bluuebunny/crossref_metadata_2025 huggingface dataset:
Changes of Gene Expression Patterns from Aquatic Organisms Exposed to Metal Nanoparticles
Authors: Kulasza Mateusz , Skuza Lidia
Published: August 2021

Metal nanoparticles are used in various branches of industry due to their physicochemical properties. However, with intensive use, most of the waste and by-products from industries and household items, and from weathering of products containing nanoparticles, end up in the waters. These pollutants pose a risk to aquatic organisms, one of which is a change in the expression of various genes. Most of the data that focus on metal nanoparticles and their effects on aquatic organisms are about copper and silver nanoparticles, which is due to their popularity in general industry, but information about other nanoparticulate metals can also be found. This review aims to evaluate gene expression patterns in aquatic organisms by metal nanoparticles, specifying details about the transcription changes of singular genes and, if possible, comparing the changes in the expression of the same genes in different organisms. To achieve this goal, available publications tackling this problem are studied and summarized. Nanometals were found to have a modulatory effect on gene expression in different aquatic organisms. Data show both up-regulation and down-regulation of genes. Nano silver, nano copper, and nano zinc show a regulatory effect on genes involved in inflammation and apoptosis, cell cycle regulation and ROS defense as well as in general stress response and have a negative effect on the expression of genes involved in development. Nano gold, nano titanium, nano zinc, and nano iron tend to elevate the transcripts of genes involved in response to ROS, but also pro-apoptotic genes and down-regulate DNA repair-involved genes and anti-apoptotic-involved genes. Nano selenium showed a rare effect that is protective against harmful effects of other nanoparticles, but also induced up-regulation of stress response genes. This review focuses only on the effects of metal nanoparticles on the expression of various genes of aquatic organisms from different taxonomic groups.
Effective Community-Based Interventions for the Prevention and Management of Heat-Related Illnesses: A Scoping Review
Authors: Hasan Fariha , Marsia Shayan , Patel Kajal , Agrawal Priyanka , Razzak Junaid Abdul
Published: August 2021

Background: Extreme temperatures have negative consequences on the environment, ecosystem, and human health. With recent increases in global temperatures, there has been a rise in the burden of heat-related illnesses, with a disproportionate impact on low- and middle-income countries. Effective population-level interventions are critical to a successful public health response. Objective: This scoping review aims to summarize the evidence on the effectiveness of population-level heat-related interventions and serve as a potential guide to the implementation of these interventions. Methods: Studies that evaluated the effectiveness of community-based interventions to mitigate or reduce the impact of extreme heat on heat-related mortality and morbidity were sought by searching four electronic databases. Studies published in the English language and those that had quantifiable, measurable mortality, morbidity or knowledge score outcomes were included. Results: The initial electronic search yielded 2324 articles, and 17 studies were included. Fourteen studies were based in high-income countries (HICs) (Europe, US, Canada) and discussed multiple versions of (1) heat action plans, which included but were not limited to establishing a heat monitoring system, informative campaigns, the mobilization of health care professionals, volunteers, social workers and trained caregivers in the surveillance and management of individuals with known vulnerabilities, or stand-alone (2) education and awareness campaigns. Multi-pronged heat action plans were highly effective in reducing heat-related mortality and morbidity, especially among vulnerable populations such as the elderly and those with chronic conditions. Conclusions: The heat action plans covered in these studies have shown promising results in reducing heat-related mortality and morbidity and have included instituting early warning systems, building local capacity to identify, prevent or treat and manage heat-related illnesses, and disseminating information. Nevertheless, they need to be cost-effective, easy to maintain, ideally should not rely on a mass effort from people and should be specifically structured to meet the local needs and resources of the community.
The Effect of Additional Private Health Insurance on Mortality in the Context of Universal Public Health Insurance
Authors: Baek Eun-Mi , Oh Jae-Il , Kwon Eun-Jung
Published: August 2021

(1) Background: Korea operates its national health insurance (NHI) system as a form of public health insurance, and is commonly regarded as having achieved universal health coverage (UHC). However, many Korean households register for additional private health insurance (PHI) programs. Typically, registration rates for PHI are higher for individuals with a higher socioeconomic status (SES). A difference in mortality between those with and without additional PHI would indicate that there are health inequalities within the Korean NHI system under UHC. Therefore, this study aimed to confirm whether additional PHI affects mortality under the Korean NHI system. (2) Methods: We conducted a longitudinal study using the Korean Longitudinal Study of Aging data from the first to the sixth wave. The analysis included 8743 participants, who were divided into two groups: those who only had NHI and those who had both NHI and PHI. Differences in mortality between the two groups were compared using the Cox proportional hazard regression. (3) Results: The group with both NHI and PHI had lower mortality than the group with only NHI (hazard ratio = 0.53, 95% confidence interval: 0.41, 0.9). (4) Conclusions: The results of this study reveal that there are health disparities according to SES and PHI within the Korean NHI system under UHC. Therefore, relevant government institutions and experts should further improve the NHI system to reduce health disparities.
Differential Access to Park Space Based on Country of Origin within Miami’s Hispanic/Latino Population: A Novel Analysis of Park Equity
Authors: Allain Marco Lorenzo , Collins Timothy W.
Published: August 2021

