bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence of Respiratory Infections during the 2018–2020 Period in the Paediatric Population of Primary Care Centres in Central Catalonia
Authors: Macías Reyes María José , Vidal-Alaball Josep , Suwezda Eduardo Alejandro , Miró Catalina Queralt , Homs Maria , Ruiz-Comellas Anna
Published: April 2023

Following the COVID-19 pandemic, policies such as social distancing, hand washing, and the use of masks were implemented, which could play an important role in the reduction of infectious diseases. An observational, descriptive, cross-sectional study was conducted to observe the prevalence of respiratory infections in children under 15 years of age during the 2018–2020 period in Primary Care centres in Central Catalonia. In 2020, there was a 44.3% decrease in total consultations for respiratory infections compared to 2019. All respiratory infections exhibited a significant decrease except flu-like syndrome; children between the ages of 6 and 12 had the highest prevalence of flu-like syndrome (87.6%), and the SARS-CoV-2-19 infection was most frequent (4%) among those between the ages of 12 and 15. Compared to urban centres, rural centres presented a higher prevalence of all infections except flu-like syndrome and SARS-CoV-2. In conclusion, the COVID-19 pandemic caused a significant decrease in the number of consultations for respiratory infections in the paediatric population, except for flu-like syndrome, which increased in cases in January, February, and March 2020. No differences were found between sexes, although differences were found in the distribution of the different age groups.
Promoting Physical Activity in a Primary Care Practice in People Living with Dementia and Their Family Caregivers
Authors: de Dios-Rodríguez Elena , Patino-Alonso Carmen , González-Sánchez Susana , Tamayo-Morales Olaya , Ripoll Joana , Mora-Simón Sara , Unzueta-Arce Jaime , Gómez-Marcos Manuel A , García-Ortiz Luis , Rodríguez-Sánchez Emiliano
Published: April 2023

People living with dementia (PLWD) and their family caregivers report higher rates of having a sedentary lifestyle than their non-disabled peers do. This study analyzed the effectiveness of an intervention designed to increase physical activity among PLWD and their family caregivers in primary health care settings. A cluster-randomized multicenter clinical trial was conducted. Participants from four health centers were randomly assigned to the intervention group (IG) or the control group (CG) in a 1:1 ratio using Epidat software. After a seven-day period with a digital pedometer (Omron Hj-321 lay-UPS), participants were asked to complete the International Physical Activity Questionnaire Short Form (IPAQ-SF). PLWD and caregivers allocated to the IG were given brief advice, educational materials and an additional 15 min appointment to prescribe an individualized physical activity plan. Seventy PLWD and 80 caregivers were assigned to the CG and 70 PLWD and 96 caregivers were assigned to the IG. Results of the pedometer assessment show that in PLWD, the IG’s activity increased by 52.89 aerobic steps at 6 months and the CG’s activity decreased by 615.93 aerobic steps, showing a net increase in the IG of 668.82 (95% CI: −444.27 to 1781.91; p = 0.227). For caregivers in the IG, activity increased by 356.91 aerobic steps and in the CG it decreased by 12.95 aerobic steps, showing a net increase in favor of the IG of 369.86 (95%CI: −659.33 to 1399.05; p = 0.476). The effectiveness of interventions to increase physical activity in this group of people with dementia and their caregivers did not achieved positive results overall but may have provided suggestions for family physicians and physical therapists to improve physical activity among people with dementia and their families.
The Role of Vaccination and Face Mask Wearing on COVID-19 Infection and Hospitalization: A Cross-Sectional Study of the MENA Region
Authors: Hamimes Ahmed , Lounis Mohamed , Aouissi Hani Amir , Roufayel Rabih , Lakehal Abdelhak , Bouzekri Hafid , Byeon Haewon , Ababsa Mostefa , Napoli Christian
Published: April 2023

Since the emergence of the Coronavirus disease (COVID-19) pandemic, the disease has affected more than 675 million people worldwide, including more than 6.87 million deaths. To mitigate the effects of this pandemic, many countries established control measures to contain its spread. Their riposte was based on a combination of pharmaceutical (vaccination) and non-pharmaceutical (such as facemask wearing, social distancing, and quarantine) measures. In this way, cross-sectional research was conducted in Algeria from 23 December 2021 to 12 March 2022 to investigate the effectiveness of preventative interventions in lowering COVID-19 infection and severity. More specifically, we investigated the link between mask-wearing and infection on one side, and the relationship between vaccination and the risk of hospitalization on the other. For this purpose, we used binary logistic regression modeling that allows learning the role of mask-wearing and vaccination in a heterogeneous society with respect to compliance with barrier measures. This study determined that wearing a mask is equally important for people of all ages. Further, findings revealed that the risk of infection was 0.79 times lower among those who were using masks (odds ratio (OR) = 0.79; confidence interval (CI) 95% = 0.668–0.936; p-value = 0.006). At the same time, vaccination is a necessary preventive measure as the risk of hospitalization increases with age. Compared with those who did not get vaccinated, those who got vaccinated were 0.429 times less likely to end up in the hospital (OR = 0.429; CI95% = 0.273–0.676; p < 0.0001). The model performance demonstrates significant relationships between the dependent and independent variables, with the absence of over-dispersion in both studied models, such as the Akaike Information Criterion (AIC) scores. These findings emphasize the significance of preventative measures and immunization in the battle against the COVID-19 pandemic.
Long-Term Effectiveness of Physical Exercise-Based Swallowing Interventions for Older Adults with Dementia in a Day-Care Center
Authors: Chen Chia-Hui , Lin Chia-Yu , Chen Chiao-Ling , Chen Kuan-Ting , Lee Cho , Yu Ya-Hsin , Shih Chiao-Yu
Published: April 2023

