bluuebunny/crossref_metadata_2025 huggingface dataset:
Notch Signaling in the Bone Marrow Lymphopoietic Niche
Authors: Sottoriva Kilian , Pajcini Kostandin V.
Published: July 2021

Lifelong mammalian hematopoiesis requires continuous generation of mature blood cells that originate from Hematopoietic Stem and Progenitor Cells (HSPCs) situated in the post-natal Bone Marrow (BM). The BM microenvironment is inherently complex and extensive studies have been devoted to identifying the niche that maintains HSPC homeostasis and supports hematopoietic potential. The Notch signaling pathway is required for the emergence of the definitive Hematopoietic Stem Cell (HSC) during embryonic development, but its role in BM HSC homeostasis is convoluted. Recent work has begun to explore novel roles for the Notch signaling pathway in downstream progenitor populations. In this review, we will focus an important role for Notch signaling in the establishment of a T cell primed sub-population of Common Lymphoid Progenitors (CLPs). Given that its activation mechanism relies primarily on cell-to-cell contact, Notch signaling is an ideal means to investigate and define a novel BM lymphopoietic niche. We will discuss how new genetic model systems indicate a pre-thymic, BM-specific role for Notch activation in early T cell development and what this means to the paradigm of lymphoid lineage commitment. Lastly, we will examine how leukemic T-cell acute lymphoblastic leukemia (T-ALL) blasts take advantage of Notch and downstream lymphoid signals in the pathological BM niche.
Movements, Habitat Use, and Diving Behavior of Shortfin Mako in the Atlantic Ocean
Authors: Santos Catarina C. , Domingo Andrés , Carlson John , Natanson Lisa J. , Travassos Paulo , Macías David , Cortés Enric , Miller Philip , Hazin Fábio , Mas Federico , Ortiz de Urbina Josetxu , Lino Pedro G. , Coelho Rui
Published: July 2021

The shortfin mako is one of the most important shark species caught in Atlantic Ocean pelagic fisheries. Given increasing concerns for the stock status of the species, the present study was designed to fill gaps in the knowledge of habitat use and movement patterns of shortfin mako in the Atlantic Ocean. From 2015 to 2019, 53 shortfin makos were tagged with pop-up satellite archival tags within the North, Central, and Southwest Atlantic Ocean, with successful transmissions received from 34 tags. Generally, sharks tagged in the Northwest and Central Atlantic moved away from tagging sites showing low to no apparent residency patterns, whereas sharks tagged in the Northeast and Southwest Atlantic spent large periods of time near the Canary Archipelago and Northwest Africa, and over shelf and oceanic waters off southern Brazil and Uruguay, respectively. These areas showed evidence of site fidelity and were identified as possible key areas for shortfin mako. Sharks spent most of their time in temperate waters (18–22°C) above 90 m; however, data indicated the depth range extended from the surface down to 979 m, in water temperatures ranging between 7.4 and 29.9°C. Vertical behavior of sharks seemed to be influenced by oceanographic features, and ranged from marked diel vertical movements, characterized by shallower mean depths during the night, to yo-yo diving behavior with no clear diel pattern observed. These results may aid in the development of more informed and efficient management measures for this species.
Toward Universal Photodynamic Coatings for Infection Control
Authors: Ghareeb C. Roland , Peddinti Bharadwaja S. T. , Kisthardt Samantha C. , Scholle Frank , Spontak Richard J. , Ghiladi Reza A.
Published: July 2021

The dual threats posed by the COVID-19 pandemic and hospital-acquired infections (HAIs) have emphasized the urgent need for self-disinfecting materials for infection control. Despite their highly potent antimicrobial activity, the adoption of photoactive materials to reduce infection transmission in hospitals and related healthcare facilities has been severely hampered by the lack of scalable and cost-effective manufacturing, in which case high-volume production methods for fabricating aPDI-based materials are needed. To address this issue here, we examined the antimicrobial efficacy of a simple bicomponent spray coating composed of the commercially-available UV-photocrosslinkable polymer N-methyl-4(4'-formyl-styryl)pyridinium methosulfate acetal poly(vinyl alcohol) (SbQ-PVA) and one of three aPDI photosensitizers (PSs): zinc-tetra(4-N-methylpyridyl)porphine (ZnTMPyP4+), methylene blue (MB), and Rose Bengal (RB). We applied these photodynamic coatings, collectively termed SbQ-PVA/PS, to a variety of commercially available materials. Scanning electron microscopy (SEM) and time-of-flight secondary ion mass spectrometry (ToF-SIMS) confirmed the successful application of the coatings, while inductively coupled plasma-optical emission spectroscopy (ICP-OES) revealed a photosensitizer loading of 0.09-0.78 nmol PS/mg material. The antimicrobial efficacy of the coated materials was evaluated against methicillin-susceptible Staphylococcus aureus ATCC-29213 and human coronavirus strain HCoV-229E. Upon illumination with visible light (60 min, 400-700 nm, 65 ± 5 mW/cm2), the coated materials inactivated S. aureus by 97-99.999% and HCoV-229E by 92-99.999%, depending on the material and PS employed. Photobleaching studies employing HCoV-229E demonstrated detection limit inactivation (99.999%) even after exposure for 4 weeks to indoor ambient room lighting. Taken together, these results demonstrate the potential for photodynamic SbQ-PVA/PS coatings to be universally applied to a wide range of materials for effectively reducing pathogen transmission.
Hyperbaric Oxygen Therapy for Venous Leg Ulcers: A 6 Year Retrospective Study of Results of a Single Center
Authors: Lalieu Rutger C. , Akkerman Ida , van Hulst Rob A.
Published: July 2021

Background: Venous leg ulcers (VLUs) are common and have a large impact on healthcare budgets worldwide. Hyperbaric oxygen therapy (HBOT) may improve healing of these ulcers.

