bluuebunny/crossref_metadata_2025 huggingface dataset:
Predictors of Consanguinity Marriage Decision in Saudi Arabia: A Pilot Study
Authors: Bakry Huny , Alaiban Reema A. , Alkhyyat Alanood A. , Alshamrani Basma H. , Naitah Rafal N. , Almoayad Fatmah
Published: July 2023

Consanguineous marriages are common in Saudi Arabia, increasing the risk of genetic blood disorders in offspring. This pilot study assessed the knowledge and perceived threats regarding genetic blood disorders, norms, and premarital screening for consanguineous marriage among unmarried university students in Saudi Arabia as a predictor of marriage decisions. A cross-sectional study was conducted from 22 January through 22 April 2022. In total, 400 unmarried students at Saudi Arabian universities were recruited using the non-probability convenience sampling technique. The data were analyzed using descriptive statistics and multinomial logistic regression. The results showed that the majority of participants had poor knowledge of genetic blood disorders. Most of the participants had a favorable attitude toward consanguineous marriage, while perceived threats towards genetic blood disorders were perceived as neutral by the participants. Moreover, their norms regarding consanguineous marriage also showed neutral results. A multinomial regression shows that participants with poor attitudes were significantly 22.3 times more likely to have poor marriage decisions (95% CI: 4.9–101.7, p < 0.001). However, participants with good and neutral norms regarding consanguinity marriage were significantly protective factors against poor marriage decisions with an RRR ratio of 0.165 (95% CI:0.030–0.918, p = 0.04) and 0.238 (95% CI: 0.071–0.797, p = 0.02), respectively. To mitigate the risk of genetic blood disorders in future generations, there is a need for targeted awareness campaigns about genetic blood disorders and the risks of consanguineous marriages by integrating this education into university curricula, and premarital counseling. It is also important to address societal norms, promoting informed decision-making, and provide premarital consultation to couples who carry the same mutated genes and are at risk of transmitting the disease to their offspring. Furthermore, there is a need for further research to assess the effectiveness of campaigns in this regard.
Adherence to the Mediterranean Diet Is Associated with Health-Related Quality of Life and Anthropometric Measurements in University Professors
Authors: López-Olivares María , Fernández-Gómez Elisabet , Mohatar-Barba Miriam , Luque-Vara Trinidad , Nestares Teresa , López-Bueno Marta , Enrique-Mirón Carmen
Published: July 2023

The main objective of this study was to assess the relationship between Mediterranean diet (MD) adherence and health-related quality of life (HRQOL) according to the anthropometric measurements of teaching and research staff (TRS) at the University of Granada (UGR), Spain. This diagnostic, non-experimental, cross-sectional, and observational study was performed on university lecturers (65 women and 62 men) using a correlational descriptive methodology. The lecturers’ anthropometric measurements were taken, while MD adherence was determined using the PREvention with MEDiterranean diet (PREDIMED) questionnaire. The Short Form Health Survey (SF-36) was used for measuring HRQOL. Better results for body composition were associated with improvements in the physical and mental dimensions and MD adherence. Statistically significant differences were found between sexes, with men showing higher values for weight, height, waist circumference, BMI, waist/hip ratio (WHR), muscle mass, and systolic and diastolic pressure than women. Similarly, MD adherence was positively correlated with vitality (r = 0.233; p = 0.009), social functioning (r = 0.229; p = 0.008), and the mental component summary (r = 0.205; p = 0.021). The regression model determined that the mental component summary (β = 0.239, p = 0.041), diastolic pressure (PD) (β = −0.473, p < 0.000), fat percentage (FP) (β = −0.241, p = 0.004), and age (β = −0.231, p = 0.022) significantly predicted MD adherence. The results obtained in this study suggest that healthy dietary patterns such as the MD and an optimum body composition contribute to an improved HRQOL.
Innovative Integrated Motivational Interviewing for Dual Management in Tuberculosis Patients with Diabetes (MID-DOT) in Malaysia
Authors: Mohd Zahiruddin Wan , Ahmad Siti Rohana , Yaacob Nor Azwany , Mohd Shariff Noorsuzana , Jaeb Mat Zuki , Hussin Zalmizy
Published: July 2023

(1) Background: Achieving successful tuberculosis (TB) treatment outcomes among diabetic patients is a real challenge as TB complicates control of diabetes. This study aimed to evaluate the effectiveness of an integrated dual management educational module, MID-DOTS, which uses the mmotivational interviewing (MI) technique implemented within directly observed treatment as part of a short course (DOTS) program in TB patients with diabetes (TB/DM). A randomized controlled trial was conducted in the northeastern state of Malaysia. (2) Methods: One hundred and twenty-four TB patients with diabetes received educational intervention using a MID-DOT module that used the MI technique, which was repetitively applied by TB nurses throughout a 6-month DOTS program while another 122 patients were given standard health education. Study outcomes include the proportion of patients with successful TB treatment, and changes in HbA1c and diabetic self-care scores at 6 months. (3) Results: The successful TB treatment outcome was 88% in the intervention group versus 72% in the control group (RR = 1.24; 95%CI 1.16, 1.58). A significant reduction of HbA1c (mean difference 0.82%; 95%CI 0.66, 0.98) and significantly higher diabetes self-care score (mean difference 8.49; 95%CI 7.38, 9.59) were also shown in the intervention group. (4) Conclusions: A dual TB/DM educational strategy which integrates the MI technique applied repetitively within the DOTS program is effective in increasing successful TB treatment as well as improving diabetic outcomes.
Quality of Life from Return to Work and Sport Activities to Sexual Dysfunction after Surgical Treatment of Pelvic Ring Fractures
Authors: Monteleone Andrea Stefano , Feltri Pietro , Müller Jochen , Molina Mauro Natale , Filardo Giuseppe , Candrian Christian
Published: July 2023

