bluuebunny/crossref_metadata_2025 huggingface dataset:
Gut Reactions: How Far Are We from Understanding and Manipulating the Microbiota Complexity and the Interaction with Its Host? Lessons from Autism Spectrum Disorder Studies
Authors: Lombardi Martina , Troisi Jacopo
Published: October 2021

Autism is a group of neurodevelopmental disorders, characterized by early onset difficulties in social communication and restricted, repetitive behaviors and interests. It is characterized by familial aggregation, suggesting that genetic factors play a role in disease development, in addition to developmentally early environmental factors. Here, we review the role of the gut microbiome in autism, as it has been characterized in case-control studies. We discuss how methodological differences may have led to inconclusive or contradictory results, even though a disproportion between harmful and beneficial bacteria is generally described in autism. Furthermore, we review the studies concerning the effects of gut microbial-based and dietary interventions on autism symptoms. Also, in this case, the results are not comparable due to the lack of standardized methods. Therefore, autism-specific microbiome signatures and, consequently, possible microbiome-oriented interventions are far from being recognized. We argue that a multi-omic longitudinal implementation may be useful to study metabolic changes connected to microbiome changes.
Feasibility and Efficiency of the BEFORE (Better Exercise and Food, Better Recovery) Prehabilitation Program
Authors: Tweed Thaís T. T. , Sier Misha A. T. , Van Bodegraven Ad A. , Van Nie Noémi C. , Sipers Walther M. W. H. , Boerma Evert-Jan G. , Stoot Jan H. M. B.
Published: October 2021

Prehabilitation has been postulated as an effective preventive intervention to reduce postoperative complications, particularly for elderly patients with a relatively high risk of complications. To date, it remains to be determined whether prehabilitation increases physical capacity and reduces postoperative complications. The aim of this study was to assess the feasibility of a 4-week multimodal prehabilitation program consisting of a personalized, supervised training program and nutritional intervention with daily fresh protein-rich food for colorectal cancer patients aged over 64 years prior to surgery. The primary outcome was the feasibility of this prehabilitation program defined as ≥80% compliance with the exercise training program and nutritional intervention. The secondary outcomes were the organizational feasibility and acceptability of the prehabilitation program. A compliance rate of ≥80% to both the exercise and nutritional intervention was accomplished by 6 patients (66.7%). Attendance of ≥80% at all 12 training sessions was achieved by 7 patients (77.8%); all patients (100%) attended ≥80% of the available training sessions. Overall, compliance with the training was 91.7%. Six patients (66.7%) accomplished compliance of ≥80% with the nutritional program. The median protein intake was 1.2 (g/kg/d). No adverse events occurred. This multimodal prehabilitation program was feasible for the majority of patients.
Is High Milk Intake Good for Children’s Health? A National Population-Based Observational Cohort Study
Authors: Kwon Yoowon , Lee Seung Won , Cho Young Sun , Jeong Su Jin , Han Man Yong
Published: October 2021

Milk is widely considered as a beneficial product for growing children. This study was designed to describe the milk consumption status of Korean children aged 30–36 months and to investigate its association with the risk of obesity and iron deficiency anemia (IDA). This nationwide administrative study used data from the Korean national health insurance system and child health screening examinations for children born in 2008 and 2009. In total, 425,583 children were included, and they were divided into three groups based on daily milk consumption: low milk group (do not drink or drink <200 mL milk per day, n = 139,659), reference group (drink 200–499 mL milk per day, n = 255,670), and high milk group (drink ≥500 mL milk per day, n = 30,254). After adjusting variable confounding factors, the consumption of a large amount of milk of ≥500 mL per day at the age of 30–36 months was associated with an increased risk of obesity at the age of 42–72 months and IDA after the age of 30 months. These results may provide partial evidence for dietary guidelines for milk consumption in children that are conducive to health.
Manganese Encephalopathy Caused by Homemade Methcathinone (Ephedrone) Prevalence in Poland
Authors: Habrat Bogusław , Silczuk Andrzej , Klimkiewicz Anna
Published: October 2021

Manganese encephalopathy is a known disorder in occupational medicine. A serious phenomenon has been the emergence of manganese encephalopathy in intravenous users of homemade methcathinone (ephedrone). A short survey was developed for clinical environments dealing with people who use psychoactive substances. The data were obtained from 72 rehabilitation therapy centers. Surveys carried out in about a third of Polish centers dealing with providing medical assistance to people addicted to substances other than alcohol and tobacco have shown that over 4% of people treated there had symptoms of manganese encephalopathy, of which more than half are people in whom the probability of a clinical diagnosis of this disorder is significant. It has been shown that knowledge of manganese encephalopathy is none or minimal in more than 70% of the surveyed institutions. An urgent need for personnel training in this field was pointed out. Attention was paid to the importance of disseminating good review articles on new and dynamically developing problem phenomena.
Feasibility of Low-Sodium, High-Potassium Processed Foods and Their Effect on Blood Pressure in Free-Living Japanese Men: A Randomized, Double-Blind Controlled Trial
Authors: Umeki Yoko , Hayabuchi Hitomi , Adachi Hisashi , Ohta Masanori
Published: October 2021

