survival (OS) for the entire population was 99.1% and was better for patients in stage IE compared with patients in stage III/IV (p=0.002). The 10-year OS for H. pylori-positive patients was better than that of H. pylori-negative patients (p=0.022). Multivariate analyses revealed initial stage III/IV as a prognostic factor associated with over-all survival.

Conclusion

The majority of gastric MALT lymphoma patients are diagnosed at an early localized stage in Korea. The overall survival rate of gastric MALT lymphoma is excellent and is associated with the initial stage of the disease.
Crizotinib in Sarcomatous Malignancies Harboring ALK Fusion With a Definitive Partner(s): Response and Efficacy
Authors: Wu Jinchun , Hu Yongbin , Abdihamid Omar , Huang Gengwen , Xiao Sheng , Li Bin
Published: October 2021

Sarcoma or sarcomatoid malignancies are a set of mesenchymal-origin malignancies with vast heterogeneity in clinical and molecular characteristics. Anaplastic lymphoma kinase (ALK) is a tyrosine kinase oncoprotein expressed by several tumors, including sarcomas. Crizotinib is an effective ALK inhibitor. In this review paper, we summarized findings from the literature regarding the use of crizotinib for the treatment of sarcoma and sarcomatoid malignancies harboring ALK fusions with definitive partners (with the given gene(s) name) from the years 2010 to 2021.One hundred and four articles were retrieved and after exclusion, 28 studies containing 33 patients were finally selected. All 33 patients were treated with crizotinib. Among the 33 cases, 19 were adult patients, 11 were pediatric patients, and 3 cases did not have data on age and/or gender. Most cases had a primary abdominal lesion (16/30), followed by thoracic (10/30), trunk (3/30), retroperitoneal (1/30), and one case of right medial thigh (case 7). Stage IV disease was reported in 76.7% (23/30) of patients. The objective response rate and disease control rate was 86.7% (26/30) and 96.7% (29/30), respectively, which were assessed on average of 8 weeks after crizotinib initiation. Rapid improvement of symptoms was observed within one to two weeks in some cases including patients with extensive diseases or poor performance. There was no difference in crizotinib response between pediatrics and adult cases. Crizotinib is effective; however, surgery remains the mainstay of therapy, with newer evidence showing concurrent crizotinib with surgery conferring long-term overall survival. However, we should still be cognizant of the heterogeneous landscape of crizotinib efficacy and its associated fatal adverse events.
NGF Signaling Interacts With the Hippo/YAP Pathway to Regulate Cervical Cancer Progression
Authors: Wang Lijun , Li Jing , Wang Rongli , Chen He , Wang Ruiqi , Wang Wei , Yang Xinyuan
Published: October 2021

Nerve growth factor (NGF) is increasingly implicated in cervical cancer progression, but its mechanism in cervical cancer is unclear. Here, studies demonstrate that NGF inhibits the Hippo signaling pathway and activates Yes-associated protein (YAP) to induce cervical cancer cell proliferation and migration. Our results suggested that stimulation of NGF promoted cell growth and migration and activated YAP in HeLa and C-33A cell lines. The expression of YAP target genes (CTGF and ANKRD1) was upregulated after NGF treatment. The NGF inhibitor Ro 08-2750 and siRNA-mediated NGF receptor gene silencing suppressed HeLa and C-33A cells proliferation and migration, activated large suppressor kinase 1 (LATS1) kinase activity, and suppressed YAP function. In addition, the expression of YAP target genes (CTGF and ANKRD1) was suppressed by Ro 08-2750 treatment in HeLa and C-33A cells. Interestingly, proliferation was significantly higher in NGF-treated cells than in control cells, and this effect was completely reversed by the YAP small molecule inhibitor-verteporfin. Furthermore, the mouse xenograft model shows that NGF regulates YAP oncogenic activity in vivo. Mechanistically, NGF stimulation inactivates LATS1 and activates YAP, and NGF inhibition was found to induce large suppressor kinase 1 (LATS1) phosphorylation. Taken together, these data provide the first direct evidence of crosstalk between the NGF signaling and Hippo cancer pathways, an interaction that affects cervical cancer progression. Our study indicates that combined targeting of the NGF signaling and the Hippo pathway represents a novel therapeutic strategy for treatment of cervical cancer.
Predictive and Prognostic Biomarkers for Lung Cancer Bone Metastasis and Their Therapeutic Value
Authors: Chai Xupeng , Yinwang Eloy , Wang Zenan , Wang Zhan , Xue Yucheng , Li Binghao , Zhou Hao , Zhang Wenkan , Wang Shengdong , Zhang Yongxing , Li Hengyuan , Mou Haochen , Sun Lingling , Qu Hao , Wang Fangqian , Zhang Zengjie , Chen Tao , Ye Zhaoming
Published: October 2021