Background: Pelvic ring fractures are life-threatening injuries that have a severe impact on patients’ lives. The aim of this clinical study was to evaluate the outcome of surgical treatment in terms of Quality of Life (QoL), return to work, functional results and sport activities, and post-operative sexual dysfunction. Methods: A retrospective study with patients retrieved from a Level 1 Trauma Center was performed. Minimum patient follow-up was 12 months: QoL was evaluated with the SF-12 (Short Form Survey) questionnaire, return to work with the Workplace Activity Limitation Survey (WALS), functional outcomes and sport activities with the Harris Hip Score and Tegner activity score, respectively, and sexual function damage with a 0–10 NRS. Results: Seventy-six patients (41 males and 35 females) were enrolled, with a mean age at surgery of 56.4 years (18–89 years). Overall, their quality of life remained significantly affected, with male patients reporting worse WALS outcomes (p = 0.036), sexual damage (p = 0.001), and SF-12 Bodily Pain (p = 0.046) than females. In particular, 70.7% of men and 45.7% of women reported sexual limitations, and only 53.7% returned to their job, with 35.2% losing their job as a consequence of the pelvic ring disruption. Conclusions: An important deterioration in general health state, return to work, and sexual function was documented in patients treated surgically for pelvic trauma, especially in male patients. There are disabling secondary sequels at all levels beyond the mere functional scores, and both patients and clinicians should be aware and have the correct expectations.
The Alonissos Study: Cross-Sectional Study of the Healthcare Access and User Satisfaction in the Community of a Non-Profit-Line Greek Island
Authors: Kassas Petros , Gogou Eudoxia , Varsamas Charalampos , Vogiatzidis Konstantinos , Psatha Aggeliki , Pinaka Maria , Siachpazidou Dimitra , Sistou Alexandra , Papazoglou Eleftherios D. , Kalousi Despoina , Vatzia Konstantina , Astara Kyriaki , Tsiouvakas Nikolaos , Zarogiannis Sotirios G. , Gourgoulianis Konstantinos
Published: July 2023

Healthcare access and a high quality of the provided services to healthcare users are fundamental human rights according to the Alma Ata Declaration of 1978. Although 45 years have passed since then, health inequalities still exist, not only among countries but also within populations of the same country. For example, several small Greek islands have only a small Primary Healthcare Center in order to provide healthcare services to the insular population. In the current study, we investigated the level of self-reported overall, dental and mental health status and the level of satisfaction regarding the access to and the quality of the healthcare services provided by the Primary Healthcare center of Alonissos, along with registering the requirements for transportation to the mainland in order to receive such services. In this questionnaire-based cross-sectional study, 235 inhabitants of the remote Greek island of Alonissos that accounts for nearly 9% of the population participated (115 males and 120 females). The self-reported overall health status was reported to be moderate to very poor at a percentage of 31.49%, and the results were similar for dental and self-reported mental health status. Although nearly 60% of the participants reported very good/good quality of the healthcare provision, only 37.45% reported that the access to healthcare was very good/good, while around 94% had at least one visit to the mainland in order to receive proper healthcare services. Strategies for improving access to healthcare services need to be placed in remote Greek islands like Alonissos.
Fluid Overload-Associated Large B-Cell Lymphoma: A Case Report and Review of Literature
Authors: Bahmad Hisham F. , Gomez Aaron S. , Deb Arunima , Safdie Fernando Martin , Sriganeshan Vathany
Published: July 2023

Fluid overload-associated large B-cell lymphoma (FO-LBCL) is a new entity described in the fifth edition of the World Health Organization (WHO) Classification of Hematolymphoid Tumors (WHO-HAEM5). It refers to malignant lymphoma present with symptoms of serous effusions in body cavities (pleural, peritoneal, and/or pericardial) in the absence of an identifiable tumor mass. We present a case of an 82-year-old man with a history of atrial fibrillation and atrial flutter, status post-ablation, essential hypertension (HTN), hyperlipidemia (HLD), and diabetes mellitus (DM) type 2 who was referred to our hospital for shortness of breath due to recurrent pleural effusion. Right video-assisted thoracoscopy with right pleural biopsy was performed. Histopathological examination of the pleural biopsy revealed dense fibrous tissue, chronic inflammation, lymphoid aggregates, and granulation tissue, with no evidence of lymphoma. Cytology of the right pleural fluid revealed large lymphoid cells, which were positive for CD45, CD20, PAX-5, MUM-1, BCL2, BCL6, and MYC protein. They were negative for CD3, CD10, CD138, and HHV-8 by immunohistochemistry (IHC). Epstein–Barr virus (EBV) was negative by in situ hybridization (ISH). Due to the absence of any evidence of lymphoma elsewhere, a diagnosis of fluid overload-associated large B-cell lymphoma (FO-LBCL) was made. We provide a synopsis of the main clinicopathological features of FO-LBCL and the two main differential diagnoses, primary effusion lymphoma (PEL) and diffuse large B-cell lymphoma (DLBCL).
Effect of Epiphytic Bacteria from Citrus against Green Mold Post-Harvest Diseases of Citrus
Authors: Hadian Shervin , Supronienė Skaidrė , Kulaitienė Jurgita , Hasanzadeh Nader
Published: July 2023

