bluuebunny/crossref_metadata_2025 huggingface dataset:
Carboxymethyl Chitosan/Sodium Alginate/Chitosan Quaternary Ammonium Salt Composite Hydrogel Supported 3J for the Treatment of Oral Ulcer
Authors: Lin Tao , Chen Dandan , Geng Yan , Li Jiayu , Ou Yanghui , Zeng Zhijun , Yin Canqiang , Qian Xudong , Qiu Xiang , Li Gang , Zhang Yali , Guan Wen , Li Mengjie , Cai Xiaojia , Wu Jiaqiang , Chen Wen-Hua , Guan Yan-Qing , Yao Hongliang
Published: August 2023

Oral ulcer is a common inflammatory disease of oral mucosa, causing severe burning pain and great inconvenience to daily life. In this study, compound 3J with anti-inflammatory activity was synthesized beforehand. Following that, an intelligent composite hydrogel supported 3J was designed with sodium alginate, carboxymethyl chitosan, and chitosan quaternary ammonium salt as the skeleton, and its therapeutic effect on the rat oral ulcer model was investigated. The results show that the composite hydrogel has a dense honeycomb structure, which is conducive to drug loading and wound ventilation, and has biodegradability. It has certain antibacterial effects and good anti-inflammatory activity. When loaded with 3J, it reduced levels of TNF-α and IL-6 in inflammatory cells by up to 50.0%. It has excellent swelling and water retention properties, with a swelling rate of up to 765.0% in a pH 8.5 environment. The existence of a large number of quaternary ammonium groups, carboxyl groups, and hydroxyl groups makes it show obvious differences in swelling in different pH environments, which proves that it has double pH sensitivity. It is beneficial to adapt to the highly dynamic changes of the oral environment. Compared with single hydrogel or drug treatment, the drug-loaded hydrogel has a better effect on the treatment of oral ulcers.
Development of Oral In Situ Gelling Liquid Formulations of Garcinia Extract for Treating Obesity
Authors: Fungfoung Kantiya , Praparatana Rachanida , Issarachot Ousanee , Wiwattanapatapee Ruedeekorn
Published: August 2023

Novel in situ gelling liquid formulations incorporating garcinia extract were developed to achieve prolonged delivery of hydroxycitric acid (HCA), an active compound displaying anti-obesity function, following oral administration. The optimized formulation was composed of sodium alginate (1.5% w/v), hydroxypropyl methylcellulose (HPMC K100) (0.25% w/v), calcium carbonate (1% w/v) and garcinia extract (2% w/v). The formulation displayed rapid gelation in less than a minute on exposure to 0.1 N hydrochloric acid (pH 1.2) and remained afloat for more than 24 h. The formulations were capable of gradually releasing more than 80% of HCA load over 8 h, depending on the composition. The resulting gels exhibited high values of gel strength by texture analysis, suggesting they would offer resistance to breakdown under the action of stomach content movement. The optimized formulation loaded garcinia extract significantly reduced lipid accumulation in 3T3-L1 adipocyte cells and displayed moderate anti-inflammatory activity by inhibiting the production of nitric oxide (NO) in LPS-stimulated RAW 264.7 macrophage cells. These findings demonstrate that oral in situ gelling liquid formulations based on sodium alginate and HPMC K100 offer much potential for sustained delivery of HCA and other anti-obesity compounds.
Implementing Core Genes and an Omnigenic Model for Behaviour Traits Prediction in Genomics
Authors: Rancelis Tautvydas , Domarkiene Ingrida , Ambrozaityte Laima , Utkus Algirdas
Published: August 2023

A high number of genome variants are associated with complex traits, mainly due to genome-wide association studies (GWAS). Using polygenic risk scores (PRSs) is a widely accepted method for calculating an individual’s complex trait prognosis using such data. Unlike monogenic traits, the practical implementation of complex traits by applying this method still falls behind. Calculating PRSs from all GWAS data has limited practical usability in behaviour traits due to statistical noise and the small effect size from a high number of genome variants involved. From a behaviour traits perspective, complex traits are explored using the concept of core genes from an omnigenic model, aiming to employ a simplified calculation version. Simplification may reduce the accuracy compared to a complete PRS encompassing all trait-associated variants. Integrating genome data with datasets from various disciplines, such as IT and psychology, could lead to better complex trait prediction. This review elucidates the significance of clear biological pathways in understanding behaviour traits. Specifically, it highlights the essential role of genes related to hormones, enzymes, and neurotransmitters as robust core genes in shaping these traits. Significant variations in core genes are prominently observed in behaviour traits such as stress response, impulsivity, and substance use.
A Rare Pathological Phenotype of Endometrioid Serous and Clear-Cell Ovarian Cancer with PIK3CA Mutations in Relation to The Excellent Response of Alpelisib
Authors: Bayram Ertugrul , Khatib Ghanim , Guney Burak , Kilicbagir Emine , Gulec Huru Rabia , Boga Ibrahim , Paydas Semra
Published: August 2023