Some U.S.-based park equity studies reveal that affluent and White neighborhoods have privileged access to greenspace. In such studies in the U.S. and elsewhere, park access indicators are typically examined in relation to measures of income, housing tenure, and broad race/ethnicity categories (e.g., Hispanic/Latino, Black, and White in the U.S.). The treatment of people as monolithic ethnic groups in park equity research is potentially misleading, particularly in global cities where ethnic populations are highly heterogeneous. In this study, we assess inequities in access to park space within the diverse Hispanic/Latino population of the Miami Metropolitan Statistical Area (MSA) based on national origin. We specified multivariable generalized estimating equations to examine social correlates of area-weighted park access at the census tract level. Our first model includes a variable for the proportion of the tract population of Hispanic/Latino ethnicity, which we substitute in the second model with variables representing the proportions of the tract population from the most populous country-of-origin groups in the MSA applicable to the Hispanic/Latino population. Our first model indicates robust negative relationships for the proportion Hispanic/Latino and Black/African American variables with area-weighted park access, adjusting for median household income, renter-occupancy, and old and young population composition. Our second model indicates negative relationships based on Cuban and Venezuelan neighborhood composition, while the four other country-of-origin subgroup variables exhibit statistically non-significant associations with area-weighted park access. Study findings have implications for the analysis of ethnicity categories in park equity research and interventions to promote park equity, especially in global cities.
Using Autoregressive Integrated Moving Average (ARIMA) Modelling to Forecast Symptom Complexity in an Ambulatory Oncology Clinic: Harnessing Predictive Analytics and Patient-Reported Outcomes
Authors: Watson Linda , Qi Siwei , DeIure Andrea , Link Claire , Chmielewski Lindsi , Hildebrand April , Rawson Krista , Ruether Dean
Published: August 2021

An increasing incidence of cancer has led to high patient volumes and time challenges in ambulatory oncology clinics. By knowing how many patients are experiencing complex care needs in advance, clinic scheduling and staff allocation adjustments could be made to provide patients with longer or shorter timeslots to address symptom complexity. In this study, we used predictive analytics to forecast the percentage of patients with high symptom complexity in one clinic population in a given time period. Autoregressive integrated moving average (ARIMA) modelling was utilized with patient-reported outcome (PRO) data and patient demographic information collected over 24 weeks. Eight additional weeks of symptom complexity data were collected and compared to assess the accuracy of the forecasting model. The predicted symptom complexity levels were compared with observation data and a mean absolute predicting error of 5.9% was determined, indicating the model’s satisfactory accuracy for forecasting symptom complexity levels among patients in this clinic population. By using a larger sample and additional predictors, this model could be applied to other clinics to allow for tailored scheduling and staff allocation based on symptom complexity forecasting and inform system level models of care to improve outcomes and provide higher quality patient care.
Secondary Analysis of a Study on Exercise Therapy in Hip Osteoarthritis: Follow-Up Data on Pain and Physical Functioning
Authors: Roesel Inka , Steinhilber Benjamin , Martus Peter , Janssen Pia , Krauss Inga
Published: August 2021

We evaluated the short- and longer-term effects of exercise therapy in hip osteoarthritis patients (OA) at baseline, three, six, and 12 months in a randomized setting, followed by a non-randomized setting. The primary randomized intervention (E = exercise, P = placebo–ultrasound, C = control) was followed by a voluntary three-month exercise therapy for P and C (renamed P-E, C-E). Participants randomized to E were not offered treatment again (E-C). Effect sizes (ES; 95% CI) were calculated for within-group effects across time for bodily pain (SF-36) and WOMAC pain, function, and stiffness. ANCOVAs of post-treatment scores were used for group comparison after the group-specific exercise intervention phase. Exercise adherence was assessed and related to post-treatment scores of clinical outcomes. Data of 115 participants of the RCT eligible for follow-up and completing exercise therapy were included into our analyses. Small to medium beneficial long-term effects of cumulative interventional effects, including exercise training, persisted in all groups. Group E-C (n = 49) showed significant 12 months vs. baseline within-group ES in all outcomes (ES 0.39–0.59) except stiffness. Findings were less prominent for exercise therapy in a non-randomized setting (C-E, P-E, both n = 33). Differences are partially explained by adherence rates, highlighting the relevance of therapy compliance strategies. Short-term between-group differences (ANCOVAs) only showed statistically significant differences for WOMAC function between P-E and E-C in favor of E-C (6.4 (95% CI 1.6–11.2; score range 0–100)).
Dietary Quality of Pregnant Women Participating in the Special Supplemental Nutrition Program for Women, Infants, and Children
Authors: Rojhani Arezoo , Ouyang Ping , Gullon-Rivera Angel , Dale Taylor Marie
Published: August 2021

Few studies have examined the dietary intake of low-income pregnant women participating in the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC). The aim of this study was to assess the dietary quality of WIC-enrolled pregnant women and examine associations with maternal characteristics, nutrition knowledge, and key health indicators. Fifty-one WIC-enrolled pregnant women completed two sets of 3-day food records. Food records were analyzed for nutrient content, and diet quality was assessed using the Healthy Eating Index (HEI)-2015. Since an HEI score of less than 60 is indicative of the need to improve dietary quality, participants’ HEI scores were divided into two categories: <60 and ≥60. The total mean HEI score of the cohort based on analysis of the first set of food records was 59.1 ± 12.5 (range 37.1–89.2), while the mean score for the second 3 days of food records was 56.8 ± 12.7 (range 30.0–89.0). The majority of participants did not consume the minimum recommended servings of whole vegetables. Those in the <60 HEI category consumed on average less than 50% of the recommended servings of whole fruits and whole grains. The diets of the majority of participants were high in saturated fat and sodium. More than one-third did not meet the recommendations for folate and iron intake, while less than half met the RDA for vitamin D. Choline intake was insufficient based on analysis of the first 3 days of food records. Our results indicate that the dietary quality of WIC-enrolled pregnant women requires improvement.
Dentist Related Factors Associated with Implementation of COVID-19 Protective Measures: A National Survey
Authors: Carvalho Joana Christina , Declerck Dominique , Jacquet Wolfgang , Bottenberg Peter
Published: August 2021