This study investigates the potential of epiphytic bacteria isolated from citrus fruits to control green mold post-harvest disease caused by Penicillium digitatum in Thompson Navel sweet oranges in the north of Iran. Twenty-three epiphytic bacteria were isolated and screened in vitro against P. digitatum, and 13 isolates with antagonistic activity were selected for further studies. Isolates B15 (Bacillus sp.), P17 (Pseudomonas sp.), and S13 (Streptomyces sp.) exhibited the most effective inhibitory effects on P. digitatum in vitro and in vivo. Among these, B15 showed the highest percentage of mycelium growth reduction and was further identified as B. cereus by 16S rRNA sequence analysis. Metabolic analysis of Bacillus sp. isolate B15 extract revealed the presence of the inhibiting antifungal substance Iturin A. The result showed that the application of epiphytic B. cereus decreased the percentage of green mold post-harvest diseases in orange fruit. This indicates their potential as an environmentally friendly alternative to chemical post-harvest control of orange diseases caused by P. digitatum.
Effects of Three Exogenous Substances on Heat Tolerance of Peony Seedlings
Authors: Guo Jiaxin , Huang Yu , Yang Xingyu , Bu Wenxuan , Tian Jianing , Zhang Minhuan , Huang Kaili , Luo Xiaoning , Ye Ye , Xing Wen , Huang Yating
Published: July 2023

In this study, one-year-old seedlings of Paeonia ostii ‘Fengdan’ were used as materials. The method of spraying exogenous salicylic acid (SA), calcium chloride (CaCl2) and abscisic acid (ABA) was used. The effects of different concentrations of SA, CaCl2 and ABA on the heat tolerance of peony seedlings under high temperature stress were studied. The optimum concentration and mechanism of SA-, CaCl2- and ABA-induced heat tolerance of peony seedlings under high temperature stress were discussed. The results showed that 100 μmol/L SA, 40 mmol/L CaCl2 and 40 mg/L ABA had the best induction effect on the heat tolerance of peony. The effects of three exogenous substances on the heat resistance of peony seedlings were ranked as SA > CaCl2 > ABA. The three exogenous substances mainly alleviated high temperature damage by alleviating the degradation of chlorophyll (Chl), relative electrical conductivity (Rec) content, increasing superoxide dismutase (SOD) activity, soluble proteins (SPs), free proline (Pro) and soluble sugars (SSs) content, and reducing SSs content under high temperature stress. The five indices had the most significant effect on the three exogenous substances in improving the heat resistance of peony seedlings. These could be used as an index to identify the heat resistance.
The Medical Community’s Role in Communication Strategies during Health Crises—Perspective from European Union of Medical Specialists (UEMS)
Authors: Nadareishvili Ilia , Bazas Theodore , Petrosillo Nicola , Berce Vojko , Firth John , Mansilha Armando , Leventer Mihaela , Renieri Alessandra , Zampolini Mauro , Papalois Vassilios
Published: July 2023

The COVID-19 pandemic was complicated by the spread of false information leading to what became widely called an “infodemic”. The present opinion paper was written by an ad hoc international team united under the European Union of Medical Specialists (UEMS) umbrella and reflects the organizations’ effort to contribute to the resolution of these issues, by highlighting and reflecting on them and by suggesting the medical community’s necessary activities resulting in the formulation of effective future communication strategies. The importance of physicians’ and other health workers’ role and mission as educators and leaders in communities in critical situations should be reassessed and upgraded. We need to equip future doctors with strong and sustainable leadership and communication skills through relevant undergraduate and postgraduate education programs, in order that compliance with preventive medical advice is increased. To avoid possible politically and otherwise biased communication in health crises of the future, European nations should establish independent advisory bodies providing evidence-based advice and participate in communication campaigns. Medical and other health professional organizations should build organizational and personal capacities of their members to enable them to reliably inform and adequately educate governments, populations, civic society, employers’ and employees’ organizations, schools and universities, and other stakeholders.
Soft Tissue Ewing Sarcoma Cell Drug Resistance Revisited: A Systems Biology Approach
Authors: Asfa Seyedehsadaf , Toy Halil Ibrahim , Arshinchi Bonab Reza , Chrousos George P. , Pavlopoulou Athanasia , Geronikolou Styliani A.
Published: July 2023

Ewing sarcoma is a rare type of cancer that develops in the bones and soft tissues. Drug therapy represents an extensively used modality for the treatment of sarcomas. However, cancer cells tend to develop resistance to antineoplastic agents, thereby posing a major barrier in treatment effectiveness. Thus, there is a need to uncover the molecular mechanisms underlying chemoresistance in sarcomas and, hence, to enhance the anticancer treatment outcome. In this study, a differential gene expression analysis was conducted on high-throughput transcriptomic data of chemoresistant versus chemoresponsive Ewing sarcoma cells. By applying functional enrichment analysis and protein–protein interactions on the differentially expressed genes and their corresponding products, we uncovered genes with a hub role in drug resistance. Granted that non-coding RNA epigenetic regulators play a pivotal role in chemotherapy by targeting genes associated with drug response, we investigated the non-coding RNA molecules that potentially regulate the expression of the detected chemoresistance genes. Of particular importance, some chemoresistance-relevant genes were associated with the autonomic nervous system, suggesting the involvement of the latter in the drug response. The findings of this study could be taken into consideration in the clinical setting for the accurate assessment of drug response in sarcoma patients and the application of tailored therapeutic strategies.
Antibiofilm Activity and Mechanism of Linalool against Food Spoilage Bacillus amyloliquefaciens
Authors: Shen Guanghui , Yang Lu , Lv Xinyu , Zhang Yingfan , Hou Xiaoyan , Li Meiliang , Zhou Man , Pan Le , Chen Anjun , Zhang Zhiqing
Published: July 2023