Patients with metastatic ovarian cancer who develop resistance to standard therapy with or without platinum need to search for other therapeutic choices. Therefore, identifying genetic alterations and selecting an approach to treatment using precision medicine techniques are important. In a patient diagnosed with mixed-type ovarian cancer after surgery, adjuvant therapy was applied with a combination of carboplatin and taxane, but the disease recurred. Upon evaluation of the patient as having platinum-sensitive epithelial ovarian cancer (EOC), combination therapy with bevacizumab was initially successful. However, disease progression was again observed, and molecular analysis revealed the presence of an E545K mutation in the PIK3CA gene; therefore, a selective PI3K inhibitor, alpelisib, was used as a treatment under the compassionate-use protocol. The patient’s complications improved after receiving the alpelisib medication. The patient has been in complete remission for over two years. This case serves as a rare example that confirms the utility of alpelisib in managing mixed-type ovarian cancer.
Considerations Regarding Online Group Psychotherapy Sessions for Breast Cancer Patients in Active Phase of Oncological Treatment
Authors: Vâlcu Elena Gabriela , Firescu Dorel , Nechita Aurel , Ciubară Anamaria , Constantin Georgiana Bianca , Rahnea-Nita Gabriela , Rebegea Laura-Florentina
Published: August 2023

Introduction: The aim of this study is to evaluate the results of online group meetings for breast cancer patients in the active phase of treatment. The group therapy sessions took place weekly, synchronously, online, on Zoom, with a total of 12 meetings lasting about 2.5 h per session, between December 2021 and February 2022. We analyzed the topics of discussion chosen by the participants, the structure of the group, the results obtained at the main scales of evaluation/monitoring of quality of life and the motivation of patients to participate in the therapeutic group. All patients were in the active phase of treatment (chemotherapy, radiotherapy, hormone therapy, etc.). The main goal of the group therapy was to reduce the stress related to the disease. Material and methods: Systematic observations included ABS psychological tests, EQ-5D-5L, HADS—Hospital Anxiety and Depression Scale, and the Recurrence Fear Questionnaire; the questionnaires were administered at the beginning and at the end of the therapeutic intervention; the participation in the therapy and in the research of the patients began after signing the informed consent document; the intervention was evaluated at the end using a feedback questionnaire. The group was closed, and the participants signed an informed consent document and agreed to have the sessions recorded. Results: Comparing the initial with the final results of the psychological tests administered, there was an improvement in the quality of life of the participants in all areas, with a clinically significant decrease in the areas of pain and depression, along with an increase in perception of well-being, a decrease in FoP scores and an increase in the level of rationality about the disease. Conclusions: Group therapy for cancer patients was useful in improving the quality of life; the closed group, even online, provided a safe environment in which they could share feelings. A close correlation was noted between the scores obtained on the FoP-Q and HADS scales. It is evident that there is a strong relationship between FoP and depression. Results on these scales correlated well with results on the EQ-5D-5L quality of life questionnaire.
The Non-Paced 3-Minute Sit-to-Stand Test: Feasibility and Clinical Relevance for Pulmonary Rehabilitation Assessment
Authors: Ernst Rachel , Bouteleux Benoit , Malhouitre Marie , Grassion Léo , Zysman Maéva , Henrot Pauline , Delorme Mathieu
Published: August 2023

Pulmonary rehabilitation (PR) improves health-related quality-of-life (HRQoL) in individuals with chronic obstructive pulmonary disease (COPD), notably by increasing exercise tolerance. Easy-to-implement sit-to-stand tests can facilitate the assessment of exercise tolerance in routine practice. This retrospective study conducted in a real-life setting was designed to describe the non-paced 3-min sit-to-stand test (3-STST) and to evaluate its relationship with HRQoL (VQ11 questionnaire) to identify the determinants of 3-STST performance and to analyze the evolution of 3-STST performance and HRQoL over the course of a community-based PR program. Seventy-one COPD patients (age 69 ± 10 years old; 51% with GOLD spirometric stages III–IV) were included. Mean ± SD 3-STST performance at the initial PR assessment was 43 ± 15 repetitions. This performance was significantly associated with HRQoL and other indicators of clinical severity (lung function, dyspnea, and functional capacities). During the multivariate analysis, younger age, exertional dyspnea with mMRC ≤ 1, and better HRQoL were significantly associated with better 3-STST performance. From the initial to second PR assessment, changes in 3-STST performance were significantly associated with changes in HRQoL. This study provides evidence that the non-paced 3-STST is feasible and might be clinically relevant in the assessment of patients with COPD referred for community-based PR. This test deserves to be prospectively validated.
Association between Muscle Fatigability, Self-Perceived Fatigue and C-Reactive Protein at Admission in Hospitalized Geriatric Patients
Authors: Hoekstra Carmen , Swart Myrthe , Bautmans Ivan , Melis René , Peeters Geeske
Published: August 2023

Background: The capacity to perceived vitality (CPV) ratio is a novel measure for intrinsic capacity or resilience based on grip work and self-perceived fatigue. CPV has been associated with pre-frailty in older adults and post-surgery inflammation in adults. To better understand the utility of this measure in a frail population, we examined the association between CPV and inflammation in geriatric inpatients. Methods: Data were obtained from 104 hospitalized geriatric patients. The average age of participants was 83.3 ± 7.5 years, and 55.8% of participants were women. In the cross-sectional analyses, associations between C-reactive protein (CRP), grip work (GW), self-perceived fatigue (SPF) and the CPV ratio (higher values indicate better capacity) were examined using linear regression adjusted for confounders. Results: The adjusted association between CRP (abnormal vs. normal) and the CPV ratio was not statistically significant (B = −0.33, 95% CI = −4.00 to 3.34). Associations between CRP and GW (B = 25.53, 95% CI = −478.23 to 529.30) and SPF (B = 0.57, 95% CI = −0.64 to 1.77) were also not statistically significant. Similar results were found in unadjusted models and analyses of cases with complete data. Conclusions: In this frail group of geriatric inpatients, inflammation, routinely assessed with CRP, was not associated with CPV or its components, GW and SPF. Further research is needed to explore whether CPV is a useful indicator of frailty or recovery capacity in hospitalized geriatric patients.
Modeling Predictors of Medication Waste Reduction Intention in Algeria: Extending the Theory of Planned Behavior
Authors: Mouloudj Kamel , Njoku Anuli , Asanza Dachel Martínez , Bouarar Ahmed Chemseddine , Evans Marian A. , Mouloudj Smail , Bouarar Achouak
Published: August 2023

