bluuebunny/crossref_metadata_2025 huggingface dataset:
The Involvement of the microRNAs miR-466c and miR-340 in the Palmitate-Mediated Dysregulation of Gonadotropin-Releasing Hormone Gene Expression
Authors: Nkechika Vanessa , Zhang Ningtong , Belsham Denise D.
Published: March 2024

Diets high in saturated fatty acids are associated with obesity and infertility. Palmitate, the most prevalent circulating saturated fatty acid, is sensed by hypothalamic neurons, contributing to homeostatic dysregulation. Notably, palmitate elevates the mRNA levels of gonadotropin-releasing hormone (Gnrh) mRNA and its activating transcription factor, GATA binding protein 4 (Gata4). GATA4 is essential for basal Gnrh expression by binding to its enhancer region, with Oct-1 (Oct1) and CEBP-β (Cebpb) playing regulatory roles. The pre- and post-transcriptional control of Gnrh by palmitate have not been investigated. Given the ability of palmitate to alter microRNAs (miRNAs), we hypothesized that palmitate-mediated dysregulation of Gnrh mRNA involves specific miRNAs. In the mHypoA-GnRH/GFP neurons, palmitate significantly downregulated six miRNAs (miR-125a, miR-181b, miR-340, miR-351, miR-466c and miR-503), and the repression was attenuated by co-treatment with 100 μM of oleate. Subsequent mimic transfections revealed that miR-466c significantly downregulates Gnrh, Gata4, and Chop mRNA and increases Per2, whereas miR-340 upregulates Gnrh, Gata4, Oct1, Cebpb, and Per2 mRNA. Our findings suggest that palmitate may indirectly regulate Gnrh at both the pre- and post-transcriptional levels by altering miR-466c and miR-340, which in turn regulate transcription factor expression levels. In summary, palmitate-mediated dysregulation of Gnrh and, consequently, reproductive function involves parallel transcriptional mechanisms.
Structural Control at Monte Somma and Vesuvio during the Last 5600 Years through Time and Space Distribution of Volcanic Vents
Authors: Principe Claudia , Giordano Daniele , Paolillo Annarita , Arrighi Simone , Brocchini Debora , La Felice Sonia
Published: March 2024

Vesuvio is likely the most if not one of the most dangerous volcanoes in the world. It is an active volcano, quiescent since 1944. The activity of the Monte Somma and Vesuvio volcanic complex is commonly referred to as two central volcanic edifices, namely Monte Somma and Vesuvio. Nevertheless, the opening of numerous eruptive fissures and related vents have characterized Monte Somma and Vesuvio throughout their lives. Spatter cones, spatter ramparts, and related eruptive fissures are disseminated downslope of Vesuvio’s main cone and on the southern slopes of the volcano. Similarly, cinder cones, spatter cones, and welded spatters are distributed in the sequence cropping out on the Monte Somma cliff and on the northern slopes of Monte Somma. In this work, a total of 168 eruptive vents have been identified and characterized in a GIS environment in which field data have been merged with relevant information from historical maps and documents. These vents have been arranged into units bounded by unconformities (Unconformity Bounded Stratigraphic Units) defining the eruptive history of the volcano. Alignments of vents and eruptive fissures within each unit have been compared with regional tectonic elements and the volcano-tectonic features affecting Monte Somma and Vesuvio during the last 5600 years, thus inferring that different structural trends were active in the different stratigraphic units. In particular, we show that the N300°–320° regional, Apennine, left-lateral, strike-slip fault system, the N040°–055° Torre del Greco direct fault system, the N70° and the EW fault system, and the generally NS oriented group of local brittle elements, all analyzed here, were differently active during the investigated time span. These tectonic trends might control the position of the eruptive fissures and vents in case of future unrest of the volcano.
Healthcare Workers: Heroes or Victims? Context of the Western World and Proposals to Prevent Violence
Authors: Volonnino Gianpietro , Spadazzi Federica , De Paola Lina , Arcangeli Mauro , Pascale Natascha , Frati Paola , La Russa Raffaele
Published: March 2024

Episodes of direct violence against healthcare workers and social workers represent a worrying and widespread phenomenon in Western countries. These violent attacks, whether verbal or physical, occur in various work environments, targeting professionals working in private facilities, medical practices, or those employed within the National Health System facilities. We conducted a search using a single search engine (PubMed) using the terms “violence against healthcare workers AND Western” for the period 2003–2023, identifying 45 results to which we added to the literature through hand searching. Our review thus analyzed the sector literature to highlight the phenomenon of violence against healthcare workers, particularly in Western countries. We began with an analysis of the problem and then focused on the true purpose of the study, which is to propose new solutions to protect healthcare workers in all work settings. Consequently, we aim to improve both the working environment for healthcare professionals and to enhance the overall healthcare and public health outcomes.
Social Support and Resilience Are Protective Factors against COVID-19 Pandemic Burnout and Job Burnout among Nurses in the Post-COVID-19 Era
Authors: Moisoglou Ioannis , Katsiroumpa Aglaia , Malliarou Maria , Papathanasiou Ioanna V. , Gallos Parisis , Galanis Petros
Published: March 2024