Swallowing safety is one of the top health concerns of dementia. Coughing and choking (coughing/choking) are signs of impaired swallowing safety. This study aimed to investigate the effectiveness of regular physical exercise-based swallowing intervention for reducing coughing-choking at the dementia day-care center. This was a retrospective analysis with data from medical records, including age, the clinical dementia rating (CDR), and the frequencies of coughing/choking in ten days (10-day coughing/choking). Those who complied with the exercise programs were assigned to the exercise-based group (n = 22), and those who could not comply were assigned to the non-exercised-based group (n = 7). The non-exercised-based group showed more advanced age and higher CDR than the exercise-based group (p < 0.05). The 10-day coughing/choking showed significant decreases at the 5-month and 19-month in the exercise-based group and at the 5-month in the non-exercise-based group (p < 0.05). Our findings suggested that regular physical exercise-based swallowing intervention effectively alleviated coughing/choking problems of older adults with dementia and its effectiveness was long-lasting. For those who could not comply with exercise programs, noticeably with more advanced age and dementia, the effective swallowing intervention period was short-term.
A Rare Case of Severe Diarrhea: Gastrocolic Fistula Caused by Migration of Percutaneous Endoscopic Gastrostomy Tube
Authors: Pugliese Maria Elena , Battaglia Riccardo , Cerasa Antonio , Lucca Lucia Francesca
Published: April 2023

Gastrocolic fistula is a rare complication of the percutaneous endoscopic gastrostomy (PEG) placement procedure. This complication occurs due to penetration of interposed colon when a PEG tube is placed into the stomach. It can go unrecognized, becoming evident only when a tube replacement is performed or tube migration occurs. We report a case of severe, intractable diarrhea occurring about one month after the PEG procedure in a patient with severe traumatic brain injury. We present our case and discuss its significance with the aim of raising clinicians’ awareness of this rare condition.
Knowledge, Attitudes, and Practices of Sex Workers of Three South African Towns towards Female Condom Use and Contraceptives
Authors: Sitonga Noluvuyo , Nomatshila Sibusiso C. , Phalane Mahlane , Chitha Wezile W. , Mabunda Sikhumbuzo A.
Published: April 2023

Female sex workers are a marginalized and highly vulnerable population who are at risk of HIV and other sexually transmitted diseases, harassment, and unplanned pregnancies. Various female condoms are available to mitigate the severity of the consequences of their work. However, little is known about the acceptability and usage of female condoms and contraceptives among sex workers in small South African towns. This descriptive cross-sectional study of conveniently selected sex workers explored the acceptability and usage of female condoms and contraceptives among sex workers in South Africa using validated questionnaires. The data were analyzed using STATA 14.1. The 95% confidence interval is used for precision, and a p-value ≤ 0.05 is considered significant. Out of 69 female-only participants, 49.3% were unemployed, 53.6% were cohabiting, and 30.4% were HIV positive. The median age of entry into sex work was 16 years old. Participants reported use of condoms in their last 3 sexual encounters (62.3%), preference of Implanon for contraception (52.2%), barriers to condom use (81.2%), condoms not being accepted by clients (63.8%), being difficult to insert (37.7%), and being unattractive (18.8%). Participants who reported barriers to condom use were 90% more likely to have adequate knowledge than those who did not (PR = 1.9; p-value < 0.0001). Knowledge of condom use was an important factor in determining knowledge of barriers to their use. Reasons for sex work, sex workers’ perceptions, and clients’ preferences negatively affect the rate of condom use. Sex worker empowerment, community education, and effective marketing of female condoms require strengthening.
Low Nocturnal Temperature Alters Tomato Foliar and Root Phosphorus Fractions Allocation by Reducing Soil Phosphorus Availability
Authors: Shi Qingwen , Ma Ru , Sun Zhouping , Liu Yufeng , Fu Hongdan , Li Tianlai
Published: April 2023

Low nocturnal temperature (LNT) is a major constraint for protected tomato production in China during winter and spring, which leads to tomato phosphorus (P) deficiency symptoms. The soil P fractions reflect soil P availability. The foliar and root P fractions reflect the adaptation strategies of tomatoes to LNT. However, the relationship between plant P fractions and soil P fractions under LNT is not well understood. Therefore, we conducted a 40-day indoor incubation experiment with four nocturnal temperatures (15, 12, 9 and 6 °C). Tomato growth status, plant P fractions and soil P fractions were determined. Then, structural equation model (SEM) was used to analyze the direct and/or indirect effects of LNT on soil P fractions, plant P fractions and tomato shoot dry weight (SDW). The results showed that LNT decreased soil P availability by decreasing soil labile P and increasing soil moderately labile P. The foliar inorganic P, metabolite P, nucleic acid P and residual P were decreased under 9 and 6 °C. The root nucleic acid P and lipid P were decreased, while metabolite P was increased under 9 and 6 °C. Tomato foliar and root P fraction allocation was directly influenced by the increase in soil moderately labile P, while the decline in SDW was directly influenced by the decrease in soil labile P. In conclusion, LNT affects tomato P fractions allocation by reducing soil P availability, which limits the shoot dry matter production in tomatoes.
Molecular Identification and Characterization of UDP-glycosyltransferase (UGT) Multigene Family in Pomegranate
Authors: Zhao Xueqing , Feng Yingyi , Ke Ding , Teng Yingfen , Chen Ying , Langjia Renzeng
Published: April 2023

