bluuebunny/crossref_metadata_2025 huggingface dataset:
Health Complaints, Mental Status and Quality of Life among the Aquaculture Workers: A Cross-Sectional Study in Northern Region of Peninsular Malaysia
Authors: Mat Zain Nur Syafiqah , Lee Lai Kuan
Published: December 2022

Aquaculture is seen as an essential food-producing sector for improving global food security and nutrition indices. This cross-sectional study examined the health complaints and mental health status of aquaculture workers, as well as their relationship with quality of life, with respect to the brackish water and freshwater aquaculture cultivation system in Penang, Malaysia. The workers’ health complaints were collected, and mental health status was evaluated as means of depression, anxiety, stress and self-esteem. Self-perceived quality of life was assessed using a structured questionnaire. This study involved the participation of 88 brackish water (84.6%) and 16 freshwater (15.4%) aquaculture workers. A total of 72.7% of the brackish water aquaculture workers were aged beyond 50 years old and had worked within five years (77.3%) in the aquaculture industry. Both brackish water and freshwater cultivation workers were confronted with fatigue, pain and insomnia. Up to 48%, 40.4%, 26% and 24% of them were facing depression, anxiety, stress and low self-esteem, respectively. A total of 3.4% of the brackish water aquaculture workers were having bad quality of life. The complaints of neck/shoulder/arm pain (F = 13.963; p < 0.001), back pain (F = 10.974; p < 0.01), hand/wrist pain (F = 8.041; p < 0.01), knee/hip pain (F = 12.910; p < 0.01) and insomnia (F = 10.936; p < 0.01) were correlated with bad quality of life among the workers. For mental health status, self-esteem (F = 4.157; p < 0.05) was found to be negatively correlated with quality of life scores. The results outlined the concerning level of health complaints and psychological distress among the aquaculture workers. The study emphasized the importance of developing an appropriate occupational health strategy in the aquaculture industry. Longitudinal investigations aimed to explore the effects of psychological distress on employment productivity among the high-risk workers are warranted.
Experience of Pharmacists with Anti-Cancer Medicine Shortages in Pakistan: Results of a Qualitative Study
Authors: Shukar Sundus , Zahoor Fatima , Omer Sumaira , Awan Sundas Ejaz , Yang Caijun , Fang Yu
Published: December 2022

This study aimed to examine the current situation of anti-cancer drug shortages in Pakistan, namely its determinants, impacts, adopted mitigation strategies, and proposed solutions. Qualitative semi-structured, in-depth interviews were conducted with 25 pharmacists in oncology hospitals in Pakistan from August to October 2021. Data were collected in person and online, recorded, and subjected to inductive thematic analysis after being transcribed verbatim. Most participants experienced anti-cancer drug shortages that increased during the pandemic. Etoposide, paclitaxel, vincristine, dacarbazine, and methotrexate were frequently short. Important causes included the compromised role of regulatory authorities, lack of local production, and inventory mismanagement. The impacts were delayed/suboptimal treatment and out-of-pocket costs for patients, patients’ prioritization, increased workload, negative work environment, and patients’ trust issues for pharmacists. The participants proposed that a cautious regulator’s role is needed to revise policies for all stakeholders and support all stakeholders financially at their level to increase access to these medicines. Based on the outcomes, it is clear that anti-cancer medicine shortages are a current issue in Pakistan. Governmental authorities need to play a role in revising policies for all levels of the drug supply chain and promoting local production of these drugs. Stakeholders should also collaborate and manage inventory.
Promoting the Integration of Elderly Healthcare and Elderly Nursing: Evidence from the Chinese Government
Authors: Hu Mo , Hao Zhiyuan , Yin Yinrui
Published: December 2022

The increase of the aging population in China and the rise of the concept of healthy aging have accelerated the transformation and upgrading of the traditional elderly nursing pattern. Nevertheless, there is a critical limitation existing in the current situation of China’s elderly care, i.e., the medical institutions do not support elderly nursing and the elderly nursing institutions do not facilitate access to medical care. To eliminate the adverse impact of this issue, twelve ministries and commissions of the Chinese government have jointly issued a document, i.e., the Several Opinions on Further Promoting the Development of Combining the Healthcare with the Elderly care (SOFPDCHE), to provide guidance from the government level for further promoting the integration of elderly healthcare and elderly nursing. Under this background, this paper constructs a healthcare–nursing information collaboration network (HnICN) based on the SOFPDCHE, proposing three novel strategies to explore the different roles and collaboration relationships of relevant government departments and public organizations in this integration process, i.e., the node identification strategy (NIS), the local adjacency subgroup strategy (LASS), and the information collaboration effect measurement strategy (ICEMS). Furthermore, this paper retrieves 484 valid policy documents related to “the integration of elderly healthcare and elderly nursing” as data samples on the official websites of 12 sponsored ministries and commissions, and finally confirms 22 government departments and public organizations as the network nodes based on these obtained documents, such as the National Health Commission of the People’s Republic of China (NHC), the Ministry of Industry and Information Technology of the People’s Republic of China (MIIT), and the National Working Commission on Aging (NWCA). In terms of the collaboration effect, the results of all node-pairs in the HnICN are significantly different, where the collaboration effect between the NHC and MIIT is best and that between the NATCM and MIIT is second best, which are 84.572% and 20.275%, respectively. This study provides the quantifiable results of the information collaboration degree between different government agencies and forms the optimization scheme for the current collaboration status based on these results, which play a positive role in integrating elderly healthcare and elderly nursing and eventually achieving healthy aging.
The Direct and Indirect Costs of Breast Cancer in Poland: Estimates for 2017–2019
Authors: Seweryn Michal , Banas Tomasz , Augustynska Joanna , Lorenc Ola , Kopel Justyna , Pluta Elzbieta , Skora Tomasz
Published: December 2022