Nurses have experienced several psychological and work-related issues during the COVID-19 pandemic, including pandemic burnout and job burnout. The aim of this study was to examine the impact of social support and resilience on COVID-19 pandemic burnout and job burnout among nurses. We conducted a cross-sectional study in Greece. The study population included 963 nurses. We measured social support, resilience, COVID-19 pandemic burnout, and job burnout with the Multidimensional Scale of Perceived Social Support, Brief Resilience Scale, COVID-19 Burnout Scale, and Single-Item Burnout Measure, respectively. Nurses received high levels of social support, while their resilience was moderate. Additionally, nurses experienced moderate levels of COVID-19 burnout and job burnout. Increased social support and increased resilience were associated with reduced COVID-19 pandemic burnout. We found a negative relationship between social support and job burnout. A similar negative relationship was found between resilience and job burnout. Social support and resilience can act as protective factors against COVID-19 pandemic burnout and job burnout among nurses. Policy makers should develop and implement appropriate strategies to improve nurses’ social support and resilience since they are the backbone of healthcare systems worldwide.
Physical Therapists’ Attitudes, Beliefs, and Barriers Regarding Fall Screening and Prevention among Patients with Knee Osteoarthritis: A Cross-Sectional Study
Authors: Alsobhi Mashael , Gmmash Afnan , Aldhabi Rawan , Almaddah Muataz R. , Ameen Alaa , Almotairi Fae , Basuodan Reem , Khan Fayaz
Published: March 2024

Falls are commonly associated with knee osteoarthritis and represent a significant financial burden on the healthcare system. Therefore, the discovery of physical therapists’ attitudes and practices regarding fall screening and prevention among patients with osteoarthritis should be investigated. Moreover, this study aimed to identify barriers that might limit its implementation among this population. A cross-sectional study design was used to collect the data. The electronic survey targeted licensed physical therapy professionals who currently work in clinical or academic settings in Saudi Arabia. The data were analyzed descriptively and inferentially using chi-square. Two hundred and six licensed physical therapists completed the survey, 119 females (57.8%) and 87 males (42.2%). The results of the structural equation modelling analysis showed that intention to use fall screening and management strategies was positively associated with the history of falls, identifying risk factors of falls, and documentation of risk factors of falls (p ≤ 0.0001). The most reported barriers to implement fall screening and prevention were lack of knowledge (n = 92, 45%), lack of training/skills (n = 84, 41%), and time constraints (n = 57, 45%), followed by patient compliance with 38% of the responses. The findings highlighted the importance of identifying the key opportunities for knowledge translation in clinical practices to enhance the sufficient implementation of fall screening and management in osteoarthritis care.
Indolent T Cell Lymphoproliferation of the Gastrointestinal Tract: An Evolving Disease Entity
Authors: Wang Luke , Koh Elaine , Kumar Beena , Low Michael S. Y.
Published: March 2024

Background: Indolent T cell lymphoproliferation of the gastrointestinal tract is a novel entity recently added to the 2016 WHO classification of lymphoid neoplasms. Classically, these patients demonstrate an immunophenotype consistent with T cell proliferation and can be either CD4-positive or CD8-positive but with a low Ki67 index, highlighting the indolent nature of this disease compared to its more aggressive T cell lymphoma counterparts such as enteropathy-associated T cell lymphoma and monomorphic epitheliotropic intestinal T cell lymphoma. Methods: Here, we describe one rare case of such a neoplasm under our care, initially presenting with non-specific signs and symptoms and requiring extensive investigations to diagnose. Available cases in the literature reflect a wide variety of ages and ethnicities affected, and any part of the gastrointestinal sites can be affected, which makes diagnosis difficult and prolonged; however, progression beyond lymph nodes is rare, and prognosis is otherwise favourable, particularly if CD8-positive. The optimal management of these patients remains yet to be defined, given the paucity of available cases currently. The current evidence suggests the utility of steroids, cyclosporine, radiotherapy, and a potential role for JAK inhibitors. Conclusions: Our case showed an excellent response to the initial course of steroids, with a subsequent successful transition to cyclosporine, keeping symptoms at bay with ongoing stable disease.
Museums for Older Adults and Mobility-Impaired People: Applying Inclusive Design Principles and Digital Storytelling Guidelines—A Review
Authors: Kasemsarn Kittichai , Sawadsri Antika , Harrison David , Nickpour Farnaz
Published: March 2024

The research problems addressed in this article pertain to the limited understanding and insufficient availability of digital storytelling guidelines for elderly and physically impaired individuals in museum presentations. The objective of this review is to explore digital storytelling guidelines along with the latest technology in museums catering to older adults and those with mobility impairments. This literature review included databases such as Scopus, ScienceDirect, and Google Scholar, covering the period from 2000 to 2023. Researchers comprehensively examined and employed content analysis to categorize all papers into three primary themes: (1) inclusive design for museum presentations; (2) trends in technology for digital storytelling in museum presentations; (3) guidelines for digital storytelling in museum presentations. This review article could enhance understanding and promote diversity, accessibility, and motivation among two specific groups of museum visitors, both onsite and online.
Contamination and Spatial Distribution of Metal(loid)s in the Stream Sediment near the Greenhouse
Authors: Yun Sung-Wook , Son Jinkwan
Published: March 2024