Methods: Retrospective, single-center cohort study between 2013 and 2019. All patients with a VLU from an outpatient clinic providing HBOT and wound care were included. The primary outcome measure was wound healing, determined at discharge from the center. Other outcome measures were improvement in patient related outcome measures (PROMs), as assessed by the EQ-5D-3L questionnaire and including quality of life (QoL) and pain score.

Results: Fifty patients were included, 53% female, with a mean age of 73.4 (±12.2). Most wounds (83%) had existed longer than 3 months before starting treatment. Patients received an average of 43 (±20) sessions of HBOT. After treatment, 37 patients (63%) achieved complete or near-complete wound healing. Wound size decreased from a median of 14 cm2 [interquartile range (IQR) 32 cm2] to 0.5 cm2 (IQR 5.3 cm2), a median decrease of 7.5 (IQR 16.2 cm2) in cm2 (94%). Patients mostly reported improvement for all health aspects on the questionnaire. Pain score decreased from 5.7 (±2.5) to 2.1 (±2.2) (p < 0.0001) and health score increased from 57.2 (±15.6) to 69.9 (±18.9) (p = 0.02).

Conclusions: Patients with non-healing VLUs may benefit from HBOT to achieve complete or substantial wound healing. We recommend a well-designed randomized clinical trial with a number of patients allowing enough statistical power, and of a reasonable duration, to establish the potential of additional HBOT on hard-to-heal venous ulcers.
Horizontal Transmission of the Symbiont Microsporidia MB in Anopheles arabiensis
Authors: Nattoh Godfrey , Maina Tracy , Makhulu Edward E. , Mbaisi Lilian , Mararo Enock , Otieno Fidel G. , Bukhari Tullu , Onchuru Thomas O. , Teal Evan , Paredes Juan , Bargul Joel L. , Mburu David M. , Onyango Everline A. , Magoma Gabriel , Sinkins Steven P. , Herren Jeremy K.
Published: July 2021

The recently discovered Anopheles symbiont, Microsporidia MB, has a strong malaria transmission-blocking phenotype in Anopheles arabiensis, the predominant Anopheles gambiae species complex member in many active transmission areas in eastern Africa. The ability of Microsporidia MB to block Plasmodium transmission together with vertical transmission and avirulence makes it a candidate for the development of a symbiont-based malaria transmission blocking strategy. We investigate the characteristics and efficiencies of Microsporidia MB transmission between An. arabiensis mosquitoes. We show that Microsporidia MB is not transmitted between larvae but is effectively transmitted horizontally between adult mosquitoes. Notably, Microsporidia MB was only found to be transmitted between male and female An. arabiensis, suggesting sexual horizontal transmission. In addition, Microsporidia MB cells were observed infecting the An. arabiensis ejaculatory duct. Female An. arabiensis that acquire Microsporidia MB horizontally are able to transmit the symbiont vertically to their offspring. We also investigate the possibility that Microsporidia MB can infect alternate hosts that live in the same habitats as their An. arabiensis hosts, but find no other non-anopheline hosts. Notably, Microsporidia MB infections were found in another primary malaria African vector, Anopheles funestus s.s. The finding that Microsporidia MB can be transmitted horizontally is relevant for the development of dissemination strategies to control malaria that are based on the targeted release of Microsporidia MB infected Anopheles mosquitoes.
Production of PHB From CO2-Derived Acetate With Minimal Processing Assessed for Space Biomanufacturing
Authors: Cestellos-Blanco Stefano , Friedline Skyler , Sander Kyle B. , Abel Anthony J. , Kim Ji Min , Clark Douglas S. , Arkin Adam P. , Yang Peidong
Published: July 2021

Providing life-support materials to crewed space exploration missions is pivotal for mission success. However, as missions become more distant and extensive, obtaining these materials from in situ resource utilization is paramount. The combination of microorganisms with electrochemical technologies offers a platform for the production of critical chemicals and materials from CO2 and H2O, two compounds accessible on a target destination like Mars. One such potential commodity is poly(3-hydroxybutyrate) (PHB), a common biopolyester targeted for additive manufacturing of durable goods. Here, we present an integrated two-module process for the production of PHB from CO2. An autotrophic Sporomusa ovata (S. ovata) process converts CO2 to acetate which is then directly used as the primary carbon source for aerobic PHB production by Cupriavidus basilensis (C. basilensis). The S. ovata uses H2 as a reducing equivalent to be generated through electrocatalytic solar-driven H2O reduction. Conserving and recycling media components is critical, therefore we have designed and optimized our process to require no purification or filtering of the cell culture media between microbial production steps which could result in up to 98% weight savings. By inspecting cell population dynamics during culturing we determined that C. basilensis suitably proliferates in the presence of inactive S. ovata. During the bioprocess 10.4 mmol acetate L –1 day–1 were generated from CO2 by S. ovata in the optimized media. Subsequently, 12.54 mg PHB L–1 hour–1 were produced by C. basilensis in the unprocessed media with an overall carbon yield of 11.06% from acetate. In order to illustrate a pathway to increase overall productivity and enable scaling of our bench-top process, we developed a model indicating key process parameters to optimize.
Differences in Gut Microbiome Composition Between Sympatric Wild and Allopatric Laboratory Populations of Omnivorous Cockroaches
Authors: Tinker Kara A. , Ottesen Elizabeth A.
Published: July 2021