Little is known about the extent to which dentists have implemented COVID-19 infection control guidelines and the factors influencing this process in daily practice. This national online survey assessed the implementation of enhanced infection control guidelines in daily practice, and explored dentist related factors influencing their application, more specifically dentist infection status and their perceived risk of cross-infection in the dental setting. The survey was validated, pretested and carried out in 2020. A total of 1436 dentists participated, of whom 9.1% presumably had COVID-19 infection experience. At least 75% of dentists complied with the core part of the recommended protective measures protocol. For each patient treated during the pandemic, an additional cost of 10–30 EUR (86.7%) and an extra time of 10–30 min (70.7%) was estimated. A stepwise binary logistic regression analysis revealed that dentists assumed to have experienced COVID-19 reported a higher self-perceived risk of virus acquisition (β = 2.090; p = 0.011), lower concern of getting infected (β = 0.576; p = 0.027), and lower confidence in being able to prevent disease transmission in the dental setting (β = 0.535; p = 0.022). Some parts of the protective measures were more difficult to apply than others; however, there was no indication of increased disease acquisition in the dental setting.
Application of Edge Computing Technology in Hydrological Spatial Analysis and Ecological Planning
Authors: Cai Xinhong , Xu Dawei
Published: August 2021

The process of rapid urbanization causes so many water security issues such as urban waterlogging, environmental water pollution, water shortages, etc. It is, therefore, necessary for us to integrate a variety of theories, methods, measures, and means to conduct ecological problem diagnosis, ecological function demand assessment, and ecological security pattern planning. Here, EC (Edge Computing) technology is applied to analyze the hydrological spatial structure characteristics and ecological planning method of waterfront green space. First, various information is collected and scientifically analyzed around the core element of ecological planning: water. Then, in-depth research is conducted on the previous hydrological spatial analysis methods to identify their defects. Subsequently, given these defects, the EC technology is introduced to design a bottom-up overall architecture of intelligent ecological planning gateway, which can be divided into field devices, EC intelligent planning gateway, transmission system, and cloud processing platform. Finally, the performance of the overall architecture of the intelligent ecological planning gateway is tested. The study aims to optimize the performance of the hydrological spatial analysis method and ecological planning method in Xianglan town of Jiamusi city. The results show that the system can detect the flood control safety system planning, analysis of water source pollution. Additionally, the system also can use the EC technology, depending on the types, hydrological characteristics, pollutants to predict treatment sludge need to put in the pollutant treatment medicament composition and dosage, protection of water source nearby residents public health security. Compared with previous hydrological spatial analysis and ecological planning methods, the system is more scientific, efficient, and expandable. The results provide a technical basis for the research in related fields.
Living with the Late Effects of Childhood Cancer Treatment: A Descriptive Qualitative Study
Authors: Hong Hye Chong , Min Ari , Choi Sungkyoung
Published: August 2021

Long-term childhood cancer survivors (CCS) may experience physical, social, and emotional struggles posttreatment. Our aim was to explore the experiences of CCS dealing with the late effects of cancer treatment from their own perspectives. This study employed a qualitative descriptive design to explore and describe the experience of dealing with late effects among CCS. Semi-structured interviews were conducted with 15 CCS in Korea. Participants were selected by purposive and snowball sampling and individually interviewed during the period from September to November 2020. Conventional content analysis was used to analyze data and identify themes. Two main themes and seven subthemes emerged. The two main themes were: “Things I encountered while crossing a bridge” and “Living as a survivor”. The participants reported both positive and negative experiences with dealing with the late effects of cancer treatment. The main themes indicated that late effects exert significant impacts on the lives of CCS in both positive and negative ways. Healthcare providers and researchers should pay attention to early intervention needs of CCS and their support systems to strengthen their positive experiences in dealing with late effects during their survivorships.
Influence of Wind Speed on CO2 and CH4 Concentrations at a Rural Site
Authors: Pérez Isidro A. , García María de los Ángeles , Sánchez María Luisa , Pardo Nuria
Published: August 2021

Meteorological variables have a noticeable impact on pollutant concentrations. Among these variables, wind speed is typically measured, although research into how pollutants respond to it can be improved. This study considers nine years of hourly CO2 and CH4 measurements at a rural site, where wind speed values were calculated by the METEX model. Nine wind speed intervals are proposed where concentrations, distribution functions, and daily as well as annual cycles are calculated. Contrasts between local and transported concentrations are around 5 and 0.03 ppm for CO2 and CH4, respectively. Seven skewed distributions are applied, and five efficiency criteria are considered to test the goodness of fit, with the modified Nash–Sutcliffe efficiency proving to be the most sensitive statistic. The Gumbel distribution is seen to be the most suitable for CO2, whereas the Weibull distribution is chosen for CH4, with the exponential function being the worst. Finally, daily and annual cycles are analysed, where a gradual decrease in amplitude is observed, particularly for the daily cycle. Parametric and nonparametric procedures are used to fit both cycles. The latter gave the best fits, with the agreement being higher for the daily cycle, where evolution is smoother than for the annual cycle.
Training Benefits and Injury Risks of Standing Yoga Applied in Musculoskeletal Problems: Lower Limb Biomechanical Analysis
Authors: Liu Ai-Min , Chu I-Hua , Lin Hwai-Ting , Liang Jing-Min , Hsu Hsiu-Tao , Wu Wen-Lan
Published: August 2021