As greenhouse horticulture continues to increase in South Korea, the effects of metal(loid)s from wastewater discharges on stream sediments were analyzed. A total of 106 samples were analyzed for cadmium (Cd), boron (B), copper (Cu), nickel (Ni), lead (Pb), zinc (Zn), chromium (Cr), manganese (Mn), and iron (Fe). The coefficient of variation (CV) of the metal(loid)s components was 96.58% for Mn, 93.40 for Zn, 62.47 for B, 58.90 for Pb, and 58.14 for Cd, suggesting anthropogenic sources. Correlation analysis suggested a cumulative source for Cd-Zn and B, and cluster analysis suggested an anthropogenic source for Cu, Pb, B, and Mn. The contamination factor (CF) suggested the need to trace the source of contamination to Pb (3.21 ± 1.89) and B (1.33 ± 0.83) and EF to Pb (3.30 ± 1.81) and B (1.44 ± 0.94). The analytical results identify anthropogenic sources of Pb, B, and Cd. The high contamination of Cd suggests the influence of mining areas, and Pb suggests the influence of traffic, fertilizers, pesticides, and fossil fuels in greenhouses, in addition to the influence of mines. B confirmed the impact of the facility’s vegetable wastewater and suggested the need to further examine the cumulative impact of Mn, Fe, etc. By utilizing the facility horticulture wastewater for ecological restoration and other agricultural uses, we aim to prevent stream sediment pollution and realize a sustainable agricultural environment.
Fungal and Fungal-like Diseases of Halophytes in the Mediterranean Basin: A State-of-the-Art Review
Authors: Delli Compagni Emiliano , Pardossi Alberto , Pecchia Susanna
Published: March 2024

Halophytes are salt-tolerant plants growing in saline ecosystems and are spread throughout the Mediterranean area. Recently, there has been a renewed interest in agricultural exploitation of halophytes, but poor attention has been given to pest and disease management of these species. The objective of this review is to assess the extent and distribution of pathogenic fungal and fungal-like (Oomycota) organisms on major Mediterranean halophytes. We retrieved 92 references spanning over 100 years, with more than half published since 2000. Ascomycota is the best-represented phylum, and the order Pleosporales has the highest species diversity. The order Pucciniales prevails in Basidiomycota, whereas Peronosporales is the richest order within Oomycota. Most of the pathogenic species have been isolated from aboveground organs, especially from leaves. Portulaca oleracea is the species with the most associated pathogens (16) and records (28). Leveillula powdery mildew, caused by Leveillula taurica, is the most common disease among the selected species. Cakile maritima was found to be vulnerable to different mycotoxigenic Alternaria species. Strengthening the research on diseases of halophytes is essential to successfully grow these species and to evaluate the risks related to the presence of mycotoxigenic species, which is crucial for the effective exploitation of halophytes as crops.
Predictors of Adolescent Internalizing and Externalizing Mental Health Symptoms: A School-Based Study in Southern India
Authors: Sekaran Varalakshmi Chandra , Prabhu Vidya , Ashok Lena , D’Souza Brayal , Shetty Surekha Devadasa , Nair Ravichandran
Published: March 2024

Introduction: Mental illnesses are one of the major contributors to the overall burden of disease among the young. We investigated the predictors of emotional and behavioral problems among in-school adolescents in the Indian context. Methods: Using stratified sampling, 1441 adolescents were recruited to participate in the study in Udupi taluk. The study instruments included a socio-demographic pro forma and the adolescent self-reporting version of the Strengths and Difficulties Questionnaire (SDQ) to assess the emotional and behavioral problems among them. We explored the predictors of total difficulties, as well as externalizing and internalizing problems and gender differences. SPSS version 25 was used to analyze the data. Descriptive statistics, a Chi-square test for associations, an independent t-test to explore the gender differences, correlation analysis, and backward stepwise logistic regression for the predictors were used. Results: The mean age of the participants was 15.31 ± 0.76. An almost equal percentage of male (49.6%) and female (50.4%) participants provided data. Abnormal scores were highest under conduct problems (8.5%), and the total difficulties reached 5.1%. The male participants had higher levels of conduct, hyperactivity, peer relationship, and externalizing problems the while the female participants experienced higher levels of emotional and internalizing problems. It was observed that there was a significant positive relationship between age and emotional problems, conduct problems, hyperactivity, peer problems, and total SDQ score. An older age predicted an abnormal total difficulties score and externalizing and internalizing behaviors, while the type of school predicted the total difficulties and internalizing behaviors. Conclusion: The age of the adolescent, their gender, and the type of school they attended emerged as predictors of the emotional and behavioral problems among them.
Galectin-3 and Autophagy in Renal Acute Tubular Necrosis
Authors: Al-Salam Suhail , Jagadeesh Govindan S. , Sudhadevi Manjusha , Yasin Javed
Published: March 2024

Acute kidney injury (AKI) is a public health burden with increasing morbidity and mortality rates and health care costs. Acute tubular necrosis (ATN) is the most common cause of AKI. Cisplatin (CIS) is a platinum-based chemotherapeutic agent used in the treatment of a wide variety of malignancies such as lung, breast, ovary, testis, bladder, cervix, and head and neck cancers. Autophagy plays an important role in AKI. Galectin-3 (Gal-3) is significantly increased in renal tubules in AKI; however, its role in autophagy is not well understood. Male C57B6/J and B6.Cg-Lgals3 /J Gal-3 knockout (KO) mice were used to induce AKI using a CIS mouse model of ATN. Renal Gal-3 and autophagy proteins’ expression were measured using standard histologic, immunofluorescent, and enzyme-linked immunosorbent assay techniques. The data were presented as the mean ± S.E. Statistically significant differences (p < 0.05) were calculated between experimental groups and corresponding control groups by one-way analysis of variance. There was a significant increase in renal concentrations of Gal-3 in the Gal-3 wild-type CIS-treated mice when compared with sham control mice. There were significantly higher concentrations of renal LC3B, ATG13, Ulk-1, Beclin, ATG5, ATG12, ATG9A, and p-AMPK in the CIS-treated Gal-3 KO mice than in the Gal-3 wild-type CIS-treated mice. Further, there were significantly higher concentrations of mTOR, p- NF-κB, beta-catenin, and p62 in the kidneys of the Gal-3 wild-type CIS-treated mice than in the Gal-3 KO CIS-treated mice. Our findings affirm the connection between Gal-3 and autophagy, revealing its central role as a connector with prosurvival signaling proteins. Gal-3 plays a pivotal role in orchestrating cellular responses by interacting with prosurvival signal pathways and engaging with autophagy proteins. Notably, our observations highlight that the absence of Gal-3 can enhance autophagy in CIS-induced ATN.
Exercise in Diabetic Nephropathy: Protective Effects and Molecular Mechanism
Authors: Li Ruo-Ying , Guo Liang
Published: March 2024