Pellicle biofilm-forming bacteria Bacillus amyloliquefaciens are the major spoilage microorganisms of soy products. Due to their inherent resistance to antibiotics and disinfectants, pellicle biofilms formed are difficult to eliminate and represent a threat to food safety. Here, we assessed linalool’s ability to prevent the pellicle of two spoilage B. amyloliquefaciens strains. The minimum biofilm inhibitory concentration (MBIC) of linalool against B. amyloliquefaciens DY1a and DY1b was 4 μL/mL and 8 μL/mL, respectively. The MBIC of linalool had a considerable eradication rate of 77.15% and 83.21% on the biofilm of the two strains, respectively. Scanning electron microscopy observations revealed that less wrinkly and thinner pellicle biofilms formed on a medium supplemented with 1/2 MBIC and 1/4 MBIC linalool. Also, linalool inhibited cell motility and the production of extracellular polysaccharides and proteins of the biofilm matrix. Furthermore, linalool exposure reduced the cell surface hydrophobicity, zeta potential, and cell auto-aggregation of B. amyloliquefaciens. Molecular docking analysis demonstrated that linalool interacted strongly with quorum-sensing ComP receptor and biofilm matrix assembly TasA through intermolecular hydrogen bonds, hydrophobic contacts, and van der Waals forces interacting with site residues. Overall, our findings suggest that linalool may be employed as a potential antibiofilm agent to control food spoilage B. amyloliquefaciens.
Receptor for the Advanced Glycation End Products (RAGE) Pathway in Adipose Tissue Metabolism
Authors: Gutowska Klaudia , Czajkowski Krzysztof , Kuryłowicz Alina
Published: July 2023

Advanced glycation end products (AGEs) are mediators in the process of cellular dysfunction in response to hyperglycemia. Numerous data indicate that the accumulation of AGEs in the extracellular matrix plays a key role in the development of obesity-related adipose tissue dysfunction. Through binding of their membrane receptor (RAGE), AGEs affect numerous intracellular pathways and impair adipocyte differentiation, metabolism, and secretory activity. Therefore, inhibiting the production and accumulation of AGEs, as well as interfering with the metabolic pathways they activate, may be a promising therapeutic strategy for restoring normal adipose tissue function and, thus, combating obesity-related comorbidities. This narrative review summarizes data on the involvement of the RAGE pathway in adipose tissue dysfunction in obesity and the development of its metabolic complications. The paper begins with a brief review of AGE synthesis and the RAGE signaling pathway. The effect of the RAGE pathway on adipose tissue development and activity is then presented. Next, data from animal and human studies on the involvement of the RAGE pathway in obesity, diabetes, and cardiovascular diseases are summarized. Finally, therapeutic perspectives based on interference with the RAGE pathway are discussed.
Review of Development and Recent Advances in Biomedical X-ray Fluorescence Imaging
Authors: Staufer Theresa , Grüner Florian
Published: July 2023

The use of X-rays for non-invasive imaging has a long history, which has resulted in several well-established methods in preclinical as well as clinical applications, such as tomographic imaging or computed tomography. While projection radiography provides anatomical information, X-ray fluorescence analysis allows quantitative mapping of different elements in samples of interest. Typical applications so far comprise the identification and quantification of different elements and are mostly located in material sciences, archeology and environmental sciences, whereas the use of the technique in life sciences has been strongly limited by intrinsic spectral background issues arising in larger objects, so far. This background arises from multiple Compton-scattering events in the objects of interest and strongly limits the achievable minimum detectable marker concentrations. Here, we review the history and report on the recent promising developments of X-ray fluorescence imaging (XFI) in preclinical applications, and provide an outlook on the clinical translation of the technique, which can be realized by reducing the above-mentioned intrinsic background with dedicated algorithms and by novel X-ray sources.
Cell-Type Specific Regulation of Cholesterogenesis by CYP46A1 Re-Expression in zQ175 HD Mouse Striatum
Authors: Pinchaud Katleen , Masson Chloé , Dayre Baptiste , Mounier Coline , Gilles Jean-François , Vanhoutte Peter , Caboche Jocelyne , Betuing Sandrine
Published: July 2023

Cholesterol metabolism dysregulation is associated with several neurological disorders. In Huntington’s disease (HD), several enzymes involved in cholesterol metabolism are downregulated, among which the neuronal cholesterol 24-hydroxylase, CYP46A1, is of particular interest. The restoration of CYP46A1 expression in striatal neurons of HD mouse models is beneficial for motor behavior, cholesterol metabolism, transcriptomic activity, and alleviates neuropathological hallmarks induced by mHTT. Among the genes regulated after CYP46A1 restoration, those involved in cholesterol synthesis and efflux may explain the positive effect of CYP46A1 on cholesterol precursor metabolites. Since cholesterol homeostasis results from a fine-tuning between neurons and astrocytes, we quantified the distribution of key genes regulating cholesterol metabolism and efflux in astrocytes and neurons using in situ hybridization coupled with S100β and NeuN immunostaining, respectively. Neuronal expression of CYP46A1 in the striatum of HD zQ175 mice increased key cholesterol synthesis driver genes (Hmgcr, Dhcr24), specifically in neurons. This effect was associated with an increase of the srebp2 transcription factor gene that regulates most of the genes encoding for cholesterol enzymes. However, the cholesterol efflux gene, ApoE, was specifically upregulated in astrocytes by CYP46A1, probably though a paracrine effect. In summary, the neuronal expression of CYP46A1 has a dual and specific effect on neurons and astrocytes, regulating cholesterol metabolism. The neuronal restoration of CYP46A1 in HD paves the way for future strategies to compensate for mHTT toxicity.
Promoting Photosynthetic Production of Dammarenediol-II in Chlamydomonas reinhardtii via Gene Loading and Culture Optimization
Authors: Zhao Mei-Li , Li Xiang-Yu , Lan Cheng-Xiang , Yuan Zi-Ling , Zhao Jia-Lin , Huang Ying , Hu Zhang-Li , Jia Bin
Published: July 2023