Pomegranate (Punica granatum L.) is regarded as one of the functional fruits because of its large amounts of secondary metabolites. The glycosylation processes mediated by UDP-glycosyltransferases (UGTs) play a decisive role in regulating secondary metabolite availability. In this study, a genome-wide search identified 145 UGT genes in pomegranate, and further phylogenetic analysis defined 17 distinct groups: A to P and R. PgUGTs were dispersed unevenly across all eight chromosomes. Duplication events analysis revealed that both segmental and tandem duplications were the main mechanisms leading to gene family expansions. The comparison of exon–intron patterns identified 53 intron-less genes. A total of 24 types of cis-acting elements related to hormone, stress, and developmental responses were predicted in the promoter regions. Expression analysis of PgUGT genes using RNA-seq data and quantitative real-time PCR (qRT-PCR) verification suggested that PgUGT genes were expressed at specific stages of fruit development, and different PgUGT members likely played different roles in specific fruit developmental stages. In an attempt to identify the UGTs involved in the glycosylation of flavonoids, 44 PgUGTs were putatively determined, and 5 well-defined orthologous groups (OGs) were characterized by the regioselectivity of these enzymes. These results provide significant insight into the UGT multi-gene family in pomegranate, and will be helpful to further elucidate their roles involved in secondary and specialized metabolism in pomegranate.
A Systematic Review and Meta-Analysis on the Impact of Statin Treatment in HIV Patients on Antiretroviral Therapy
Authors: Mokgalaboni Kabelo , Phoswa Wendy Nokhwezi , Yates Samantha , Lebelo Sogolo Lucky , Madiba Sphiwe , Modjadji Perpetua
Published: April 2023

The rate of new human immunodeficiency virus (HIV) infections globally is alarming. Although antiretroviral therapy (ART) improves the quality of life among this group of patients, ARTs are associated with risk of cardiovascular diseases (CVD). Moreover, virally suppressed patients still experience immune activation associated with HIV migration from reservoir sites. Statins are widely recommended as therapeutic agents to control ART-related CVD; however, their impacts on the cluster of differentiation (CD)4 count and viral load are inconsistent. To assess the effect of statins on markers of HIV infections, immune activation and cholesterol, we thoroughly reviewed evidence from randomised controlled trials. We found 20 relevant trials from three databases with 1802 people living with HIV (PLHIV) on statin–placebo treatment. Our evidence showed no significant effect on CD4 T-cell count standardised mean difference (SMD): (−0.59, 95% confidence intervals (CI): (−1.38, 0.19), p = 0.14) following statin intervention in PLHIV on ART. We also found no significant difference in baseline CD4 T-cell count (SD: (−0.01, 95%CI: (−0.25, 0.23), p = 0.95). Our findings revealed no significant association between statins and risk of viral rebound in PLHIV with undetectable viral load risk ratio (RR): (1.01, 95% CI: (0.98, 1.04), p = 0.65). Additionally, we found a significant increase in CD8+CD38+HLA-DR+ T-cells (SMD (1.10, 95% CI: (0.93, 1.28), p < 0.00001) and CD4+CD38+HLA-DR+ T-cells (SMD (0.92, 95% CI: (0.32, 1.52), p = 0.003). Finally, compared to placebo, statins significantly reduced total cholesterol (SMD: (−2.87, 95% CI: (−4.08, −1.65), p < 0.0001)). Our results suggest that the statin lipid-lowering effect in PLHIV on ART may elevate immune activation without influencing the viral load and CD4 count. However, due to the limited evidence synthesised in this meta-analysis, we recommend that future powered trials with sufficient sample sizes evaluate statins’ effect on CD4 count and viral load, especially in virally suppressed patients.
Co-Creating a Feasible, Acceptable and Safe Home-Based High-Intensity Interval Training Programme for People with Parkinson’s: The HIIT-Home4Parkinson’s Study
Authors: Harpham Conrad , Gunn Hilary , Marsden Jonathan , Connolly Luke
Published: April 2023

High-intensity interval training (HIIT) is useful and feasible for some people with Parkinson’s (PwP), although long-term adherence may be problematic. If practical, undertaking HIIT in the home setting could be a way to encourage continued participation. However, no home-based HIIT programme has been developed for this population. Therefore, the objectives of this study were to co-create a feasible, accessible, and safe home-based HIIT programme for PwP, including intervention components and logic model. This supports the longer term aim to assess the practicality and utility of home-based HIIT for PwP. The study included three stages. Firstly, an initial HIIT programme and logic model proposal was developed based on existing evidence. This was refined through an iterative, co-creative process of focus groups, exercise testing and interviews involving end-users and relevant stakeholders. Finally, a draft intervention was produced with further co-creator input. During the iterative process, five focus groups, 10 exercise testing sessions and 10 post exercise interviews were undertaken, involving academic researchers, 6 PwP, one family member and two clinicians. These co-creators developed HIIT-Home4Parkinson’s (HH4P), a 12-week thrice weekly home-based HIIT programme for PwP based on adaptability, individualisation, and remote support. Despite methodological limitations within the development process, the co-created HH4P programme could be feasible, safe, and useful for PwP. A feasibility study should now be undertaken to address remaining uncertainties prior to a full trial.
Correction: Kovács et al. The Effects and Types of Parental Involvement in School-Based Sport and Health Programs Still Represent a Knowledge Gap: A Systematic Review. Int. J. Environ. Res. Public Health 2022, 19, 12859
Authors: Kovács Klára , Kovács Karolina Eszter , Bacskai Katinka , Békési Zsolt , Oláh Ádám József , Pusztai Gabriella
Published: April 2023