Background: In Poland, breast cancer (BC) is the most frequently diagnosed cancer in women and the second most common cause of death after lung cancer. This disease has important economic implications for patients, public payers, and the whole Polish economy. This study aimed to estimate the total National Health Fund (NHF) expenditures on the diagnosis and treatment of patients with breast cancer. In addition, the costs of productivity losses were also calculated. Methods: Cost estimation was prepared using a top-down approach. Direct cost calculations were based on data reported by NHF for patients with the diagnosis of breast cancer. Medical care costs included the following components: screening program, oncological package, surgical treatment, hospitalization, drug program, chemotherapy, radiotherapy, and outpatient care. Indirect costs in the form of absenteeism costs were calculated based on data from Statistics Poland (gross domestic product, number of employees) and the Social Insurance Institution database (the number of sick leave days). Results: Total expenditures for BC including direct costs and indirect costs amounted to EUR 305,371, EUR 332,998, and EUR 344,649, respectively in 2017, 2018, and 2019. Total healthcare costs in 2019 were EUR 4114 lower than in 2018, which resulted from the reduction in expenditure on the drug program (decrease of EUR 13,527), despite the observed increase in all remaining resources. From direct costs, the highest expense was spent on the drug program (nearly 50% of total direct costs), but this expense dropped significantly in 2019. For the remaining parameters, the costs increased year by year, of which the most expensive were surgical treatment (15%), radiotherapy (12%), and the screening program (10%). BC generated over EUR 120 thousand of social costs in 2019 and compared to 2017, there was an increase in productivity loss by 26%. Conclusions: Our results from 2017–2019 demonstrated that total expenditure for BC in Poland increased from year to year. Breast cancer generated almost EUR 345 thousand expenses in 2019, which translates into a significant burden on the public payer’s budget and the society in Poland.
Atmospheric Air Pollution by Stationary Sources in Ulan-Ude (Buryatia, Russia) and Its Impact on Public Health
Authors: Gomboev Bair O. , Dambueva Irina K. , Khankhareev Sergey S. , Batomunkuev Valentin S. , Zangeeva Natalya R. , Tsydypov Vitaly E. , Sharaldaev Bayanzhargal B. , Badmaev Aldar G. , Zhamyanov Daba Ts.-D. , Bagaeva Elena E. , Madeeva Ekaterina V. , Motoshkina Marina A. , Ayusheeva Valentina G. , Rygzynov Tumun Sh. , Tsybikova Aryuna B. , Ayurzhanaev Alexander A. , Sodnomov Bator V. , Banzaraktcaev Zorikto E. , Alekseev Aleksei V. , Lygdenova Aryuna B. , Norboeva Beligma S.
Published: December 2022

For the first time in the territory of the Russian Far East, a study related to the establishment of correlations between air quality and public health in Ulan-Ude (Buryatia, Russia) was carried out. This study is based on the analysis of official medical statistics on morbidity over several years, the data on the composition and volume of emissions of harmful substances into the air from various stationary sources, and laboratory measurements of air pollutants in different locations in Ulan-Ude. This study confirmed that the morbidity of the population in Ulan-Ude has been increasing every year and it is largely influenced by air pollutants, the main of which are benzo(a)pyrene, suspended solids, PM2.5, PM10, and nitrogen dioxide. It was found that the greatest contribution to the unfavorable environmental situation is made by three types of stationary sources: large heating networks, autonomous sources (enterprises and small businesses), and individual households. The main air pollutants whose concentrations exceed the limits are benzo(a)pyrene, formaldehyde, suspended particles PM2.5, PM10, and nitrogen dioxide. A comprehensive assessment of the content of various pollutants in the atmospheric air showed that levels of carcinogenic and non-carcinogenic risks to public health exceeded allowable levels. Priority pollutants in the atmosphere of Ulan-Ude whose concentrations create unacceptable levels of risk to public health are benzo(a)pyrene, suspended solids, nitrogen dioxide, PM2.5, PM10, formaldehyde, and black carbon. The levels of morbidity in Ulan-Ude were higher than the average for Buryatia by the main disease classes: respiratory organs—by 1.19 times, endocrine system—by 1.25 times, circulatory system—by 1.11 times, eye diseases—by 1.06 times, neoplasms—by 1.47 times, congenital anomalies, and deformations and chromosomal aberrations—by 1.63 times. There is an increase in the incidence of risk-related diseases of respiratory organs and the circulatory system. A strong correlation was found between this growth of morbidity and atmospheric air pollution in Ulan-Ude.
Inclusive Socialization? The Relationships between Parents’ and Their Child’s Attitudes toward Students with Disabilities
Authors: Santilli Sara , Ginevra Maria Cristina , Israelashvili Moshe , Nota Laura
Published: December 2022