Ginsenosides are major bioactive compounds found in Panax ginseng that exhibit various pharmaceutical properties. Dammarenediol-II, the nucleus of dammarane-type ginsenosides, is a promising candidate for pharmacologically active triterpenes. Dammarenediol-II synthase (DDS) cyclizes 2,3-oxidosqualene to produce dammarenediol-II. Based on the native terpenoids synthetic pathway, a dammarane-type ginsenosides synthetic pathway was established in Chlamydomonas reinhardtii by introducing P. ginseng PgDDS, CYP450 enzyme (PgCYP716A47), or/and Arabidopsis thaliana NADPH-cytochrome P450 reductase gene (AtCPR), which is responsible for producing dammarane-type ginsenosides. To enhance productivity, strategies such as “gene loading” and “culture optimizing” were employed. Multiple copies of transgene expression cassettes were introduced into the genome to increase the expression of the key rate-limiting enzyme gene, PgDDS, significantly improving the titer of dammarenediol-II to approximately 0.2 mg/L. Following the culture optimization in an opt2 medium supplemented with 1.5 mM methyl jasmonate under a light:dark regimen, the titer of dammarenediol-II increased more than 13-fold to approximately 2.6 mg/L. The C. reinhardtii strains engineered in this study constitute a good platform for the further production of ginsenosides in microalgae.
Different Kinetics of Serum ADAMTS13, GDF-15, and Neutrophil Gelatinase-Associated Lipocalin in the Early Phase of Aneurysmal Subarachnoid Hemorrhage
Authors: Csecsei Peter , Olah Csaba , Varnai Reka , Simon Diana , Erdo-Bonyar Szabina , Berki Timea , Czabajszki Mate , Zavori Laszlo , Schwarcz Attila , Molnar Tihamer
Published: July 2023

Growth differentiation factor 15 (GDF-15), neutrophil gelatinase-associated lipocalin (NGAL), and ADAMTS13 have previously been implicated in the pathophysiological processes of SAH. In the present study, we aim to examine their role in the early period of SAH and their relationship to primary and secondary outcomes. Serum samples were collected at five time periods after SAH (at 24 h (D1), at 72 h (D3), at 120 h (D5), at 168 h (D7) and at 216 h (D9), post-admission) and) were measured by using MILLIPLEX Map Human Cardiovascular Disease (CVD) Magnetic Bead Panel 2. We included 150 patients with SAH and 30 healthy controls. GDF-15 levels at D1 to D9 were significantly associated with a 3-month unfavorable outcome. Based on the ROC analysis, in patients with a good clinical grade at admission (WFNS I-III), the GDF-15 value measured at time point D3 predicted a 3-month unfavorable outcome (cut-off value: 3.97 ng/mL, AUC:0.833, 95%CI: 0.728–0.938, sensitivity:73.7%, specificity:82.6%, p < 0.001). Univariate binary logistic regression analysis showed that serum NGAL levels at D1-D5 and ADAMTS13 levels at D7-D9 were associated with MVS following SAH. GDF-15 is an early indicator of a poor 3-month functional outcome even in patients with mild clinical conditions at admission.
Differentiation between Weissella cibaria and Weissella confusa Using Machine-Learning-Combined MALDI-TOF MS
Authors: Kim Eiseul , Yang Seung-Min , Jung Dae-Hyun , Kim Hae-Yeong
Published: July 2023

Although Weissella cibaria and W. confusa are essential food-fermenting bacteria, they are also opportunistic pathogens. Despite these species being commercially crucial, their taxonomy is still based on inaccurate identification methods. In this study, we present a novel approach for identifying two important Weissella species, W. cibaria and W. confusa, by combining matrix-assisted laser desorption/ionization and time-of-flight mass spectrometer (MALDI-TOF MS) data using machine-learning techniques. After on- and off-plate protein extraction, we observed that the BioTyper database misidentified or could not differentiate Weissella species. Although Weissella species exhibited very similar protein profiles, these species can be differentiated on the basis of the results of a statistical analysis. To classify W. cibaria, W. confusa, and non-target Weissella species, machine learning was used for 167 spectra, which led to the listing of potential species-specific mass-to-charge (m/z) loci. Machine-learning techniques including artificial neural networks, principal component analysis combined with the K-nearest neighbor, support vector machine (SVM), and random forest were used. The model that applied the Radial Basis Function kernel algorithm in SVM achieved classification accuracy of 1.0 for training and test sets. The combination of MALDI-TOF MS and machine learning can efficiently classify closely-related species, enabling accurate microbial identification.
Combined Inhibition of the TGF-β1/Smad Pathway by Prevotella copri and Lactobacillus murinus to Reduce Inflammation and Fibrosis in Primary Sclerosing Cholangitis
Authors: Shen Yu , Jiang Baorong , Zhang Chenchen , Wu Qian , Li Lei , Jiang Ping
Published: July 2023