Standing yoga poses strengthen a person’s legs and helps to achieve the goal of musculoskeletal rehabilitation, but inadequate exercise planning can cause injuries. This study investigated changes in the electromyogram and joint moments of force (JMOFs) of lower extremities during common standing yoga poses in order to explore the feasibility and possible injury risk in dealing with musculoskeletal problems. Eleven yoga instructors were recruited to execute five yoga poses (Chair, Tree, Warrior 1, 2, and 3). The results revealed significant differences in hip, knee, and ankle JMOFs and varying degrees of muscle activation among the poses. Among these poses, rectus femoris muscle activation during the Chair pose was the highest, Warrior 2 produced the highest muscle activation in the vastus lateralis of the front limb, while Warrior 1 had the highest muscle activation in the vastus medialis of the back limb. Therefore, all three poses can possibly be suggested as a therapeutic intervention for quadriceps strengthening. Warrior 1 was possibly suggested as a therapeutic intervention in order to reduce excessive lateral overload of the patella, but the possible adverse effects of Warrior 2 with the highest knee adductor JMOF in the back limb could raise joint reaction forces across the medial condyles. In single-leg balance postures, Warrior 3 had unique training effects on the hamstring, and is therefore suggested as a part of hamstring rehabilitation exercises. The Tree pose induced low lower-extremity JMOFs and a low level of thigh muscle activations when it was performed by senior instructors with excellent balance control; however, for yoga beginners with insufficient stability, it will be a useful training mode for strengthening the muscles that help to keep one upright. This study quantified the physical demands of yoga poses using biomechanical data and elucidated the structures and principles underlying each yoga movement. This is crucial for yoga practitioners.
Tumor-Associated Macrophages (TAMs) in Colorectal Cancer (CRC): From Mechanism to Therapy and Prognosis
Authors: Wang Hui , Tian Tian , Zhang Jinhua
Published: August 2021

Colorectal cancer (CRC) is a malignant tumor in the digestive system whose incidence and mortality is high-ranking among tumors worldwide. The initiation and progression of CRC is a complex process involving genetic alterations in cancer cells and multiple factors from the surrounding tumor cell microenvironment. As accumulating evidence has shown, tumor-associated macrophages (TAMs)—as abundant and active infiltrated inflammatory cells in the tumor microenvironment (TME)—play a crucial role in CRC. This review focuses on the different mechanisms of TAM in CRC, including switching of phenotypical subtypes; promoting tumor proliferation, invasion, and migration; facilitating angiogenesis; mediating immunosuppression; regulating metabolism; and interacting with the microbiota. Although controversy remains in clinical evidence regarding the role of TAMs in CRC, clarifying their significance in therapy and the prognosis of CRC may shed new light on the optimization of TAM-centered approaches in clinical care.
Decreased Levels of Microfibril-Associated Glycoprotein (MAGP)-1 in Patients with Colon Cancer and Obesity Are Associated with Changes in Extracellular Matrix Remodelling
Authors: Gómez de Segura Iranzu , Ahechu Patricia , Gómez-Ambrosi Javier , Rodríguez Amaia , Ramírez Beatriz , Becerril Sara , Unamuno Xabier , Mentxaka Amaia , Baixauli Jorge , Valentí Víctor , Moncada Rafael , Silva Camilo , Frühbeck Gema , Catalán Victoria
Published: August 2021

Objective: The protein microfibril-associated glycoprotein (MAGP)-1 constitutes a crucial extracellular matrix protein. We aimed to determine its impact on visceral adipose tissue (VAT) remodelling during obesity-associated colon cancer (CC). Methods: Samples obtained from 79 subjects (29 normoponderal (NP) (17 with CC) and 50 patients with obesity (OB) (19 with CC)) were used in the study. Circulating concentrations of MAGP-1 and its gene expression levels (MFAP2) in VAT were analysed. The impact of inflammation-related factors and adipocyte-conditioned media (ACM) on MFAP2 mRNA levels in colon adenocarcinoma HT-29 cells were further analysed. The effects of MAGP-1 in the expression of genes involved in the extracellular matrix (ECM) remodelling and tumorigenesis in HT-29 cells was also explored. Results: Obesity (p < 0.01) and CC (p < 0.001) significantly decreased MFAP2 gene expression levels in VAT whereas an opposite trend in TGFB1 mRNA levels was observed. Increased mRNA levels of MFAP2 after the stimulation of HT-29 cells with lipopolysaccharide (LPS) (p < 0.01) and interleukin (IL)-4 (p < 0.01) together with a downregulation (p < 0.05) after hypoxia mimicked by CoCl2 treatment was observed. MAGP-1 treatment significantly enhanced the mRNA levels of the ECM-remodelling genes collagen type 6 α3 chain (COL6A3) (p < 0.05), decorin (DCN) (p < 0.01), osteopontin (SPP1) (p < 0.05) and TGFB1 (p < 0.05). Furthermore, MAGP-1 significantly reduced (p < 0.05) the gene expression levels of prostaglandin-endoperoxide synthase 2 (COX2/PTGS2), a key gene controlling cell proliferation, growth and adhesion in CC. Interestingly, a significant decrease (p < 0.01) in the mRNA levels of MFAP2 in HT-29 cells preincubated with ACM from volunteers with obesity compared with control media was observed. Conclusion: The decreased levels of MAGP-1 in patients with obesity and CC together with its capacity to modulate key genes involved in ECM remodelling and tumorigenesis suggest MAGP-1 as a link between AT excess and obesity-associated CC development.
Tamoxifen Application Is Associated with Transiently Increased Loss of Hippocampal Neurons following Virus Infection
Authors: Hülskötter Kirsten , Lühder Fred , Flügel Alexander , Herder Vanessa , Baumgärtner Wolfgang
Published: August 2021