COVID-19 caused an increase in the demand for medications, which led to an increase in pharmaceutical waste and there is no doubt that this contributes to environmental pollution. Hence, it became necessary to search for how to protect and improve the environment by encouraging the behavior of medication waste reduction. Accordingly, this study aims to investigate the factors affecting intentions to reduce medication waste. Considering this, we develop an extended theory of planned behavior (TPB) framework by incorporating the constructs of moral obligation, environmental awareness, and medication waste risk perception. Using the convenience sampling method and based on a self-administered questionnaire, a total of 225 usable responses were collected in five Algerian cities. The results showed that positive attitudes (β = 0.316, p < 0.001), moral obligation (β = 0.291, p < 0.001), environmental awareness (β = 0.227, p < 0.001), perceived behavior control (PBC) (β = 0.151, p = 0.001), greater perceived risks (β = 0.127, p < 0.001), and subjective norm (β = 0.096, p < 0.05) significantly and positively influence the medication waste minimization intention. Furthermore, our analyses revealed that the extended TPB model explained 73.40% of the intention variance. In conclusion, we have explored the intentions, and there may be a gap between intent and actual behavior. Therefore, we recommend future studies to examine the factors affecting the actual behavior of medication waste reduction and to investigate environmental ethics and religious commitment as predictors of waste reduction intentions.
Correction: Colbeth et al. Mortality among Fire Department of the City of New York Rescue and Recovery Workers Exposed to the World Trade Center Disaster, 2001–2017. Int. J. Environ. Res. Public Health 2020, 17, 6266
Authors: Colbeth Hilary L. , Zeig-Owens Rachel , Hall Charles B. , Webber Mayris P. , Schwartz Theresa M. , Prezant David J.
Published: August 2023

The original publication [...]
Critical Illness in Migrant Workers in the Windsor-Essex Region: A Descriptive Analysis
Authors: Zhou Alex , Osman Abdelhady , Flores Genesis , Srikrishnaraj Dhuvaraha , Mohanty Jayashree , Al Bader Retage , Llancari Amy , El-Hashemi Aya , Elias Manahel , Mirza Kanza , Muldoon Maureen , Palazzolo Ryan , Zaib Farwa , Woldie Indryas , Hamm Caroline
Published: August 2023

Despite their essential role in Canadian agriculture, migrant workers face numerous healthcare barriers. There is a knowledge gap regarding the healthcare experiences of migrant workers with critical illness in the Windsor-Essex region. Our objective was to collect information on the experiences of migrant workers experiencing a critical illness at Windsor Regional Hospital (WRH) between 31 December 2011 and 31 December 2021. We conducted a retrospective chart review and interviews with migrant workers. We identified 14 migrant workers who presented to WRH with a critical illness over these 10 years. Despite occasional barriers regarding access to care, the migrant workers received an appropriate standard of care in Canada. Five of the fourteen patients identified were repatriated to their home countries. The migrant worker patients interviewed expressed satisfaction with the care they received in Canada but identified repatriation as a specific concern to receiving continuity of care. The health and financial burden imposed by critical illness on migrant workers and their employers makes critically ill workers vulnerable to medical repatriation as a unique social determinant of health. Considering the critical role of migrant workers in Canada’s food security, policy changes should be considered to ensure critically ill workers are able to remain until recovery.
Endothelial Cell Response to Combined Photon or Proton Irradiation with Doxorubicin
Authors: Bernardo Teresa , Kuntze Anna , Klein Diana , Heinzelmann Feline , Timmermann Beate , von Neubeck Cläre
Published: August 2023

Surgery, radiotherapy, and chemotherapy are essential treatment modalities to target cancer cells, but they frequently cause damage to the normal tissue, potentially leading to side effects. As proton beam radiotherapy (PBT) can precisely spare normal tissue, this therapeutic option is of increasing importance regarding (neo-)adjuvant and definitive anti-cancer therapies. Akin to photon-based radiotherapy, PBT is often combined with systemic treatment, such as doxorubicin (Dox). This study compares the cellular response of human microvascular endothelial cells (HMEC-1) following irradiation with photons (X) or protons (H) alone and also in combination with different sequences of Dox. The cellular survival, cell cycle, apoptosis, proliferation, viability, morphology, and migration were all investigated. Dox monotreatment had minor effects on all endpoints. Both radiation qualities alone and in combination with longer Dox schedules significantly reduced clonogenic survival and proliferation, increased the apoptotic cell fraction, induced a longer G2/M cell cycle arrest, and altered the cell morphology towards endothelial-to-mesenchymal-transition (EndoMT) processes. Radiation quality effects were seen for metabolic viability, proliferation, and motility of HMEC-1 cells. Additive effects were found for longer Dox schedules. Overall, similar effects were found for H/H-Dox and X/X-Dox. Significant alterations between the radiation qualities indicate different but not worse endothelial cell damage by H/H-Dox.
Evaluating the Molecular Properties and Function of ANKHD1, and Its Role in Cancer
Authors: Mullenger Jordan L. , Zeidler Martin P. , Fragiadaki Maria
Published: August 2023