Primary sclerosing cholangitis (PSC) is a chronic cholestatic disease characterized by inflammation and fibrosis of the bile ducts. Cholestasis may lead to hepatic inflammation and fibrosis, and amelioration of cholestasis may allow recovery from inflammatory and fibrotic pathological damage. Prevotella copri (P. copri) interventions have been reported to significantly improve cholestasis and liver fibrosis in 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-induced PSC mouse models. Even though P. copri treatment alone cannot bring about recovery from DDC-induced inflammation, it increases the abundance of Lactobacillus murinus (L. murinus) compared with DDC treatment, which has been reported to have anti-inflammatory effects. The abundance of L. murinus still not recovering to a normal level may underlie hepatic inflammation in P. copri + DDC mice. Separate or combined interventions of P. copri and L. murinus were used to investigate the molecular mechanism underlying the improvement in PSC inflammation and fibrosis. P. copri and L. murinus significantly reduced the hepatic inflammatory cell aggregation and inflammatory factor expression as well as the hepatic collagen content and fibrin factor expression in the PSC mice. Further analysis of phosphorylation and dephosphorylation levels revealed that treating the PSC mice with the P. copri and L. murinus combined intervention inhibited the activity of the DDC-activated TGF-β1/Smad pathway, thereby reducing liver inflammation and fibrosis. The combination of P. copri and L. murinus inhibits the TGF-β1/Smad pathway and reduces inflammation and fibrosis in PSC.
Harnessing Autophagy to Overcome Antigen-Specific T-Cell Dysfunction: Implication for People Living with HIV-1
Authors: Ghahari Nazanin , Telittchenko Roman , Loucif Hamza , Isnard Stephane , Routy Jean-Pierre , Olagnier David , van Grevenynghe Julien
Published: July 2023

Like other chronic viral infections, HIV-1 persistence inhibits the development of antigen-specific memory T-cells, resulting in the exhaustion of the immune response and chronic inflammation. Autophagy is a major lysosome-dependent mechanism of intracellular large-target degradation such as lipid and protein aggregates, damaged organelles, and intracellular pathogens. Although it is known that autophagy may target HIV-1 for elimination, knowledge of its function as a metabolic contributor in such viral infection is only in its infancy. Recent data show that elite controllers (EC), who are HIV-1-infected subjects with natural and long-term antigen (Ag)-specific T-cell protection against the virus, are characterized by distinct metabolic autophagy-dependent features in their T-cells compared to other people living with HIV-1 (PLWH). Despite durable viral control with antiretroviral therapy (ART), HIV-1-specific immune dysfunction does not normalize in non-controller PLWH. Therefore, the hypothesis of inducing autophagy to strengthen their Ag-specific T-cell immunity against HIV-1 starts to be an enticing concept. The aim of this review is to critically analyze promises and potential limitations of pharmacological and dietary interventions to activate autophagy in an attempt to rescue Ag-specific T-cell protection among PLWH.
The Carbonic Anhydrase βCA1 Functions in PopW-Mediated Plant Defense Responses in Tomato
Authors: Zhao Jieru , Yuan Zhixiang , Han Xixi , Bao Tingting , Yang Tingmi , Liu Zhuang , Liu Hongxia
Published: July 2023

β-Carbonic anhydrase (βCA) is very important for plant growth and development, but its function in immunity has also been examined. In this study, we found that the expression level of Solanum lycopersicum βCA1 (SlβCA1) was significantly upregulated in plants treated with Xanthomonas euvesicatoria 85-10. The protein was localized in the nucleus, cell membrane and chloroplast. Using tomato plants silenced with SlβCA1, we demonstrated that SlβCA1 plays an active role in plant disease resistance. Moreover, we found that the elicitor PopW upregulated the expression of SlβCA1, while the microbe-associated molecular pattern response induced by PopW was inhibited in TRV-SlβCA1. The interaction between PopW and SlβCA1 was confirmed. Here, we found that SlβCA1 was positively regulated during PopW-induced resistance to Xanthomonas euvesicatoria 85-10. These data indicate the importance of SlβCA1 in plant basic immunity and its recognition by the Harpin protein PopW as a new target for elicitor recognition.
Dysfunction of an Anaphase-Promoting Complex Subunit 8 Homolog Leads to Super-Short Petioles and Enlarged Petiole Angles in Soybean
Authors: Gao Yi , Zhu Jinlong , Zhai Hong , Xu Kun , Zhu Xiaobin , Wu Hongyan , Zhang Wenjing , Wu Shihao , Chen Xin , Xia Zhengjun
Published: July 2023

Plant height, petiole length, and the angle of the leaf petiole and branch angles are crucial traits determining plant architecture and yield in soybean (Glycine max L.). Here, we characterized a soybean mutant with super-short petioles (SSP) and enlarged petiole angles (named Gmssp) through phenotypic observation, anatomical structure analysis, and bulk sequencing analysis. To identify the gene responsible for the Gmssp mutant phenotype, we established a pipeline involving bulk sequencing, variant calling, functional annotation by SnpEFF (v4.0e) software, and Integrative Genomics Viewer analysis, and we initially identified Glyma.11G026400, encoding a homolog of Anaphase-promoting complex subunit 8 (APC8). Another mutant, t7, with a large deletion of many genes including Glyma.11G026400, has super-short petioles and an enlarged petiole angle, similar to the Gmssp phenotype. Characterization of the t7 mutant together with quantitative trait locus mapping and allelic variation analysis confirmed Glyma.11G026400 as the gene involved in the Gmssp phenotype. In Gmssp, a 4 bp deletion in Glyma.11G026400 leads to a 380 aa truncated protein due to a premature stop codon. The dysfunction or absence of Glyma.11G026400 caused severe defects in morphology, anatomical structure, and physiological traits. Transcriptome analysis and weighted gene co-expression network analysis revealed multiple pathways likely involved in these phenotypes, including ubiquitin-mediated proteolysis and gibberellin-mediated pathways. Our results demonstrate that dysfunction of Glyma.11G026400 leads to diverse functional consequences in different tissues, indicating that this APC8 homolog plays key roles in cell differentiation and elongation in a tissue-specific manner. Deciphering the molecular control of petiole length and angle enriches our knowledge of the molecular network regulating plant architecture in soybean and should facilitate the breeding of high-yielding soybean cultivars with compact plant architecture.
Using Human ‘Personalized’ Cybrids to Identify Drugs/Agents That Can Regulate Chronic Lymphoblastic Leukemia Mitochondrial Dysfunction
Authors: Singh Lata , Atilano Shari , Chwa Marilyn , Singh Mithalesh K. , Ozgul Mustafa , Nesburn Anthony , Kenney M. Cristina
Published: July 2023