We aimed to verify the effect of new low-sodium high-potassium seasonings and processed foods containing poly-γ-glutamic acid on blood pressure in free-living settings. To this end, we conducted a randomized, double-blind controlled trial on 187 Japanese men, aged 35–67 years, who did not use antihypertensives. Participants were randomly allocated to an intervention (n = 93) or a control group (n = 94). They were given a boxed lunch and miso soup (average Na and K content for the intervention group: 1175 and 1476 mg; for the control group: 2243 and 703 mg, respectively). Blood pressure was measured three times every morning for 1 week immediately before and during the final week of the trial. On the day before and the final day of the intervention period, 24 h urine samples were collected. After intervention, the intervention group showed a significantly stronger decrease in the urinary sodium-to-potassium ratio than the control group (p < 0.001). The mean difference in systolic blood pressure change after adjustment for baseline values between the two groups was −2.1 (95% CI: −3.6, −0.6) mmHg. Compliance between the groups was similar, suggesting successful blinding. In conclusion, the use of new seasonings and processed foods aimed at lowering blood pressure in free-living settings may be feasible and effective.
Change in Micronutrient Intake among People with Relapsing-Remitting Multiple Sclerosis Adapting the Swank and Wahls Diets: An Analysis of Weighed Food Records
Authors: Titcomb Tyler J. , Brooks Lisa , Smith Karen L. , Ten Eyck Patrick , Rubenstein Linda M. , Wahls Terry L. , Snetselaar Linda G.
Published: October 2021

The low-saturated fat (Swank) and modified Paleolithic elimination (Wahls) diets have shown promise for MS symptoms; however, due to their restriction of specific foods, inadequate intake of micronutrients is concerning. Therefore, as part of a randomized trial, weighed food records were collected on three consecutive days and were used to evaluate the intake of micronutrients among people with relapsing remitting MS adapting these diets. After randomization to either the Swank or Wahls diets, diet education and support was provided by registered dietitians at baseline and throughout the first 12 weeks of the intervention. Usual intake of each micronutrient was estimated and then evaluated with the EAR-cut point method. At 12 weeks, the Swank group had significant reductions in the proportion with inadequate intake from food for vitamins C, D, and E, while the Wahls group had significant reductions for magnesium and vitamins A, C, D, and E. However, the proportion with inadequate intake significantly increased for calcium, thiamin, and vitamin B12 in the Wahls group and for vitamin A in the Swank group. Inclusion of intake from supplements reduced the proportion with inadequate intake for all micronutrients except calcium among the Wahls group but increased the proportion with excessive intake for vitamin D and niacin among both groups and magnesium among the Swank group. Both diets, especially when including intake from supplements, are associated with reduced inadequate intake compared to the normal diet of people with relapsing remitting MS.
Impacts of Fructose on Intestinal Barrier Function, Inflammation and Microbiota in a Piglet Model
Authors: Guo Pingting , Wang Haichao , Ji Linbao , Song Peixia , Ma Xi
Published: October 2021

The metabolic disorder caused by excessive fructose intake was reported extensively and often accompanied by intestinal barrier dysfunction. And the rising dietary fructose was consumed at an early age of human. However, related researches were almost conducted in rodent models, while in the anatomy and physiology of gastrointestinal tract, pig is more similar to human beings than rodents. Hence, weaned piglets were chosen as the model animals in our study to investigate the fructose’s impacts on intestinal tight junction, inflammation response and microbiota structure of piglets. Herein, growth performance, inflammatory response, oxidation resistance and ileal and colonic microbiota of piglet were detected after 35-day fructose supplementation. Our results showed decreased tight junction gene expressions in piglets after fructose addition, with no obvious changes in the growth performance, antioxidant resistance and inflammatory response. Moreover, fructose supplementation differently modified the microbiota structures in ileum and colon. In ileum, the proportions of Streptococcus and Faecalibacterium were higher in Fru group (fructose supplementation). In colon, the proportions of Blautia and Clostridium sensu stricto 1 were higher in Fru group. All the results suggested that tight junction dysfunction might be an earlier fructose-induced event than inflammatory response and oxidant stress and that altered microbes in ileum and colon might be the potential candidates to alleviate fructose-induced intestinal permeability alteration.
Training and Racing Behaviors of Omnivorous, Vegetarian, and Vegan Endurance Runners—Results from the NURMI Study (Step 1)
Authors: Wirnitzer Katharina , Motevalli Mohamad , Tanous Derrick , Wirnitzer Gerold , Leitzmann Claus , Wagner Karl-Heinz , Rosemann Thomas , Knechtle Beat
Published: October 2021

As a key modulator of training adaptations and racing performance, nutrition plays a critical role in endurance runners’ success, and the training/racing behaviors of runners are potentially affected by their diet types. The present study aimed to investigate whether distance runners with a vegan diet (i.e., devoid of foods or ingredients from animal sources), vegetarian diet (i.e., devoid of meat and flesh foods), and omnivorous diet (i.e., a mixed diet with no restriction on food sources) have different training and racing patterns in general and based on race distance subgroups. A total of 3835 recreational runners completed an online survey. Runners were assigned to dietary (omnivorous, vegetarian, and vegan) and race distance (<21 km, half-marathon, and marathon/ultra-marathon) groups. In addition to sociodemographic information, a complete profile of data sets focusing on running and racing behaviors/patterns was evaluated using a questionnaire-based epidemiological approach. There were 1272 omnivores (47% females), 598 vegetarians (64% females), and 994 vegans (65% females). Compared to vegans and vegetarians, omnivorous runners prepared for a longer time period for running events, had a higher number of half-marathons and marathons completed with a better finish time, and had more reliance on training under supervision (p < 0.05). The present findings indicate an important association of diet types with patterns of training and racing amongst endurance runners that may be related to different motives of omnivorous, vegetarian, and vegan runners for participating in events.
Detection of Anaplasma phagocytophilum, Babesia odocoilei, Babesia sp., Borrelia burgdorferi Sensu Lato, and Hepatozoon canis in Ixodes scapularis Ticks Collected in Eastern Canada
Authors: Scott John D. , Pesapane Risa R.
Published: October 2021