Ankyrin repeat and single KH domain-containing protein 1 (ANKHD1) is a large, scaffolding protein composed of two stretches of ankyrin repeat domains that mediate protein–protein interactions and a KH domain that mediates RNA or single-stranded DNA binding. ANKHD1 interacts with proteins in several crucial signalling pathways, including receptor tyrosine kinase, JAK/STAT, mechanosensitive Hippo (YAP/TAZ), and p21. Studies into the role of ANKHD1 in cancer cell lines demonstrate a crucial role in driving uncontrolled cellular proliferation and growth, enhanced tumorigenicity, cell cycle progression through the S phase, and increased epithelial-to-mesenchymal transition. Furthermore, at a clinical level, the increased expression of ANKHD1 has been associated with greater tumour infiltration, increased metastasis, and larger tumours. Elevated ANKHD1 resulted in poorer prognosis, more aggressive growth, and a decrease in patient survival in numerous cancer types. This review aims to gather the current knowledge about ANKHD1 and explore its molecular properties and functions, focusing on the protein’s role in cancer at both a cellular and clinical level.
Correlation between Circulating miR-16, miR-29a, miR-144 and miR-150, and the Radiotherapy Response and Survival of Non-Small-Cell Lung Cancer Patients
Authors: Bache Matthias , Kadler Frauke , Struck Olivia , Medenwald Daniel , Ostheimer Christian , Güttler Antje , Keßler Jacqueline , Kappler Matthias , Riemann Anne , Thews Oliver , Seliger Barbara , Vordermark Dirk
Published: August 2023

Despite the success of current therapy concepts, patients with advanced non-small-cell lung cancer (NSCLC) still have a very poor prognosis. Therefore, biological markers are urgently needed, which allow the assessment of prognosis, or prediction of the success of therapy or resistance in this disease. Circulating microRNAs (miRs) have potential as biomarkers for the prognosis and prediction of response to therapy in cancer patients. Based on recent evidence that circulating miR-16, miR-29a, miR-144 and miR-150 can be regulated by ionizing radiation, the concentration of these four miRs was assessed in the plasma of NSCLC patients at different time points of radiotherapy by digital droplet PCR (ddPCR). Furthermore, their impact on patients’ prognosis was evaluated. The mean plasma levels of miR-16, miR-29a, miR-144 and miR-150 significantly differed intra- and inter-individually, and during therapy in NSCLC patients, but showed a strong positive correlation. The individual plasma levels of miR-16, miR-29a and miR-144 had prognostic value in NSCLC patients during or at the end of radiotherapy in Cox’s regression models. NSCLC patients with low levels of these three miRs at the end of radiotherapy had the worst prognosis. However, miR-150 plasma levels and treatment-dependent changes were not predictive. In conclusion, circulating miR-16, miR-29a and miR-144, but not miR-150, have a prognostic value in NSCLC patients undergoing radiotherapy.
Real-World Experience in Treatment of Patients with Non-Small-Cell Lung Cancer with BRAF or cMET Exon 14 Skipping Mutations
Authors: Janzic Urska , Shalata Walid , Szymczak Katarzyna , Dziadziuszko Rafał , Jakopovic Marko , Mountzios Giannis , Płużański Adam , Araujo Antonio , Charpidou Andriani , Agbarya Abed
Published: August 2023

BRAF and cMET exon 14 skipping are rare mutations of NSCLC. The treatment sequence in these cases for the first and second line is not clear. An international registry was created for patients with advanced NSCLC harboring BRAF or cMET exon 14 skipping mutations, diagnosed from January 2017 to June 2022. Clinicopathological and molecular data and treatment patterns were recorded. Data on 58 patients, from eight centers across five countries, were included in the final analysis. We found that 40 patients had the cMET exon 14 skipping mutation and 18 had the BRAF V600E mutation. In total, 53 and 28 patients received first- and second-line treatments, respectively, among which 52.8% received targeted therapy (TT) in the first line and 53.5% in the second line. The overall response rate (ORR) and disease control rate (DCR) for first-line treatment with TT vs. other treatment such as immune checkpoint inhibitors ± chemotherapy (IO ± CT) were 55.6% vs. 21.7% (p = 0.0084) and 66.7% vs. 39.1% (p = 0.04), respectively. The type of treatment in first-line TT vs. other affected time to treatment discontinuation (TTD) was 11.6 m vs. 4.6 m (p= 0.006). The overall survival for the whole group was 15.4 m and was not statistically affected by the type of treatment (19.2 m vs. 13.5 m; p = 0.83).
Influential Serum Kinases (Non-sFlt-1) and Phosphatases in Preeclampsia—Systemic Review and Metanalysis
Authors: Marrufo-Gallegos Karla Cecilia , Villafán-Bernal Jose Rafael , Espino-y-Sosa Salvador , Estrada-Gutierrez Guadalupe , Guzmán-Guzmán Iris Paola , Martinez-Portilla Raigam Jafet , Torres-Torres Johnatan
Published: August 2023