Diabetic nephropathy (DN) is a serious complication of diabetes, and its progression is influenced by factors like oxidative stress, inflammation, cell death, and fibrosis. Compared to drug treatment, exercise offers a cost-effective and low-risk approach to slowing down DN progression. Through multiple ways and mechanisms, exercise helps to control blood sugar and blood pressure and reduce serum creatinine and albuminuria, thereby alleviating kidney damage. This review explores the beneficial effects of exercise on DN improvement and highlights its potential mechanisms for ameliorating DN. In-depth understanding of the role and mechanism of exercise in improving DN would pave the way for formulating safe and effective exercise programs for the treatment and prevention of DN.
The Novel SSTR3 Agonist ITF2984 Exerts Antimitotic and Proapoptotic Effects in Human Non-Functioning Pituitary Neuroendocrine Tumor (NF-PitNET) Cells
Authors: Di Muro Genesio , Catalano Rosa , Treppiedi Donatella , Barbieri Anna Maria , Mangili Federica , Marra Giusy , Di Bari Sonia , Esposito Emanuela , Nozza Emma , Lania Andrea G. , Ferrante Emanuele , Locatelli Marco , Modena Daniela , Steinkuhler Christian , Peverelli Erika , Mantovani Giovanna
Published: March 2024

Somatostatin receptor ligands (SRLs) with high affinity for somatostatin receptors 2 and 5 (SSTR2 and SSTR5) are poorly efficacious in NF-PitNETs, expressing high levels of SSTR3. ITF2984 is a pan-SSTR ligand with high affinity for SSTR3, able to induce SSTR3 activation and to exert antitumoral activity in the MENX rat model. The aim of this study was to test ITF2984’s antiproliferative and proapoptotic effects in NF-PitNET primary cultured cells derived from surgically removed human tumors and to characterize their SSTR expression profile. We treated cells derived from 23 NF-PitNETs with ITF2984, and a subset of them with octreotide, pasireotide (SRLs with high affinity for SSTR2 or 5, respectively), or cabergoline (DRD2 agonist) and we measured cell proliferation and apoptosis. SSTR3, SSTR2, and SSTR5 expression in tumor tissues was analyzed by qRT-PCR and Western blot. We demonstrated that ITF2984 reduced cell proliferation (−40.8 (17.08)%, p < 0.001 vs. basal, n = 19 NF-PitNETs) and increased cell apoptosis (+41.4 (22.1)%, p < 0.001 vs. basal, n = 17 NF-PitNETs) in all tumors tested, whereas the other drugs were only effective in some tumors. In our model, SSTR3 expression levels did not correlate with ITF2984 antiproliferative nor proapoptotic effects. In conclusion, our data support a possible use of ITF2984 in the pharmacological treatment of NF-PitNET.
On the Possible Effect of Phytic Acid (Myo-Inositol Hexaphosphoric Acid, IP6) on Cytochromes P450 and Systems of Xenobiotic Metabolism in Different Hepatic Models
Authors: Frybortova Veronika , Satka Stefan , Jourova Lenka , Zapletalova Iveta , Srejber Martin , Briolotti Philippe , Daujat-Chavanieu Martine , Gerbal-Chaloin Sabine , Anzenbacher Pavel , Otyepka Michal , Anzenbacherova Eva
Published: March 2024

As compounds of natural origin enter human body, it is necessary to investigate their possible interactions with the metabolism of drugs and xenobiotics in general, namely with the cytochrome P450 (CYP) system. Phytic acid (myo-inositol hexaphosphoric acid, IP6) is mainly present in plants but is also an endogenous compound present in mammalian cells and tissues. It has been shown to exhibit protective effect in many pathological conditions. For this paper, its interaction with CYPs was studied using human liver microsomes, primary human hepatocytes, the HepG2 cell line, and molecular docking. Docking experiments and absorption spectra demonstrated the weak ability of IP6 to interact in the heme active site of CYP1A. Molecular docking suggested that IP6 preferentially binds to the protein surface, whereas binding to the active site of CYP1A2 was found to be less probable. Subsequently, we investigated the ability of IP6 to modulate the metabolism of xenobiotics for both the mRNA expression and enzymatic activity of CYP1A enzymes. Our findings revealed that IP6 can slightly modulate the mRNA levels and enzyme activity of CYP1A. However, thanks to the relatively weak interactions of IP6 with CYPs, the chances of the mechanisms of clinically important drug–drug interactions involving IP6 are low.
Potential of Curcumin in the Management of Skin Diseases
Authors: Kasprzak-Drozd Kamila , Niziński Przemysław , Hawrył Anna , Gancarz Marek , Hawrył Dominika , Oliwa Weronika , Pałka Magdalena , Markowska Julia , Oniszczuk Anna
Published: March 2024