Tick-borne pathogens cause infectious diseases that inflict much societal and financial hardship worldwide. Blacklegged ticks, Ixodes scapularis, are primary vectors of several epizootic and zoonotic pathogens. The aim was to find varius pathogens of I. scapularis and to determine their prevalence. In Ontario and Quebec, 113 I. scapularis ticks were collected from songbirds, mammals, including humans, and by flagging. PCR and DNA sequencing detected five different microorganisms: Anaplasma phagocytophilum, 1 (0.9%); Babesia odocoilei, 17 (15.3%); Babesia microti-like sp., 1 (0.9%); Borrelia burgdorferi sensu lato (Bbsl), 29 (26.1%); and Hepatozoon canis, 1 (0.9%). Five coinfections of Bbsl and Babesia odocoilei occurred. Notably, H. canis was documented for the first time in Canada and, at the same time, demonstrates the first transstadial passage of H. canis in I. scapularis. Transstadial passage of Bbsl and B. odocoilei was also witnessed. A novel undescribed piroplasm (Babesia microti-like) was detected. An established population of I. scapularis ticks was detected at Ste-Anne-de-Bellevue, Quebec. Because songbirds widely disperse I. scapularis larvae and nymphs, exposure in an endemic area is not required to contract tick-borne zoonoses. Based on the diversity of zoonotic pathogens in I. scapularis ticks, clinicians need to be aware that people who are bitten by I. scapularis ticks may require select antimicrobial regimens.
Coronavirus Disease 2019 on the Heels of Ebola Virus Disease in West Africa
Authors: Dembek Zygmunt F. , Schwartz-Watjen Kierstyn T. , Swiatecka Anna L. , Broadway Katherine M. , Hadeed Steven J. , Mothershead Jerry L. , Chekol Tesema , Owens Akeisha N. , Wu Aiguo
Published: October 2021

This study utilized modeling and simulation to examine the effectiveness of current and potential future COVID-19 response interventions in the West African countries of Guinea, Liberia, and Sierra Leone. A comparison between simulations can highlight which interventions could have an effect on the pandemic in these countries. An extended compartmental model was used to run simulations incorporating multiple vaccination strategies and non-pharmaceutical interventions (NPIs). In addition to the customary categories of susceptible, exposed, infected, and recovered (SEIR) compartments, this COVID-19 model incorporated early and late disease states, isolation, treatment, and death. Lessons learned from the 2014–2016 Ebola virus disease outbreak—especially the optimization of each country’s resource allocation—were incorporated in the presented models. For each country, models were calibrated to an estimated number of infections based on actual reported cases and deaths. Simulations were run to test the potential future effects of vaccination and NPIs. Multiple levels of vaccination were considered, based on announced vaccine allocation plans and notional scenarios. Increased vaccination combined with NPI mitigation strategies resulted in thousands of fewer COVID-19 infections in each country. This study demonstrates the importance of increased vaccinations. The levels of vaccination in this study would require substantial increases in vaccination supplies obtained through national purchases or international aid. While this study does not aim to develop a model that predicts the future, it can provide useful information for decision-makers in low- and middle-income nations. Such information can be used to prioritize and optimize limited available resources for targeted interventions that will have the greatest impact on COVID-19 pandemic response.
Uncertainty around the Long-Term Implications of COVID-19
Authors: Desforges Marc , Gurdasani Deepti , Hamdy Adam , Leonardi Anthony J.
Published: October 2021

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected more than 231 million people globally, with more than 4.7 million deaths recorded by the World Health Organization as of 26 September 2021. In response to the pandemic, some countries (New Zealand, Vietnam, Taiwan, South Korea and others) have pursued suppression strategies, so-called Zero COVID policies, to drive and maintain infection rates as close to zero as possible and respond aggressively to new cases. In comparison, European countries and North America have adopted mitigation strategies (of varying intensity and effectiveness) that aim primarily to prevent health systems from being overwhelmed. With recent advances in our understanding of SARS-CoV-2 and its biology, and the increasing recognition there is more to COVID-19 beyond the acute infection, we offer a perspective on some of the long-term risks of mutational escape, viral persistence, reinfection, immune dysregulation and neurological and multi-system complications (Long COVID).
Dirofilaria spp. and Angiostrongylus vasorum: Current Risk of Spreading in Central and Northern Europe
Authors: Fuehrer Hans-Peter , Morelli Simone , Unterköfler Maria Sophia , Bajer Anna , Bakran-Lebl Karin , Dwużnik-Szarek Dorota , Farkas Róbert , Grandi Giulio , Heddergott Mike , Jokelainen Pikka , Knific Tanja , Leschnik Michael , Miterpáková Martina , Modrý David , Petersen Heidi Huus , Skírnisson Karl , Vergles Rataj Aleksandra , Schnyder Manuela , Strube Christina
Published: October 2021