Lung cancer is the leading cause of cancer-related death worldwide. Bone metastasis, which usually accompanies severe skeletal-related events, is the most common site for tumor distant dissemination and detected in more than one-third of patients with advanced lung cancer. Biopsy and imaging play critical roles in the diagnosis of bone metastasis; however, these approaches are characterized by evident limitations. Recently, studies regarding potential biomarkers in the serum, urine, and tumor tissue, were performed to predict the bone metastases and prognosis in patients with lung cancer. In this review, we summarize the findings of recent clinical research studies on biomarkers detected in samples obtained from patients with lung cancer bone metastasis. These markers include the following: (1) bone resorption-associated markers, such as N-terminal telopeptide (NTx)/C-terminal telopeptide (CTx), C-terminal telopeptide of type I collagen (CTx-I), tartrate-resistant acid phosphatase isoform 5b (TRACP-5b), pyridinoline (PYD), and parathyroid hormone related peptide (PTHrP); (2) bone formation-associated markers, including total serum alkaline phosphatase (ALP)/bone specific alkaline phosphatase(BAP), osteopontin (OP), osteocalcin (OS), amino-terminal extension propeptide of type I procollagen/carboxy-terminal extension propeptide of type I procollagen (PICP/PINP); (3) signaling markers, including epidermal growth factor receptor/Kirsten rat sarcoma/anaplastic lymphoma kinase (EGFR/KRAS/ALK), receptor activator of nuclear factor κB ligand/receptor activator of nuclear factor κB/osteoprotegerin (RANKL/RANK/OPG), C-X-C motif chemokine ligand 12/C-X-C motif chemokine receptor 4 (CXCL12/CXCR4), complement component 5a receptor (C5AR); and (4) other potential markers, such as calcium sensing receptor (CASR), bone sialoprotein (BSP), bone morphogenetic protein 2 (BMP2), cytokeratin 19 fragment/carcinoembryonic antigen (CYFRA/CEA), tissue factor, cell-free DNA, long non-coding RNA, and microRNA. The prognostic value of these markers is also investigated. Furthermore, we listed some clinical trials targeting hotspot biomarkers in advanced lung cancer referring for their therapeutic effects.
Tumor Endothelial Marker 8 Promotes Proliferation and Metastasis via the Wnt/β-Catenin Signaling Pathway in Lung Adenocarcinoma
Authors: Ding Chen , Liu Jun , Zhang Jiali , Wan Yang , Hu Linhui , Charwudzi Alice , Zhan Heqin , Meng Ye , Zheng Huimin , Wang HuiPing , Wang Youliang , Gao Lihua , Hu Xianwen , Li Jingrong , Xiong Shudao
Published: October 2021

Tumor endothelial marker 8 (TEM8), also known as ANTXR1, was highly expressed in cancers, and was identified as a biomarker for early diagnosis and prognosis in some cancers. However, the clinical role and molecular mechanisms of TEM8 in lung adenocarcinoma (LUAD) are still unclear. The present study aimed to explore its clinical value and the molecular mechanisms of TEM8 underlying the progression of LUAD. Our study found the elevation of TEM8 in LUAD cell lines and tissues. What’s more, we observed that the TEM8 expression level was associated with tumor size, primary tumor, and AJCC stage, and LUAD patients with high TEM8 expression usually have a poor prognosis. Then, we conducted a series of experiments by the strategy of loss-of-function and gain-of-function, and our results suggested that the knockdown of TEM8 suppressed proliferation, migration, and invasion and induced apoptosis in LUAD whereas overexpression of TEM8 had the opposite effect. Molecular mechanistic investigation showed that TEM8 exerted its promoting effects mainly through activating the Wnt/β-catenin signaling pathway. In short, our findings suggested that TEM8 played a crucial role in the progression of LUAD by activating the Wnt/β-catenin signaling pathway and could serve as a potential therapeutic target for LUAD.
Single-Cell RNA Sequencing in Multiple Pathologic Types of Renal Cell Carcinoma Revealed Novel Potential Tumor-Specific Markers
Authors: Su Cheng , Lv Yufang , Lu Wenhao , Yu Zhenyuan , Ye Yu , Guo Bingqian , Liu Deyun , Yan Haibiao , Li Tianyu , Zhang Qingyun , Cheng Jiwen , Mo Zengnan
Published: October 2021

Background

Renal cell carcinoma (RCC) is the most common type of kidney cancer. Studying the pathogenesis of RCC is particularly important, because it could provide a direct guide for clinical treatment. Given that tumor heterogeneity is probably reflected at the mRNA level, the study of mRNA in RCC may reveal some potential tumor-specific markers, especially single-cell RNA sequencing (scRNA-seq).

Methods

We performed an exploratory study on three pathological types of RCC with a small sample size. This study presented clear-cell RCC (ccRCC), type 2 pRCC, and chRCC in a total of 30,263 high-quality single-cell transcriptome information from three pathological types of RCC. In addition, scRNA-seq was performed on normal kidneys. Tumor characteristics were well identified by the comparison between different pathological types of RCC and normal kidneys at the scRNA level.

Results

Some new tumor-specific markers for different pathologic types of RCC, such as SPOCK1, PTGIS, REG1A, CP and SPAG4 were identified and validated. We also discovered that NDUFA4L2 both highly expressed in tumor cells of ccRCC and type 2 pRCC. The presence of two different types of endothelial cells in ccRCC and type 2 pRCC was also identified and verified. An endothelial cell in ccRCC may be associated with fibroblasts and significantly expressed fibroblast markers, such as POSTN and COL3A1. At last, by applying scRNA-seq results, the activation of drug target pathways and sensitivity to drug responses was predicted in different pathological types of RCC.

Conclusions

Taken together, these findings considerably enriched the single-cell transcriptomic information for RCC, thereby providing new insights into the diagnosis and treatment of RCC.