Curcumin is a polyphenolic molecule derived from the rhizoma of Curcuma longa L. This compound has been used for centuries due to its anti-inflammatory, antioxidant, and antimicrobial properties. These make it ideal for preventing and treating skin inflammation, premature skin ageing, psoriasis, and acne. Additionally, it exhibits antiviral, antimutagenic, and antifungal effects. Curcumin provides protection against skin damage caused by prolonged exposure to UVB radiation. It reduces wound healing times and improves collagen deposition. Moreover, it increases fibroblast and vascular density in wounds. This review summarizes the available information on the therapeutic effect of curcumin in treating skin diseases. The results suggest that curcumin may be an inexpensive, well-tolerated, and effective agent for treating skin diseases. However, larger clinical trials are needed to confirm these observations due to limitations in its in vivo use, such as low bioavailability after oral administration and metabolism.
Molecular Evolution of GII.P31/GII.4_Sydney_2012 Norovirus over a Decade in a Clinic in Japan
Authors: Ushijima Hiroshi , Hoque Sheikh Ariful , Akari Yuki , Pham Ngan Thi Kim , Phan Tung , Nishimura Shuichi , Kobayashi Masaaki , Sugita Kumiko , Okitsu Shoko , Komoto Satoshi , Thongprachum Aksara , Khamrin Pattara , Maneekarn Niwat , Hayakawa Satoshi
Published: March 2024

Norovirus (NoV) genogroup II, polymerase type P31, capsid genotype 4, Sydney_2012 variant (GII.P31/GII.4_Sydney_2012) has been circulating at high levels for over a decade, raising the question of whether this strain is undergoing molecular alterations without demonstrating a substantial phylogenetic difference. Here, we applied next-generation sequencing to learn more about the genetic diversity of 14 GII.P31/GII.4_Sydney_2012 strains that caused epidemics in a specific region of Japan, with 12 from Kyoto and 2 from Shizuoka, between 2012 and 2022, with an emphasis on amino acid (aa) differences in all three ORFs. We found numerous notable aa alterations in antigenic locations in the capsid region (ORF2) as well as in other ORFs. In all three ORFs, earlier strains (2013–2016) remained phylogenetically distinct from later strains (2019–2022). This research is expected to shed light on the evolutionary properties of dominating GII.P31/GII.4_Sydney_2012 strains, which could provide useful information for viral diarrhea prevention and treatment.
DEAD Box Helicase 24 Is Increased in the Brain in Alzheimer’s Disease and AppN-LF Mice and Influences Presymptomatic Pathology
Authors: Axenhus Michael , Doeswijk Tosca , Nilsson Per , Matton Anna , Winblad Bengt , Tjernberg Lars , Schedin-Weiss Sophia
Published: March 2024

At the time of diagnosis, Alzheimer’s disease (AD) patients already suffer from significant neuronal loss. The identification of proteins that influence disease progression before the onset of symptoms is thus an essential part of the development of new effective drugs and biomarkers. Here, we used an unbiased 18O labelling proteomics approach to identify proteins showing altered levels in the AD brain. We studied the relationship between the protein with the highest increase in hippocampus, DEAD box Helicase 24 (DDX24), and AD pathology. We visualised DDX24 in the human brain and in a mouse model for Aβ42-induced AD pathology—AppNL-F—and studied the interaction between Aβ and DDX24 in primary neurons. Immunohistochemistry in the AD brain confirmed the increased levels and indicated an altered subcellular distribution of DDX24. Immunohistochemical studies in AppNL-F mice showed that the increase of DDX24 starts before amyloid pathology or memory impairment is observed. Immunocytochemistry in AppNL-F primary hippocampal neurons showed increased DDX24 intensity in the soma, nucleus and nucleolus. Furthermore, siRNA targeting of DDX24 in neurons decreased APP and Aβ42 levels, and the addition of Aβ42 to the medium reduced DDX24. In conclusion, we have identified DDX24 as a protein with a potential role in Aβ-induced AD pathology.
Synthesis of Novel Triazine-Based Chalcones and 8,9-dihydro-7H-pyrimido[4,5-b][1,4]diazepines as Potential Leads in the Search of Anticancer, Antibacterial and Antifungal Agents
Authors: Moreno Leydi M. , Quiroga Jairo , Abonia Rodrigo , Crespo María del P. , Aranaga Carlos , Martínez-Martínez Luis , Sortino Maximiliano , Barreto Mauricio , Burbano María E. , Insuasty Braulio
Published: March 2024

This study presents the synthesis of four series of novel hybrid chalcones (20,21)a–g and (23,24)a–g and six series of 1,3,5-triazine-based pyrimido[4,5-b][1,4]diazepines (28–33)a–g and the evaluation of their anticancer, antibacterial, antifungal, and cytotoxic properties. Chalcones 20b,d, 21a,b,d, 23a,d–g, 24a–g and the pyrimido[4,5-b][1,4]diazepines 29e,g, 30g, 31a,b,e–g, 33a,b,e–g exhibited outstanding anticancer activity against a panel of 60 cancer cell lines with GI50 values between 0.01 and 100 μM and LC50 values in the range of 4.09 μM to >100 μM, several of such derivatives showing higher activity than the standard drug 5-fluorouracil (5-FU). On the other hand, among the synthesized compounds, the best antibacterial properties against N. gonorrhoeae, S. aureus (ATCC 43300), and M. tuberculosis were exhibited by the pyrimido[4,5-b][1,4]diazepines (MICs: 0.25–62.5 µg/mL). The antifungal activity studies showed that triazinylamino-chalcone 29e and triazinyloxy-chalcone 31g were the most active compounds against T. rubrum and T. mentagrophytes and A. fumigatus, respectively (MICs = 62.5 μg/mL). Hemolytic activity studies and in silico toxicity analysis demonstrated that most of the compounds are safe.
Influence of Thermal Treatment on the Composition of Alpinia officinarum Rhizome
Authors: Zagórska Justyna , Pietrzak Karolina , Kukula-Koch Wirginia , Czop Marcin , Wojtysiak Karolina , Koch Wojciech
Published: March 2024