In the past few decades, the relevance of Dirofilaria immitis and Dirofilaria repens, causing cardiopulmonary and subcutaneous dirofilariosis in dogs and cats, and of Angiostrongylus vasorum, causing canine angiostrongylosis, has steadily increased in Central and Northern Europe. In this review, a summary of published articles and additional reports dealing with imported or autochthonous cases of these parasites is provided for Central (Austria, Czechia, Germany, Hungary, Luxemburg, Poland, Slovakia, Slovenia, and Switzerland) and Northern (Denmark, Finland, Iceland, Norway, and Sweden) Europe. Research efforts focusing on Dirofilaria spp. and A. vasorum have varied by country, and cross-border studies are few. The housing conditions of dogs, pet movements, the spread of competent vectors, and climate change are important factors in the spread of these nematodes. Dogs kept outside overnight are a major factor for the establishment of Dirofilaria spp. However, the establishment of invasive, diurnal, synanthropic, competent mosquito vectors such as Aedes albopictus may also influence the establishment of Dirofilaria spp. The drivers of the spread of A. vasorum remain not fully understood, but it seems to be influenced by habitats shared with wild canids, dog relocation, and possibly climatic changes; its pattern of spreading appears to be similar in different countries. Both Dirofilaria spp. and A. vasorum merit further monitoring and research focus in Europe.
Occurrence of Neobenedenia girellae (Monogenea: Capsalidae) in Gilthead Seabream Sparus aurata (Actinopterygii: Sparidae) Cultured in Portugal
Authors: Tedesco Perla , Caffara Monica , Ribeiro Moreira Nuno Miguel , Gomes César , Gustinelli Andrea , Fioravanti Maria Letizia
Published: October 2021

Monogenean capsalids of the genus Neobenedenia are widespread parasites of wild and farmed marine fish, and represent a potential threat to mariculture due to their pathogenicity and ability to cause mortality in fish maintained in controlled conditions. The identification of Neobenedenia species and, consequently, the definition of their host specificity is often problematic due to their highly conserved morphology; therefore, in order to establish their specific identity, microscopic observation should be complemented with molecular analysis. The present work aims at characterizing Neobenedenia specimens infecting the skin of cage reared gilthead seabream Sparus aurata from Portugal. Parasite samples obtained from caged fish were processed for morphological analysis, through observation in light and scanning electron microscopy, and for molecular analysis, through amplification and sequencing of 28S rDNA and cytB, aimed at identifying them to the species level. Our results showed that the collected parasites belonged to the species Neobenedenia girellae; the susceptibility of S. aurata towards this pathogenic capsalid monogenean highlighted in the present work represents an important risk in the farming of this valuable fish species.
Comparative Efficacy of State-of-the-Art and New Biological Stump Treatments in Forests Infested by the Native and the Alien Invasive Heterobasidion Species Present in Europe
Authors: Pellicciaro Martina , Lione Guglielmo , Ongaro Silvia , Gonthier Paolo
Published: October 2021

The Heterobasidion annosum species complex includes major fungal pathogens of conifers worldwide. State-of-the-art preventative stump treatments with urea or with commercial formulations of the fungal biological control agent Phlebiopsis gigantea (i.e., Rotstop®) may become no longer available or are not approved for use in many areas of Europe infested by the three native Heterobasidion species and by the North American invasive H. irregulare, making the development of new treatments timely. The efficacy of Proradix® (based on Pseudomonas protegens strain DSMZ 13134), the cell-free filtrate (CFF) of the same bacterium, a strain of P. gigantea (MUT 6212) collected in the invasion area of H. irregulare in Italy, Rotstop®, and urea was comparatively investigated on a total of 542 stumps of Abies alba, Picea abies, Pinus pinea, and P. sylvestris in forest stands infested by the host-associated Heterobasidion species. Additionally, 139 logs of P. pinea were also treated. Results support the good performances of Rotstop®, and especially of urea against the native Heterobasidion species on stumps of their preferential hosts and, for the first time, towards the invasive North American H. irregulare on stumps of P. pinea. In some experiments, the effectiveness of Proradix® and of the strain of P. gigantea was weak, whereas the CFF of P. protegens strain DSMZ 13134 performed as a valid alternative to urea and Rotstop®. The mechanism of action of this treatment hinges on antibiosis; therefore, further improvements could be possible by identifying the active molecules and/or by optimizing their production. Generally, the performance of the tested treatments is not correlated with the stump size.
Ticks and Tick-Borne Diseases in Central America and the Caribbean: A One Health Perspective
Authors: Charles Roxanne A. , Bermúdez Sergio , Banović Pavle , Alvarez Dasiel Obregón , Díaz-Sánchez Adrian Alberto , Corona-González Belkis , Etter Eric Marcel Charles , Rodríguez González Islay , Ghafar Abdul , Jabbar Abdul , Moutailler Sara , Cabezas-Cruz Alejandro
Published: October 2021

Ticks have complex life cycles which involve blood-feeding stages found on wild and domestic animals, with humans as accidental hosts. At each blood-feeding stage, ticks can transmit and/or acquire pathogens from their hosts. Therefore, the circulation of tick-borne pathogens (TBPs), especially the zoonotic ones, should be studied in a multi-layered manner, including all components of the chain of infections, following the ‘One Health’ tenets. The implementation of such an approach requires coordination among major stakeholders (such as veterinarians, physicians, acarologists, and researchers) for the identification of exposure and infection risks and application of effective prevention measures. In this review, we summarize our current knowledge on the epidemiology of tick-borne diseases in Central America and the Caribbean and the challenges associated with the implementation of ‘One Health’ surveillance and control programs in the region.
Epstein-Barr Virus Promotes Tumor Angiogenesis by Activating STIM1-Dependent Ca2+ Signaling in Nasopharyngeal Carcinoma
Authors: Ye Jiaxiang , Wei Jiazhang , Luo Yue , Deng Yayan , Que Ting , Zhang Xiaojian , Liu Fei , Zhang Jinyan , Luo Xiaoling
Published: October 2021

