bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy of Extracts of Cyanthillium Cinereum, Khaya senegalensis and Lippia multiflora on Candida Strains Isolated From Urine Samples in Benin (West Africa)
Authors: Fanou Brice Armand , Klotoe Jean Robert , Dougnon Victorien , Assogba Phénix , Agbodjento Eric , Koudokpon Charles Hornel , Fah Lauris , Sintondji Kévin , Kpoze Rodrigue , Loko Frédéric
Published: June 2022

The search for new bioactive molecules with antifungal properties to combat resistance to classical antifungals represents a great challenge. This study aimed to explore the virulence factors and resistance profile of Candida species isolated from urine samples in Benin and the in vitro efficacy of organic extracts of Cyanthillium cinereum (L.) H.Rob., Lippia multiflora Moldenke and Khaya senegalensis (Desv.) A.Juss. on the growth of these Candida spp. The study focused on Candida strains isolated from urine samples collected from patients admitted to the bacteriological analysis laboratories of hospitals in Southern Benin. The sensitivity of these strains to classical antifungal agents was determined by the simple diffusion method. Their pathogenicity was investigated via several virulence factors (gelatinase, hemolysin, hydrophobicity, adhesin, biofilm and lecithinase). The in vitro efficacy of the aqueous, ethanolic and hydro-ethanolic extracts of the plants on Candida albicans ATCC 90028 and on six clinical strains was evaluated by the method of determination of the inhibition diameters. The results obtained showed that 51 different Candida strains were isolated from the collected urine samples with a respective predominance of Candida albicans (52.94%) and Candida glabrata (17.64%) species. All identified species were sensitive to amphotericin B and nystatin but 20% are resistant to fluconazole and present 15 different resistance profiles. Six different virulence factors were identified with a high frequency of hydrophobicity (96.08%) and adhesin (94.12%). Antifungal tests revealed that at 100 mg/mL the plant extracts were active on the tested strains with better activity for Cyanthilium cinereum and Khaya senegalensis. Cyanthilium cinereum, Khaya senegalensis and Lippia multiflora showed antifungal activity on virulent Candida strains suggesting the possibility to explore them further for the discovery of new antifungal molecules.
Reef-Building Corals Do Not Develop Adaptive Mechanisms to Better Cope With Microplastics
Authors: Rades Marvin , Schubert Patrick , Wilke Thomas , Reichert Jessica
Published: June 2022

Microplastics are omnipresent in the oceans and threaten marine animals through physical contact or ingestion. Short-term studies have already shown that reef-building stony corals respond differently to microplastics than natural food. However, it remains unknown whether corals exhibit acclimation mechanisms to combat the effects of microplastic exposure. Specifically, the long-term effects of microplastics on the feeding and defense behavior of reef-building corals remain unexplored. Therefore, the goal of this study was to infer potential acclimation mechanisms in the behavior of the corals. For this, four reef-building species (Acropora muricata, Porites lutea, Pocillopora verrucosa, and Heliopora coerulea) were exposed in a long-term experiment to microplastics for 15 months. Subsequently, coral feeding rates on microplastics and natural food (Artemia sp. cysts), feeding discrimination, and reactions to both were assessed in a 24 h pulse exposure experiment. The results showed that corals’ feeding rates did not decrease after long-term exposure to microplastics. Similarly, the feeding discrimination (i.e., ratio of feeding on microplastics and natural food) did not differ after long-term exposure to microplastics. Moreover, corals showed no changes in defense behavior (i.e., mucus production or extrusion of mesenterial filaments) against microplastics. These findings suggest that symbiotic, reef-building corals do not develop mechanisms to adapt to long-term microplastic exposure. Thus, microplastic pollution might constitute a constant stressor for coral organisms, likely leading to sustained energy expenditures and impaired health.
Science and Dissemination for the UN Ocean Decade Outcomes: Current Trends and Future Perspectives
Authors: Caruso Francesco , Tedesco Pietro , Della Sala Gerardo , Palma Esposito Fortunato , Signore Marco , Canese Simonepietro , Romeo Teresa , Borra Marco , Gili Claudia , de Pascale Donatella
Published: June 2022

The Ocean Decade (OD) is the name of a United Nations (UN) initiative devoted to ocean science for sustainable development. It started in 2021 and will provide an opportunity to create a new foundation, across the science-policy interface, to strengthen the sustainable management of oceans and coasts and, at same time, bring benefits for future generations. The OD will establish a common strategy to achieve the objectives of the 2030 Agenda for Sustainable Development and the other European Union (EU) and international agreements, such as the EU Marine Strategy Framework Directive (MSFD), the Marine Biodiversity Strategy and the UN World Assessment I and II aimed at preserving ocean health. Furthermore, the OD has several expected outcomes that concern different aspects of marine environment, including its enormous values for humans. Several entities will combine efforts to achieve these goals and science is at the forefront of the sustainable blue economy. Marine research is solving complex challenges through interdisciplinary approaches, revolutionizing our life and our interaction with the ocean. This review discusses recent advancements in science related to the OD outcomes. The role of new technology for ocean exploration and monitoring, the importance of omics science and biotechnology to deal with ocean pollution, and other innovative solutions are discussed. All of these are inspired by the idea of using marine resources in a sustainable way and without impacting in a negative way on marine ecosystems. The role of science communication is therefore considered a crucial issue to spread the OD messages and to reach the general public and stakeholders. Only by the integration of science, governance, industry and public, the OD will have any chance to succeed.
Genomic Characterization of mcr-1-Carrying Foodborne Salmonella enterica serovar Typhimurium and Identification of a Transferable Plasmid Carrying mcr-1, blaCTX-M-14, qnrS2, and oqxAB Genes From Ready-to-Eat Pork Product in China
Authors: Li Lili , Wan Xiulin , Olsen Rikke Heidemann , Xiao Jian , Wang Chong , Xu Xuebin , Meng Hecheng , Shi Lei
Published: June 2022