The early identification of women with an increased risk of preeclampsia (PE) is desirable, but apart from soluble fms-like tyrosine kinase-1 (sFlt-1), few biomarkers have previously been identified as relevant for predicting preeclampsia. Since kinases and phosphatases regulate critical biological processes and previous evidence suggests a potential role of these molecules in preeclampsia, we performed this systematic review and metanalysis. The objective was to determine if there are kinases and phosphatases whose serum levels are different between women with and without PE, being relevant biomarkers of PE. We followed the recommendations of Cochrane and the Preferred Reported Items for Systematic Reviews and Metanalysis (PRISMA) to perform this study. The MESH terms preeclampsia, kinases, phosphatases, angiopoietins, soluble tyrosine protein kinase receptor (sTIE2), and cellular-mesenchymal-epithelial transition factor (c-MET) were combined to find relevant articles in the PubMed, PROSPERO, and Cochrane databases. Then, a qualitative and quantitative analysis was performed in R Studio software. From 580 abstracts identified, 37 were included in the final analysis, which comprised 24,211 pregnant women (2879 with PE and 21,332 women without PE [HP]. The pooled analysis showed that serum creatine kinase (CK) (SMD: 2.43, CI 95% 0.25–4.62) was significantly higher in PE, whereas sTIE2 and anti-angiogenic factor soluble c-Met (sMet)were significantly lower in PE than in HP (SMD: −0.23, CI95% −0.37 to −0.09; and SMD:0.24, CI95% 0.01–0.47, respectively). Adenosine monophosphate-activated protein kinase (AMPK), angiopoietin-1 (ANG-1), angiopoietin-2 (ANG-2), the ratio angiopoietin-1/angiopoietin-2, acid phosphatase, and alkaline phosphatase were not different between women with PE and HP. In summary CK, sTIE2, and c-MET are relevant biomarkers of PE. It is desirable to incorporate them into current models for PE prediction to evaluate their utility as biomarkers.
Nicotiana benthamiana Class 1 Reversibly Glycosylated Polypeptides Suppress Tobacco Mosaic Virus Infection
Authors: Kamarova Kamila A. , Ershova Natalia M. , Sheshukova Ekaterina V. , Arifulin Eugene A. , Ovsiannikova Natalia L. , Antimonova Alexandra A. , Kudriashov Andrei A. , Komarova Tatiana V.
Published: August 2023

Reversibly glycosylated polypeptides (RGPs) have been identified in many plant species and play an important role in cell wall formation, intercellular transport regulation, and plant–virus interactions. Most plants have several RGP genes with different expression patterns depending on the organ and developmental stage. Here, we report on four members of the RGP family in N. benthamiana. Based on a homology search, NbRGP1-3 and NbRGP5 were assigned to the class 1 and class 2 RGPs, respectively. We demonstrated that NbRGP1–3 and 5 mRNA accumulation increases significantly in response to tobacco mosaic virus (TMV) infection. Moreover, all identified class 1 NbRGPs (as distinct from NbRGP5) suppress TMV intercellular transport and replication in N. benthamiana. Elevated expression of NbRGP1–2 led to the stimulation of callose deposition at plasmodesmata, indicating that RGP-mediated TMV local spread could be affected via a callose-dependent mechanism. It was also demonstrated that NbRGP1 interacts with TMV movement protein (MP) in vitro and in vivo. Therefore, class 1 NbRGP1–2 play an antiviral role by impeding intercellular transport of the virus by affecting plasmodesmata callose and directly interacting with TMV MP, resulting in the reduced viral spread and replication.
Cardiomyocyte Damage: Ferroptosis Relation to Ischemia-Reperfusion Injury and Future Treatment Options
Authors: Laukaitiene Jolanta , Gujyte Greta , Kadusevicius Edmundas
Published: August 2023

About half a century ago, Eugene Braunwald, a father of modern cardiology, shared a revolutionary belief that “time is muscle”, which predetermined never-ending effort to preserve the unaffected myocardium. In connection to that, researchers are constantly trying to better comprehend the ongoing changes of the ischemic myocardium. As the latest studies show, metabolic changes after acute myocardial infarction (AMI) are inconsistent and depend on many constituents, which leads to many limitations and lack of unification. Nevertheless, one of the promising novel mechanistic approaches related to iron metabolism now plays an invaluable role in the ischemic heart research field. The heart, because of its high levels of oxygen consumption, is one of the most susceptible organs to iron-induced damage. In the past few years, a relatively new form of programmed cell death, called ferroptosis, has been gaining much attention in the context of myocardial infarction. This review will try to summarize the main novel metabolic pathways and show the pivotal limitations of the affected myocardium metabolomics.
Aerobic Exercise Facilitates the Nuclear Translocation of SREBP2 by Activating AKT/SEC24D to Contribute Cholesterol Homeostasis for Improving Cognition in APP/PS1 Mice
Authors: Hu Zelin , Yuan Yangqi , Tong Zhen , Liao Meiqing , Yuan Shunling , Wu Weijia , Tang Yingzhe , Wang Yirong , Tang Changfa , Liu Wenfeng
Published: August 2023

Impaired cholesterol synthesizing ability is considered a risk factor for the development of Alzheimer’s disease (AD), as evidenced by reduced levels of key proteases in the brain that mediate cholesterol synthesis; however, cholesterol deposition has been found in neurons in tangles in the brains of AD patients. Although it has been shown that statins, which inhibit cholesterol synthesis, reduce the incidence of AD, this seems paradoxical for AD patients whose cholesterol synthesizing capacity is already impaired. In this study, we aimed to investigate the effects of aerobic exercise on cholesterol metabolism in the brains of APP/PS1 mice and to reveal the mechanisms by which aerobic exercise improves cognitive function in APP/PS1 mice. Our study demonstrates that the reduction of SEC24D protein, a component of coat protein complex II (COPII), is a key factor in the reduction of cholesterol synthesis in the brain of APP/PS1 mice. 12 weeks of aerobic exercise was able to promote the recovery of SEC24D protein levels in the brain through activation of protein kinase B (AKT), which in turn promoted the expression of mem-brane-bound sterol regulatory element-binding protein 2 (SREBP2) nuclear translocation and the expression of key proteases mediating cholesterol synthesis. Simultaneous aerobic exercise restored cholesterol transport capacity in the brain of APP/PS1 mice with the ability to efflux excess cholesterol from neurons and reduced neuronal lipid rafts, thereby reducing cleavage of the APP amyloid pathway. Our study emphasizes the potential of restoring intracerebral cholesterol homeostasis as a therapeutic strategy to alleviate cognitive impairment in AD patients.
The Molecular Mechanism of Positive Allosteric Modulation at the Dopamine D1 Receptor
Authors: Goldberg Alexander , Xie Bing , Shi Lei
Published: August 2023