Tamoxifen is frequently used in murine knockout systems with CreER/LoxP. Besides possible neuroprotective effects, tamoxifen is described as having a negative impact on adult neurogenesis. The present study investigated the effect of a high-dose tamoxifen application on Theiler’s murine encephalomyelitis virus (TMEV)-induced hippocampal damage. Two weeks after TMEV infection, 42% of the untreated TMEV-infected mice were affected by marked inflammation with neuronal loss, whereas 58% exhibited minor inflammation without neuronal loss. Irrespective of the presence of neuronal loss, untreated mice lacked TMEV antigen expression within the hippocampus at 14 days post-infection (dpi). Interestingly, tamoxifen application 0, 2 and 4, or 5, 7 and 9 dpi decelerated virus elimination and markedly increased neuronal loss to 94%, associated with increased reactive astrogliosis at 14 dpi. T cell infiltration, microgliosis and expression of water channels were similar within the inflammatory lesions, regardless of tamoxifen application. Applied at 0, 2 and 4 dpi, tamoxifen had a negative impact on the number of doublecortin (DCX)-positive cells within the dentate gyrus (DG) at 14 dpi, without a long-lasting effect on neuronal loss at 147 dpi. Thus, tamoxifen application during a TMEV infection is associated with transiently increased neuronal loss in the hippocampus, increased reactive astrogliosis and decreased neurogenesis in the DG.
Structural Basis of Inhibition of DCLK1 by Ruxolitinib
Authors: Jang Dong Man , Lim Hyo Jin , Hahn Hyunggu , Lee Yeon , Kim Hark Kyun , Kim Hyoun Sook
Published: August 2021

Given the functional attributes of Doublecortin-like kinase 1 (DCLK1) in tumor growth, invasion, metastasis, cell motility, and tumor stemness, it is emerging as a therapeutic target in gastrointestinal cancers. Although a series of specific or nonspecific ATP-competitive inhibitors were identified against DCLK1, different types of scaffolds that can be utilized for the development of highly selective inhibitors or structural understanding of binding specificities of the compounds remain limited. Here, we present our work to repurpose a Janus kinase 1 inhibitor, ruxolitinib as a DCLK1 inhibitor, showing micromolar binding affinity and inhibitory activity. Furthermore, to gain an insight into its interaction mode with DCLK1, a crystal structure of the ruxolitinib-complexed DCLK1 has been determined and analyzed. Ruxolitinib as a nonspecific DCLK1 inhibitor characterized in this work is anticipated to provide a starting point for the structure-guided discovery of selective DCLK1 inhibitors.
Cancer Cachexia: Its Mechanism and Clinical Significance
Authors: Nishikawa Hiroki , Goto Masahiro , Fukunishi Shinya , Asai Akira , Nishiguchi Shuhei , Higuchi Kazuhide
Published: August 2021

The term “cachexia” is derived from the Greek words kakos (bad) and hexis (habit). Cachexia is a malnutrition associated with chronic diseases such as cancer, chronic heart failure, chronic renal failure, and autoimmune diseases, and is characterized by decreased skeletal muscle mass. Cancer cachexia is quite common in patients with advanced cancer. Weight loss is also a characteristic symptom of cancer cachexia, along with decreased skeletal muscle mass. As nutritional supplementation alone cannot improve cachexia, cytokines and tumor-derived substances have been attracting attention as its relevant factors. Cancer cachexia can be also associated with reduced chemotherapeutic effects, increased side effects and treatment interruptions, and even poorer survival. In 2011, a consensus definition of cachexia has been proposed, and the number of relevant research reports has increased significantly. However, the pathogenesis of cachexia is not fully understood, and there are currently few regulatory-approved standard treatments for cachexia. The main reason for this is that multiple etiologies are involved in the development of cachexia. In this review, we will outline the current status of cachexia, the mechanisms of which have been elucidated in recent years, especially from the perspective of advanced cancer.
Major Facilitator Superfamily Transporter Gene FgMFS1 Is Essential for Fusarium graminearum to Deal with Salicylic Acid Stress and for Its Pathogenicity towards Wheat
Authors: Chen Qing , Lei Lu , Liu Caihong , Zhang Yazhou , Xu Qiang , Zhu Jing , Guo Zhenru , Wang Yan , Li Qingcheng , Li Yang , Kong Li , Jiang Yunfeng , Lan Xiujin , Wang Jirui , Jiang Qiantao , Chen Guoyue , Ma Jian , Wei Yuming , Zheng Youliang , Qi Pengfei
Published: August 2021