Epstein-Barr virus (EBV) promotes tumor angiogenesis in nasopharyngeal carcinoma (NPC) by activating store-operated Ca2+ entry. Since such entry has been linked to stromal interaction molecule 1 (STIM1), we examined whether the virus acts via STIM1-dependent Ca2+ signaling to promote tumor angiogenesis in NPC. STIM1 expression was detected in NPC cell lines HK1 and CNE2 that were negative or positive for EBV. STIM1 was knocked down in EBV-positive cells using recombinant lentivirus, then cytosolic Ca2+ levels were measured based on fluorescence resonance energy transfer. Cells were also exposed to epidermal growth factor (EGF), and secretion of vascular endothelial growth factor (VEGF) was measured using an enzyme-linked immunosorbent assay. Endothelial tube formation was quantified in an in vitro angiogenesis assay. Growth of CNE2-EBV xenografts was measured in mice, and angiogenesis was assessed based on immunohistochemical staining against CD31. Paraffin-embedded NPC tissues from patients were assayed for CD31 and STIM1. EGFR and ERK signaling pathways were assessed in NPC cell lines. STIM1 expression was higher in EBV-positive than in EBV-negative NPC cell lines. STIM1 knockdown in EBV-positive NPC cells significantly reduced Ca2+ influx and VEGF production after EGF treatment. STIM1 knockdown also inhibited xenograft growth and angiogenesis. Moreover, CD31 expression level was higher in EBV-positive than EBV-negative NPC tissues, and high expression of CD31 co-localized with high expression of STIM1 in EBV-positive tissues from NPC patients. Viral infection of NPC cells led to higher levels of phosphorylated ERK1/2 after EGF treatment, which STIM1 knockdown partially reversed. Our results suggest that EBV promotes EGF-induced ERK1/2 signaling by activating STIM1-dependent Ca2+ signaling, and that blocking such signaling may inhibit EBV-promoted angiogenesis in NPC.
High Mutation Frequency and Significant Population Differentiation in Papaya Ringspot Virus-W Isolates
Authors: Khanal Vivek , Ali Akhtar
Published: October 2021

A total of 101 papaya ringspot virus-W (PRSV-W) isolates were collected from five different cucurbit hosts in six counties of Oklahoma during the 2016–2018 growing seasons. The coat protein (CP) coding region of these isolates was amplified by reverse transcription-polymerase chain reaction, and 370 clones (3–5 clones/isolate) were sequenced. Phylogenetic analysis revealed three phylogroups while host, location, and collection time of isolates had minimal impact on grouping pattern. When CP gene sequences of these isolates were compared with sequences of published PRSV isolates (both P and W strains), they clustered into four phylogroups based on geographical location. Oklahoman PRSV-W isolates formed one of the four distinct major phylogroups. The permutation-based tests, including Ks, Ks *, Z *, Snn, and neutrality tests, indicated significant genetic differentiation and polymorphisms among PRSV-W populations in Oklahoma. The selection analysis confirmed that the CP gene is undergoing purifying selection. The mutation frequencies among all PRSV-W isolates were within the range of 1 × 10−3. The substitution mutations in 370 clones of PRSV-W isolates showed a high proportion of transition mutations, which gave rise to higher GC content. The N-terminal region of the CP gene mostly contained the variable sites with numerous mutational hotspots, while the core region was highly conserved.
Vascular Changes and Hypoxia in Periodontal Disease as a Link to Systemic Complications
Authors: Celik Dilek , Kantarci Alpdogan
Published: October 2021

The hypoxic microenvironment caused by oral pathogens is the most important cause of the disruption of dynamic hemostasis between the oral microbiome and the immune system. Periodontal infection exacerbates the inflammatory response with increased hypoxia and causes vascular changes. The chronicity of inflammation becomes systemic as a link between oral and systemic diseases. The vascular network plays a central role in controlling infection and regulating the immune response. In this review, we focus on the local and systemic vascular network change mechanisms of periodontal inflammation and the pathological processes of inflammatory diseases. Understanding how the vascular network influences the pathology of periodontal diseases and the systemic complication associated with this pathology is essential for the discovery of both local and systemic proactive control mechanisms.
Kinetic Study of BLV Infectivity in BLV Susceptible and Resistant Cattle in Japan from 2017 to 2019
Authors: Bai Lanlan , Borjigin Liushiqi , Sato Hirotaka , Takeshima Shin-Nosuke , Asaji Sakurako , Ishizaki Hiroshi , Kawashima Keiji , Obuchi Yuko , Sunaga Shinji , Ando Asako , Inoko Hidehito , Wada Satoshi , Aida Yoko
Published: October 2021