Promoting social and school inclusion of children with disabilities has been associated with their health-related quality of life. This study aimed to analyze the connection between parents and children’s attitudes toward disabilities as one factor contributing to the inclusion and well-being of individuals with disabilities. Three types of disabilities—i.e., attitudes toward a child with a sensory disability (hearing), a child with an intellectual disability (Down syndrome), and a child with problems with aggressiveness and angry outbursts (behavioral problems)—were examined. A sample of 598 White Italian elementary school students (303 boys and 295 girls) aged 6 to 11 years 33tudes toward students with disabilities, rather than each parent’s attitude, contributed to a better understanding of the child’s attitudes toward students with disabilities. The theoretical and practical implications of these results are discussed.
A Review of PFAS Destruction Technologies
Authors: Meegoda Jay N. , Bezerra de Souza Bruno , Casarini Melissa Monteiro , Kewalramani Jitendra A.
Published: December 2022

Per- and polyfluoroalkyl substances (PFASs) are a family of highly toxic emerging contaminants that have caught the attention of both the public and private sectors due to their adverse health impacts on society. The scientific community has been laboriously working on two fronts: (1) adapting already existing and effective technologies in destroying organic contaminants for PFAS remediation and (2) developing new technologies to remediate PFAS. A common characteristic in both areas is the separation/removal of PFASs from other contaminants or media, followed by destruction. The widely adopted separation technologies can remove PFASs from being in contact with humans; however, they remain in the environment and continue to pose health risks. On the other hand, the destructive technologies discussed here can effectively destroy PFAS compounds and fully address society’s urgent need to remediate this harmful family of chemical compounds. This review reports and compare widely accepted as well as emerging PFAS destruction technologies. Some of the technologies presented in this review are still under development at the lab scale, while others have already been tested in the field.
The Three-Level Model of Factors Contributing to High-Intensity Intermittent Performance in Male Soccer Players
Authors: Pecho Juraj , Kováčiková Zuzana , Šiška Ľuboslav , Mikulič Martin , Čurgali Marcel , Štefan Lovro , Zemková Erika
Published: December 2022

High-intensity intermittent performance in soccer is widely assessed using the yo-yo intermittent recovery level 2 test (YYIR2). This test is usually associated with aerobic–anaerobic performance. However, less is known about the direct or indirect contributions of abilities, including the anaerobic component. This study aims to propose a three-level model of factors contributing to YYIR2 performance, based on the investigation of relationships with aerobic endurance, repeated-sprint ability (RSA), and the linear and change-of-direction speed and power variables. Eighteen soccer players performed the YYIR2, with a 20-m shuttle run test (20mSR), an RSA test with change-of-direction, 5-m and 20-m sprints, and a 505 test, countermovement jump, squat jump, and drop jump. The results showed a significant relationship between the YYIR2 distance and the 20mSR distance (r = 0.721, p = 0.001), as well as with the RSA test mean time (r = −0.594, p = 0.009). In the second level, the 20mSR distance performance was not associated with any of the speed and power variables. However, the RSA test mean time correlated with the 5-m sprint (r = 0.587, p = 0.010), 20-m sprint (r = 0.702, p = 0.001), and 505 test (r = 0.585 p = 0.011) performance. In the third level, the 20-m sprint time was related to the squat jump (r = −0.577 p = 0.012) and countermovement jump (r = −0.768 p < 0.001) heights. In addition to aerobic endurance, this study highlights the importance of the anaerobic component in YYIR2 performance. More specifically, aerobic endurance (52%) and RSA (36%) are the main determinants of YYIR2 performance. Subsequently, the RSA performance is determined by the linear (34–49%) and change-of-direction speed (35%), while the explosive power of lower limbs contributes to sprinting performance (33–59%). Coaches should focus on the development of these abilities to improve the high-intensity intermittent performance of soccer players.
Interplay between Discrete Emotions and Preventive Behavior in Health Crises: Big Data Analysis of COVID-19
Authors: Zhu Huiyun
Published: December 2022

Understanding the interplay between discrete emotions and COVID-19 prevention behaviors will help healthcare professionals and providers to implement effective risk communication and effective risk decision making. This study analyzes data related to COVID-19 posted by the American public on Twitter and identifies three discrete negative emotions (anger, anxiety, and sadness) of the public from massive text data. Next, econometric analyses (i.e., the Granger causality test and impulse response functions) are performed to evaluate the interplay between discrete emotions and preventive behavior based on emotional time series and Google Shopping Trends time series, representing public preventive behavior. Based on the textual analysis of tweets from the United States, the following conclusions are drawn: Anger is a Granger cause of preventive behavior and has a slightly negative effect on the public’s preventive behavior. Anxiety is a Granger cause of preventive behavior and has a positive effect on preventive behavior. Furthermore, preventive behavior is a Granger cause of anxiety and has a negative and lagging effect on anxiety. Exploring how discrete emotions, such as anger and anxiety, affect preventive behaviors will effectively demonstrate how discrete emotions play qualitatively different roles in promoting preventive behaviors. Moreover, understanding the impact of preventive behaviors on discrete emotions is useful for better risk communication.
Addressing the Clinical Feasibility of Adopting Circulating miRNA for Breast Cancer Detection, Monitoring and Management with Artificial Intelligence and Machine Learning Platforms
Authors: Ling Lloyd , Aldoghachi Ahmed Faris , Chong Zhi Xiong , Ho Wan Yong , Yeap Swee Keong , Chin Ren Jie , Soo Eugene Zhen Xiang , Khor Jen Feng , Yong Yoke Leng , Ling Joan Lucille , Yan Naing Soe , Ong Alan Han Kiat
Published: December 2022