Salmonella enterica resistant to colistin, third-generation cephalosporins (3GCs), and fluoroquinolones (FQs) has been deemed a high-priority pathogen by the World Health Organization (WHO). The objective of this study was to characterize 11 mcr-1-harboring Salmonella enterica serovar Typhimurium isolates from raw pork and ready-to-eat (RTE) pork products in Guangzhou, China. All isolates were multi-drug resistant and contained 6–24 antibiotic-resistant genes. The mcr-1 gene was localized in the most conserved structure (mcr-1-orf ) in eight isolates and in mobile structure (ISApl1-mcr-1-orf ) in three isolates. One raw pork isolate SH16SF0850, co-harbored mcr-1, blaCTX−M−14, and oqxAB genes. One isolate 17Sal008 carried mcr-1, blaCTX−M−14, qnrS2, and oqxAB genes located on a 298,622 bp IncHI2 plasmid pSal008, which was obtained from an RTE pork product for the first time. The pSal008 was closely related to a plasmid in an S. typhimurium isolate from a 1-year-old diarrheal outpatient in China and was found to be transferable to Escherichia coli J53 by conjugation. Genome sequence comparisons by core-genome Multi Locus Sequence Typing (cgMLST) based on all S. typhimurium isolates from China inferred highly probably epidemiological links between selected pork isolates and no possible epidemiologically links between RTE pork isolate 17Sal008 and other isolates. Our findings indicate that raw pork and pork products are potential reservoirs of mcr-1-harboring S. typhimurium and highlight the necessity for continuous monitoring of colistin, 3GCs, and FQs resistant S. typhimurium from different origins.
Comparison of Anticancer Activities and Biosafety Between Salmonella enterica Serovar Typhimurium ΔppGpp and VNP20009 in a Murine Cancer Model
Authors: Liu Xiaoqing , Guo Yanxia , Sun Yujie , Chen Yu , Tan Wenzhi , Min Jung-Joon , Zheng Jin Hai
Published: June 2022

Salmonella Typhimurium defective in guanosine 5′-diphosphate-3′-diphosphate (ppGpp) synthesis (ΔppGpp) is an attenuated strain with good biosafety and excellent anticancer efficacy. It has been widely applied in preclinical studies of anticancer therapy for various types of solid cancer. VNP20009 is another genetically modified auxotrophic strain with 108-kb deletion, purI−, msbB−, and many single nucleotide polymorphisms (SNPs); it has shown promising therapeutic efficacy in various preclinical tumor models and entered phase I clinical trials. Here, the invasion activities and virulence of ΔppGpp were obviously lower than those of the VNP20009 strain when tested with cancer cells in vitro. In addition, the MC38 tumor-bearing mice showed comparable cancer suppression when treated with ΔppGpp or VNP20009 intravenously. However, the ΔppGpp-treated mice showed 16.7% of complete cancer eradication and prolonged survival in mice, whereas VNP20009 showed higher toxicity to animals, even with equal tumor size individually. Moreover, we found decreased levels of inflammatory cytokines in circulation but strengthened immune boost in tumor microenvironments of ΔppGpp-treated mice. Therefore, the engineered ΔppGpp has high potential for cancer therapeutics, and it is a promising option for future clinical cancer therapy.
Mitochondrial Function and Microbial Metabolites as Central Regulators of Intestinal Immune Responses and Cancer
Authors: Weber-Stiehl Saskia , Järke Lea , Castrillón-Betancur Juan Camilo , Gilbert Felix , Sommer Felix
Published: June 2022

Energy and anabolic metabolism are essential for normal cellular homeostasis but also play an important role in regulating immune responses and cancer development as active immune and cancer cells show an altered metabolic profile. Mitochondria take a prominent position in these metabolic reactions. First, most key energetic reactions take place within or in conjunction with mitochondria. Second, mitochondria react to internal cues from within the cell but also to external cues originating from the microbiota, a vast diversity of associated microorganisms. The impact of the microbiota on host physiology has been largely investigated in the last decade revealing that the microbiota contributes to the extraction of calories from the diet, energy metabolism, maturation of the immune system and cellular differentiation. Thus, changes in the microbiota termed dysbiosis have been associated with disease development including metabolic diseases, inflammation and cancer. Targeting the microbiota to modulate interactions with the mitochondria and cellular metabolism to delay or inhibit disease development and pathogenesis appears an attractive therapeutic approach. Here, we summarize recent advances in developing the therapeutic potential of microbiota-mitochondria interactions for inflammation and cancer.
Essential Dynamics Ensemble Docking for Structure-Based GPCR Drug Discovery
Authors: McKay Kyle , Hamilton Nicholas B. , Remington Jacob M. , Schneebeli Severin T. , Li Jianing
Published: June 2022