In the original article [...]
Annual Prevalence of Opioid Receipt by South Carolina Medicaid-Enrolled Children and Adolescents: 2000–2020
Authors: Basco William T. , Bundy David G. , Garner Sandra S. , Ebeling Myla , Simpson Kit N.
Published: April 2023

Understanding patterns of opioid receipt by children and adolescents over time and understanding differences between age groups can help identify opportunities for future opioid stewardship. We conducted a retrospective cohort study, using South Carolina Medicaid data for children and adolescents 0–18 years old between 2000–2020, calculating the annual prevalence of opioid receipt for medical diagnoses in ambulatory settings. We examined differences in prevalence by calendar year, race/ethnicity, and by age group. The annual prevalence of opioid receipt for medical diagnoses changed significantly over the years studied, from 187.5 per 1000 in 2000 to 41.9 per 1000 in 2020 (Cochran–Armitage test for trend, p < 0.0001). In all calendar years, older ages were associated with greater prevalence of opioid receipt. Adjusted analyses (logistic regression) assessed calendar year differences in opioid receipt, controlling for age group, sex, and race/ethnicity. In the adjusted analyses, calendar year was inversely associated with opioid receipt (aOR 0.927, 95% CI 0.926–0.927). Males and older ages were more likely to receive opioids, while persons of Black race and Hispanic ethnicity had lower odds of receiving opioids. While opioid receipt declined among all age groups during 2000–2020, adolescents 12–18 had persistently higher annual prevalence of opioid receipt when compared to younger age groups.
Comparison of Fucoidans from Saccharina latissima Regarding Age-Related Macular Degeneration Relevant Pathomechanisms in Retinal Pigment Epithelium
Authors: Dörschmann Philipp , Thalenhorst Tabea , Seeba Charlotte , Tischhöfer Marie-Theres , Neupane Sandesh , Roider Johann , Alban Susanne , Klettner Alexa
Published: April 2023

Fucoidans from brown algae are described as anti-inflammatory, antioxidative, and antiangiogenic. We tested two Saccharina latissima fucoidans (SL-FRO and SL-NOR) regarding their potential biological effects against age-related macular degeneration (AMD). Primary porcine retinal pigment epithelium (RPE), human RPE cell line ARPE-19, and human uveal melanoma cell line OMM-1 were used. Cell survival was assessed in tetrazolium assay (MTT). Oxidative stress assays were induced with erastin or H2O2. Supernatants were harvested to assess secreted vascular endothelial growth factor A (VEGF-A) in ELISA. Barrier function was assessed by measurement of trans-epithelial electrical resistance (TEER). Protectin (CD59) and retinal pigment epithelium-specific 65 kDa protein (RPE65) were evaluated in western blot. Polymorphonuclear elastase and complement inhibition assays were performed. Phagocytosis of photoreceptor outer segments was tested in a fluorescence assay. Secretion and expression of proinflammatory cytokines were assessed with ELISA and real-time PCR. Fucoidans were chemically analyzed. Neither toxic nor antioxidative effects were detected in ARPE-19 or OMM-1. Interleukin 8 gene expression was slightly reduced by SL-NOR but induced by SL-FRO in RPE. VEGF secretion was reduced in ARPE-19 by SL-FRO and in RPE by both fucoidans. Polyinosinic:polycytidylic acid induced interleukin 6 and interleukin 8 secretion was reduced by both fucoidans in RPE. CD59 expression was positively influenced by fucoidans, and they exhibited a complement and elastase inhibitory effect in cell-free assay. RPE65 expression was reduced by SL-NOR in RPE. Barrier function of RPE was transiently reduced. Phagocytosis ability was slightly reduced by both fucoidans in primary RPE but not in ARPE-19. Fucoidans from Saccharina latissima, especially SL-FRO, are promising agents against AMD, as they reduce angiogenic cytokines and show anti-inflammatory and complement inhibiting properties; however, potential effects on gene expression and RPE functions need to be considered for further research.
Iron Saturation Drives Lactoferrin Effects on Oxidative Stress and Neurotoxicity Induced by HIV-1 Tat
Authors: Ianiro Giusi , D’Ezio Veronica , Carpinelli Ludovica , Casella Cecilia , Bonaccorsi di Patti Maria Carmela , Rosa Luigi , Valenti Piera , Colasanti Marco , Musci Giovanni , Cutone Antimo , Persichini Tiziana
Published: April 2023

The Trans-Activator of Transcription (Tat) of Human Immunodeficiency Virus (HIV-1) is involved in virus replication and infection and can promote oxidative stress in human astroglial cells. In response, host cells activate transcription of antioxidant genes, including a subunit of System Xc− cystine/glutamate antiporter which, in turn, can trigger glutamate-mediated excitotoxicity. Here, we present data on the efficacy of bovine Lactoferrin (bLf), both in its native (Nat-bLf) and iron-saturated (Holo-bLf) forms, in counteracting oxidative stress in U373 human astroglial cells constitutively expressing the viral protein (U373-Tat). Our results show that, dependent on iron saturation, both Nat-bLf and Holo-bLf can boost host antioxidant response by up-regulating System Xc− and the cell iron exporter Ferroportin via the Nuclear factor erythroid 2-related factor (Nrf2) pathway, thus reducing Reactive Oxygen Species (ROS)-mediated lipid peroxidation and DNA damage in astrocytes. In U373-Tat cells, both forms of bLf restore the physiological internalization of Transferrin (Tf) Receptor 1, the molecular gate for Tf-bound iron uptake. The involvement of astrocytic antioxidant response in Tat-mediated neurotoxicity was evaluated in co-cultures of U373-Tat with human neuronal SH-SY5Y cells. The results show that the Holo-bLf exacerbates Tat-induced excitotoxicity on SH-SY5Y, which is directly dependent on System-Xc− upregulation, thus highlighting the mechanistic role of iron in the biological activities of the glycoprotein.
Injectable Hydrogel Guides Neurons Growth with Specific Directionality
Authors: Tseng Yun-Hsiu , Ma Tien-Li , Tan Dun-Heng , Su An-Jey A. , Washington Kia M. , Wang Chun-Chieh , Huang Yu-Ching , Wu Ming-Chung , Su Wei-Fang
Published: April 2023