Detecting breast cancer (BC) at the initial stages of progression has always been regarded as a lifesaving intervention. With modern technology, extensive studies have unraveled the complexity of BC, but the current standard practice of early breast cancer screening and clinical management of cancer progression is still heavily dependent on tissue biopsies, which are invasive and limited in capturing definitive cancer signatures for more comprehensive applications to improve outcomes in BC care and treatments. In recent years, reviews and studies have shown that liquid biopsies in the form of blood, containing free circulating and exosomal microRNAs (miRNAs), have become increasingly evident as a potential minimally invasive alternative to tissue biopsy or as a complement to biomarkers in assessing and classifying BC. As such, in this review, the potential of miRNAs as the key BC signatures in liquid biopsy are addressed, including the role of artificial intelligence (AI) and machine learning platforms (ML), in capitalizing on the big data of miRNA for a more comprehensive assessment of the cancer, leading to practical clinical utility in BC management.
Programmed Cell Death-Ligand 1 in Head and Neck Squamous Cell Carcinoma: Molecular Insights, Preclinical and Clinical Data, and Therapies
Authors: Meliante Piero Giuseppe , Barbato Christian , Zoccali Federica , Ralli Massimo , Greco Antonio , de Vincentiis Marco , Colizza Andrea , Petrella Carla , Ferraguti Giampiero , Minni Antonio , Fiore Marco
Published: December 2022

Aberrant expression of the programmed cell death protein ligand 1 (PD-L1) constitutes one of the main immune evasion mechanisms of cancer cells. The approval of drugs against the PD-1-PD-L1 axis has given new impetus to the chemo-therapy of many malignancies. We performed a literature review from 1992 to August 2022, summarizing evidence regarding molecular structures, physiological and pathological roles, mechanisms of PD-L1 overexpression, and immunotherapy evasion. Furthermore, we summarized the studies concerning head and neck squamous cell carcinomas (HNSCC) immunotherapy and the prospects for improving the associated outcomes, such as identifying treatment response biomarkers, new pharmacological combinations, and new molecules. PD-L1 overexpression can occur via four mechanisms: genetic modifications; inflammatory signaling; oncogenic pathways; microRNA or protein-level regulation. Four molecular mechanisms of resistance to immunotherapy have been identified: tumor cell adaptation; changes in T-cell function or proliferation; alterations of the tumor microenvironment; alternative immunological checkpoints. Immunotherapy was indeed shown to be superior to traditional chemotherapy in locally advanced/recurrent/metastatic HNSCC treatments.
Pharmacological Mechanism of NRICM101 for COVID-19 Treatments by Combined Network Pharmacology and Pharmacodynamics
Authors: Singh Sher , Yang Ying-Fei
Published: December 2022

Symptom treatments for Coronavirus disease 2019 (COVID-19) infection and Long COVID are one of the most critical issues of the pandemic era. In light of the lack of standardized medications for treating COVID-19 symptoms, traditional Chinese medicine (TCM) has emerged as a potentially viable strategy based on numerous studies and clinical manifestations. Taiwan Chingguan Yihau (NRICM101), a TCM designed based on a medicinal formula with a long history of almost 500 years, has demonstrated its antiviral properties through clinical studies, yet the pharmacogenomic knowledge for this formula remains unclear. The molecular mechanism of NRICM101 was systematically analyzed by using exploratory bioinformatics and pharmacodynamics (PD) approaches. Results showed that there were 434 common interactions found between NRICM101 and COVID-19 related genes/proteins. For the network pharmacology of the NRICM101, the 434 common interacting genes/proteins had the highest associations with the interleukin (IL)-17 signaling pathway in the Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Moreover, the tumor necrosis factor (TNF) was found to have the highest association with the 30 most frequently curated NRICM101 chemicals. Disease analyses also revealed that the most relevant diseases with COVID-19 infections were pathology, followed by cancer, digestive system disease, and cardiovascular disease. The 30 most frequently curated human genes and 2 microRNAs identified in this study could also be used as molecular biomarkers or therapeutic options for COVID-19 treatments. In addition, dose–response profiles of NRICM101 doses and IL-6 or TNF-α expressions in cell cultures of murine alveolar macrophages were constructed to provide pharmacodynamic (PD) information of NRICM101. The prevalent use of NRICM101 for standardized treatments to attenuate common residual syndromes or chronic sequelae of COVID-19 were also revealed for post-pandemic future.
Complex Formation between Cytochrome c and a Tetra-alanino-calix[4]arene
Authors: Volpi Stefano , Doolan Aishling , Baldini Laura , Casnati Alessandro , Crowley Peter B. , Sansone Francesco
Published: December 2022

Owing to their remarkable features, calix[n]arenes are being exploited to study different aspects of molecular recognition, including protein complexation. Different complexation modes have been described, depending on the moieties that complement the aromatic cavity, allowing for function regulation and/or controlled assembly of the protein target. Here, a rigid cone calix[4]arene, bearing four anionic alanine units at the upper rim, was tested as a ligand for cytochrome c. Cocrystallization attempts were unfruitful, preventing a solid-state study of the system. Next, the complex was studied using NMR spectroscopy, which revealed the presence of two binding sites at lysine residues with dissociation constants (Kd) in the millimolar range.
Ameliorative Effects of a Rhenium (V) Compound with Uracil-Derived Ligand Markers Associated with Hyperglycaemia-Induced Renal Dysfunction in Diet-Induced Prediabetic Rats
Authors: Siboto Angezwa , Akinnuga Akinjide Moses , Khumalo Bongiwe , Ismail Muhammed Bilaal , Booysen Irvin Noel , Sibiya Ntethelelo Hopewell , Ngubane Phikelelani , Khathi Andile
Published: December 2022