The lack of biologically relevant protein structures can hinder rational design of small molecules to target G protein-coupled receptors (GPCRs). While ensemble docking using multiple models of the protein target is a promising technique for structure-based drug discovery, model clustering and selection still need further investigations to achieve both high accuracy and efficiency. In this work, we have developed an original ensemble docking approach, which identifies the most relevant conformations based on the essential dynamics of the protein pocket. This approach is applied to the study of small-molecule antagonists for the PAC1 receptor, a class B GPCR and a regulator of stress. As few as four representative PAC1 models are selected from simulations of a homology model and then used to screen three million compounds from the ZINC database and 23 experimentally validated compounds for PAC1 targeting. Our essential dynamics ensemble docking (EDED) approach can effectively reduce the number of false negatives in virtual screening and improve the accuracy to seek potent compounds. Given the cost and difficulties to determine membrane protein structures for all the relevant states, our methodology can be useful for future discovery of small molecules to target more other GPCRs, either with or without experimental structures.
Untargeted Metabolomics Studies of H9c2 Cardiac Cells Submitted to Oxidative Stress, β-Adrenergic Stimulation and Doxorubicin Treatment: Investigation of Cardiac Biomarkers
Authors: Lima Monica Força , Amaral Alan Gonçalves , Moretto Isabela Aparecida , Paiva-Silva Franckson Jhonne Torres Neves , Pereira Flávia Oliveira Borges , Barbas Coral , dos Santos Aline Mara , Simionato Ana Valéria Colnaghi , Rupérez Francisco Javier
Published: June 2022

One of the biggest challenges in the search for more effective treatments for diseases is understanding their etiology. Cardiovascular diseases (CVD) are an important example of this, given the high number of deaths annually. Oxidative stress (the imbalance between oxidant and antioxidant species in biological system) is one of the factors responsible for CVD occurrence, demanding extensive investigation. Excess of reactive oxygen species (ROS) are primarily responsible for this condition, and clinical and scientific literature have reported a significant increase in ROS when therapeutic drugs, such as doxorubicin and isoproterenol, are administered. In this context, the aim of this study is the investigation of potential biomarkers that might be associated with oxidative stress in cardiomyocytes. For this purpose, H9c2 cardiomyocytes were submitted to oxidative stress conditions by treatment with doxorubicin (DOX), isoproterenol (ISO) and hydrogen peroxide (PER). Metabolomics analyses of the cell extract and the supernatant obtained from the culture medium were then evaluated by CE-ESI(+)-TOF-MS. Following signal processing, statistical analyses, and molecular features annotations, the results indicate changes in the aspartate, serine, pantothenic acid, glycerophosphocholine and glutathione metabolism in the cell extract.
Molecular Mechanisms of Epigenetic Regulation, Inflammation, and Cell Death in ADPKD
Authors: Agborbesong Ewud , Li Linda Xiaoyan , Li Lu , Li Xiaogang
Published: June 2022

Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disorder, which is caused by mutations in thePKD1andPKD2genes, characterizing by progressive growth of multiple cysts in the kidneys, eventually leading to end-stage kidney disease (ESKD) and requiring renal replacement therapy. In addition, studies indicate that disease progression is as a result of a combination of factors. Understanding the molecular mechanisms, therefore, should facilitate the development of precise therapeutic strategies for ADPKD treatment. The roles of epigenetic modulation, interstitial inflammation, and regulated cell death have recently become the focuses in ADPKD. Different epigenetic regulators, and the presence of inflammatory markers detectable even before cyst growth, have been linked to cyst progression. Moreover, the infiltration of inflammatory cells, such as macrophages and T cells, have been associated with cyst growth and deteriorating renal function in humans and PKD animal models. There is evidence supporting a direct role of the PKD gene mutations to the regulation of epigenetic mechanisms and inflammatory response in ADPKD. In addition, the role of regulated cell death, including apoptosis, autophagy and ferroptosis, have been investigated in ADPKD. However, there is no consensus whether cell death promotes or delays cyst growth in ADPKD. It is therefore necessary to develop an interactive picture between PKD gene mutations, the epigenome, inflammation, and cell death to understand why inherited PKD gene mutations in patients may result in the dysregulation of these processes that increase the progression of renal cyst formation.
Sevoflurane Exposure in the Developing Brain Induces Hyperactivity, Anxiety–Free, and Enhancement of Memory Consolidation in Mice
Authors: Li Rui , Wang Bei , Cao Xiaohong , Li Chao , Hu Yuhan , Yan Dandan , Yang Yanchang , Wang Liqing , Meng Lingzhong , Hu Zhiyong
Published: June 2022

Background

Sevoflurane exposure at brain developmental stages has been reported to induce neurotoxicity and, subsequently, results in learning deficits at the juvenile age. In this study, we aimed to investigate the effects of prior early-age sevoflurane exposure on locomotor activity, anxiety, CA1-dependent learning, and spatial memory, as well as synapse changes in mice.

Methods

Totally, 3% sevoflurane was given to neonatal mice at postnatal day 7 for 4 h. These sevoflurane-treated mice were later subjected to open field and Morris water maze tests at their adult age (postnatal days 60–90) to assess their motor activity and spatial learning ability, respectively. The brain slices of sevoflurane-treated and control mice were examined for dendritic spine density and long-term potentiation (LTP) features following behavior tests (postnatal day 60). Protein levels of N-methyl-D-aspartate (NMDA) receptor subtypes and PSD95 in brain lysate were measured by using immunoblotting at the same age (postnatal day 60).