Visual disabilities affect more than 250 million people, with 43 million suffering from irreversible blindness. The eyes are an extension of the central nervous system which cannot regenerate. Neural tissue engineering is a potential method to cure the disease. Injectability is a desirable property for tissue engineering scaffolds which can eliminate some surgical procedures and reduce possible complications and health risks. We report the development of the anisotropic structured hydrogel scaffold created by a co-injection of cellulose nanofiber (CNF) solution and co-polypeptide solution. The positively charged poly (L-lysine)-r-poly(L-glutamic acid) with 20 mol% of glutamic acid (PLLGA) is crosslinked with negatively charged CNF while promoting cellular activity from the acid nerve stimulate. We found that CNF easily aligns under shear forces from injection and is able to form hydrogel with an ordered structure. Hydrogel is mechanically strong and able to support, guide, and stimulate neurite growth. The anisotropy of our hydrogel was quantitatively determined in situ by 2D optical microscopy and 3D X-ray tomography. The effects of PLLGA:CNF blend ratios on cell viability, neurite growth, and neuronal signaling are systematically investigated in this study. We determined the optimal blend composition for stimulating directional neurite growth yielded a 16% increase in length compared with control, reaching anisotropy of 30.30% at 10°/57.58% at 30°. Using measurements of calcium signaling in vitro, we found a 2.45-fold increase vs. control. Based on our results, we conclude this novel material and unique injection method has a high potential for application in neural tissue engineering.
Effects of Essential Oils and Fragrant Compounds on Appetite: A Systematic Review
Authors: Nguyen Nhi Phuc Khanh , Tran Khoa Nguyen , Nguyen Ly Thi Huong , Shin Heung-Mook , Yang In-Jun
Published: April 2023

Appetite dysregulation is one of the factors contributing to anorexia, bulimia nervosa, obesity, and diabetes. Essential oils or fragrant compounds have been proven to regulate food intake and energy expenditure; hence, this study aimed to summarize their effects on appetite and the underlying mechanisms. The PubMed and Web of Science databases were searched until July 2022. Only two of the 41 studies were performed clinically, and the remaining 39 used animal models. Oral administration was the most common route, and a dosage range of 100–2000 mg/kg for mice or 2–32 mg/kg for rats was applied, with a duration of 12 days to 4 weeks, followed by inhalation (10−6–10−3 mg/cage or 10−9–10−2 mg/cm3 within 1 h). Approximately 11 essential oil samples and 22 fragrant compounds were found to increase appetite, while 12 essential oils and seven compounds decreased appetite. These fragrant components can exert appetite-regulating effects via leptin resistance, the activity of sympathetic/parasympathetic nerves, or the mRNA expression of neuropeptide Y (NPY)/agouti-related protein (AgRP), cocaine- and amphetamine-regulated transcript (CART)/proopiomelanocortin (POMC) in the hypothalamus. Fragrance memory and cognitive processes may also play roles in appetite regulation. The findings of this study accentuate the potential of essential oils and fragrant compounds to regulate appetite and eating disorders.
Wheat ABA Receptor TaPYL5 Constitutes a Signaling Module with Its Downstream Partners TaPP2C53/TaSnRK2.1/TaABI1 to Modulate Plant Drought Response
Authors: Zhang Yanyang , Zhao Yingjia , Hou Xiaoyang , Ni Chenyang , Han Le , Du Pingping , Xiao Kai
Published: April 2023

Abscisic acid receptors (ABR) play crucial roles in transducing the ABA signaling initiated by osmotic stresses, which has a significant impact on plant acclimation to drought by modulating stress-related defensive physiological processes. We characterized TaPYL5, a member of the ABR family in wheat (Triticum aestivum), as a mediator of drought stress adaptation in plants. The signals derived from the fusion of TaPYL5-GFP suggest that the TaPYL5 protein was directed to various subcellular locations, namely stomata, plasma membrane, and nucleus. Drought stress significantly upregulated the TaPYL5 transcripts in roots and leaves. The biological roles of ABA and drought responsive cis-elements, specifically ABRE and recognition sites MYB, in mediating gene transcription under drought conditions were confirmed by histochemical GUS staining analysis for plants harbouring a truncated TaPYL5 promoter. Yeast two-hybrid and BiFC assays indicated that TaPYL5 interacted with TaPP2C53, a clade A member of phosphatase (PP2C), and the latter with TaSnRK2.1, a kinase member of the SnRK2 family, implying the formation of an ABA core signaling module TaPYL5/TaPP2C53/TaSnRK2.1. TaABI1, an ABA responsive transcription factor, proved to be a component of the ABA signaling pathway, as evidenced by its interaction with TaSnRK2.1. Transgene analysis of TaPYL5 and its module partners, as well as TaABI1, revealed that they have an effect on plant drought responses. TaPYL5 and TaSnRK2.1 positively regulated plant drought acclimation, whereas TaPP2C53 and TaABI1 negatively regulated it. This coincided with the osmotic stress-related physiology shown in their transgenic lines, such as stomata movement, osmolytes biosynthesis, and antioxidant enzyme function. TaPYL5 significantly altered the transcription of numerous genes involved in biological processes related to drought defense. Our findings suggest that TaPYL5 is one of the most important regulators in plant drought tolerance and a valuable target for engineering drought-tolerant cultivars in wheat.
Bridging the Gap in Cancer-Related Stroke Management: Update on Therapeutic and Preventive Approaches
Authors: Sun Ming-Yee , Bhaskar Sonu M. M.
Published: April 2023