Kidney disease is characterised by the improper functioning of the kidney as a result of kidney damage caused by hyperglycaemia-induced oxidative stress. The moderate hyperglycaemia seen in prediabetes can be treated using a combination of metformin and lifestyle interventions (low-calorie diets and exercising). However, patients have been reported to over-rely on pharmacological interventions, thus decreasing the efficacy of metformin, which leads to the development of type 2 diabetes mellitus (T2DM). In this study, we investigated the effects of a rhenium (V) compound in ameliorating renal dysfunction in both the presence and absence of dietary modification. Kidney function parameters, such as fluid intake and urine output, glomerular filtration rate (GFR), kidney injury molecule (KIM 1), creatinine, urea, albumin and electrolytes, were measured after 12 weeks of treatment. After treatment with the rhenium (V) compound, kidney function was restored, as evidenced by increased GRF and reduced KIM 1, podocin and aldosterone. The rhenium (V) compound ameliorated kidney function by preventing hyperglycaemia-induced oxidative stress in the kidney in both the presence and absence of dietary modification.
Induction of Corneal Endothelial-like Cells from Mesenchymal Stem Cells of the Umbilical Cord
Authors: Ye Eun Ah , Chung Ho Seok , Park Yoonkyung , Sunwoo Jeong Hye , Lee Whanseo , Kim Jin , Tchah Hungwon , Lee Hun , Kim Jae Yong
Published: December 2022

Because of the limited differentiation capacity of human corneal endothelial cells (CECs), stem cells have emerged as a potential remedy for corneal endothelial dysfunction (CED). This study aimed to demonstrate the differentiation of human umbilical cord-derived mesenchymal stem cells (UC-MSCs) into CECs and to investigate the efficacy of MSC-induced CEC injection into the anterior chamber in a rabbit model of CED. Human UC-MSCs were differentiated into CECs using medium containing glycogen synthase kinase 3β inhibitor and two types of Rho-associated protein kinase inhibitors. In the MSC-induced CECs, CEC-specific proteins were identified through immunohistochemistry and changes in CEC-specific gene expressions over time were confirmed through quantitative RT-PCR. When MSC-induced CECs were injected into a rabbit model of CED, corneal opacity and neovascularization were improved compared with the non-transplanted control or MSC injection group. We also confirmed that MSC-induced CECs were well engrafted as evidenced by human mitochondrial DNA in the central cornea of an animal model. Therefore, we demonstrated the differentiation of UC-MSCs into CECs in vitro and demonstrated the clinical efficacy of MSC-induced CEC injection, providing in vivo evidence that MSC-induced CECs have potential as a treatment option for CED.
Role of the Intermediate Filament Protein Peripherin in Health and Disease
Authors: Romano Roberta , Del Fiore Victoria Stefania , Bucci Cecilia
Published: December 2022

Intermediate filaments are the most heterogeneous class among cytoskeletal elements. While some of them have been well-characterized, little is known about peripherin. Peripherin is a class III intermediate filament protein with a specific expression in the peripheral nervous system. Epigenetic modifications are involved in this cell-type-specific expression. Peripherin has important roles in neurite outgrowth and stability, axonal transport, and axonal myelination. Moreover, peripherin interacts with proteins involved in vesicular trafficking, signal transduction, DNA/RNA processing, protein folding, and mitochondrial metabolism, suggesting a role in all these processes. This review collects information regarding peripherin gene regulation, post-translational modifications, and functions and its involvement in the onset of a number of diseases.
A Review of Genetic Polymorphisms and Susceptibilities to Complications after Aneurysmal Subarachnoid Hemorrhage
Authors: Medina-Suárez Jose , Rodríguez-Esparragón Francisco , Sosa-Pérez Coralia , Cazorla-Rivero Sara , Torres-Mata Laura B. , Jiménez-O’Shanahan Aruma , Clavo Bernardino , Morera-Molina Jesús
Published: December 2022

Delayed cerebral ischemia (DCI) and vasospasm are two complications of subarachnoid hemorrhages (SAHs) which entail high risks of morbidity and mortality. However, it is unknown why only some patients who suffer SAHs will experience DCI and vasospasm. The purpose of this review is to describe the main genetic single nucleotide polymorphisms (SNPs) that have demonstrated a relationship with these complications. The SNP of the nitric oxide endothelial synthase (eNOS) has been related to the size and rupture of an aneurysm, as well as to DCI, vasospasm, and poor neurological outcome. The SNPs responsible for the asymmetric dimetilarginine and the high-mobility group box 1 have also been associated with DCI. An association between vasospasm and the SNPs of the eNOS, the haptoglobin, and the endothelin-1 receptor has been found. The SNPs of the angiotensin-converting enzyme have been related to DCI and poor neurological outcome. Studies on the SNPs of the Ryanodine Receptor yielded varying results regarding their association with vasospasm.
Analysis of Intrinsic Breast Cancer Subtypes: The Clinical Utility of Epigenetic Biomarkers and TP53 Mutation Status in Triple-Negative Cases
Authors: Sadzeviciene Ieva , Snipaitiene Kristina , Scesnaite-Jerdiakova Asta , Daniunaite Kristina , Sabaliauskaite Rasa , Laurinaviciene Aida , Drobniene Monika , Ostapenko Valerijus , Jarmalaite Sonata
Published: December 2022