Bovine leukemia virus (BLV) is the causative agent of enzootic bovine leukosis. Polymorphism in bovine lymphocyte antigen (BoLA)-DRB3 alleles is related to susceptibility to BLV proviral load (PVL), which is a useful index for estimating disease progression and transmission risk. However, whether differential BoLA-DRB3 affects BLV infectivity remains unknown. In a three-year follow-up investigation using a luminescence syncytium induction assay for evaluating BLV infectivity, we visualized and evaluated the kinetics of BLV infectivity in cattle with susceptible, resistant and neutral BoLA-DRB3 alleles which were selected from 179 cattle. Susceptible cattle showed stronger BLV infectivity than both resistant and neutral cattle. The order of intensity of BLV infectivity was as follows: susceptible cattle > neutral cattle > resistant cattle. BLV infectivity showed strong positive correlation with PVL at each testing point. BLV-infected susceptible cattle were found to be at higher risk of horizontal transmission, as they had strong infectivity and high PVL, whereas BLV-infected resistant cattle were low risk of BLV transmission owing to weak BLV infection and low PVL. Thus, this is the first study to demonstrate that the BoLA-DRB3 polymorphism is associated with BLV infection.
Emerging Mutations in Nsp1 of SARS-CoV-2 and Their Effect on the Structural Stability
Authors: Mou Kejie , Mukhtar Farwa , Khan Muhammad Tahir , Darwish Doaa B. , Peng Shaoliang , Muhammad Shabbir , Al-Sehemi Abdullah G. , Wei Dong-Qing
Published: October 2021

The genome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) encodes 16 non-structural (Nsp) and 4 structural proteins. Among the Nsps, Nsp1 inhibits host gene expression and also evades the immune system. This protein has been proposed as a target for vaccine development and also for drug design. Owing to its important role, the current study aimed to identify mutations in Nsp1 and their effect on protein stability and flexibility. This is the first comprehensive study in which 295,000 complete genomes have been screened for mutations after alignment with the Wuhan-Hu-1 reference genome (Accession NC_045512), using the CoVsurver app. The sequences harbored 933 mutations in the entire coding region of Nsp1. The most frequently occurring mutation in the 180-amino-acid Nsp1 protein was R24C (n = 1122), followed by D75E (n = 890), D48G (n = 881), H110Y (n = 860), and D144A (n = 648). Among the 933 non-synonymous mutations, 529 exhibited a destabilizing effect. Similarly, a gain in flexibility was observed in 542 mutations. The majority of the most frequent mutations were detected in the loop regions. These findings imply that Nsp1 mutations might be useful to exploit SARS-CoV-2′s pathogenicity. Genomic sequencing of SARS-CoV-2 on a regular basis will further assist in analyzing variations among the drug targets and to test the diagnostic accuracy. This wide range of mutations and their effect on Nsp1’s stability may have some consequences for the host’s innate immune response to SARS-CoV-2 infection and also for the vaccines’ efficacy. Based on this mutational information, geographically strain-specific drugs, vaccines, and antibody combinations could be a useful strategy against SARS-CoV-2 infection.
Persistence of Antibody Responses to the SARS-CoV-2 in Dialysis Patients and Renal Transplant Recipients Recovered from COVID-19
Authors: Cappuccilli Maria , Bruno Paolo Ferdinando , Spazzoli Alessandra , Righini Matteo , Flachi Marta , Semprini Simona , Grumiro Laura , Marino Maria Michela , Schiavone Pasqua , Fabbri Elisabetta , Fantini Michela , Buscaroli Andrea , Rigotti Angelo , La Manna Gaetano , Sambri Vittorio , Mosconi Giovanni
Published: October 2021

Nephropathic subjects with impaired immune responses show dramatically high infection rates of coronavirus disease 2019 (COVID-19). This work evaluated the ability to acquire and maintain protective antibodies over time in 26 hemodialysis patients and 21 kidney transplant recipients. The subjects were followed-up through quantitative determination of circulating SARS-CoV-2 S1/S2 IgG and neutralizing antibodies in the 6-month period after clinical and laboratory recovery. A group of 143 healthcare workers with no underlying chronic pathologies or renal diseases recovered from COVID was also evaluated. In both dialysis and transplanted patients, antibody titers reached a zenith around the 3rd month, and then a decline occurred on average between the 270th and 300th day. Immunocompromised patients who lost antibodies around the 6th month were more common than non-renal subjects, although the difference was not significant (38.5% vs. 26.6%). Considering the decay of antibody levels below the positivity threshold (15 AU/mL) as “failure”, a progressive loss of immunisation was found in the overall population starting 6 months after recovery. A longer overall antibody persistence was observed in severe forms of COVID-19 (p = 0.0183), but within each group, given the small number of patients, the difference was not significant (dialysis: p = 0.0702; transplant: p = 0.1899). These data suggest that immunocompromised renal patients recovered from COVID-19 have weakened and heterogeneous humoral responses that tend to decay over time. Despite interindividual variability, an association emerged between antibody persistence and clinical severity, similar to the subjects with preserved immune function.
Detection of Toxocara cati Larvae from Ostrich and Wild Boar Meat Intended for Human Consumption
Authors: Michelutti Alice , Sgubin Sofia , Falcaro Christian , Cagnin Valentina , Zoroaster Alessia , Danesi Patrizia
Published: October 2021

Toxocara cati is a common roundworm of cats and wild felids and, together with T. canis, it is the main causative agent of human toxocariasis. Humans may become infected by ingestion of embryonated eggs via contaminated soil, food, or water, or by ingestion of raw or undercooked meat of paratenic hosts that are infected by Toxocara larvae. In this study, we report the detection of T. cati larvae from meat samples of ostriches and wild boars. These samples were inspected by enzymatic digestion, as part of the trichinellosis surveillance. As ostrich meat is intended for “carpaccio” preparation, a traditional Italian raw meat preparation, there is the need to make the consumption of this meat safe. For this purpose, it is recommended to freeze the meat before preparation. Our findings confirmed that T. cati larvae can contaminate muscle tissues of paratenic hosts, increasing the risk of infection due to the consumption of raw or undercooked meat.
Neuraminidase in Virus-like Particles Contributes to the Protection against High Dose of Avian Influenza Virus Challenge Infection
Authors: Kang Hae-Ji , Chu Ki-Back , Yoon Keon-Woong , Eom Gi-Deok , Mao Jie , Kim Min-Ju , Lee Su-Hwa , Moon Eun-Kyung , Quan Fu-Shi
Published: October 2021