This study uses personalized chronic lymphoblastic leukemia (CLL) cybrid cells to test various drugs/agents designed to improve mitochondrial function and cell longevity. Age-matched control (NL) and CLL cybrids were created. The NL and CLL cybrids were treated with ibrutinib (Ibr-10 μM), mitochondrial-targeted nutraceuticals such as alpha lipoic acid (ALA-1 mM), amla (Aml-300 μg), melatonin (Mel-1 mM), resveratrol (Res-100 μM) alone, or a combination of ibrutinib with nutraceuticals (Ibr + ALA, Ibr + Aml, Ibr + Mel, or Ibr + Res) for 48 h. MTT (3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazoliumbromide), H2DCFDA(2′,7′ Dichlorodihydrofluorescein diacetate), and JC1 assays were used to measure the cellular metabolism, intracellular ROS levels, and mitochondrial membrane potential (∆ψm), respectively. The expression levels of genes associated with antioxidant enzymes (SOD2, GPX3, and NOX4), apoptosis (BAX and CASP3), and inflammation (IL6, IL-1β, TNFα, and TGFβ) were measured using quantitative real-time PCR (qRT-PCR). CLL cybrids treated with Ibr + ALA, Ibr + Aml, Ibr + Mel, and Ibr + Res had (a) reduced cell survivability, (b) increased ROS production, (c) increased ∆ψm levels, (d) decreased antioxidant gene expression levels, and (e) increased apoptotic and inflammatory genes in CLL cybrids when compared with ibrutinib-alone-treated CLL cybrids. Our findings show that the addition of nutraceuticals makes the CLL cybrids more pro-apoptotic with decreased cell survival compared with CLL cybrids exposed to ibrutinib alone.
Exploring the Role of Circulating Cell-Free RNA in the Development of Colorectal Cancer
Authors: Kan Chau-Ming , Pei Xiao Meng , Yeung Martin Ho Yin , Jin Nana , Ng Simon Siu Man , Tsang Hin Fung , Cho William Chi Shing , Yim Aldrin Kay-Yuen , Yu Allen Chi-Shing , Wong Sze Chuen Cesar
Published: July 2023

Circulating tumor RNA (ctRNA) has recently emerged as a novel and attractive liquid biomarker. CtRNA is capable of providing important information about the expression of a variety of target genes noninvasively, without the need for biopsies, through the use of circulating RNA sequencing. The overexpression of cancer-specific transcripts increases the tumor-derived RNA signal, which overcomes limitations due to low quantities of circulating tumor DNA (ctDNA). The purpose of this work is to present an up-to-date review of current knowledge regarding ctRNAs and their status as biomarkers to address the diagnosis, prognosis, prediction, and drug resistance of colorectal cancer. The final section of the article discusses the practical aspects involved in analyzing plasma ctRNA, including storage and isolation, detection technologies, and their limitations in clinical applications.
Anti-Inflammatory Effects of Nutritionally Relevant Concentrations of Oleuropein and Hydroxytyrosol on Peripheral Blood Mononuclear Cells: An Age-Related Analysis
Authors: Pojero Fanny , Gervasi Francesco , Fiore Salvatore Davide , Aiello Anna , Bonacci Sonia , Caldarella Rosalia , Attanzio Alessandro , Candore Giuseppina , Caruso Calogero , Ligotti Mattia Emanuela , Procopio Antonio , Restivo Ignazio , Tesoriere Luisa , Allegra Mario , Accardi Giulia
Published: July 2023

Immunosenescence and inflammaging facilitate the insurgence of chronic diseases. The Mediterranean diet is a non-invasive intervention to improve the chronic low-grade inflammatory status associated with aging. Olive oil oleuropein (OLE) and hydroxytyrosol (HT) demonstrated a controversial modulatory action on inflammation in vitro when tested at concentrations exceeding those detectable in human plasma. We studied the potential anti-inflammatory effects of OLE and HT at nutritionally relevant concentrations on peripheral blood mononuclear cells (PBMCs) as regards cell viability, frequency of leukocyte subsets, and cytokine release, performing an age-focused analysis on two groups of subjects: Adult (age 18–64 years) and Senior (age ≥ 65 years). OLE and HT were used alone or as a pre-treatment before challenging PBMCs with lipopolysaccharide (LPS). Both polyphenols had no effect on cell viability irrespective of LPS, but 5 µM HT had an LPS-like effect on monocytes, reducing the intermediate subset in Adult subjects. OLE and HT had no effect on LPS-triggered release of TNF-α, IL-6 and IL-8, but 5 µM HT reduced IL-10 secretion by PBMCs from Adult vs. Senior group. In summary, nutritionally relevant concentrations of OLE and HT elicit no anti-inflammatory effect and influence the frequency of immune cell subsets with age-related different outcomes.
Experimental Insights into the Interplay between Histone Modifiers and p53 in Regulating Gene Expression
Authors: Kim Hyun-Min , Zheng Xiaoyu , Lee Ethan
Published: July 2023