This study aimed at analyzing the DNA methylation pattern and TP53 mutation status of intrinsic breast cancer (BC) subtypes for improved characterization and survival prediction. DNA methylation of 17 genes was tested by methylation-specific PCR in 116 non-familial BRCA mutation-negative BC and 29 control noncancerous cases. At least one gene methylation was detected in all BC specimens and a 10-gene panel statistically significantly separated tumors from noncancerous breast tissues. Methylation of FILIP1L and MT1E was predominant in triple-negative (TN) BC, while other BC subtypes were characterized by RASSF1, PRKCB, MT1G, APC, and RUNX3 hypermethylation. TP53 mutation (TP53-mut) was found in 38% of sequenced samples and mainly affected TN BC cases (87%). Cox analysis revealed that TN status, age at diagnosis, and RUNX3 methylation are independent prognostic factors for overall survival (OS) in BC. The combinations of methylated biomarkers, RUNX3 with MT1E or FILIP1L, were also predictive for shorter OS, whereas methylated FILIP1L was predictive of a poor outcome in the TP53-mut subgroup. Therefore, DNA methylation patterns of specific genes significantly separate BC from noncancerous breast tissues and distinguishes TN cases from non-TN BC, whereas the combination of two-to-three epigenetic biomarkers can be an informative tool for BC outcome predictions.
Comparative Transcriptome Analysis Unravels the Response Mechanisms of Fusarium oxysporum f.sp. cubense to a Biocontrol Agent, Pseudomonas aeruginosa Gxun-2
Authors: Li Shuyan , Ma Junpeng , Li Shiyong , Chen Fuhui , Song Chaodong , Zhang Hongyan , Jiang Mingguo , Shen Naikun
Published: December 2022

Banana Fusarium wilt, which is caused by Fusarium oxysporum f.sp. cubense Tropical Race 4 (FOC TR4), is one of the most serious fungal diseases in the banana-producing regions in east Asia. Pseudomonas aeruginosa Gxun-2 could significantly inhibit the growth of FOC TR4. Strain Gxun-2 strongly inhibited the mycelial growth of FOC TR4 on dual culture plates and caused hyphal wrinkles, ruptures, and deformities on in vitro cultures. Banana seedlings under pot experiment treatment with Gxun-2 in a greenhouse resulted in an 84.21% reduction in the disease. Comparative transcriptome analysis was applied to reveal the response and resistance of FOC TR4 to Gxun-2 stress. The RNA-seq analysis of FOC TR4 during dual-culture with P. aeruginosa Gxun-2 revealed 3075 differentially expressed genes (DEGs) compared with the control. Among the genes, 1158 genes were up-regulated, and 1917 genes were down-regulated. Further analysis of gene function and the pathway of DEGs revealed that genes related to the cell membrane, cell wall formation, peroxidase, ABC transporter, and autophagy were up-regulated, while down-regulated DEGs were enriched in the sphingolipid metabolism and chitinase. These results indicated that FOC TR4 upregulates a large number of genes in order to maintain cell functions. The results of qRT-PCR conducted on a subset of 13 genes were consistent with the results of RNA-seq data. Thus, this study serves as a valuable resource regarding the mechanisms of fungal pathogen resistance to biocontrol agents.
Experimental Chemotherapy-Induced Mucositis: A Scoping Review Guiding the Design of Suitable Preclinical Models
Authors: Huang Junhua , Hwang Alan Yaw Min , Jia Yuting , Kim Brian , Iskandar Melania , Mohammed Ali Ibrahim , Cirillo Nicola
Published: December 2022

Mucositis is a common and most debilitating complication associated with the cytotoxicity of chemotherapy. The condition affects the entire alimentary canal from the mouth to the anus and has a significant clinical and economic impact. Although oral and intestinal mucositis can occur concurrently in the same individual, these conditions are often studied independently using organ-specific models that do not mimic human disease. Hence, the purpose of this scoping review was to provide a comprehensive yet systematic overview of the animal models that are utilised in the study of chemotherapy-induced mucositis. A search of PubMed/MEDLINE and Scopus databases was conducted to identify all relevant studies. Multiple phases of filtering were conducted, including deduplication, title/abstract screening, full-text screening, and data extraction. Studies were reported according to the updated Preferred Reporting Items for Systematic reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) guidelines. An inter-rater reliability test was conducted using Cohen’s Kappa score. After title, abstract, and full-text screening, 251 articles met the inclusion criteria. Seven articles investigated both chemotherapy-induced intestinal and oral mucositis, 198 articles investigated chemotherapy-induced intestinal mucositis, and 46 studies investigated chemotherapy-induced oral mucositis. Among a total of 205 articles on chemotherapy-induced intestinal mucositis, 103 utilised 5-fluorouracil, 34 irinotecan, 16 platinum-based drugs, 33 methotrexate, and 32 other chemotherapeutic agents. Thirteen articles reported the use of a combination of 5-fluorouracil, irinotecan, platinum-based drugs, or methotrexate to induce intestinal mucositis. Among a total of 53 articles on chemotherapy-induced oral mucositis, 50 utilised 5-fluorouracil, 2 irinotecan, 2 methotrexate, 1 topotecan and 1 with other chemotherapeutic drugs. Three articles used a combination of these drugs to induce oral mucositis. Various animal models such as mice, rats, hamsters, piglets, rabbits, and zebrafish were used. The chemotherapeutic agents were introduced at various dosages via three routes of administration. Animals were mainly mice and rats. Unlike intestinal mucositis, most oral mucositis models combined mechanical or chemical irritation with chemotherapy. In conclusion, this extensive assessment of the literature revealed that there was a large variation among studies that reproduce oral and intestinal mucositis in animals. To assist with the design of a suitable preclinical model of chemotherapy-induced alimentary tract mucositis, animal types, routes of administration, dosages, and types of drugs were reported in this study. Further research is required to define an optimal protocol that improves the translatability of findings to humans.
Structural and Functional Changes in Aging Kidneys
Authors: Dybiec Jill , Szlagor Magdalena , Młynarska Ewelina , Rysz Jacek , Franczyk Beata
Published: December 2022