Neuraminidase is an important target for influenza vaccination. In this study, we generated avian influenza VLPs, expressing hemagglutinin (HA), neuraminidase (NA), HA and NA co-expressed (HANA), to evaluate the protective role of NA against a high (10LD50) and low (2LD50) dose of avian influenza virus challenge infections. A single immunization with HANA VLPs elicited the highest level of virus-specific IgG, IgG1, and IgG2a responses from the sera post-vaccination and the lungs post-challenge-infection. Potent antibody-secreting cell responses were observed from the spleens and lungs of HANA-VLP-immunized mice post-challenge-infection. HANA VLPs induced the highest CD4+ T cell, CD8+ T cell, and germinal center B cells, while strongly limiting inflammatory cytokine production in the lungs compared to other VLP immunization groups. In correlation with these findings, the lowest bodyweight losses and lung virus titers were observed from HANA VLP immunization, and all of the immunized mice survived irrespective of the challenge dose. Contrastingly, VLPs expressing either HA or NA alone failed to elicit complete protection. These results indicated that NA in VLPs played a critical role in inducing protection against a high dose of the challenge infection.
The Long Journey to BVD Eradication
Authors: Moennig Volker , Yarnall Matt J.
Published: October 2021

This paper provides a short review of bovine virus diarrhoea (BVD) control programmes across Europe, with a particular focus on current efforts from a stakeholder perspective. Using outputs gained from a global, virtual congress on BVD control, the theory of the journey from BVD control to possible eradication is enriched with insight from stakeholders representing the major parts of the cattle industry. Current control programmes were presented by Javier Dieguez (Galicia), Neil Shand (England), Neil Paton (Wales), Jenny Purcell (Scotland), Maria Guelbenzu (Ireland), Jörn Gethmann (Germany), and Matthias Schweizer (Switzerland).
Phenotypic Switching of B16F10 Melanoma Cells as a Stress Adaptation Response to Fe3O4/Salicylic Acid Nanoparticle Therapy
Authors: Mîndrilă Ion , Osman Andrei , Mîndrilă Bogdan , Predoi Maria Cristina , Mihaiescu Dan Eduard , Buteică Sandra Alice
Published: October 2021

Melanoma is a melanocyte-derived skin cancer that has a high heterogeneity due to its phenotypic plasticity, a trait that may explain its ability to survive in the case of physical or molecular aggression and to develop resistance to therapy. Therefore, the therapy modulation of phenotypic switching in combination with other treatment modalities could become a common approach in any future therapeutic strategy. In this paper, we used the syngeneic model of B16F10 melanoma implanted in C57BL/6 mice to evaluate the phenotypic changes in melanoma induced by therapy with iron oxide nanoparticles functionalized with salicylic acid (SaIONs). The results of this study showed that the oral administration of the SaIONs aqueous dispersion was followed by phenotypic switching to highly pigmented cells in B16F10 melanoma through a cytotoxicity-induced cell selection mechanism. The hyperpigmentation of melanoma cells by the intra- or extracellular accumulation of melanic pigment deposits was another consequence of the SaIONs therapy. Additional studies are needed to assess the reversibility of SaIONs-induced phenotypic switching and the impact of tumor hyperpigmentation on B16F10 melanoma’s progression and metastasis abilities.
Molecular Targets and Promising Therapeutics of Triple-Negative Breast Cancer
Authors: Ryu Won-Ji , Sohn Joo Hyuk
Published: October 2021

Triple-negative breast cancer (TNBC) is one of the most heterogeneous diseases in solid tumors and has limited therapeutic options. Due to the lack of appropriate targetable markers, the mainstay therapeutic strategy for patients with TNBC has been chemotherapy for the last several decades. Indeed, TNBC tumors have no expression of estrogen receptor, progesterone receptor, or human epidermal growth factor receptor 2 (HER2); therefore, they do not respond to hormone therapy and HER2-targeted therapy. In this review paper, the molecular heterogeneities, possible therapeutic targets, and recently approved and upcoming drugs for TNBC will be summarized.
HIV-1 Reverse Transcriptase Inhibition by Major Compounds in a Kenyan Multi-Herbal Composition (CareVid™): In Vitro and In Silico Contrast
Authors: Rotich Winnie , Sadgrove Nicholas J. , Mas-Claret Eduard , Padilla-González Guillermo F. , Guantai Anastasia , Langat Moses K.
Published: October 2021