Gut microbiome composition is determined by a complex interplay of host genetics, founder’s effects, and host environment. We are using omnivorous cockroaches as a model to disentangle the relative contribution of these factors. Cockroaches are a useful model for host–gut microbiome interactions due to their rich hindgut microbial community, omnivorous diet, and gregarious lifestyle. In this study, we used 16S rRNA sequencing to compare the gut microbial community of allopatric laboratory populations of Periplaneta americana as well as sympatric, wild-caught populations of P. americana and Periplaneta fuliginosa, before and after a 14 day period of acclimatization to a common laboratory environment. Our results showed that the gut microbiome of cockroaches differed by both species and rearing environment. The gut microbiome from the sympatric population of wild-captured cockroaches showed strong separation based on host species. Laboratory-reared and wild-captured cockroaches from the same species also exhibited distinct gut microbiome profiles. Each group of cockroaches had a unique signature of differentially abundant uncharacterized taxa still present after laboratory cultivation. Transition to the laboratory environment resulted in decreased microbiome diversity for both species of wild-caught insects. Interestingly, although laboratory cultivation resulted in similar losses of microbial diversity for both species, it did not cause the gut microbiome of those species to become substantially more similar. These results demonstrate how competing factors impact the gut microbiome and highlight the need for a greater understanding of host–microbiome interactions.
Phase Variation During Host Colonization and Invasion by Campylobacter jejuni and Other Campylobacter Species
Authors: Cayrou Caroline , Barratt Natalie A. , Ketley Julian M. , Bayliss Christopher D.
Published: July 2021

Phase variation (PV) is a phenomenon common to a variety of bacterial species for niche adaption and survival in challenging environments. Among Campylobacter species, PV depends on the presence of intergenic and intragenic hypermutable G/C homopolymeric tracts. The presence of phase-variable genes is of especial interest for species that cause foodborne or zoonotic infections in humans. PV influences the formation and the structure of the lipooligosaccharide, flagella, and capsule in Campylobacter species. PV of components of these molecules is potentially important during invasion of host tissues, spread within hosts and transmission between hosts. Motility is a critical phenotype that is potentially modulated by PV. Variation in the status of the phase-variable genes has been observed to occur during colonization in chickens and mouse infection models. Interestingly, PV is also involved in bacterial survival of attack by bacteriophages even during chicken colonization. This review aims to explore and discuss observations of PV during model and natural infections by Campylobacter species and how PV may affect strategies for fighting infections by this foodborne pathogen.
Supervised Learning With Perceptual Similarity for Multimodal Gene Expression Registration of a Mouse Brain Atlas
Authors: Krepl Jan , Casalegno Francesco , Delattre Emilie , Erö Csaba , Lu Huanxiang , Keller Daniel , Rodarie Dimitri , Markram Henry , Schürmann Felix
Published: July 2021

The acquisition of high quality maps of gene expression in the rodent brain is of fundamental importance to the neuroscience community. The generation of such datasets relies on registering individual gene expression images to a reference volume, a task encumbered by the diversity of staining techniques employed, and by deformations and artifacts in the soft tissue. Recently, deep learning models have garnered particular interest as a viable alternative to traditional intensity-based algorithms for image registration. In this work, we propose a supervised learning model for general multimodal 2D registration tasks, trained with a perceptual similarity loss on a dataset labeled by a human expert and augmented by synthetic local deformations. We demonstrate the results of our approach on the Allen Mouse Brain Atlas (AMBA), comprising whole brain Nissl and gene expression stains. We show that our framework and design of the loss function result in accurate and smooth predictions. Our model is able to generalize to unseen gene expressions and coronal sections, outperforming traditional intensity-based approaches in aligning complex brain structures.
The Neural Processing of Vocal Emotion After Hearing Reconstruction in Prelingual Deaf Children: A Functional Near-Infrared Spectroscopy Brain Imaging Study
Authors: Wang Yuyang , Liu Lili , Zhang Ying , Wei Chaogang , Xin Tianyu , He Qiang , Hou Xinlin , Liu Yuhe
Published: July 2021

As elucidated by prior research, children with hearing loss have impaired vocal emotion recognition compared with their normal-hearing peers. Cochlear implants (CIs) have achieved significant success in facilitating hearing and speech abilities for people with severe-to-profound sensorineural hearing loss. However, due to the current limitations in neuroimaging tools, existing research has been unable to detail the neural processing for perception and the recognition of vocal emotions during early stage CI use in infant and toddler CI users (ITCI). In the present study, functional near-infrared spectroscopy (fNIRS) imaging was employed during preoperative and postoperative tests to describe the early neural processing of perception in prelingual deaf ITCIs and their recognition of four vocal emotions (fear, anger, happiness, and neutral). The results revealed that the cortical response elicited by vocal emotional stimulation on the left pre-motor and supplementary motor area (pre-SMA), right middle temporal gyrus (MTG), and right superior temporal gyrus (STG) were significantly different between preoperative and postoperative tests. These findings indicate differences between the preoperative and postoperative neural processing associated with vocal emotional stimulation. Further results revealed that the recognition of vocal emotional stimuli appeared in the right supramarginal gyrus (SMG) after CI implantation, and the response elicited by fear was significantly greater than the response elicited by anger, indicating a negative bias. These findings indicate that the development of emotional bias and the development of emotional perception and recognition capabilities in ITCIs occur on a different timeline and involve different neural processing from those in normal-hearing peers. To assess the speech perception and production abilities, the Infant-Toddler Meaningful Auditory Integration Scale (IT-MAIS) and Speech Intelligibility Rating (SIR) were used. The results revealed no significant differences between preoperative and postoperative tests. Finally, the correlates of the neurobehavioral results were investigated, and the results demonstrated that the preoperative response of the right SMG to anger stimuli was significantly and positively correlated with the evaluation of postoperative behavioral outcomes. And the postoperative response of the right SMG to anger stimuli was significantly and negatively correlated with the evaluation of postoperative behavioral outcomes.
Deletion of ErbB4 Disrupts Synaptic Transmission and Long-Term Potentiation of Thalamic Input to Amygdalar Medial Paracapsular Intercalated Cells
Authors: Asede Douglas , Okoh James , Ali Sabah , Doddapaneni Divyesh , Bolton M. McLean
Published: July 2021