Wheat is a major staple food crop worldwide, due to its total yield and unique processing quality. Its grain yield and quality are threatened by Fusarium head blight (FHB), which is mainly caused by Fusarium graminearum. Salicylic acid (SA) has a strong and toxic effect on F. graminearum and is a hopeful target for sustainable control of FHB. F. graminearum is capable of efficientdealing with SA stress. However, the underlying mechanisms remain unclear. Here, we characterized FgMFS1 (FGSG_03725), a major facilitator superfamily (MFS) transporter gene in F. graminearum. FgMFS1 was highly expressed during infection and was upregulated by SA. The predicted three-dimensional structure of the FgMFS1 protein was consistent with the schematic for the antiporter. The subcellular localization experiment indicated that FgMFS1 was usually expressed in the vacuole of hyphae, but was alternatively distributed in the cell membrane under SA treatment, indicating an element of F. graminearum in response to SA. ΔFgMFS1 (loss of function mutant of FgMFS1) showed enhanced sensitivity to SA, less pathogenicity towards wheat, and reduced DON production under SA stress. Re-introduction of a functional FgMFS1 gene into ∆FgMFS1 recovered the mutant phenotypes. Wheat spikes inoculated with ΔFgMFS1 accumulated more SA when compared to those inoculated with the wild-type strain. Ecotopic expression of FgMFS1 in yeast enhanced its tolerance to SA as expected, further demonstrating that FgMFS1 functions as an SA exporter. In conclusion, FgMFS1 encodes an SA exporter in F. graminearum, which is critical for its response to wheat endogenous SA and pathogenicity towards wheat.
The Role of the Second Extracellular Loop of Norepinephrine Transporter, Neurotrophin-3 and Tropomyosin Receptor Kinase C in T Cells: A Peripheral Biomarker in the Etiology of Schizophrenia
Authors: Rodrigues-Amorim Daniela , Iglesias-Martínez-Almeida Marta , Rivera-Baltanás Tania , Fernández-Palleiro Patricia , Freiría-Martínez Luis , Rodríguez-Jamardo Cynthia , Comís-Tuche María , Vallejo-Curto María del Carmen , Álvarez-Ariza María , López-García Marta , de las Heras Elena , García-Caballero Alejandro , Olivares Jose Manuel , Spuch Carlos
Published: August 2021

The neurobiology of schizophrenia is multifactorial, comprising the dysregulation of several biochemical pathways and molecules. This research proposes a peripheral biomarker for schizophrenia that involves the second extracellular loop of norepinephrine transporter (NEText), the tropomyosin receptor kinase C (TrkC), and the neurotrophin-3 (NT-3) in T cells. The study of NEText, NT-3, and TrkC was performed in T cells and plasma extracted from peripheral blood of 54 patients with schizophrenia and 54 healthy controls. Levels of NT-3, TrkC, and NET were significantly lower in plasma and T cells of patients compared to healthy controls. Co-immunoprecipitation (co-IPs) showed protein interactions with Co-IP NEText–NT-3 and Co-IP NEText–TrkC. Computational modelling of protein–peptide docking by CABS-dock provided a medium–high accuracy model for NT-3–NEText (4.6935 Å) and TrkC–NEText (2.1365 Å). In summary, immunocomplexes reached statistical relevance in the T cells of the control group contrary to the results obtained with schizophrenia. The reduced expression of NT-3, TrkC, and NET, and the lack of molecular complexes in T cells of patients with schizophrenia may lead to a peripheral dysregulation of intracellular signaling pathways and an abnormal reuptake of norepinephrine (NE) by NET. This peripheral molecular biomarker underlying schizophrenia reinforces the role of neurotrophins, and noradrenergic and immune systems in the pathophysiology of schizophrenia.
Different Patterns of mRNA Nuclear Retention during Meiotic Prophase in Larch Microsporocytes
Authors: Majewska Karolina , Wróblewska-Ankiewicz Patrycja , Rudzka Magda , Hyjek-Składanowska Malwina , Gołębiewski Marcin , Smoliński Dariusz Jan , Kołowerzo-Lubnau Agnieszka
Published: August 2021

Recent studies show a crucial role of post-transcriptional processes in the regulation of gene expression. Our research has shown that mRNA retention in the nucleus plays a significant role in such regulation. We studied larch microsporocytes during meiotic prophase, characterized by pulsatile transcriptional activity. After each pulse, the transcriptional activity is silenced, but the transcripts synthesized at this time are not exported immediately to the cytoplasm but are retained in the cell nucleus and especially in Cajal bodies, where non-fully-spliced transcripts with retained introns are accumulated. Analysis of the transcriptome of these cells and detailed analysis of the nuclear retention and transport dynamics of several mRNAs revealed two main patterns of nuclear accumulation and transport. The majority of studied transcripts followed the first one, consisting of a more extended retention period and slow release to the cytoplasm. We have shown this in detail for the pre-mRNA and mRNA encoding RNA pol II subunit 10. In this pre-mRNA, a second (retained) intron is posttranscriptionally spliced at a precisely defined time. Fully mature mRNA is then released into the cytoplasm, where the RNA pol II complexes are produced. These proteins are necessary for transcription in the next pulse to occur.mRNAs encoding translation factors and SERRATE followed the second pattern, in which the retention period was shorter and transcripts were rapidly transferred to the cytoplasm. The presence of such a mechanism in various cell types from a diverse range of organisms suggests that it is an evolutionarily conserved mechanism of gene regulation.
TRPM8 Channels: Advances in Structural Studies and Pharmacological Modulation
Authors: Izquierdo Carolina , Martín-Martínez Mercedes , Gómez-Monterrey Isabel , González-Muñiz Rosario
Published: August 2021