The underlying aetiopathophysiology of cancer-related strokes and thromboembolisms differs from that of noncancer-related strokes, which makes treating cancer-related strokes and thromboembolisms a distinct clinical challenge. This necessitates the development of novel, individualised diagnostic and treatment strategies. However, limited guidelines are available for the management of cancer-related strokes and the prevention of acute strokes or other thromboembolic events in this patient population. In this article, we present an updated overview of the therapeutic and preventive strategies for strokes in cancer settings. These strategies include acute reperfusion therapy, anticoagulant therapy, antiplatelet therapy, and lifestyle management options. We also outline comprehensive pathways and highlight gaps in the evidence-based clinical management of cancer-related strokes or thromboembolisms. Additionally, future recommendations for the management of strokes in cancer patients are provided.
U0126 Compound Triggers Thermogenic Differentiation in Preadipocytes via ERK-AMPK Signaling Axis
Authors: Onikanni Sunday Amos , Yang Cheng-Ying , Noriega Lloyd , Wang Chih-Hao
Published: April 2023

In recent years, thermogenic differentiation and activation in brown and white adipose tissues have been regarded as one of the major innovative and promising strategies for the treatment and amelioration of obesity. However, the pharmacological approach towards this process has had limited and insufficient commitments, which presents a greater challenge for obesity treatment. This research evaluates the effects of U0126 compound on the activation of thermogenic differentiation during adipogenesis. The results show that U0126 pretreatment primes both white and brown preadipocytes to upregulate thermogenic and mitochondrial genes as well as enhance functions during the differentiation process. We establish that U0126-mediated thermogenic differentiation induction occurs partially via AMPK activation signaling. The findings of this research suggest U0126 as a promising alternative ligand in pursuit of a pharmacological option to increase thermogenic adipocyte formation and improve energy expenditure. Thus it could pave the way for the discovery of therapeutic drugs for the treatment of obesity and its related complications.
CRISPR/Cas9 and piggyBac Transposon-Based Conversion of a Pathogenic Biallelic TBCD Variant in a Patient-Derived iPSC Line Allows Correction of PEBAT-Related Endophenotypes
Authors: Muto Valentina , Benigni Federica , Magliocca Valentina , Borghi Rossella , Flex Elisabetta , Pallottini Valentina , Rosa Alessandro , Compagnucci Claudia , Tartaglia Marco
Published: April 2023

Induced pluripotent stem cells (iPSCs) have been established as a reliable in vitro disease model system and represent a particularly informative tool when animal models are not available or do not recapitulate the human pathophenotype. The recognized limit in using this technology is linked to some degree of variability in the behavior of the individual patient-derived clones. The development of CRISPR/Cas9-based gene editing solves this drawback by obtaining isogenic iPSCs in which the genetic lesion is corrected, allowing a straightforward comparison with the parental patient-derived iPSC lines. Here, we report the generation of a footprint-free isogenic cell line of patient-derived TBCD-mutated iPSCs edited using the CRISPR/Cas9 and piggyBac technologies. The corrected iPSC line had no genetic footprint after the removal of the selection cassette and maintained its “stemness”. The correction of the disease-causing TBCD missense substitution restored proper protein levels of the chaperone and mitotic spindle organization, as well as reduced cellular death, which were used as read-outs of the TBCD KO-related endophenotype. The generated line represents an informative in vitro model to understand the impact of pathogenic TBCD mutations on nervous system development and physiology.
NAMPT and PARylation Are Involved in the Pathogenesis of Atopic Dermatitis
Authors: Arroyo Ana B. , Bernal-Carrión Martín , Cantón-Sandoval Joaquín , Cabas Isabel , Corbalán-Vélez Raúl , Martínez-Menchón Teresa , Ferri Belén , Cayuela María L. , García-Moreno Diana , Mulero Victoriano
Published: April 2023

Atopic dermatitis (AD) is a chronic inflammatory skin disease of very high prevalence, especially in childhood, with no specific treatment or cure. As its pathogenesis is complex, multifactorial and not fully understood, further research is needed to increase knowledge and develop new targeted therapies. We have recently demonstrated the critical role of NAD+ and poly (ADP-ribose) (PAR) metabolism in oxidative stress and skin inflammation. Specifically, we found that hyperactivation of PARP1 in response to DNA damage induced by reactive oxygen species, and fueled by NAMPT-derived NAD+, mediated inflammation through parthanatos cell death in zebrafish and human organotypic 3D skin models of psoriasis. Furthermore, the aberrant induction of NAMPT and PARP activity was observed in the lesional skin of psoriasis patients, supporting the role of these signaling pathways in psoriasis and pointing to NAMPT and PARP1 as potential novel therapeutic targets in treating skin inflammatory disorders. In the present work, we report, for the first time, altered NAD+ and PAR metabolism in the skin of AD patients and a strong correlation between NAMPT and PARP1 expression and the lesional status of AD. Furthermore, using a human 3D organotypic skin model of AD, we demonstrate that the pharmacological inhibition of NAMPT and PARP reduces pathology-associated biomarkers. These results help to understand the complexity of AD and reveal new potential treatments for AD patients.
Tracking Adaptive Pathways of Invasive Insects: Novel Insight from Genomics
Authors: Sun Zhongxiang , Chen Yao , Chen Yaping , Lu Zhihui , Gui Furong
Published: April 2023