Identification of candidate risk genes and alteration in the expression of proteins involved in regulating inhibitory neuron function in various psychiatric disorders, support the notion that GABAergic neuron dysfunction plays an important role in disease etiology. Genetic variations in neuregulin and its receptor kinase ErbB4, expressed exclusively by GABAergic neurons in the CNS, have been linked with schizophrenia. In the amygdala, ErbB4 is highly expressed in GABAergic intercalated cell clusters (ITCs), which play a critical role in amygdala-dependent behaviors. It is however unknown whether ErbB4 deletion from ITCs affects their synaptic properties and function in amygdala circuitry. Here, we examined the impact of ErbB4 deletion on inhibitory and excitatory circuits recruiting medial paracapsular ITCs (mpITCs) using electrophysiological techniques. Ablation of ErbB4 in mpITCs suppressed NMDA receptor-mediated synaptic transmission at thalamo-mpITC synapses and enhanced thalamic driven GABAergic transmission onto mpITCs. Furthermore, long-term potentiation (LTP) at thalamo-mpITC synapses was compromised in ErbB4 mutant mice, indicating that ErbB4 activity is critical for LTP at these synapses. Together, our findings suggest that ErbB4 deletion from mpITCs disrupts excitation-inhibition balance and learning mechanisms in amygdala circuits.
A Systematic Review and Meta-Analysis of the Potential of Millets for Managing and Reducing the Risk of Developing Diabetes Mellitus
Authors: Anitha Seetha , Kane-Potaka Joanna , Tsusaka Takuji W. , Botha Rosemary , Rajendran Ananthan , Givens D. Ian , Parasannanavar Devraj J. , Subramaniam Kowsalya , Prasad Kanaka Durga Veera , Vetriventhan Mani , Bhandari Raj Kumar
Published: July 2021

Millets (including sorghum) are known to be highly nutritious besides having a low carbon footprint and the ability to survive in high temperatures with minimal water. Millets are widely recognised as having a low Glycaemic Index (GI) helping to manage diabetes. This systematic review and meta-analyzes across the different types of millets and different forms of processing/cooking collated all evidences. Of the 65 studies that were collected globally, 39 studies with 111 observations were used to analyze GI outcomes and 56 studies were used to analyze fasting, post-prandial glucose level, insulin index and HbA1c outcomes in a meta-analysis. It is evident from the descriptive statistics that the mean GI of millets is 52.7 ± 10.3, which is about 36% lower than in typical staples of milled rice (71.7 ± 14.4) and refined wheat (74.2 ± 14.9). The descriptive, meta and regression analyses revealed that Job's tears, fonio, foxtail, barnyard, and teff were the millets with low mean GI (<55) that are more effective (35–79%) in reducing dietary GI than the control samples. Millets with intermediate GI (55–69) are pearl millet, finger millet, kodo millet, little millet, and sorghum which have a 13–35% lower GI than the control with high GI (>69). A meta-analysis also showed that all millets had significantly (p < 0.01) lower GI than white rice, refined wheat, standard glucose or white wheat bread except little millet which had inconsistent data. Long term millet consumption lowered fasting and post-prandial blood glucose levels significantly (p < 0.01) by 12 and 15%, respectively, in diabetic subjects. There was a significant reduction in HbA1c level (from 6.65 ± 0.4 to 5.67 ± 0.4%) among pre-diabetic individuals (p < 0.01) who consumed millets for a long period. Minimally processed millets were 30% more effective in lowering GI of a meal compared to milled rice and refined wheat. In conclusion, millets can be beneficial in managing and reducing the risk of developing diabetes and could therefore be used to design appropriate meals for diabetic and pre-diabetic subjects as well as for non-diabetic people for a preventive approach.
Perennial Ryegrass Contains Gluten-Like Proteins That Could Contaminate Cereal Crops
Authors: Escobar-Correas Sophia , Broadbent James A. , Andraszek Alicja , Stockwell Sally , Howitt Crispin A. , Juhász Angéla , Colgrave Michelle L.
Published: July 2021

Background: To ensure safe consumption of gluten-free products, there is a need to understand all sources of unintentional contamination with gluten in the food chain. In this study, ryegrass (Lolium perenne), a common weed infesting cereal crop, is analysed as a potential source of gluten-like peptide contamination.

Materials and Methods: Ten ryegrass cultivars were analysed using shotgun proteomics for the presence of proteins from the prolamin superfamily. A relative quantitative assay was developed to detect ryegrass gluten-like peptides in comparison with those found in 10 common wheat cultivars.