Alpinia officinarum is a representative of the Zingiberaceae family, which is known for its wide use in the food and pharmaceutical industries also due to its precious pharmacological potential. The major aim of the present study was to evaluate the influence of thermal treatment on the composition of the rhizome of Alpinia officinarum and its antioxidant activity. The fresh rhizome was subjected to various thermal treatment processes—boiling, frying and microwave heating during various time intervals—and their composition and antioxidant activity were determined using chromatographic (HPLC – High Performance Liquid Chromatography and HPLC-MS - High Performance Liquid Chromatography Mass Spectrometry) and spectrophotometric (DPPH and TPC – Total Phenolic Content) methods. Pinobanksin was the main compound found in the extract of the fresh rhizome (537.79 mg/kg), followed by galangin (197.7 mg/kg) and zingerone (185.5 mg/kg). The effect of thermal treatment on the rhizome composition was varied. In general, thermal processing significantly decreased the content of active compounds in the rhizome. However, there were some exceptions—boiling for 4 min significantly increased the content of pinobanksin (1162.4 mg/kg) and galangin (280.7 mg/kg), and microwave processing for 4 min increased the content of pinocembrin (213 mg/kg). It was found that boiling and microwave treatment significantly increased the antioxidant activity of the processed rhizomes.
Unraveling the Contribution of MulSOS2 in Conferring Salinity Tolerance in Mulberry (Morus atropurpurea Roxb)
Authors: Wang Hai-Rui , Han Sheng-Mei , Wang Dong-Hao , Zhao Zhen-Rui , Ling Hui , Yu Yun-Na , Liu Zhao-Yang , Gai Ying-Ping , Ji Xian-Ling
Published: March 2024

Salinity is one of the most serious threats to sustainable agriculture. The Salt Overly Sensitive (SOS) signaling pathway plays an important role in salinity tolerance in plants, and the SOS2 gene plays a critical role in this pathway. Mulberry not only has important economic value but also is an important ecological tree species; however, the roles of the SOS2 gene associated with salt stress have not been reported in mulberry. To gain insight into the response of mulberry to salt stress, SOS2 (designated MulSOS2) was cloned from mulberry (Morus atropurpurea Roxb), and sequence analysis of the amino acids of MulSOS2 showed that it shares some conserved domains with its homologs from other plant species. Our data showed that the MulSOS2 gene was expressed at different levels in different tissues of mulberry, and its expression was induced substantially not only by NaCl but also by ABA. In addition, MulSOS2 was exogenously expressed in Arabidopsis, and the results showed that under salt stress, transgenic MulSOS2 plants accumulated more proline and less malondialdehyde than the wild-type plants and exhibited increased tolerance to salt stress. Moreover, the MulSOS2 gene was transiently overexpressed in mulberry leaves and stably overexpressed in the hairy roots, and similar results were obtained for resistance to salt stress in transgenic mulberry plants. Taken together, the results of this study are helpful to further explore the function of the MulSOS2 gene, which provides a valuable gene for the genetic breeding of salt tolerance in mulberry.
The Role of Heat-Induced Stress Granules in the Blood–Testis Barrier of Mice
Authors: Zhao Zhifeng , Cai Yuqing , Lin Xinyi , Liu Ning , Qin Yinghe , Wu Yingjie
Published: March 2024

Stress granules (SGs) are membraneless ribonucleoprotein (RNP)-based cellular foci formed in response to stress, facilitating cell survival by protecting against damage. Mammalian spermatogenesis should be maintained below body temperature for proper development, indicating its vulnerability to heat stress (HS). In this study, biotin tracer permeability assays showed that the inhibition of heat-induced SG assembly in the testis by 4–8 mg/kg cycloheximide significantly increased the percentage of seminiferous tubules with a damaged blood–testis barrier (BTB). Western blot results additionally revealed that the suppression of heat-induced SG assembly in Sertoli cell line, TM4 cells, by RNA inference of G3bp1/2 aggravated the decline in the BTB-related proteins ZO-1, β-Catenin and Claudin-11, indicating that SGs could protect the BTB against damage caused by HS. The protein components that associate with SGs in Sertoli cells were isolated by sequential centrifugation and immunoprecipitation, and were identified by liquid chromatography with tandem mass spectrometry. Gene Ontology and KEGG pathway enrichment analysis revealed that their corresponding genes were mainly involved in pathways related to proteasomes, nucleotide excision repair, mismatch repair, and DNA replication. Furthermore, a new SG component, the ubiquitin associated protein 2 (UBAP2), was found to translocate to SGs upon HS in TM4 cells by immunofluorescence. Moreover, SG assembly was significantly diminished after UBAP2 knockdown by RNA inference during HS, suggesting the important role of UBAP2 in SG assembly. In addition, UBAP2 knockdown reduced the expression of ZO-1, β-Catenin and Claudin-11, which implied its potential role in the function of the BTB. Overall, our study demonstrated the role of SGs in maintaining BTB functions during HS and identified a new component implicated in SG formation in Sertoli cells. These findings not only offer novel insights into the biological functions of SGs and the molecular mechanism of low fertility in males in summer, but also potentially provide an experimental basis for male fertility therapies.
Preparation of Bispecific IgY-scFvs Inhibition Adherences of Enterotoxigenic Escherichia coli (K88 and F18) to Porcine IPEC-J2 Cell
Authors: Yang Luqing , Yang Yuanhe , Liu Anguo , Lei Siqi , He Pingli
Published: March 2024