Results

Prior early-age sevoflurane exposure increased the overall moving distance, prolonged the central-area lingering time, and increased the central-area entries of adult mice. Sevoflurane-treated mice spent more time in the target quadrant during the probe test. An increase of the spine density of pyramidal neurons in the CA1 region was observed in sevoflurane-treated mice. NMDA receptor GluN2A subunit, but not the GluN2B or PSD95, was increased in the brain lysate of sevoflurane-treated mice compared with that of control mice. LTP in the hippocampus did not significantly differ between sevoflurane-treated and control mice.

Conclusion

Exposure to sevoflurane for mice during an early brain developmental stage (P7) induces later-on hyperactivity, anxiety-free, and enhancement of memory retention. These observations shed light on future investigations on the underlying mechanisms of sevoflurane’s effect on neuronal development.
Application of Deep Learning Technology in Strength Training of Football Players and Field Line Detection of Football Robots
Authors: Zhou Daliang , Chen Gang , Xu Fei
Published: June 2022

The purpose of the study is to improve the performance of intelligent football training. Based on deep learning (DL), the training of football players and detection of football robots are analyzed. First, the research status of the training of football players and football robots is introduced, and the basic structure of the neuron model and convolutional neural network (CNN) and the mainstream framework of DL are mainly expounded. Second, combined with the spatial stream network, a CNN-based action recognition system is constructed in the context of artificial intelligence (AI). Finally, by the football robot, a field line detection model based on a fully convolutional network (FCN) is proposed, and the effective applicability of the system is evaluated. The results demonstrate that the recognition effect of the dual-stream network is the best, reaching 92.8%. The recognition rate of the timestream network is lower than that of the dual-stream network, and the maximum recognition rate is 88%. The spatial stream network has the lowest recognition rate of 86.5%. The processing power of the four different algorithms on the dataset is stronger than that of the ordinary video set. The recognition rate of the time-segmented dual-stream fusion network is the highest, which is second only to the designed network. The recognition rate of the basic dual-stream network is 88.6%, and the recognition rate of the 3D CNN is the lowest, which is 86.2%. Under the intelligent training system, the recognition accuracy rates of jumping, kicking, grabbing, and starting actions range to 97.6, 94.5, 92.5, and 89.8% respectively, which are slightly lower than other actions. The recognition accuracy rate of passing action is 91.3%, and the maximum upgrade rate of intelligent training is 25.7%. The pixel accuracy of the improved field line detection of the model and the mean intersection over union (MIoU) are both improved by 5%. Intelligent training systems and the field line detection of football robots are more feasible. The research provides a reference for the development of AI in the field of sports training.
A Framework for Text Classification Using Evolutionary Contiguous Convolutional Neural Network and Swarm Based Deep Neural Network
Authors: Prabhakar Sunil Kumar , Rajaguru Harikumar , So Kwangsub , Won Dong-Ok
Published: June 2022

To classify the texts accurately, many machine learning techniques have been utilized in the field of Natural Language Processing (NLP). For many pattern classification applications, great success has been obtained when implemented with deep learning models rather than using ordinary machine learning techniques. Understanding the complex models and their respective relationships within the data determines the success of such deep learning techniques. But analyzing the suitable deep learning methods, techniques, and architectures for text classification is a huge challenge for researchers. In this work, a Contiguous Convolutional Neural Network (CCNN) based on Differential Evolution (DE) is initially proposed and named as Evolutionary Contiguous Convolutional Neural Network (ECCNN) where the data instances of the input point are considered along with the contiguous data points in the dataset so that a deeper understanding is provided for the classification of the respective input, thereby boosting the performance of the deep learning model. Secondly, a swarm-based Deep Neural Network (DNN) utilizing Particle Swarm Optimization (PSO) with DNN is proposed for the classification of text, and it is named Swarm DNN. This model is validated on two datasets and the best results are obtained when implemented with the Swarm DNN model as it produced a high classification accuracy of 97.32% when tested on the BBC newsgroup text dataset and 87.99% when tested on 20 newsgroup text datasets. Similarly, when implemented with the ECCNN model, it produced a high classification accuracy of 97.11% when tested on the BBC newsgroup text dataset and 88.76% when tested on 20 newsgroup text datasets.
Increased Frequency of Myeloid-Derived Suppressor Cells in Myasthenia Gravis After Immunotherapy
Authors: Wang Yan , Yan Chong , Su Caixia , Wang Ying , Luo Sushan , Lu Jun , Zhao Chongbo , Zhao Gan , Xi Jianying
Published: June 2022

Myeloid-derived suppressor cells (MDSCs) are a population of myeloid progenitor cells with immunoregulatory functions and their role in myasthenia gravis (MG) was unknown. In this study, we investigated the phenotypic and functional alterations of MDSCs in MG before and after immunotherapy. The frequency of MDSCs significantly increased and negatively correlated to that of Th1 or Th17 cells after immunotherapy. MDSCs from untreated patients with MG showed an impaired suppression of IFN-γ production in T-cells and improved immunosuppressive function was identified after immunotherapy. The MFI of Arg-1 in MDSCs also increased after immunotherapy. These findings suggested the functional difference in MDSCs before and after immunotherapy, and MDSCs might play a role in disease remission.
The Use of Nanoparticles in Otoprotection
Authors: Barbara Maurizio , Margani Valerio , Covelli Edoardo , Filippi Chiara , Volpini Luigi , El-Borady Ola M. , El-Kemary Maged , Elzayat Saad , Elfarargy Haitham H.
Published: June 2022