Results: A total of 19 protein accessions were found across 10 cultivars of ryegrass for the protein families of PF00234-Tryp_alpha_amyl, PF13016-Gliadin, and PF03157-Glutenin_HMW. Protein and peptide homology searches revealed that gliadin-like peptides were similar to avenin and gamma-gliadin peptides. A total of 20 peptides, characteristic of prolamin superfamily proteins, were selected for liquid chromatography mass spectrometry (LC-MS) with multiple reaction monitoring (MRM). Only two of the monitored peptides were detected with high abundance in wheat, and all others were detected in ryegrass. Glutenin and alpha-amylase/trypsin inhibitor peptides were reported for the first time in ryegrass and were noted to be conserved across the Poaceae family.

Conclusion: A suite of gluten-like peptides were identified using proteomics that showed consistent abundance across ryegrass cultivars but were not detected in wheat cultivars. These peptides will be useful for differentiating wheat gluten contamination from ryegrass gluten contamination.
Suppression of Tumorigenicity 5 Ameliorates Tumor Characteristics of Invasive Breast Cancer Cells via ERK/JNK Pathway
Authors: Cheng Jianghong , Li Mingli , Tzeng Chi-Meng , Gou Xingchun , Chen Shuai
Published: July 2021

Background

Suppression of tumorigenicity 5 (ST5) has been considered as a tumor suppressor gene in HeLa tumor cells. However, its role in the progression of breast cancer remains vague.

Methods

Online database analysis was determined by Oncomine and Breast Cancer Gene-Expression Miner v4.4 (bc-GenExMiner v4.4). Tumor biology behaviors were measured by MTT assay, wound healing model, Transwell and Flow cytometry assays. Methylation-specific PCR (MSP) was employed to detect promoter methylation.

Results

Low level of ST5 was observed in breast cancer specimens, particularly in recurrent, invasive breast cancer cases compared to para-carcinoma tissue or non-invasive breast cancer. The downregulation of ST5 was also proved in MDA-MB-231 and SKBR3 cell lines with a high invasive capability as compared to MCF-7 cell with a low invasive capability. ST5 was negatively associated with pathological stages of breast cancer. ST5-downregulation promoted, while ST5-upregulation inhibited the progression of cell proliferation, cell cycle and migration of MDA-MB-231 cells. Additionally, ST5 knockdown inhibited, whereas ST5 overexpression promoted apoptosis of MDA-MB-231 cells. However, ST5 modification, either upregulation or downregulation, had no significant impact on tumor behaviors of MCF-7 cells. Mechanistically, ST5 protein ablation activated, while ST5-upregulation repressed the activities of phosphorylated ERK1/2 and JNK, and subsequently the expression of c-Myc. PD98059-mediated ERK1/2 inhibition abolished the stimulatory effects of ST5-depletion on ERK1/2/JNK/c-Myc signaling axis, and ST5 depletion-mediated cell over-proliferation and migration. Of note, ST5 reduction in invasive breast cancer cells should implicate in the hypermethylation of ST5 promoter region.

Conclusion

Our findings suggest that ST5 potentially acts as a tumor suppressor gene in invasive breast cancer through regulating ERK/JNK signaling pathway and provide a novel insight for breast cancer treatment.
A Novel Mechanism of the c-Myc/NEAT1 Axis Mediating Colorectal Cancer Cell Response to Photodynamic Therapy Treatment
Authors: Liu Kuijie , Lei Sanlin , Kuang Yong , Jin Qianqian , Long Dongju , Liu Chao , Jiang Yuhong , Zhao Hua , Yao Hongliang
Published: July 2021

Photodynamic therapy (PDT) is considered a potential treatment regimen for colorectal cancer cases (CRC). p53 signaling and the miR-124/iASPP axis play an essential role in the PDT resistance of CRC cells. PDT treatment downregulated NEAT1 expression in p53wt HCT116 and RKO cells. In these two cell lines, NEAT1 silencing enhanced the suppressive effects of PDT on cell viability and apoptosis. Within the subcutaneously implanted tumor model, NEAT1 silencing enhanced PDT-induced suppression on tumor growth. Regarding p53-deleted HCT116 cells, PDT only moderately affected cell proliferation but induced downregulation of NEAT1. NEAT1 directly targeted miR-124, acting as a ceRNA, competing with iASPP for miR-124 binding, and counteracting miR-124–mediated repression on iASPP under PDT treatment. NEAT1 silencing was enhanced, whereas miR-124 inhibition attenuated PDT effects on CRC cells; miR-124 inhibition significantly reversed the roles of NEAT1 silencing in PDT-treated CRC cells. miR-124 negatively correlated with NEAT1 and iASPP, respectively, whereas NEAT1 and iASPP positively correlated with each other. PDT downregulated c-Myc in CRC cells, and c-Myc activated the transcription of NEAT1 through the targeting of its promoter region. Within p53mut SW480 cells, PDT failed to alter cell viability and apoptosis but still downregulated c-Myc, NEAT1, and iASPP and upregulated miR-124. In p53 mutant high-abundant CRC tissues, c-Myc and NEAT1 were up-regulated, and miR-124 was downregulated. In c-Myc high-abundant CRC tissues, NEAT1 and iASPP were up-regulated, and miR-124 was downregulated. The critical role of the c-Myc/NEAT1 axis in mediating CRC response to PDT treatment via the miR-124/iASPP/p53 feedback loop was conclusively demonstrated.
Gankyrin as Potential Biomarker for Colorectal Cancer With Occult Liver Metastases
Authors: Wang Chengxing , Li Xiaoping , Ren Liangliang , Ma Changyi , Wu Meimei , Liang Weijun , Zhao Jinglin , Li Shangren , Tan Qunying , Liao Yuehua , Sun Lixia , Zhang Xin , He Yaoming
Published: July 2021