The transient receptor potential melastatin subtype 8 (TRPM8) is a cold sensor in humans, activated by low temperatures (>10, <28 °C), but also a polymodal ion channel, stimulated by voltage, pressure, cooling compounds (menthol, icilin), and hyperosmolarity. An increased number of experimental results indicate the implication of TRPM8 channels in cold thermal transduction and pain detection, transmission, and maintenance in different tissues and organs. These channels also have a repercussion on different kinds of life-threatening tumors and other pathologies, which include urinary and respiratory tract dysfunctions, dry eye disease, and obesity. This compendium firstly covers newly described papers on the expression of TRPM8 channels and their correlation with pathological states. An overview on the structural knowledge, after cryo-electron microscopy success in solving different TRPM8 structures, as well as some insights obtained from mutagenesis studies, will follow. Most recently described families of TRPM8 modulators are also covered, along with a section of molecules that have reached clinical trials. To finalize, authors provide an outline of the potential prospects in the TRPM8 field.
Mitochondrial Metabolism behind Region-Specific Resistance to Ischemia-Reperfusion Injury in Gerbil Hippocampus. Role of PKCβII and Phosphate-Activated Glutaminase
Authors: Beręsewicz-Haller Małgorzata , Krupska Olga , Bochomulski Paweł , Dudzik Danuta , Chęcińska Anita , Hilgier Wojciech , Barbas Coral , Zablocki Krzysztof , Zablocka Barbara
Published: August 2021

Ischemic episodes are a leading cause of death worldwide with limited therapeutic interventions. The current study explored mitochondrial phosphate-activated glutaminase (GLS1) activity modulation by PKCβII through GC-MS untargeted metabolomics approach. Mitochondria were used to elucidate the endogenous resistance of hippocampal CA2-4 and dentate gyrus (DG) to transient ischemia and reperfusion in a model of ischemic episode in gerbils. In the present investigation, male gerbils were subjected to bilateral carotids occlusion for 5 min followed by reperfusion (IR). Gerbils were randomly divided into three groups as vehicle-treated sham control, vehicle-treated IR and PKCβII specific inhibitor peptide βIIV5-3-treated IR. Vehicle or βIIV5-3 (3 mg/kg, i.v.) were administered at the moment of reperfusion. The gerbils hippocampal tissue were isolated at various time of reperfusion and cell lysates or mitochondria were isolated from CA1 and CA2-4,DG hippocampal regions. Recombinant proteins PKCβII and GLS1 were used in in vitro phosphorylation reaction and organotypic hippocampal cultures (OHC) transiently exposed to NMDA (25 μM) to evaluate the inhibition of GLS1 on neuronal viability. PKCβII co-precipitates with GAC (GLS1 isoform) in CA2-4,DG mitochondria and phosphorylates GLS1 in vitro. Cell death was dose dependently increased when GLS1 was inhibited by BPTA while inhibition of mitochondrial pyruvate carrier (MPC) attenuated cell death in NMDA-challenged OHC. Fumarate and malate were increased after IR 1h in CA2-4,DG and this was reversed by βIIV5-3 what correlated with GLS1 activity increases and earlier showed elevation of neuronal death (Krupska et al., 2017). The present study illustrates that CA2-4,DG resistance to ischemic episode at least partially rely on glutamine and glutamate utilization in mitochondria as a source of carbon to tricarboxylic acid cycle. This phenomenon depends on modulation of GLS1 activity by PKCβII and remodeling of MPC: all these do not occur in ischemia-vulnerable CA1.
PARP Inhibitors Display Differential Efficacy in Models of BRCA Mutant High-Grade Serous Ovarian Cancer
Authors: Dickson Kristie-Ann , Xie Tao , Evenhuis Christian , Ma Yue , Marsh Deborah J.
Published: August 2021

Several poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitors are now in clinical use for tumours with defects in BReast CAncer genes BRCA1 or BRCA2 that result in deficient homologous recombination repair (HRR). Use of olaparib, niraparib or rucaparib for the treatment of high-grade serous ovarian cancer, including in the maintenance setting, has extended both progression free and overall survival for women with this malignancy. While different PARP inhibitors (PARPis) are mechanistically similar, differences are apparent in their chemical structures, toxicity profiles, PARP trapping abilities and polypharmacological landscapes. We have treated ovarian cancer cell line models of known BRCA status, including the paired cell lines PEO1 and PEO4, and UWB1.289 and UWB1.289+BRCA1, with five PARPis (olaparib, niraparib, rucaparib, talazoparib and veliparib) and observed differences between PARPis in both cell viability and cell survival. A cell line model of acquired resistance to veliparib showed increased resistance to the other four PARPis tested, suggesting that acquired resistance to one PARPi may not be able to be rescued by another. Lastly, as a proof of principle, HRR proficient ovarian cancer cells were sensitised to PARPis by depletion of BRCA1. In the future, guidelines will need to emerge to assist clinicians in matching specific PARPis to specific patients and tumours.
Highlighting Immune System and Stress in Major Depressive Disorder, Parkinson’s, and Alzheimer’s Diseases, with a Connection with Serotonin
Authors: Correia Ana Salomé , Cardoso Armando , Vale Nuno
Published: August 2021