The inner ear can be insulted by various noxious stimuli, including drugs (cisplatin and aminoglycosides) and over-acoustic stimulation. These stimuli damage the hair cells giving rise to progressive hearing loss. Systemic drugs have attempted protection from ototoxicity. Most of these drugs poorly reach the inner ear with consequent ineffective action on hearing. The reason for these failures resides in the poor inner ear blood supply, the presence of the blood-labyrinthine barrier, and the low permeability of the round window membrane (RWM). This article presents a review of the use of nanoparticles (NPs) in otoprotection. NPs were recently used in many fields of medicine because of their ability to deliver drugs to the target organs or cells. The studies included in the review regarded the biocompatibility of the used NPs by in vitro and in vivo experiments. In most studies, NPs proved safe without a significant decrease in cell viability or signs of ototoxicity. Many nano-techniques were used to improve the drugs' kinetics and efficiency. These techniques included encapsulation, polymerization, surface functionalization, and enhanced drug release. In such a way, it improved drug transmission through the RWM with increased and prolonged intra-cochlear drug concentrations. In all studies, the fabricated drug-NPs effectively preserved the hair cells and the functioning hearing from exposure to different ototoxic stimuli, simulating the actual clinical circumstances. Most of these studies regarded cisplatin ototoxicity due to the wide use of this drug in clinical oncology. Dexamethasone (DEX) and antioxidants represent the most used drugs in most studies. These drugs effectively prevented apoptosis and reactive oxygen species (ROS) production caused by ototoxic stimuli. These various successful experiments confirmed the biocompatibility of different NPs and made it successfully to human clinical trials.
Abnormal Dynamics of Functional Connectivity Density Associated With Chronic Neck Pain
Authors: Ni Xixiu , Zhang Jiabao , Sun Mingsheng , Wang Linjia , Xu Tao , Zeng Qian , Wang Xiao , Wang Ziwen , Liao Huaqiang , Hu Yimei , Gao Qing , Zhao Ling
Published: June 2022

Background: Chronic neck pain (CNP) is highly prevalent and complicated, associated with limited movement, and accompanied by shoulder pain and other clinical manifestations such as dizziness, anxiety, and insomnia. Brain structural and functional abnormalities often occur in patients with CNP. However, knowledge of the brain’s functional organization and temporal dynamics in CNP patients is limited. Dynamic functional connectivity density (dFCD) can reflect the ability of brain areas or voxels to integrate information, and could become neuroimaging markers for objectively reflecting pain to a certain extent. Therefore, this study compared the dFCD between CNP patients and healthy controls (HCs) and investigated potential associations of the abnormal density variability in dynamic functional connectivity with pain characteristics in CNP patients.

Methods: Resting functional magnetic resonance imaging was performed for 89 CNP patients and 57 HCs. After preprocessing resting-state fMRI images by the Data Processing and Analysis of Brain Imaging toolbox, the sliding window method was applied to investigate dFCD changes in CNP patients and HCs using the DynamicBC toolbox. Then we quantified dFCD variability using their standard deviation. Based on the pain-associated factors collected from the case report form of CNP patients, the mean dFCD variability values of each dFCD from region of interest were extracted to calculate Pearson’s correlation coefficient to study the potential correlation between dFCD abnormal variability and pain.

Results: Compared with HCs, the dFCD values of the anterior cingulate cortex, occipital lobe, temporal lobe, and cerebellum were statistically different in patients with CNP. Subsequent correlation analysis showed that the variable dFCD in the related brain region was correlative with the course of the disease and clinical symptoms, such as pain and depression, in patients with CNP.

Conclusion: Dynamic functional alterations were observed in the brain regions of CNP patients, and the dFCD of these brain regions could become neuroimaging markers for objectively reflecting pain to a certain extent. This suggests that chronic pain may cause changes in pain processing and emotional feedback and highlights the link between dynamic neural communication in brain regions and disease conditions, deepening our understanding of chronic pain diseases, and guiding clinical practice.
Effect of red meat, vegetable, tobacco, and alcohol consumption on national cancer mortality index: Data from 1989 to 2013 in 37 developed countries
Authors: Park Myung-Bae
Published: June 2022

This study aimed to examine the association between red meat (RM) and death from all types of cancer, as well as its association with the incidence of colon cancer in developed countries. We selected RM, vegetable, tobacco, alcohol consumption, and socioeconomic status as the dependent variables' risk factors and performed ordinary least squares (OLS) and a fixed-effect model (FEM) analysis. Data from 1989 to 2013 for 37 Organization for Economic Cooperation and Development (OECD) countries. According to the FEM, cancer death had statistically significant associations with education level (Coef = −0.022, P = 0.009), total health expenditure (Coef = −0.049, P = 0.000), aging rate (Coef = −0.178, P = 0.000), tobacco consumption (Coef = 0.096, P = 0.000), RM consumption (Coef = 0.107, P = 0.000), and vegetable consumption (Coef = −0.034, P = 0.000). A similar trend was also observed in the 3 and 5-year lagged models. RM consumption also demonstrated a significantly positive association with the incidence of colon cancer in the OLS. According to the scatter plots and fitted lines based on the recommended allowance RM consumption, cancer deaths and incidence of colon cancer increased as consumption increased in the excess consumption group. Regarding vegetable consumption, cancer deaths and incidence of colon cancer decreased as consumption increased in the group exceeding the recommended allowance level. RM consumption was found to be higher than the recommended allowance level. RM consumption increased cancer deaths and the incidence of colon cancer. There is justification for public health interventions to limit RM consumption in major developed countries.
Aquaporins in Cancer Biology
Authors: Moon Chul So , Moon David , Kang Sung Koo
Published: June 2022