The majority of occult liver metastases cannot be detected by computed tomography (CT), magnetic resonance imaging (MRI) or other traditionally morphological imaging approaches since the lesions are too small or they have not yet formed cancer nodules. Gankyrin is a small molecular protein composed of seven ankyrin domains. In this study, the expression of Gankyrin in colorectal cancer (CRC) patients with liver metastases was investigated to determine its prognosis value. Gankyrin expression in CRC patients was initially analyzed using data from The Cancer Genome Atlas (TCGA) database and bioinformatics tools. RT-qPCR, western blotting, immunohistochemistry (IHC) and transwell migration and invasion assays were then performed to verify the expression and function of Gankyrin in CRC cell line, CRC tissues and matched non-tumor tissues of clinical patients. General clinicopathological information including TNM stage as well as preoperative and postoperative imaging results were collected. The main outcome indicator was overall survival (OS), referring to the length of time from surgery to either death or the last visit. Statistical analyses included chi-squared tests, Cox analyses, progression free survival (PFS) rates and OS rates. Elevated Gankyrin expression was confirmed in CRC patients. The upregulated Gankyrin expression was positively correlated with the progression of disease and liver metastasis in CRC patients. OS analysis revealed that prognosis was worse in CRC patients with high Gankyrin expression compared to those with low expression. CRC patients with higher Gankyrin expression also had a higher risk of occult liver metastases and a lower PFS rate. Therefore, Gankyrin can be used as a potential biomarker for early diagnosis of CRC with occult liver metastasis.
The Survival Effect of Radiotherapy on Stage II/III Rectal Cancer in Different Age Groups: Formulating Radiotherapy Decision-Making Based on Age
Authors: Li Yuqiang , Liu Heli , Zhou Yuan , Zhou Zhongyi , Liu Wenxue , Zhao Lilan , Güngör Cenap , Wang Dan , Pei Qian , Pei Haiping , Tan Fengbo
Published: July 2021

Introduction

Total mesorectal excision (TME), chemotherapy (CT), and radiotherapy (RT) are usually integrated into the comprehensive treatment of stage II/III rectal cancer (RC). Neoadjuvant radiotherapy (nRT) has become the standard treatment for stage II/III RC patients to help reduce the size of a tumor or kill cancer cells that have spread. Adjuvant RT is delivered after the resection to destroy remaining cancer cells and used mainly in stage II/III RC patients who have not received preoperative radiotherapy, such as those who suffered from a bowel obstruction before surgery. It is controversial whether radiotherapy can improve the survival of stage II/III RC patients. An increasing number of studies have reported that rectal cancer exhibited mismatched biology, epidemiology, and therapeutic response to current treatment strategy in different age groups. It is necessary to investigate whether radiotherapy exhibits disparate effects in different age groups of patients with stage II/III RC.

Methods

Data from the Surveillance, Epidemiology, and End Results (SEER) Program was extracted to identify stage II/III RC diagnosed in the periods of 2004–2016. The statistical methods included Pearson’s chi-square test, log-rank test, Cox regression model, and propensity score matching.

Results

Neoadjuvant radiotherapy (nRT) cannot improve the prognosis, and postoperative RT may even reduce the survival time for early onset stage II/III RC. Postoperative RT was not able to improve the overall survival (OS), while nRT may provide limited survival improvement for middle-aged stage II/III RC patients. In addition, radiotherapy can significantly improve the prognosis for elderly stage II/III RC.

Conclusions

This study indicated the inconsistent survival effect of radiotherapy on stage II/III rectal cancer patients in different age groups. Hence, we formulated a novel flow chart of radiotherapy decision-making based on age in stage II/III RC patients.
Association of Preoperative Coagulability With Incidence and Extent of Portal Vein Tumor Thrombus and Survival Outcomes in Hepatocellular Carcinoma After Hepatectomy: A Large-Scale, Multicenter Study
Authors: Zhang Xiu-Ping , Zhou Teng-Fei , Feng Jin-Kai , Sun Zi-Yang , Zhen Zuo-Jun , Zhou Dong , Zhang Fan , Hu Yi-Ren , Zhong Cheng-Qian , Chen Zhen-Hua , Chai Zong-Tao , Wang Kang , Shi Jie , Guo Wei-Xing , Wu Meng-Chao , Lau Wan Yee , Cheng Shu-Qun
Published: July 2021

Background

Occurrence of portal vein tumor thrombus (PVTT) worsens the outcomes of hepatocellular carcinoma (HCC) and imparts high economic burden on society. Patients with high risks of having hypercoagulation are more likely to experience thrombosis. Herein, we examined how preoperative international normalized ratio (INR) was related to the incidence and extent of PVTT, and associated with survival outcomes in HCC patients following R0 liver resection (LR).

Methods

Patients with HCC and PVTT were enrolled from six major hospitals in China. The overall survival (OS) and recurrence-free survival (RFS) rates of individuals with different INR levels were assessed with Cox regression analysis as well as Kaplan-Meier method.