The dopamine D1 receptor (D1R) is a promising target for treating various psychiatric disorders. While upregulation of D1R activity has shown potential in alleviating motor and cognitive symptoms, orthosteric agonists have limitations, restricting their clinical applications. However, the discovery of several allosteric compounds specifically targeting the D1R, such as LY3154207, has opened new therapeutic avenues. Based on the cryo-EM structures of the D1R, we conducted molecular dynamics simulations to investigate the binding and allosteric mechanisms of LY3154207. Our simulations revealed that LY3154207 preferred the horizontal orientation above intracellular loop 2 (IL2) and stabilized the helical conformation of IL2. Moreover, LY3154207 binding induced subtle yet significant changes in key structural motifs and their neighboring residues. Notably, a cluster of residues centered around the Na+-binding site became more compact, while interactions involving the PIF motif and its neighboring residues were loosened upon LY3154207 binding, consistent with their role in opening the intracellular crevice for receptor activation. Additionally, we identified an allosteric pathway likely responsible for the positive allosteric effect of LY3154207 in enhancing Gs protein coupling. This mechanistic understanding of LY3154207’s allosteric action at the D1R paves the way for the rational design of more potent and effective allosteric modulators.
The Effect of Stimulants on Nectar Composition, Flowering, and Seed Yield of Common Buckwheat (Fagopyrum esculentum Moench)
Authors: Płażek Agnieszka , Dziurka Michał , Słomka Aneta , Kopeć Przemysław
Published: August 2023

Common buckwheat is a valuable plant producing seeds containing a number of health-promoting compounds and elements. Buckwheat does not contain gluten and is characterized by an excellent composition of amino acids. This species is also a melliferous plant. Despite many advantages, the area of buckwheat cultivation is decreasing due to unstable yields. One of the reasons for low seed yield is its sensitivity to drought, high temperatures, and assimilate deficiencies. These factors have a significant impact on the nectar composition, which is important for visiting pollinators and thus for pollination. High temperature during flowering increases the degeneration of embryo sacs and embryos, which is high anyway (genetic determination) in common buckwheat. This phenomenon seems to be unbreakable by breeding methods. The authors aimed to determine whether stimulants commonly used in agriculture could increase the seed yield of this plant species. The aim of the work was to choose from eight different stimulants the most effective one that would improve the seed yield of two accessions of common buckwheat by increasing the efficiency of nectar production and reducing the number of empty seeds. The plants were sprayed at either the beginning of flowering or at full bloom. The content of sugars and amino acids was higher in the nectar produced at the beginning of flowering. The nectar of both lines included also polyamines. The level of sugars in the nectar increased mainly after spraying with the stimulants in the second phase of flowering. A positive correlation between the total amount of sugars and amino acids in the nectar and seed yield was found. All the stimulants used reduced the number of empty seeds in both accessions. Seed production in the PA15 line increased significantly under the influence of all stimulants used at the beginning of flowering, and the most effective were ASAHI SL and TYTANIT®.
Brassinosteroids Regulate the Water Deficit and Latex Yield of Rubber Trees
Authors: Guo Bingbing , Liu Mingyang , Yang Hong , Dai Longjun , Wang Lifeng
Published: August 2023

Brassinolide (BR) is an important plant hormone that regulates the growth and development of plants and the formation of yield. The yield and quality of latex from Hevea brasiliensis are regulated by phytohormones. The understanding of gene network regulation mechanism of latex formation in rubber trees is still very limited. In this research, the rubber tree variety CATAS73397 was selected to analyze the relationship between BR, water deficit resistance, and latex yield. The results showed that BR improves the vitality of rubber trees under water deficit by increasing the rate of photosynthesis, reducing the seepage of osmotic regulatory substances, increasing the synthesis of energy substances, and improving the antioxidant system. Furthermore, BR increased the yield and quality of latex by reducing the plugging index and elevating the lutoid bursting index without decreasing mercaptan, sucrose, and inorganic phosphorus. This was confirmed by an increased expression of genes related to latex flow. RNA-seq analysis further indicated that DEG encoded proteins were enriched in the MAPK signaling pathway, plant hormone signal transduction and sucrose metabolism. Phytohormone content displayed significant differences, in that trans-Zeatin, ethylene, salicylic acid, kinetin, and cytokinin were induced by BR, whereas auxin, abscisic acid, and gibberellin were not. In summary, the current research lays a foundation for comprehending the molecular mechanism of latex formation in rubber trees and explores the potential candidate genes involved in natural rubber biosynthesis to provide useful information for further research in relevant areas.
A Comparative and Critical Analysis for In Vitro Cytotoxic Evaluation of Magneto-Crystalline Zinc Ferrite Nanoparticles Using MTT, Crystal Violet, LDH, and Apoptosis Assay
Authors: de la Fuente-Jiménez Juan Luis , Rodríguez-Rivas César Iván , Mitre-Aguilar Irma Beatriz , Torres-Copado Andrea , García-López Eric Alejandro , Herrera-Celis José , Arvizu-Espinosa María Goretti , Garza-Navarro Marco Antonio , Arriaga Luis Gerardo , García Janet Ledesma , García-Gutiérrez Domingo Ixcóatl , Dehesa Alejandro Zentella , Sharma Ashutosh , Oza Goldie
Published: August 2023