There is recognition that both stress and immune responses are important factors in a variety of neurological disorders. Moreover, there is an important role of several neurotransmitters that connect these factors to several neurological diseases, with a special focus in this paper on serotonin. Accordingly, it is known that imbalances in stressors can promote a variety of neuropsychiatric or neurodegenerative pathologies. Here, we discuss some facts that link major depressive disorder, Alzheimer’s, and Parkinson’s to the stress and immune responses, as well as the connection between these responses and serotonergic signaling. These are important topics of investigation which may lead to new or better treatments, improving the life quality of patients that suffer from these conditions.
Roles of CCL2-CCR2 Axis in the Tumor Microenvironment
Authors: Kadomoto Suguru , Izumi Kouji , Mizokami Atsushi
Published: August 2021

Chemokines are a small family of cytokines that were first discovered as chemotactic factors in leukocytes during inflammation, and reports on the relationship between chemokines and cancer progression have recently been increasing. The CCL2-CCR2 axis is one of the major chemokine signaling pathways, and has various functions in tumor progression, such as increasing tumor cell proliferation and invasiveness, and creating a tumor microenvironment through increased angiogenesis and recruitment of immunosuppressive cells. This review discusses the roles of the CCL2-CCR2 axis and the tumor microenvironment in cancer progression and their future roles in cancer therapy.
The Clinical Significance of Drug–Food Interactions of Direct Oral Anticoagulants
Authors: Grześk Grzegorz , Rogowicz Daniel , Wołowiec Łukasz , Ratajczak Agnieszka , Gilewski Wojciech , Chudzińska Małgorzata , Sinkiewicz Anna , Banach Joanna
Published: August 2021

Cardiovascular diseases are the most common cause of death in the world. For almost 60 years, vitamin K antagonists (VKAs) were the mainstay of anticoagulation therapy, but in recent years direct oral anticoagulants (DOACs) have become the anticoagulant treatment of choice. DOACs were initially considered drugs with no significant food interactions; however, clinical observations from daily practice have proved otherwise as interactions with food ingredients have been reported. Food, dietary supplements or herbs may contain substances that, when administered concomitantly with DOACs, can potentially affect the plasma concentration of the drugs. The aim of this paper was to evaluate the clinical significance of drug–food interactions of DOACs, such as dabigatran, rivaroxaban, apixaban, edoxaban and betrixaban. Patients treated with anticoagulants should avoid products containing St. John’s wort and take special care with other food ingredients. As the interest in dietary supplements is on the rise, healthcare providers can contribute to the development of well-designed clinical trials on interactions between DOACs and food, and distribute sufficient knowledge about the proper use of these supplements among patients.
Single- and Two-Electron Reduction of Nitroaromatic Compounds by Flavoenzymes: Mechanisms and Implications for Cytotoxicity
Authors: Čėnas Narimantas , Nemeikaitė-Čėnienė Aušra , Kosychova Lidija
Published: August 2021

Nitroaromatic compounds (ArNO2) maintain their importance in relation to industrial processes, environmental pollution, and pharmaceutical application. The manifestation of toxicity/therapeutic action of nitroaromatics may involve their single- or two-electron reduction performed by various flavoenzymes and/or their physiological redox partners, metalloproteins. The pivotal and still incompletely resolved questions in this area are the identification and characterization of the specific enzymes that are involved in the bioreduction of ArNO2 and the establishment of their contribution to cytotoxic/therapeutic action of nitroaromatics. This review addresses the following topics: (i) the intrinsic redox properties of ArNO2, in particular, the energetics of their single- and two-electron reduction in aqueous medium; (ii) the mechanisms and structure-activity relationships of reduction in ArNO2 by flavoenzymes of different groups, dehydrogenases-electrontransferases (NADPH:cytochrome P-450 reductase, ferredoxin:NADP(H) oxidoreductase and their analogs), mammalian NAD(P)H:quinone oxidoreductase, bacterial nitroreductases, and disulfide reductases of different origin (glutathione, trypanothione, and thioredoxin reductases, lipoamide dehydrogenase), and (iii) the relationships between the enzymatic reactivity of compounds and their activity in mammalian cells, bacteria, and parasites.
Nanotechnology-Based Strategies to Overcome Current Barriers in Gene Delivery
Authors: Mirón-Barroso Sofía , Domènech Elena B. , Trigueros Sonia
Published: August 2021

Nanomaterials are currently being developed for the specific cell/tissue/organ delivery of genetic material. Nanomaterials are considered as non-viral vectors for gene therapy use. However, there are several requirements for developing a device small enough to become an efficient gene-delivery tool. Considering that the non-viral vectors tested so far show very low efficiency of gene delivery, there is a need to develop nanotechnology-based strategies to overcome current barriers in gene delivery. Selected nanostructures can incorporate several genetic materials, such as plasmid DNA, mRNA, and siRNA. In the field of nanotechnologies, there are still some limitations yet to be resolved for their use as gene delivery systems, such as potential toxicity and low transfection efficiency. Undeniably, novel properties at the nanoscale are essential to overcome these limitations. In this paper, we will explore the latest advances in nanotechnology in the gene delivery field.