Aquaporins (AQPs) are a family of transmembrane water channel proteins, which were initially characterized as a novel protein family that plays a vital role in transcellular and transepithelial water movement. AQP1, AQP2, AQP4, AQP5, and AQP8 are primarily water selective, whereas AQP3, AQP7, AQP9, and AQP10 (called “aqua-glyceroporins”) also transport glycerol and other small solutes. Recently, multiple reports have suggested that AQPs have important roles in cancer cell growth, migration, invasion, and angiogenesis, each of which is important in human carcinogenesis. Here, we review recent data concerning the involvement of AQPs in tumor growth, angiogenesis, and metastasis and explore the expression profiles from various resected cancer samples to further dissect the underlying molecular mechanisms. Moreover, we discuss the potential role of AQPs during the development of genomic instability and performed modeling to describe the integration of binding between AQPs with various SH3 domain binning adaptor molecules. Throughout review and discussion of numerous reports, we have tried to provide key evidence that AQPs play key roles in tumor biology, which may provide a unique opportunity in designing a novel class of anti-tumor agents.
Identification of Novel Tumor Microenvironment Regulating Factor That Facilitates Tumor Immune Infiltration in Cervical Cancer
Authors: Xu Jingjing , Huang Zhe , Wang Yishu , Xiang Zhenxian , Xiong Bin
Published: June 2022

Cervical cancer is one of the most common gynecologic malignancies and one of the leading causes of cancer-related deaths in women worldwide. There are more than 30 categories of human papillomavirus infections in the genital tract. The recently discovered immune checkpoint suppression is a potential approach to improve clinical outcomes in these patients by altering immune cell function. However, many questions remain unanswered in terms of this method. For example, the proportion of responders is limited and the exact mechanism of action is uncertain. The tumor microenvironment (TME) has long been regarded as having nonnegligible influence on effectiveness of immunotherapy. The programmed cell death protein 1 (PD-1) pathway has received much attention due to its involvement in activating T-cell immune checkpoint responses. Since tumor cells may evade immune detection and become highly resistant to conventional treatments, anti-PD-1/PD-L1 antibodies are preferred as a kind of cancer treatment and many have just been licensed. To provide a theoretical basis for the development of new therapies, investigating the effect of tumor microenvironment on the prognosis of cervical cancer is necessary. In this work, immunological scores obtained from the ESTIMATE algorithm were used to differentiate between patients with high and low immune cell infiltration. We identified 11 immunologically significant differentially expressed genes (DEGs). For example, CXCR3 was found to be an important factor in CD8+ T cell recruitment and tumor immunological infiltration in cervical cancer. These results may lead to novel directions of understanding complex interactions between cancer cells and the tumor microenvironment, as well as new treatment options for cervical cancer.
Silence in Conversations About Advancing Pediatric Cancer
Authors: Rockwell Sarah L. , Woods Cameka L. , Lemmon Monica E. , Baker Justin N. , Mack Jennifer W. , Andes Karen L. , Kaye Erica C.
Published: June 2022

Background and Objectives

Skillful use of silence by clinicians can support patient-centered communication. However, what makes a period of silence feel meaningful is not well understood. This study aimed to characterize profound, skillful silences during difficult conversations between pediatric oncologists, children with advancing cancer, and their families.

Methods

We audio-recorded serial disease reevaluation discussions between pediatric oncologists, patients with high-risk cancer, and their families across 24 months or until death, whichever occurred first. Using an inductive process, we performed content analysis across all dialogue recorded at timepoints of disease progression to examine types of silence.

Results

17 patient-parent dyads with disease progression yielded 141 recorded conversations. Inductive coding yielded a layered typology of silence, including “intentional silence” (≥5 seconds), “profound silence” (≥5 seconds following receipt of difficult information, juxtaposed with statements of shared understanding, emotion, or enlightenment), and “stacked silence” (series of silences juxtaposed within dialogue). Intentional silence lasting ≥5 seconds occurred 238 times in 35/49 “bad news” recordings; nearly half (103/238) of these silences were identified as profound silence, in which silences appeared to create space for processing, allowed for questions to emerge, and synergized with empathic and affirmational statements. In most cases, profound silences involved the juxtaposition, or stacking, of multiple silences close together.