Zinc ferrite nanoparticles (ZFO NPs) are a promising magneto-crystalline platform for nanomedicine-based cancer theranostics. ZFO NPs synthesized using co-precipitation method are characterized using different techniques. UV-visible spectroscopy exhibits absorption peaks specific for ZFO. Raman spectroscopy identifies Raman active, infrared active, and silent vibrational modes while Fourier transforms infrared spectroscopic (FTIR) spectra display IR active modes that confirm the presence of ZFO. X-ray diffraction pattern (XRD) exhibits the crystalline planes of single-phase ZFO with a face-centered cubic structure that coincides with the selected area electron diffraction pattern (SAED). The average particle size according to high-resolution transmission electron microscopy (HR-TEM) is 5.6 nm. X-ray photoelectron spectroscopy (XPS) signals confirm the chemical states of Fe, Zn, and O. A superconducting quantum interference device (SQUID) displays the magnetic response of ZFO NPs, showing a magnetic moment of 45.5 emu/gm at 70 kOe. These ZFO NPs were then employed for comparative cytotoxicity evaluation using MTT, crystal violet, and LDH assays on breast adenocarcinoma epithelial cell (MCF-7), triple-negative breast cancer lines (MDA-MB 231), and human embryonic kidney cell lines (HEK-293). Flow cytometric analysis of all the three cell lines were performed in various concentrations of ZFO NPs for automated cell counting and sorting based on live cells, cells entering in early or late apoptotic phase, as well as in the necrotic phase. This analysis confirmed that ZFO NPs are more cytotoxic towards triple-negative breast cancer cells (MDA-MB-231) as compared to breast adenocarcinoma cells (MCF-7) and normal cell lines (HEK-293), thus corroborating that ZFO can be exploited for cancer therapeutics.
Pharmacological Prevention of Ectopic Erythrophagocytosis by Cilostazol Mitigates Ferroptosis in NASH
Authors: Park Joon Beom , Ko Kangeun , Baek Yang Hyun , Kwon Woo Young , Suh Sunghwan , Han Song-Hee , Kim Yun Hak , Kim Hye Young , Yoo Young Hyun
Published: August 2023

Hepatic iron overload (HIO) is a hallmark of nonalcoholic fatty liver disease (NAFLD) with a poor prognosis. Recently, the role of hepatic erythrophagocytosis in NAFLD is emerging as a cause of HIO. We undertook various assays using human NAFLD patient pathology samples and an in vivo nonalcoholic steatohepatitis (NASH) mouse model named STAMTM. To make the in vitro conditions comparable to those of the in vivo NASH model, red blood cells (RBCs) and platelets were suspended and subjected to metabolic and inflammatory stresses. An insert-coculture system, in which activated THP-1 cells and RBCs are separated from HepG2 cells by a porous membrane, was also employed. Through various analyses in this study, the effect of cilostazol was examined. The NAFLD activity score, including steatosis, ballooning degeneration, inflammation, and fibrosis, was increased in STAMTM mice. Importantly, hemolysis occurred in the serum of STAMTM mice. Although cilostazol did not improve lipid or glucose profiles, it ameliorated hepatic steatosis and inflammation in STAMTM mice. Platelets (PLTs) played an important role in increasing erythrophagocytosis in the NASH liver. Upregulated erythrophagocytosis drives cells into ferroptosis, resulting in liver cell death. Cilostazol inhibited the augmentation of PLT and RBC accumulation. Cilostazol prevented the PLT-induced increase in ectopic erythrophagocytosis in in vivo and in vitro NASH models. Cilostazol attenuated ferroptosis of hepatocytes and phagocytosis of RBCs by THP-1 cells. Augmentation of hepatic erythrophagocytosis by activated platelets in NASH exacerbates HIO. Cilostazol prevents ectopic erythrophagocytosis, mitigating HIO-mediated ferroptosis in NASH models.
New Therapeutics for Heart Failure: Focusing on cGMP Signaling
Authors: Mangmool Supachoke , Duangrat Ratchanee , Parichatikanond Warisara , Kurose Hitoshi
Published: August 2023

Current drugs for treating heart failure (HF), for example, angiotensin II receptor blockers and β-blockers, possess specific target molecules involved in the regulation of the cardiac circulatory system. However, most clinically approved drugs are effective in the treatment of HF with reduced ejection fraction (HFrEF). Novel drug classes, including angiotensin receptor blocker/neprilysin inhibitor (ARNI), sodium-glucose co-transporter-2 (SGLT2) inhibitor, hyperpolarization-activated cyclic nucleotide-gated (HCN) channel blocker, soluble guanylyl cyclase (sGC) stimulator/activator, and cardiac myosin activator, have recently been introduced for HF intervention based on their proposed novel mechanisms. SGLT2 inhibitors have been shown to be effective not only for HFrEF but also for HF with preserved ejection fraction (HFpEF). In the myocardium, excess cyclic adenosine monophosphate (cAMP) stimulation has detrimental effects on HFrEF, whereas cyclic guanosine monophosphate (cGMP) signaling inhibits cAMP-mediated responses. Thus, molecules participating in cGMP signaling are promising targets of novel drugs for HF. In this review, we summarize molecular pathways of cGMP signaling and clinical trials of emerging drug classes targeting cGMP signaling in the treatment of HF.
Investigating Cryptosporidium spp. Using Genomic, Proteomic and Transcriptomic Techniques: Current Progress and Future Directions
Authors: Dąbrowska Joanna , Sroka Jacek , Cencek Tomasz
Published: August 2023