Results

This study included 2207 HCC patients, among whom 1005 patients had concurrent PVTT. HCC patients in the Low INR group had a significantly higher incidence of PVTT and more extensive PVTT than the Normal and High INR groups (P<0.005). Of the 592 HCC subjects who had types I/II PVTT following R0 LR, there were 106 (17.9%), 342 (57.8%) and 144 (24.3%) patients in the High, Normal and Low INR groups, respectively. RFS and OS rates were markedly worse in patients in the Low INR group relative to those in the Normal and High INR groups (median RFS, 4.87 versus 10.77 versus 11.40 months, P<0.001; median OS, 6.30 versus 11.83 versus 12.67 months, P<0.001).

Conclusion

Preoperative INR influenced the incidence and extent of PVTT in HCC. Particularly, patients with HCC and PVTT in the Low INR group had worse postoperative prognosis relative to the High and Normal INR groups.
Comprehensive Analysis of the Expression and Prognosis Value of Chromobox Family Members in Clear Cell Renal Cell Carcinoma
Authors: Zhu Yuanyuan , Pu Zhangya , Li Zhenfen , Lin Ying , Li Ning , Peng Fang
Published: July 2021

Clear cell renal cell carcinoma (ccRCC) accounts for 80% of all renal cancers and has a poor prognosis. Chromobox (CBX) family protein expression has been reported in a variety of human malignancies, but the roles of CBXs in ccRCC remain unclear. In this study, by using ONCOMINE, UALCAN, GEPIA, Kaplan-Meier Plotter, cBioPortal, and TIMER, we found the transcriptional levels of CBX3 and CBX4 in ccRCC tissues were significantly higher than those in normal kidney tissues, whereas the transcriptional levels of CBX1, CBX5, CBX6, and CBX7 were significantly reduced in ccRCC tissues. The promoters of CBX2, CBX3, CBX4, CBX5, CBX6, CBX7, and CBX8 were hypermethylated, whereas the CBX1 promoter was hypomethylated in ccRCC. The expression of CBX1, CBX3, CBX4, CBX5, CBX6, and CBX7 was significantly associated with clinicopathological parameters in ccRCC patients. ccRCC patients with high expression levels of CBX3, CBX4, and CBX8 and low expression levels of CBX1, CBX5, CBX6, and CBX7 showed a strong association with poor overall survival. Genetic alterations in CBXs were correlated with poor overall survival and disease-free survival in patients with ccRCC. Moreover, we found significant associations between the expression of CBXs and infiltration of immune cells (B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells). Our results provide novel insights into the development of CBX-based biomarkers and therapeutic targets for ccRCC.
Incorporating PSMA-Targeting Theranostics Into Personalized Prostate Cancer Treatment: a Multidisciplinary Perspective
Authors: Ng Thomas S. C. , Gao Xin , Salari Keyan , Zlatev Dimitar V. , Heidari Pedram , Kamran Sophia C.
Published: July 2021

Recent developments in prostate-specific membrane antigen (PSMA) targeted diagnostic imaging and therapeutics (theranostics) promise to advance the management of primary, biochemically recurrent, and metastatic prostate cancer. In order to maximize the clinical impact of PSMA-targeted theranostics, a coordinated approach between the clinical stakeholders involved in prostate cancer management is required. Here, we present a vision for multidisciplinary use of PSMA theranostics from the viewpoints of nuclear radiology, medical oncology, urology, and radiation oncology. We review the currently available and forthcoming PSMA-based imaging and therapeutics and examine current and potential impacts on prostate cancer management from early localized disease to advanced treatment-refractory disease. Finally, we highlight the clinical and research opportunities related to PSMA-targeted theranostics and describe the importance of multidisciplinary collaboration in this space.
Cervicovaginal Microbiome Factors in Clearance of Human Papillomavirus Infection
Authors: Dai Wenkui , Du Hui , Li Shuaicheng , Wu Ruifang
Published: July 2021

Persistent high-risk human papillomavirus (hrHPV) infection is the highest risk to cervical cancer which is the fourth most common cancer in women worldwide. A growing body of literatures demonstrate the role of cervicovaginal microbiome (CVM) in hrHPV susceptibility and clearance, suggesting the promise of CVM-targeted interventions in protecting against or eliminating HPV infection. Nevertheless, the CVM-HPV-host interactions are largely unknown. In this review, we summarize imbalanced CVM in HPV-positive women, with or without cervical diseases, and the progress of exploring CVM resources in HPV clearance. In addition, microbe- and host-microbe interactions in HPV infection and elimination are reviewed to understand the role of CVM in remission of HPV infection. Lastly, the feasibility of CVM-modulated and -derived products in promoting HPV clearance is discussed. Information in this article will provide valuable reference for researchers interested in cervical cancer prevention and therapy.
Access to Aboriginal Community-Controlled Primary Health Organizations Can Explain Some of the Higher Pap Test Participation Among Aboriginal and Torres Strait Islander Women in North Queensland, Australia
Authors: Dasgupta Paramita , Condon John R. , Whop Lisa J. , Aitken Joanne F. , Garvey Gail , Wenitong Mark , Baade Peter D.
Published: July 2021

Background

Aboriginal and Torres Strait Islander Community-Controlled Health Organisations (ACCHOs) provides culturally appropriate primary care for Aboriginal and Torres Strait Islander people in Australia. The population of North Queensland has a higher proportion of Aboriginal and Torres Strait Islander people, a greater population coverage of ACCHOs, and higher cervical screening participation than the Rest of Queensland. The association between regional differences in the use of ACCHOs for cervical screening and variations in screening participation among Aboriginal and Torres Strait Islander women is currently unknown.