CareVid is a multi-herbal product used in southwest Kenya as an immune booster and health tonic and has been anecdotally described as improving the condition of HIV-positive patients. The product is made up of roots, barks and whole plant of 14 African medicinal plants: Acacia nilotica (L.) Willd. ex Delile (currently, Vachelia nilotica (L.) P.J.H Hurter & Mabb.), Adenia gummifera (Harv.) Harms, Anthocleista grandiflora Gilg, Asparagus africanus Lam., Bersama abyssinica Fresen., Clematis hirsuta Guill. & Perr., Croton macrostachyus Hochst. ex Delile, Clutia robusta Pax (accepted as Clutia kilimandscharica Engl.), Dovyalis abyssinica (A. Rich.) Warb, Ekebergia capensis Sparm., Periploca linearifolia Quart.-Dill. & A. Rich., Plantago palmata Hook.f., Prunus africana Hook.f. Kalkman and Rhamnus prinoides L’Her. The objective of this study was to determine the major chemical constituents of CareVid solvent extracts and screen them for in vitro and in silico activity against the HIV-1 reverse transcriptase enzyme. To achieve this, CareVid was separately extracted using CH2Cl2, MeOH, 80% EtOH in H2O, cold H2O, hot H2O and acidified H2O (pH 1.5–3.5). The extracts were analysed using HPLC–MS equipped with UV diode array detection. HIV-1 reverse transcriptase inhibition was performed in vitro and compared to in silico HIV-1 reverse transcriptase inhibition, with the latter carried out using MOE software, placing the docking on the hydrophobic pocket in the subdomain of p66, the NNRTI pocket. The MeOH and 80% EtOH extracts showed strong in vitro HIV-1 reverse transcriptase inhibition, with an EC50 of 7 μg·mL−1. The major components were identified as sucrose, citric acid, ellagic acid, catechin 3-hexoside, epicatechin 3-hexoside, procyanidin B, hesperetin O-rutinoside, pellitorine, mangiferin, isomangiferin, 4-O-coumaroulquinic acid, ellagic acid, ellagic acid O-pentoside, crotepoxide, oleuropein, magnoflorine, tremulacin and an isomer of dammarane tetrol. Ellagic acid and procyanidin B inhibited the HIV-1 reverse transcription process at 15 and 3.2 µg/mL−1, respectively. Docking studies did not agree with in vitro results because the best scoring ligand was crotepoxide (ΔG = −8.55 kcal/mol), followed by magnoflorine (ΔG = −8.39 kcal/mol). This study showed that CareVid has contrasting in vitro and in silico activity against HIV-1 reverse transcriptase. However, the strongest in vitro inhibitors were ellagic acid and procyanidin B.
Targeting SARS-CoV-2 Variants with Nucleic Acid Therapeutic Nanoparticle Conjugates
Authors: Huber Hanah F. , Jaberi-Douraki Majid , DeVader Sarah , Aparicio-Lopez Cesar , Nava-Chavez Juliet , Xu Xuan , Millagaha Gedara Nuwan Indika , Gaudreault Natasha N. , Delong Robert K.
Published: October 2021

The emergence of SARS-CoV-2 variants is cause for concern, because these may become resistant to current vaccines and antiviral drugs in development. Current drugs target viral proteins, resulting in a critical need for RNA-targeted nanomedicines. To address this, a comparative analysis of SARS-CoV-2 variants was performed. Several highly conserved sites were identified, of which the most noteworthy is a partial homopurine palindrome site with >99% conservation within the coding region. This sequence was compared among recently emerged, highly infectious SARS-CoV-2 variants. Conservation of the site was maintained among these emerging variants, further contributing to its potential as a regulatory target site for SARS-CoV-2. RNAfold was used to predict the structures of the highly conserved sites, with some resulting structures being common among coronaviridae. An RNA-level regulatory map of the conserved regions of SARS-CoV-2 was produced based on the predicted structures, with each representing potential target sites for antisense oligonucleotides, triplex-forming oligomers, and aptamers. Additionally, homopurine/homopyrimidine sequences within the viral genome were identified. These sequences also demonstrate appropriate target sites for antisense oligonucleotides and triplex-forming oligonucleotides. An experimental strategy to investigate these is summarized along with potential nanoparticle types for delivery, and the advantages and disadvantages of each are discussed.
Inhibition of Matrix Metalloproteinases and Cancer Cell Detachment by Ru(II) Polypyridyl Complexes Containing 4,7-Diphenyl-1,10-phenanthroline Ligands—New Candidates for Antimetastatic Agents
Authors: Gajda-Morszewski Przemysław , Gurgul Ilona , Janczy-Cempa Ewelina , Mazuryk Olga , Łomzik Michał , Brindell Małgorzata
Published: October 2021

Primary tumor targeting is the dominant approach in drug development, while metastasis is the leading cause of cancer death. Therefore, in addition to the cytotoxic activity of a series of Ru(II) polypyridyl complexes of the type [Ru(dip)2L]2+ (dip: 4,7-diphenyl-1,10-phenanthroline while L = dip; bpy: 2,2′-bipyridine; bpy-SC: bipyridine derivative bearing a semicarbazone 2-formylopyridine moiety; dpq, dpq(CH3)2, dpb: quinoxaline derivatives) their ability to inhibit cell detachment was investigated. In vitro studies performed on lung cancer A549 cells showed that they accumulate in cells very well and exhibit moderate cytotoxicity with IC50 ranging from 4 to 13 µM. Three of the studied compounds that have dip, bpy-SC, or dpb ligands after treatment of the cells with a non-toxic dose (<1/2IC50) enhanced their adhesion properties demonstrated by lower detachment in the trypsin resistance assay. The same complexes inhibited both MMP-2 and MMP-9 enzyme activities with IC50 ranging from 2 to 12 µM; however, the MMP-9 inhibition was stronger. More detailed studies for [Ru(dip)2(bpy-SC)]2+, which induced the greatest increase in cell adhesion, revealed that it is predominately accumulated in the cytoskeletal fraction of A549 cells. Moreover, cells treated with this compound showed the localization of MMP-9 to a greater extent also in the cytoskeleton. Taken together, our results indicate the possibility of a reduction of metastatic cells escaping from the primary lesion to the surrounding tissue by prevention of their detachment and by influencing the activity of MMP-2 and MMP-9.