Cryptosporidiosis is a widespread disease caused by the parasitic protozoan Cryptosporidium spp., which infects various vertebrate species, including humans. Once unknown as a gastroenteritis-causing agent, Cryptosporidium spp. is now recognized as a pathogen causing life-threatening disease, especially in immunocompromised individuals such as AIDS patients. Advances in diagnostic methods and increased awareness have led to a significant shift in the perception of Cryptosporidium spp. as a pathogen. Currently, genomic and proteomic studies play a main role in understanding the molecular biology of this complex-life-cycle parasite. Genomics has enabled the identification of numerous genes involved in the parasite’s development and interaction with hosts. Proteomics has allowed for the identification of protein interactions, their function, structure, and cellular activity. The combination of these two approaches has significantly contributed to the development of new diagnostic tools, vaccines, and drugs for cryptosporidiosis. This review presents an overview of the significant achievements in Cryptosporidium research by utilizing genomics, proteomics, and transcriptomics approaches.
Proposal and Validation of New Diagnostic Criteria for Diagnostic Weights of Endoultrasonographic Findings for Early Chronic Pancreatitis
Authors: Kashima Ken , Yamamiya Akira , Abe Yoko , Nagashima Kazunori , Minaguchi Takahito , Kunogi Yasuhito , Sakuma Fumi , Fukushi Koh , Inaba Yasunori , Sugaya Takeshi , Tominaga Keiichi , Goda Kenichi , Irisawa Atsushi
Published: August 2023

[Background and study aim] A commonly applied method for diagnosing chronic pancreatitis (CP) uses endoscopic ultrasonography (EUS), assigning weights to each EUS diagnostic finding. It is the Rosemont classification (RC). In 2019, to improve EUS diagnostic specificity, Japanese diagnostic criteria for early chronic pancreatitis (ECP) were revised. Nevertheless, the criteria use no weighting of EUS diagnostic findings, as the RC does. This study was undertaken to propose diagnostic criteria that would weight each EUS finding of ECP and that would be more specific than the RC. [Methods] By EUS of the pancreas, 773 patients underwent detailed observation from January 2018 to March 2019 at our institution. An expert finalized all cases when patients were diagnosed. Using data from the medical records, 97 consecutive patients with EUS diagnostic findings of ECP based on the Japanese diagnostic criteria of ECP2009 (JDCECP2009) were selected. The definition under the RC of “Indeterminate for CP” was equivalent to ECP. Each case was diagnosed using (1) JDCECP2009 and (2) the Japanese diagnostic criteria of ECP2019 (JDCECP2019). Moreover, the four diagnostic EUS findings in JDCECP2019 were applied to the RC, weighted (modified-JDCECP2019), and subsequently compared with the earlier diagnostic criteria. As Modified-JDCECP2019, we suggested (3) RC-A—the current four items scored related to the RC, and (4) RC-B—the five items scored by dividing lobularity with and without honeycombing. [Results] Diagnoses produced based on each criterion were normal: ECP = (1) 20:77, (2) 46:51, (3) 52:42, and (4) 60:35. [Conclusions] Modified-JDCECP2019 may provide EUS diagnoses for ECP with higher specificity.
Surgical Management of Ovarian Endometrioma: Impact on Ovarian Reserve Parameters and Reproductive Outcomes
Authors: Daniilidis Angelos , Grigoriadis Georgios , Kalaitzopoulos Dimitrios Rafail , Angioni Stefano , Kalkan Üzeyir , Crestani Adrien , Merlot Benjamin , Roman Horace
Published: August 2023

Ovarian endometriomas have a negative impact on a patient’s reproductive potential and are likely to cause a reduction in ovarian reserve. The most commonly employed ovarian reserve parameters are anti-Müllerian hormone (AMH) and antral follicular count (AFC). Surgical management options of endometrioma include cystectomy, ablative methods, ethanol sclerotherapy and combined techniques. The optimal surgical approach remains a matter of debate. Our review aimed to summarize the literature on the impact of surgical management of endometrioma on AMH, AFC and fertility outcomes. Cystectomy may reduce recurrence rates and increase chances of spontaneous conception. However, a postoperative reduction in AMH is to be anticipated, despite there being evidence of recovery during follow-up. The reduction in ovarian reserve is likely multi-factorial. Cystectomy does not appear to significantly reduce, and may even increase, AFC. Ablative methods achieve an ovarian-tissue-sparing effect, and improved ovarian reserve, compared to cystectomy, has been demonstrated. A single study reported on AMH and AFC post sclerotherapy, and both were significantly reduced. AMH levels may be useful in predicting the chances of conception postoperatively. None of the aforementioned approaches has a clearly demonstrated superiority in terms of overall chances of conception. Surgical management of endometrioma may, overall, improve the probability of pregnancy. Evidence on its value before medically assisted reproduction (MAR) is conflicting; however, a combination of surgery followed by MAR may achieve the optimal fertility outcome. In view of the complexity of available evidence, individualization of care, combined with optimal surgical technique, is highly recommended.