The renal condition is one of the crucial predictors of longevity; therefore, early diagnosis of any dysfunction plays an important role. Kidneys are highly susceptible to the aging process. Unfavorable conditions may lead to a significant disturbance of the body’s homeostasis. Apart from physiological changes, there are some conditions such as hypertension, diabetes or obesity which contribute to the acceleration of the aging process. A determination of macroscopic and microscopic changes is essential for assessing the progression of aging. With age, we observe a decrease in the volume of renal parenchyma and an increase in adipose tissue in the renal sinuses. Senescence may also be manifested by the roughness of the kidney surface or simple renal cysts. The main microscopic changes are a thickening of the glomerular basement membrane, nephrosclerosis, an accumulation of extracellular matrix, and mesangial widening. The principal aspect of stopping unfavorable changes is to maintain health. Studies have shown many useful ways to mitigate renal aging. This review is focused especially on medications such as renin-angiotensin-aldosterone system blockers or resveratrol, but even eating habits and lifestyle.
A Novel R2R3-MYB Transcription Factor SbMYB12 Positively Regulates Baicalin Biosynthesis in Scutellaria baicalensis Georgi
Authors: Wang Wentao , Hu Suying , Yang Jing , Zhang Caijuan , Zhang Tong , Wang Donghao , Cao Xiaoyan , Wang Zhezhi
Published: December 2022

Scutellaria baicalensis Georgi is an annual herb from the Scutellaria genus that has been extensively used as a traditional medicine for over 2000 years in China. Baicalin and other flavonoids have been identified as the principal bioactive ingredients. The biosynthetic pathway of baicalin in S. baicalensis has been elucidated; however, the specific functions of R2R3-MYB TF, which regulates baicalin synthesis, has not been well characterized in S. baicalensis to date. Here, a S20 R2R3-MYB TF (SbMYB12), which encodes 263 amino acids with a length of 792 bp, was expressed in all tested tissues (mainly in leaves) and responded to exogenous hormone methyl jasmonate (MeJA) treatment. The overexpression of SbMYB12 significantly promoted the accumulation of flavonoids such as baicalin and wogonoside in S. baicalensis hairy roots. Furthermore, biochemical experiments revealed that SbMYB12 is a nuclear-localized transcription activator that binds to the SbCCL7-4, SbCHI-2, and SbF6H-1 promoters to activate their expression. These results illustrate that SbMYB12 positively regulates the generation of baicalin and wogonoside. In summary, this work revealed a novel S20 R2R3-MYB regulator and enhances our understanding of the transcriptional and regulatory mechanisms of baicalin biosynthesis, as well as sheds new light on metabolic engineering in S. baicalensis.
The Generation of Nitric Oxide from Aldehyde Dehydrogenase-2: The Role of Dietary Nitrates and Their Implication in Cardiovascular Disease Management
Authors: Maiuolo Jessica , Oppedisano Francesca , Carresi Cristina , Gliozzi Micaela , Musolino Vincenzo , Macrì Roberta , Scarano Federica , Coppoletta Annarita , Cardamone Antonio , Bosco Francesca , Mollace Rocco , Muscoli Carolina , Palma Ernesto , Mollace Vincenzo
Published: December 2022

Reduced bioavailability of the nitric oxide (NO) signaling molecule has been associated with the onset of cardiovascular disease. One of the better-known and effective therapies for cardiovascular disorders is the use of organic nitrates, such as glyceryl trinitrate (GTN), which increases the concentration of NO. Unfortunately, chronic use of this therapy can induce a phenomenon known as “nitrate tolerance”, which is defined as the loss of hemodynamic effects and a reduction in therapeutic effects. As such, a higher dosage of GTN is required in order to achieve the same vasodilatory and antiplatelet effects. Mitochondrial aldehyde dehydrogenase 2 (ALDH2) is a cardioprotective enzyme that catalyzes the bio-activation of GTN to NO. Nitrate tolerance is accompanied by an increase in oxidative stress, endothelial dysfunction, and sympathetic activation, as well as a loss of the catalytic activity of ALDH2 itself. On the basis of current knowledge, nitrate intake in the diet would guarantee a concentration of NO such as to avoid (or at least reduce) treatment with GTN and the consequent onset of nitrate tolerance in the course of cardiovascular diseases, so as not to make necessary the increase in GTN concentrations and the possible inhibition/alteration of ALDH2, which aggravates the problem of a positive feedback mechanism. Therefore, the purpose of this review is to summarize data relating to the introduction into the diet of some natural products that could assist pharmacological therapy in order to provide the NO necessary to reduce the intake of GTN and the phenomenon of nitrate tolerance and to ensure the correct catalytic activity of ALDH2.
Physiological Consequences of Targeting 14-3-3 and Its Interacting Partners in Neurodegenerative Diseases
Authors: Ganne Akshatha , Balasubramaniam Meenakshisundaram , Mainali Nirjal , Atluri Paavan , Shmookler Reis Robert J. , Ayyadevara Srinivas
Published: December 2022