Despite the huge human and economic costs of invasive insects, which are the main group of invasive species, their environmental impacts through various mechanisms remain inadequately explained in databases and much of the invasion biology literature. High-throughput sequencing technology, especially whole-genome sequencing, has been used as a powerful method to study the mechanisms through which insects achieve invasion. In this study, we reviewed whole-genome sequencing-based advances in revealing several important invasion mechanisms of invasive insects, including (1) the rapid genetic variation and evolution of invasive populations, (2) invasion history and dispersal paths, (3) rapid adaptation to different host plant ranges, (4) strong environmental adaptation, (5) the development of insecticide resistance, and (6) the synergistic damage caused by invasive insects and endosymbiotic bacteria. We also discussed prevention and control technologies based on whole-genome sequencing and their prospects.
Prediction of Early- and Late-Onset Pre-Eclampsia in the Preclinical Stage via Placenta-Specific Extracellular miRNA Profiling
Authors: Timofeeva Angelika V. , Fedorov Ivan S. , Sukhova Yuliya V. , Ivanets Tatyana Y. , Sukhikh Gennady T.
Published: April 2023

Pre-eclampsia (PE) is one of the severe complications of pregnancy in 3–8% of all cases and is one of the leading causes of maternal and perinatal mortality. The fundamental role in the pathogenesis of PE is assigned to maternal and/or placental factors, whereby the combination and manifestation of which determines the time of onset of the clinical symptoms of PE (before or after 34 weeks of gestation) and their severity. It is known that the expression level of miRNAs, the regulators of signaling cascades in the cell, depends on gestational age. In the present study, we focused on the identification of the placenta-specific miRNAs that differentiate between early- and late-onset pre-eclampsia (ePE and lPE) throughout pregnancy, from the first to the third trimester. A total of 67 patients were analyzed using small RNA deep sequencing and real-time quantitative PCR, which resulted in a core list of miRNAs (let-7b-5p, let-7d-3p, let-7f-5p, let-7i-5p, miR-22-5p, miR-451a, miR-1246, miR-30e-5p, miR-20a-5p, miR-1307-3p, and miR-320e), which in certain combinations can predict ePE or lPE with 100% sensitivity and 84–100% specificity in the 1st trimester of pregnancy. According to the literature data, these miRNA predictors of PE control trophoblast proliferation, invasion, migration, syncytialization, the endoplasmic reticulum unfolded protein response, immune tolerance, angiogenesis, and vascular integrity. The simultaneous detection of let-7d-3p, miR-451a, and miR-1307-3p, resistant to the repeated freezing/thawing of blood serum samples, in combination with biochemical (b-hCG and PAPP-A) and ultrasound (UAPI) parameters, allowed us to develop a universal model for the prediction of ePE and lPE onset (FPR = 15.7% and FNR = 9.5%), which was validated using a test cohort of 48 patients and demonstrated false-positive results in 26.7% of cases and false negatives in 5.6% of cases. For comparison, the use of the generally accepted Astraia program in the analysis of the test cohort of patients led to worse results: FPR = 62.1% and FNR = 33.3%.
Bna.EPF2 Enhances Drought Tolerance by Regulating Stomatal Development and Stomatal Size in Brassica napus
Authors: Jiao Peipei , Liang Yuanlin , Chen Shaoping , Yuan Yang , Chen Yongqiang , Hu Honghong
Published: April 2023

Drought stress severely affects global plant growth and production. The enhancement of plant water-use efficiency (WUE) and drought tolerance by the manipulation of the stomata is an effective strategy to deal with water shortage. However, increasing the WUE and drought tolerance by manipulation on the stomata has rarely been tested in Brassica napus. Here, we isolated Bna.EPF2, an epidermal patterning factor (EPF) in Brassica napus (ecotype Westar), and identified its role in drought performance. Bna.EPF2 overexpression lines had a reduction average of 19.02% in abaxial stomatal density and smaller stomatal pore size, leading to approximately 25% lower transpiration, which finally resulted in greater instantaneous WUE and enhanced drought tolerance. Interestingly, the reduction in stomatal density did not affect the CO2 assimilation or yield-related agronomic traits in Bna.EPF2 overexpression plants. Together with the complementation of Bna.EPF2 significantly decreasing the stomatal density of Arabidopsis epf2, and Bna.EPF2 being expressed in mature guard cells, these results suggest that Bna.EPF2 not only functions in stomatal density development, but also in stomatal dimension in Brassicas. Taken together, our results suggest that Bna.EPF2 improves WUE and drought tolerance by the regulation of stomatal density and stomatal size in Brassica without growth and yield penalty, and provide insight into the manipulation of this gene in the breeding of drought tolerant plants with increased production under water deficit conditions.
Synthesis and Evaluation of Hypoglycemic Activity of Structural Isomers of ((Benzyloxy)phenyl)propanoic Acid Bearing an Aminobornyl Moiety
Authors: Kuranov Sergey O. , Pon`kina Darya A. , Meshkova Yulia V. , Marenina Mariya K. , Khvostov Mikhail V. , Luzina Olga A. , Tolstikova Tatiana G. , Salakhutdinov Nariman F.
Published: April 2023