Methods

This is a population-based study of 1,107,233 women, aged 20–69 years who underwent cervical screening between 2013 and 2017. Of these women, 132,972 (12%) were from North Queensland, of which 9% were identified as Aboriginal and Torres Strait Islander women (2% Rest of Queensland) through linkage to hospital records. Regional differentials in screening by Aboriginal and Torres Strait Islander status were quantified using participation rate ratios (PRRs) with 95% confidence intervals (CIs) from negative binomial regression models. Logistic regression was used to identify factors associated with Aboriginal and Torres Strait Islander women being screened at ACCHOs.

Results

Aboriginal and Torres Strait Islander women from North Queensland (versus) Rest of Queensland had higher odds of screening at ACCHOs after adjusting for age and area-level variables. After adjustment for non-ACCHO variables, the regional differential in screening among Aboriginal and Torres Strait Islander women was significantly higher (PRR 1.28, 95% CI 1.20–1.37) than that among other Australian women [PRR = 1.11 (1.02–1.18)], but was attenuated on further adjustment for ACCHO variables, [PRR = 1.15, (1.03–1.28)] to become similar to the corresponding point estimate for other Australian women [PRR = 1.09, (1.01–1.20)]. However, the significant interaction between Aboriginal and Torres Strait Islander status and region (p < 0.001) remained, possibly reflecting the large cohort size. Screening participation increased with better access to health services for all women.

Conclusions

Improving access to primary health care for Aboriginal and Torres Strait Islander women, especially through ACCHOs, may reduce existing disparities in cervical screening participation. Further gains will require greater levels of local community engagement and understanding of the experiences of screened Aboriginal and Torres Strait Islander women to inform effective interventions.
Feasibility and Mechanism Analysis of Shenfu Injection in the Treatment of Idiopathic Pulmonary Fibrosis
Authors: Liu Peipei , Yang Shengnan , Wang Zai , Dai Huaping , Wang Chen
Published: July 2021

Background: Idiopathic pulmonary fibrosis (IPF) is disease with high mortality, and its effective treatment is limited. Shenfu injection is a traditional Chinese medicine which can improve circulation and protect cells. In this study, we aimed to investigate the feasibility and mechanism of Shenfu injection in the treatment of IPF.

Methods: The components and targets of Shenfu injection were mainly retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) database. The targets of Shenfu injection were standardized by UniProt database. The Genecards and OMIM databases was used to search for IPF-related genes. The Venn diagram of gene intersection was drawn using the OmicStudio tools, and the protein-protein interaction network was visualized using the Cytoscape 3.7.2 software. Moreover, the metascape online software was applied to explore the enriched Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, and the Cytoscape 3.7.2 software was used to construct the target-pathway network. Molecular docking was used to visualize the interactions between the main active compounds and targeted proteins. Animal experiments were performed to validate the effects and mechanisms of Shenfu injection.

Results: We obtained 46 co-targets of Shenfu injection and IPF. Among the hub target genes, several genes with important functions were enriched, including TNF, IL-6, IL-1B, TP53, JUN, CASP3 and CASP8. The pathway enrichment analysis for the hub target genes identified pathways in infection/inflammation, apoptosis and cancer. Molecular docking results showed that the main active compound Ginsenoside Re had high affinity to the core target proteins. These results suggested that Shenfu injection may have a positive effect in the treatment of IPF. Consistent with this finding, animal experiments showed that Shenfu injection significantly reduced pulmonary fibrosis in a mouse model with inhibition of apoptosis and inflammation by downregulating IL-1β, caspase-3 and phosphorylated NF-κB.

Conclusion: Our results demonstrated that Shenfu injection efficiently alleviate bleomycin-induced pulmonary fibrosis through multi-targets in inflammation-, apoptosis- and cancer-related pathways, which provided first evidence and reference to the feasibility of Shenfu injection in the treatment of IPF.
β-Asarone Attenuates Aβ-Induced Neuronal Damage in PC12 Cells Overexpressing APPswe by Restoring Autophagic Flux
Authors: Li Zhenwan , Ma Jin , Kuang Zhongsheng , Jiang Yong
Published: July 2021

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by progressive memory damage and cognitive dysfunction. Studies have shown that defective autophagic flux is associated with neuronal dysfunction. Modulating autophagic activity represents a potential method of combating AD. In Chinese medicine, Acori Tatarinowii Rhizoma is used to treat dementia and amnesia. β-Asarone, an active component of this rhizome can protect PC12 cells from Aβ-induced injury and modulate expression of autophagy factors. However, its cytoprotective mechanisms have yet to be discerned. It is unclear whether β-asarone affects autophagic flux and, if it does, whether this effect can alleviate Aβ cell damage. In the present study, we constructed APPswe-overexpressing PC12 cell line as a cell model of Aβ-induced damage and assessed expression of autophagic flux-related proteins as well as the number and morphology of autophagosomes and autolysosomes. Our results show that β-asarone decreases the expression levels of Beclin-1, p62, LC3-Ⅱ, and Aβ1-42. β-Asarone reduced the number of autophagosomes and increased the number of autolysosomes, as determined by confocal laser scanning microscopy and transmission electron microscopy. Our results suggest that β-asarone can protect PC12 cells from Aβ-induced damage by promoting autophagic flux, which may be achieved by enhancing autophagosome-lysosome fusion and/or lysosome function.