Enterotoxigenic Escherichia coli (ETEC) strains are significant contributors to postweaning diarrhea in piglets. Of the ETEC causing diarrhea, K88 and F18 accounted for 92.7%. Despite the prevalence of ETEC K88 and F18, there is currently no effective vaccine available due to the diversity of these strains. This study presents an innovative approach by isolating chicken-derived single-chain variable fragment antibodies (scFvs) specific to K88 and F18 fimbrial antigens from chickens immunized against these ETEC virulence factors. These scFvs effectively inhibited adhesion of K88 and F18 to porcine intestinal epithelial cells (IPEC-J2), with the inhibitory effect demonstrating a dose-dependent increase. Furthermore, a bispecific scFv was designed and expressed in Pichia pastoris. This engineered construct displayed remarkable potency; at a concentration of 25.08 μg, it significantly reduced the adhesion rate of ETEC strains to IPEC-J2 cells by 72.10% and 69.11% when challenged with either K88 or F18 alone. Even in the presence of both antigens, the adhesion rate was notably decreased by 57.92%. By targeting and impeding the initial adhesion step of ETEC pathogenesis, this antibody-based intervention holds promise as a potential alternative to antibiotics, thereby mitigating the risks associated with antibiotic resistance and residual drug contamination in livestock production. Overall, this study lays the groundwork for the development of innovative treatments against ETEC infections in piglets.
Biochemical Fractionation of Human α-Synuclein in a Drosophila Model of Synucleinopathies
Authors: Imomnazarov Khondamir , Lopez-Scarim Joshua , Bagheri Ila , Joers Valerie , Tansey Malú Gámez , Martín-Peña Alfonso
Published: March 2024

Synucleinopathies are a group of central nervous system pathologies that are characterized by the intracellular accumulation of misfolded and aggregated α-synuclein in proteinaceous depositions known as Lewy Bodies (LBs). The transition of α-synuclein from its physiological to pathological form has been associated with several post-translational modifications such as phosphorylation and an increasing degree of insolubility, which also correlate with disease progression in post-mortem specimens from human patients. Neuronal expression of α-synuclein in model organisms, including Drosophila melanogaster, has been a typical approach employed to study its physiological effects. Biochemical analysis of α-synuclein solubility via high-speed ultracentrifugation with buffers of increasing detergent strength offers a potent method for identification of α-synuclein biochemical properties and the associated pathology stage. Unfortunately, the development of a robust and reproducible method for the evaluation of human α-synuclein solubility isolated from Drosophila tissues has remained elusive. Here, we tested different detergents for their ability to solubilize human α-synuclein carrying the pathological mutation A53T from the brains of aged flies. We also assessed the effect of sonication on the solubility of human α-synuclein and optimized a protocol to discriminate the relative amounts of soluble/insoluble human α-synuclein from dopaminergic neurons of the Drosophila brain. Our data established that, using a 5% SDS buffer, the three-step protocol separates cytosolic soluble, detergent-soluble and insoluble proteins in three sequential fractions according to their chemical properties. This protocol shows that sonication breaks down α-synuclein insoluble complexes from the fly brain, making them soluble in the SDS buffer and thus enriching the detergent-soluble fraction of the protocol.
Analysis of SIRT1 Gene SNPs and Clinical Characteristics in Medication-Related Osteonecrosis of the Jaw
Authors: Bojtor Bence , Vaszilko Mihaly , Armos Richard , Tobias Balint , Podani Janos , Szentpeteri Szofia , Balla Bernadett , Lengyel Balazs , Piko Henriett , Illes Anett , Kiss Andras , Putz Zsuzsanna , Takacs Istvan , Kosa Janos P. , Lakatos Peter
Published: March 2024

Certain genetic factors, including single-nucleotide polymorphisms (SNPs) in the SIRT1 gene, have been linked to medication-related osteonecrosis of the jaw (MRONJ). This study examined four SNPs in the SIRT1 gene and implemented multivariate statistical analysis to analyze genetic and clinical factors in MRONJ patients. Genomic DNA was isolated from peripheral blood samples of 63 patients of European origin treated for MRONJ, and four SNP genotypes in the gene encoding the SIRT-1 protein were determined by Sanger sequencing. The allele frequencies measured in the MRONJ population were compared with allele frequencies measured in the European population in the National Center for Biotechnology Information Allele Frequency Aggregator (NCBI ALFA) database. Genetic and clinical factors were examined with multivariate statistical analysis. A C:A allele distribution ratio of 77.8:22.2 was measured in the rs932658 SNP. In the ALFA project, a C:A allele distribution ratio of 59.9:40.1 was detected in the European population, which was found to be a significant difference (p = 4.5 × 10−5). Multivariate statistical analysis revealed a positive correlation (0.275) between the genotype of SNP rs932658 and the number of stages improved during appropriate MRONJ therapy. It is concluded that allele A in SNP rs932658 in the SIRT1 gene acts as a protective factor in MRONJ.
Protective Effect of Mesenchymal Stem Cell Active Factor Combined with Alhagi maurorum Extract on Ulcerative Colitis and the Underlying Mechanism
Authors: Cao Xuanhong , Aierken Aili , Wang Jie , Guo Xinrui , Peng Sha , Jin Yaping
Published: March 2024