Conclusions

Profound silences occur often during conversations about advancing pediatric cancer and share distinct characteristics. Opportunities exist to teach clinicians to use profound and stacked silences with intention during difficult conversations as a fundamental aspect of communication.
Increased Severe Cases and New-Onset Type 1 Diabetes Among Children Presenting With Diabetic Ketoacidosis During First Year of COVID-19 Pandemic in Turkey
Authors: Kiral Eylem , Kirel Birgul , Havan Merve , Keskin Mehmet , Karaoglan Murat , Yildirim Ahmet , Kangin Murat , Talay Mehmet Nur , Urun Tuba , Altug Umit , Kesici Selman , Tufan Erennur , Kacmaz Ebru , Bozan Gurkan , Azapagasi Ebru , Uysal Yazici Mutlu , Ozturk Zeynelabidin , Yesilbas Osman , Karaguzel Gulay , Kaya Gulay , Barlas Ulkem , Duyu Muhterem , Boyraz Merve , Sevketoglu Esra , Akcay Nihal , Hancili Suna , Guven Ayla , Dursun Oǧuz , Ulgen Tekerek Nazan , Ozcifci Gokçen , Yazici Pinar , Turanli Eda , Kendirli Tanil , Kahveci Fevzi , Yetimakman Ayse Filiz , Citak Agop , Şik Guntulu , Bingol Ibrahim , Aygun Fatih , Durak Cansu , Yilmaz Resul , Bugrul Fuat , Sari Yusuf , Tekguç Hakan , Albayrak Hatice , Yener Nazik , Agin Hasan , Soydan Ekin , Yildizdas Dincer , Dilek Semine Ozdemir , Yalindag Nilufer , Incekoy-Girgin Feyza , Alacakir Nuri , Tutunculer Filiz , Arslanaoglu Mehmet Ozgur , Aydin Can , Bilgin Muzaffer , Simsek Enver , Dinleyici Ener Cagri
Published: June 2022

Introduction

There have been some significant changes regarding healthcare utilization during the COVID-19 pandemic. Majority of the reports about the impact of the COVID-19 pandemic on diabetes care are from the first wave of the pandemic. We aim to evaluate the potential effects of the COVID-19 pandemic on the severity of diabetic ketoacidosis (DKA) and new onset Type 1 diabetes presenting with DKA, and also evaluate children with DKA and acute COVID-19 infection.

Methods

This is a retrospective multi-center study among 997 children and adolescents with type 1 diabetes who were admitted with DKA to 27 pediatric intensive care units in Turkey between the first year of pandemic and pre-pandemic year.

Results

The percentage of children with new-onset Type 1 diabetes presenting with DKA was higher during the COVID-19 pandemic (p < 0.0001). The incidence of severe DKA was also higher during the COVID-19 pandemic (p < 0.0001) and also higher among children with new onset Type 1 diabetes (p < 0.0001). HbA1c levels, duration of insulin infusion, and length of PICU stay were significantly higher/longer during the pandemic period. Eleven patients tested positive for SARS-CoV-2, eight were positive for new onset Type 1 diabetes, and nine tested positive for severe DKA at admission.

Discussion

The frequency of new onset of Type 1 diabetes and severe cases among children with DKA during the first year of the COVID-19 pandemic. Furthermore, the cause of the increased severe presentation might be related to restrictions related to the pandemic; however, need to evaluate the potential effects of SARS-CoV-2 on the increased percentage of new onset Type 1 diabetes.
Impact of the COVID-19 Pandemic on the Diagnosis of Tuberculosis in Brazil: Is the WHO End TB Strategy at Risk?
Authors: Souza Mariana do Rosário , Paz Wandklebson Silva da , Sales Vinícius Barbosa dos Santos , Jesus Gleidson Felipe Hilario de , Tavares Débora dos Santos , Lima Shirley V. M. Almeida , Sousa Álvaro Francisco Lopes , Melo Enaldo Vieira de , Carmo Rodrigo Feliciano do , Souza Carlos Dornels Freire de , Bezerra-Santos Márcio
Published: June 2022

Background: In 2014, the World Health Organization (WHO) launched the “post-2015 End TB strategy”, that aims to end the global tuberculosis (TB) epidemic by 2030. However, the COVID-19 pandemic has severely impacted global public health and the strict measures to control the coronavirus spread can affect the management of other diseases, such as TB. Herein, we aimed to assess the impact of the COVID-19 pandemic on the diagnosis of TB in Brazil, during 2020.

Methods: We carried out an ecological and population-based study, using spatial analysis techniques. The variables used were the new cases of TB, pulmonary tuberculosis (PTB), and also baciloscopy-positive (BP) cases in Brazil between 2015 and 2020. The percentage of changes (% change) was calculated to verify if there was an increase or decrease of TB cases in 2020, along with time trend analyses given by Joinpoint regression model. Also, interrupted time series analyses were used to assess the trend of TB diagnosis before and after the onset of the COVID-19 in Brazil. Spatial distribution maps were elaborated, considering the % change of each Brazilian state.

Findings: Data analyses showed a reduction in the diagnosis of TB (−8.3%) and PTB (−8.1%) in Brazil after the irruption of the COVID-19 pandemic. Likewise, 22 states depicted a reduction in TB diagnosis. An expressive reduction of BP cases (−17.1%) was also observed. Interestingly, interrupted time series analysis showed decline in TB and PTB diagnoses from March 2020. Spatial analyses revealed that all states had a progressive reduction of TB, PTB and PB cases, from March on, with the highest percentages of reduction in December (−100% to −75%).