Chromatin structure plays a fundamental role in regulating gene expression, with histone modifiers shaping the structure of chromatin by adding or removing chemical changes to histone proteins. The p53 transcription factor controls gene expression, binds target genes, and regulates their activity. While p53 has been extensively studied in cancer research, specifically in relation to fundamental cellular processes, including gene transcription, apoptosis, and cell cycle progression, its association with histone modifiers has received limited attention. This review explores the interplay between histone modifiers and p53 in regulating gene expression. We discuss how histone modifications can influence how p53 binds to target genes and how this interplay can be disrupted in cancer cells. This review provides insights into the complex mechanisms underlying gene regulation and their implications for potential cancer therapy.
Transcriptomic and Metabolomic Analyses Reveal Differences in Flavonoid Pathway Gene Expression Profiles between Two Dendrobium Varieties during Vernalization
Authors: Shu Wenbo , Shi Meirong , Zhang Qiqi , Xie Wenyu , Chu Liwei , Qiu Mingxuan , Li Linyan , Zeng Zhixin , Han Lei , Sun Zhenyuan
Published: July 2023

Dendrobium (Orchidaceae, Epidendoideae) plants have flowers with a wide variety of colors that persist for a long period throughout the year. The yellow coloration of Dendrobium flowers is mainly determined by the flavonol pathway and the flavone pathway, but the relevant biosynthesis mechanisms during vernalization remain unclear. To explore the similarities and differences in flavonoid biosynthesis in different tissues during vernalization, we selected two species of Dendrobium for a flower color study: Dendrobium capillipes Rchb (which has yellow flowers) and Dendrobium nobile Lindl (which has white flowers). We collected a total of 36 samples from six tissue types and both Dendrobium species during vernalization and subjected the samples to metabolic profiling and transcriptome sequencing. A total of 31,504 differentially expressed genes (DEGs) were identified between different tissues of the two Dendrobium species by transcriptomic analysis. However, many differentially accumulated metabolites (DAMs) and DEGs were enriched not only in the general pathway of “flavonoid biosynthesis” but also in multiple subpathways of “flavone and flavonol biosynthesis”. According to a combined transcriptome and metabolome analysis, Putrescine hydroxycinnamoyl transferase 1 (LOC110093422) may be the main gene responsible for the differences in flavonoid accumulation during vernalization, which is closely associated with yellow flowers. Taken together, the results of our study preliminarily revealed the metabolites responsible for and the key genes regulating flavonoid biosynthesis during vernalization. These results provide a basis for the further study of the molecular mechanism of flavonoid synthesis during vernalization.
Biological Activity of Bursera schlechtendalii Essential oil and the Roles of Its Chemical Components in the Wound Healing Process
Authors: Espinosa-Espinosa Lesslie , Canales-Alvarez Octavio , Rodríguez-López Marlene Guadalupe , Flores-Tinajero César Antonio , Canales-Martinez Maria Margarita , Rodriguez-Monroy Marco Aurelio
Published: July 2023

Essential oils are composed of terpenes, some of which have properties related to healing. Bursera schlechtendalii essential oil (BSEO) is used to heal superficial wounds. However, there have been no studies verifying this property. The objectives of this study were to evaluate the healing activity of BSEO in a murine model and to propose the roles of its chemical components in this process. Healing activity was evaluated by an incision model, histological analysis was performed, and tensile strength and antibacterial activity were measured. The chemical composition of BSEO was determined by gas chromatography coupled with mass spectrometry (GC–MS), and the mechanisms of action of each chemical component during the phases of the healing process were proposed. In addition, acute dermal toxicity was evaluated. BSEO showed better wound closure at the macroscopic, histological, and tensile strength levels compared to controls and had an antibacterial effect. The major compound in BSEO was α-phellandrene. However, most of the monoterpenes identified in BSEO were in agreement with information found in the literature, so the possibility of synergy between the chemical components and their different targets in the healing process was schematically proposed. BSEO was shown to be safe in the dermal toxicity evaluation.
Design, Synthesis, and Biological Evaluation of Novel Quinazolin-4(3H)-one-Based Histone Deacetylase 6 (HDAC6) Inhibitors for Anticancer Activity
Authors: Khetmalis Yogesh Mahadu , Fathima Ashna , Schweipert Markus , Debarnot Cécile , Bandaru Naga Venkata Madhusudhan Rao , Murugesan Sankaranarayanan , Jamma Trinath , Meyer-Almes Franz-Josef , Sekhar Kondapalli Venkata Gowri Chandra
Published: July 2023

A series of novel quinazoline-4-(3H)-one derivatives were designed and synthesized as histone deacetylase 6 (HDAC6) inhibitors based on novel quinazoline-4-(3H)-one as the cap group and benzhydroxamic acid as the linker and metal-binding group. A total of 19 novel quinazoline-4-(3H)-one analogues (5a–5s) were obtained. The structures of the target compounds were characterized using 1H-NMR, 13C-NMR, LC–MS, and elemental analyses. Characterized compounds were screened for inhibition against HDAC8 class I, HDAC4 class IIa, and HDAC6 class IIb. Among the compounds tested, 5b proved to be the most potent and selective inhibitor of HDAC6 with an IC50 value 150 nM. Some of these compounds showed potent antiproliferative activity in several tumor cell lines (HCT116, MCF7, and B16). Amongst all the compounds tested for their anticancer effect against cancer cell lines, 5c emerged to be most active against the MCF-7 line with an IC50 of 13.7 μM; it exhibited cell-cycle arrest in the G2 phase, as well as promoted apoptosis. Additionally, we noted a significant reduction in the colony-forming capability of cancer cells in the presence of 5c. At the intracellular level, selective inhibition of HDAC6 was enumerated by monitoring the acetylation of a-tubulin with a limited effect on acetyl-H3. Importantly, the obtained results suggested a potent effect of 5c at sub-micromolar concentrations as compared to the other molecules as HDAC6 inhibitors in vitro.