Free fatty acid receptor-1 (FFAR1) agonists are promising candidates for therapy of type 2 diabetes because of their ability to normalize blood sugar levels during hyperglycemia without the risk of hypoglycemia. Previously, we synthesized compound QS-528, a FFA1 receptor agonist with a hypoglycemic effect in C57BL/6NCrl mice. In the present work, structural analogs of QS-528 based on (hydroxyphenyl)propanoic acid bearing a bornyl fragment in its structure were synthesized. The seven novel compounds synthesized were structural isomers of compound QS-528, varying the positions of the substituents in the aromatic fragments as well as the configuration of the asymmetric center in the bornyl moiety. The studied compounds were shown to have the ability to activate FFAR1 at a concentration of 10 μM. The cytotoxicity of the compounds as well as their effect on glucose uptake in HepG2 cells were studied. The synthesized compounds were found to increase glucose uptake by cells and have no cytotoxic effect. Two compounds, based on the meta-substituted phenylpropanoic acid, 3-(3-(4-(((1R,2R,4R)-1,7,7-trimethylbicyclo-[2.2.1]heptan-2-ylamino)methyl)benzyloxy)phenyl)propanoic acid and 3-(3-(3-(((1R,2R,4R)-1,7,7-trimethylbicyclo [2.2.1]heptan-2-ylamino)methyl)benzyloxy)phenyl)propanoic acid, were shown to have a pronounced hypoglycemic effect in the oral glucose tolerance test with CD-1 mice.
Achievement of the Selectivity of Cytotoxic Agents against Cancer Cells by Creation of Combined Formulation with Terpenoid Adjuvants as Prospects to Overcome Multidrug Resistance
Authors: Zlotnikov Igor D. , Dobryakova Natalia V. , Ezhov Alexander A. , Kudryashova Elena V.
Published: April 2023

Oncological diseases are difficult to treat even with strong drugs due to development the multidrug resistance (MDR) of cancer cells. A strategy is proposed to increase the efficiency and selectivity of cytotoxic agents against cancer cells to engage the differences in the morphology and microenvironment of tumor and healthy cells, including the pH, membrane permeability, and ion channels. Using this approach, we managed to develop enhanced formulations of cytotoxic agents with adjuvants (which are known as efflux inhibitors and as ion channel inhibitors in tumors)—with increased permeability in A549 and a protective effect on healthy HEK293T cells. The composition of the formulation is as follows: cytotoxic agents (doxorubicin (Dox), paclitaxel (Pac), cisplatin) + adjuvants (allylbenzenes and terpenoids) in the form of inclusion complexes with β–cyclodextrin. Modified cyclodextrins make it possible to obtain soluble forms of pure substances of the allylbenzene and terpenoid series and increase the solubility of cytotoxic agents. A comprehensive approach based on three methods for studying the interaction of drugs with cells is proposed: MTT test—quantitative identification of surviving cells; FTIR spectroscopy—providing information on the molecular mechanisms inaccessible to study by any other methods (including binding to DNA, surface proteins, or lipid membrane); confocal microscopy for the visualization of observed effects of Dox accumulation in cancer or healthy cells depending on the drug formulation as a direct control of the correctness of interpretation of the results obtained by the two other methods. We found that eugenol (EG) and apiol increase the intracellular concentration of cytostatic in A549 cells by 2–4 times and maintain it for a long time. However, an important aspect is the selectivity of the enhancing effect of adjuvants on tumor cells in relation to healthy ones. Therefore, the authors focused on adjuvant’s effect on the control healthy cells (HEK293T): EG and apiol demonstrate “protective” properties from cytostatic penetration by reducing intracellular concentrations by about 2–3 times. Thus, a combined formulation of cytostatic drugs has been found, showing promise in the aspects of improving the efficiency and selectivity of antitumor drugs; thereby, one of the perspective directions for overcoming MDR is suggested.
Biomarkers for Pregnancy Latency Prediction after Preterm Premature Rupture of Membranes–A Systematic Review
Authors: Feduniw Stepan , Pruc Michal , Ciebiera Michal , Zeber-Lubecka Natalia , Massalska Diana , Zgliczynska Magdalena , Pawlowska Agnieszka , Szarpak Lukasz
Published: April 2023

Preterm premature rupture of membranes, leading to preterm birth, is associated with neonatal and maternal morbidity and mortality. The study aimed to review the existing data on the best predictive value of pregnancy latency for known biomarkers in pregnancies after preterm premature rupture of membranes. The following databases were screened for the purposes of this systematic review: Pubmed/MEDLINE, Web of Science, EMBASE, Scopus, and the Cochrane Library. The study was conducted according to the PRISMA guidelines for systematic reviews. Only a few studies assessed biomarkers predicting pregnancy duration after PPROM. IL-6, IL-8, CRP, IL1RA, s-endoglin, βhCG, AFP, PCT, urea, creatinine, oxygen radical absorbance capacity, MDA, lipocalin-2, endotoxin activity, MMP-8, MMP-9 and S100 A8/A9 were found to have a positive predictive value for delivery timing prediction. Proinflammatory biomarkers, such as IL-6 or CRP, proved to be best correlated with delivery timing, independent of the occurrence of intrauterine infection.