The mammalian 14-3-3 family comprises seven intrinsically unstructured, evolutionarily conserved proteins that bind >200 protein targets, thereby modulating cell-signaling pathways. The presence of 14-3-3 proteins in cerebrospinal fluid provides a sensitive and specific biomarker of neuronal damage associated with Alzheimer’s disease (AD), Creutzfeldt–Jakob disease (CJD), spongiform encephalitis, brain cancers, and stroke. We observed significant enrichment of 14-3-3 paralogs G, S, and Z in human brain aggregates diagnostic of AD. We used intra-aggregate crosslinking to identify 14-3-3 interaction partners, all of which were significantly enriched in AD brain aggregates relative to controls. We screened FDA-approved drugs in silico for structures that could target the 14-3-3G/hexokinase interface, an interaction specific to aggregates and AD. C. elegans possesses only two 14-3-3 orthologs, which bind diverse proteins including DAF-16 (a FOXO transcription factor) and SIR-2.1 (a sensor of nutrients and stress), influencing lifespan. Top drug candidates were tested in C. elegans models of neurodegeneration-associated aggregation and in a human neuroblastoma cell-culture model of AD-like amyloidosis. Several drugs opposed aggregation in all models assessed and rescued behavioral deficits in C. elegans AD-like neuropathy models, suggesting that 14-3-3 proteins are instrumental in aggregate accrual and supporting the advancement of drugs targeting 14-3-3 protein complexes with their partners.
Photocatalytic Performance of Undoped and Al-Doped ZnO Nanoparticles in the Degradation of Rhodamine B under UV-Visible Light:The Role of Defects and Morphology
Authors: Piras Alessandra , Olla Chiara , Reekmans Gunter , Kelchtermans An-Sofie , De Sloovere Dries , Elen Ken , Carbonaro Carlo Maria , Fusaro Luca , Adriaensens Peter , Hardy An , Aprile Carmela , Van Bael Marlies K.
Published: December 2022

Quasi-spherical undoped ZnO and Al-doped ZnO nanoparticles with different aluminum content, ranging from 0.5 to 5 at% of Al with respect to Zn, were synthesized. These nanoparticles were evaluated as photocatalysts in the photodegradation of the Rhodamine B (RhB) dye aqueous solution under UV-visible light irradiation. The undoped ZnO nanopowder annealed at 400 °C resulted in the highest degradation efficiency of ca. 81% after 4 h under green light irradiation (525 nm), in the presence of 5 mg of catalyst. The samples were characterized using ICP-OES, PXRD, TEM, FT-IR, 27Al-MAS NMR, UV-Vis and steady-state PL. The effect of Al-doping on the phase structure, shape and particle size was also investigated. Additional information arose from the annealed nanomaterials under dynamic N2 at different temperatures (400 and 550 °C). The position of aluminum in the ZnO lattice was identified by means of 27Al-MAS NMR. FT-IR gave further information about the type of tetrahedral sites occupied by aluminum. Photoluminescence showed that the insertion of dopant increases the oxygen vacancies reducing the peroxide-like species responsible for photocatalysis. The annealing temperature helps increase the number of red-emitting centers up to 400 °C, while at 550 °C, the photocatalytic performance drops due to the aggregation tendency.
Anti-Oxidant and Anti-Inflammatory Effects of Astaxanthin on Gastrointestinal Diseases
Authors: Lee Jaeeun , Kim Min-Hyun , Kim Hyeyoung
Published: December 2022

A moderate amount of reactive oxygen species (ROS) is produced under normal conditions, where they play an important role in cell signaling and are involved in many aspects of the immune response to pathogens. On the other hand, the excessive production of ROS destructs macromolecules, cell membranes, and DNA, and activates pro-inflammatory signaling pathways, which may lead to various pathologic conditions. Gastrointestinal (GI) mucosa is constantly exposed to ROS due to the presence of bacteria and other infectious pathogens in food, as well as alcohol consumption, smoking, and the use of non-steroidal anti-inflammatory drugs (NSAID). Prolonged excessive oxidative stress and inflammation are two major risk factors for GI disorders such as ulcers and cancers. Bioactive food compounds with potent anti-oxidant and anti-inflammatory activity have been tested in experimental GI disease models to evaluate their therapeutic potential. Astaxanthin (AST) is a fat-soluble xanthophyll carotenoid that is naturally present in algae, yeast, salmon, shrimp, and krill. It has been shown that AST exhibits protective effects against GI diseases via multiple mechanisms. Residing at the surface and inside of cell membranes, AST directly neutralizes ROS and lipid peroxyl radicals, enhances the activity of anti-oxidant enzymes, and suppresses pro-inflammatory transcription factors and cytokines. In addition, AST has been shown to inhibit cancer cell growth and metastasis via modulating cell proliferation-related pathways, apoptosis, and autophagy. Considering the potential benefits of AST in GI diseases, this review paper aims to summarize recent advances in AST research, focusing on its anti-oxidant and anti-inflammatory effects against gastric and intestinal ulcers and cancers.