Interpretation: Taken together, our analyses demonstrated a reduction in TB diagnosis after the irruption of the COVID-19 pandemic in Brazil and its regions, signaling a serious impact on the WHO “End TB Strategy” global plan.
Antidepressant Effects of South African Plants: An Appraisal of Ethnobotanical Surveys, Ethnopharmacological and Phytochemical Studies
Authors: Bonokwane Melia Bokaeng , Lekhooa Makhotso , Struwig Madeleen , Aremu Adeyemi Oladapo
Published: June 2022

Globally, the search for safe and potent natural-based treatment for depression is receiving renewed interest given the numerous side-effects associated with many existing drugs. In South Africa, the use of plants to manage depression and related symptoms is fairly documented among different ethnic groups. In the current study, we reviewed existing ethnobotanical, ethnopharmacological and phytochemical studies on South African medicinal plants used to manage depression. Electronic databases were accessed for scientific literature that meets the inclusion criteria. Plants with ethnobotanical evidence were subjected to a further pharmacological review to establish the extent (if any) of their effectiveness as antidepressants. Critical assessment resulted in 20 eligible ethnobotanical records, which generated an inventory of 186 plants from 63 plant families. Due to the cultural differences observed in the definition of depression, or lack of definition in some cultures, most plants are reported to treat a wide range of atypical symptoms related to depression. Boophone disticha, Leonotis leonurus and Mentha longifolia were identified as the three most popular plants, with over eight mentions each from the ethnobotanical records. The dominant families were Asteraceae (24), Fabaceae (16), Amaryllidaceae (10), and Apocynaceae (10) which accounted for about 32% of the 186 plants. Only 27 (≈14.5%) of the plants have been screened for antidepressant activity using in vitro and in vivo models. Agapanthus campanulatus, Boophone disticha, Hypericum perforatum, Mondia whitei and Xysmalobium undulatum, represent the most studied plants. Phytochemical investigation on nine out of the 27 plants revealed 24 compounds with antidepressant-like effects. Some of these included buphanidrine and buphanamine which were isolated from the leaves of Boophone disticha, Δ9-tetrahydrocannabinol, cannabidiol and cannabichromene obtained from the buds of Cannabis sativa and carnosic acid, rosmarinic acid and salvigenin from Rosmarinus officinalis, A significant portion (≈85%) of 186 plants with ethnobotanical records still require pharmacological studies to assess their potential antidepressant-like effects. This review remains a valuable reference material that may guide future ethnobotanical surveys to ensure their robustness and validity as well as database to identify promising plants to screen for pharmacology efficacy.
Astragalus–Scorpion Drug Pair Inhibits the Development of Prostate Cancer by Regulating GDPD4-2/PI3K/AKT/mTOR Pathway and Autophagy
Authors: You Xujun , Wu Yongrong , Li Qixin , Sheng Wen , Zhou Qing , Fu Wei
Published: June 2022

Objective: Prostate cancer (PCa) is an epithelial malignancy of the prostate that currently lacks effective treatment. Traditional Chinese medicine (TCM) can play an anticancer role through regulating the immune system, anti-tumor angiogenesis, regulating tumor cell apoptosis, autophagy dysfunction, and other mechanisms. This study attempted to explore the active ingredients and potential mechanism of action of the Astragalus–Scorpion (A–S) drug pair in PCa, in order to provide new insights into the treatment of PCa.

Methods: Network pharmacology was used to analyze the A–S drug pair and PCa targets. Bioinformatics analysis was used to analyze the LncRNAs with significant differences in PCa. The expression of LC3 protein was detected by immunofluorescence. CCK8 was used to detect cell proliferation. The expressions of GDPD4-2, AC144450.1, LINC01513, AC004009.2, AL096869.1, AP005210.1, and BX119924.1 were detected by RT-qPCR. The expression of the PI3K/AKT/mTOR pathway and autophagy-related proteins were detected by western blot. LC-MS/MS was used to identify the active components of Astragalus and Scorpion.

Results: A–S drug pair and PCa have a total of 163 targets, which were mainly related to the prostate cancer and PI3K/AKT pathways. A–S drug pair inhibited the formation of PCa, promoted the expression of LC3Ⅱ and Beclin1 proteins, and inhibited the expression of P62 and PI3K–AKT pathway proteins in PCa mice. Astragaloside IV and polypeptide extract from scorpion venom (PESV) were identified as the main active components of the A–S drug pair. GDPD4-2 was involved in the treatment of PCa by Astragaloside IV-PESV. Silencing GDPD4-2 reversed the therapeutic effects of Astragaloside IV-PESV by regulating the PI3K/AKT/mTOR pathway.

Conclusion: Astragaloside IV-PESV is the main active components of A–S drug pair treated PCa by regulating the GDPD4-2/PI3K–AKT/mTOR pathway and autophagy.
Bilberries: Curative and Miraculous – A Review on Bioactive Constituents and Clinical Research
Authors: Vaneková Zuzana , Rollinger Judith M.
Published: June 2022

Bilberry (Vaccinium myrtillus L.) fruits are an important part of local diets in many countries and are used as a medicinal herb to treat various disorders. Extracts from fruits are often a part of eye health-promoting supplements, whereas extracts from leaves are advertised for type 2 diabetes mellitus and glycemic control. This review provides an overview of the current knowledge of the phytochemical contents of bilberry fruits and leaves and their bioactivities, critically summarizes origins of the health claims and the outcome of clinical trials, with special attention towards those published in the past 10 years. Overall, the three most referenced indications, which are type 2 diabetes mellitus, vision disorders and circulatory diseases, all include contradictory results with no clear conclusion as to the benefits and recommended dosages. Moreover, the indications for vision disorders and diabetes originate from unproven or false claims that have been repeated in research since the 20th century without consistent fact-checking. Beneficial clinical results have been attested for the treatment of dyslipidemia and chronic inflammatory disorders when applied as dietary supplementation of fresh bilberries or as anthocyanin-rich bilberry fruit extracts. However, there is a general lack of double-blinded controlled research with larger sample sizes.