Ulcerative colitis (UC) is a relapsing and reoccurring inflammatory bowel disease. The treatment effect of Alhagi maurorum and stem cell extracts on UC remains unclear. The aim of the present study was to investigate the protective role of Alhagi maurorum combined with stem cell extract on the intestinal mucosal barrier in an intestinal inflammation mouse model. Sixty mice were randomly divided into a control group, model group, Alhagi group, MSC group, and MSC/Alhagi group. MSC and Alhagi extract were found to reduce the disease activity index (DAI) scores in mice with colitis, alleviate weight loss, improve intestinal inflammation in mice (p < 0.05), preserve the integrity of the ileal wall and increase the number of goblet cells and mucin in colon tissues. Little inflammatory cell infiltration was observed in the Alhagi, MSC, or MSC/Alhagi groups, and the degree of inflammation was significantly alleviated compared with that in the model group. The distribution of PCNA and TNF-alpha in the colonic tissues of the model group was more disperse than that in the normal group (p < 0.05), and the fluorescence intensity was lower. After MSC/Alhagi intervention, PCNA and TNF-alpha were distributed along the cellular membrane in the MSC/Alhagi group (p < 0.05). Compared with that in the normal control group, the intensity was slightly reduced, but it was still stronger than that in the model group. In conclusion, MSC/Alhagi can alleviate inflammatory reactions in mouse colonic tissue, possibly by strengthening the protective effect of the intestinal mucosal barrier.
Dietary Methionine Restriction Improves Gut Health and Alters the Plasma Metabolomic Profile in Rats by Modulating the Composition of the Gut Microbiota
Authors: Yang Mei , Xie Qian , Xiao Yintao , Xia Minglong , Chen Jiashun , Tan Bi-E , Yin Yulong
Published: March 2024

Dietary methionine restriction (MetR) offers an integrated set of beneficial health effects, including delaying aging, extending health span, preventing fat accumulation, and reducing oxidative stress. This study aimed to investigate whether MetR exerts entero-protective effects by modulating intestinal flora, and the effect of MetR on plasma metabolites in rats. Rats were fed diets containing 0.86% methionine (CON group) and 0.17% methionine (MetR group) for 6 weeks. Several indicators of inflammation, gut microbiota, plasma metabolites, and intestinal barrier function were measured. 16S rRNA gene sequencing was used to analyze the cecal microbiota. The MetR diet reduced the plasma and colonic inflammatory factor levels. The MetR diet significantly improved intestinal barrier function by increasing the mRNA expression of tight junction proteins, such as zonula occludens (ZO)-1, claudin-3, and claudin-5. In addition, MetR significantly increased the levels of short-chain fatty acids (SCFAs) by increasing the abundance of SCFAs-producing Erysipclotxichaceae and Clostridium_sensu_stricto_1 and decreasing the abundance of pro-inflammatory bacteria Proteobacteria and Escherichia-Shigella. Furthermore, MetR reduced the plasma levels of taurochenodeoxycholate-7-sulfate, taurocholic acid, and tauro-ursodeoxycholic acid. Correlation analysis identified that colonic acetate, total colonic SCFAs, 8-acetylegelolide, collettiside I, 6-methyladenine, and cholic acid glucuronide showed a significant positive correlation with Clostridium_sensu_stricto_1 abundance but a significant negative correlation with Escherichia-Shigella and Enterococcus abundance. MetR improved gut health and altered the plasma metabolic profile by regulating the gut microbiota in rats.
A Review of FDA-Approved Anti-HIV-1 Drugs, Anti-Gag Compounds, and Potential Strategies for HIV-1 Eradication
Authors: Sever Belgin , Otsuka Masami , Fujita Mikako , Ciftci Halilibrahim
Published: March 2024

Acquired immunodeficiency syndrome (AIDS) is an enormous global health threat stemming from human immunodeficiency virus (HIV-1) infection. Up to now, the tremendous advances in combination antiretroviral therapy (cART) have shifted HIV-1 infection from a fatal illness into a manageable chronic disorder. However, the presence of latent reservoirs, the multifaceted nature of HIV-1, drug resistance, severe off-target effects, poor adherence, and high cost restrict the efficacy of current cART targeting the distinct stages of the virus life cycle. Therefore, there is an unmet need for the discovery of new therapeutics that not only bypass the limitations of the current therapy but also protect the body’s health at the same time. The main goal for complete HIV-1 eradication is purging latently infected cells from patients’ bodies. A potential strategy called “lock-in and apoptosis” targets the budding phase of the life cycle of the virus and leads to susceptibility to apoptosis of HIV-1 infected cells for the elimination of HIV-1 reservoirs and, ultimately, for complete eradication. The current work intends to present the main advantages and disadvantages of United States Food and Drug Administration (FDA)-approved anti-HIV-1 drugs as well as plausible strategies for the design and development of more anti-HIV-1 compounds with better potency, favorable pharmacokinetic profiles, and improved safety issues.
Multiomics-Based Feature Extraction and Selection for the Prediction of Lung Cancer Survival
Authors: Jaksik Roman , Szumała Kamila , Dinh Khanh Ngoc , Śmieja Jarosław
Published: March 2024

Lung cancer is a global health challenge, hindered by delayed diagnosis and the disease’s complex molecular landscape. Accurate patient survival prediction is critical, motivating the exploration of various -omics datasets using machine learning methods. Leveraging multi-omics data, this study seeks to enhance the accuracy of survival prediction by proposing new feature extraction techniques combined with unbiased feature selection. Two lung adenocarcinoma multi-omics datasets, originating from the TCGA and CPTAC-3 projects, were employed for this purpose, emphasizing gene expression, methylation, and mutations as the most relevant data sources that provide features for the survival prediction models. Additionally, gene set aggregation was shown to be the most effective feature extraction method for mutation and copy number variation data. Using the TCGA dataset, we identified 32 molecular features that allowed the construction of a 2-year survival prediction model with an AUC of 0.839. The selected features were additionally tested on an independent CPTAC-3 dataset, achieving an AUC of 0.815 in nested cross-validation, which confirmed the robustness of the identified features.