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23 pages, 824 KB  
Article
Leading with Integrity: Impact of Ethical Leadership on Performance of Healthcare Professionals in Saudi Arabia
by Badr K. Aldhmadi, Rakesh Kumar, Bilesha Perera and Mohammad A. Algarni
Healthcare 2025, 13(24), 3205; https://doi.org/10.3390/healthcare13243205 - 8 Dec 2025
Viewed by 758
Abstract
Background/Objectives: Ethical leadership (EL) propels and enhances employee performance (EP), especially in healthcare, where ethics are paramount. However, existing research lacks a focus on how EL functions within Saudi Arabia (SA)’s public healthcare context. Primarily, this research investigates how EL directly affects EP. [...] Read more.
Background/Objectives: Ethical leadership (EL) propels and enhances employee performance (EP), especially in healthcare, where ethics are paramount. However, existing research lacks a focus on how EL functions within Saudi Arabia (SA)’s public healthcare context. Primarily, this research investigates how EL directly affects EP. The research also investigates how organizational support (OS) influences EP and moderates the EL-to-EP relationship. Methods: This cross-sectional study consisted of 312 responses from doctors, nurses, and other administrators within Saudi public healthcare units. To analyze the collected data statistically, structural equation modeling (SEM) was opted for with the help of Smart-PLS 4. It helped to assess the direct effects of EL and OS on EP and further examine OS’s moderating role. A multigroup analysis (MGA) was also conducted in comparative form. It examined subgroup variations across gender, age, marital status, experience, and departmental affiliation. Results: The findings confirmed a positive impact of EL on EP. Moreover, a positive effect of OS on EP was also confirmed. Similarly, OS strengthened the positive effect of EL on EP. The MGA revealed variations across employee groups. It offered practical insights into how EL and OS function in diverse organizational contexts. These differences across groups reflect cultural and structural features of Saudi public healthcare. Conclusions: The extended research contributes to the literature on ethical leadership (EL) theory by applying contextual and demographic contingencies within the Saudi public healthcare sector. It also introduces OS as a significant moderator and provides actionable implications for improving performance through context-sensitive leadership and support strategies. Full article
(This article belongs to the Section Healthcare Organizations, Systems, and Providers)
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27 pages, 3604 KB  
Article
Predicting Survival in Bevacizumab-Treated Colorectal Cancer: Personalized Mathematical Models Based on Clinical and Angiogenic Biomarkers
by Diana Cornelia Moisuc, Mihai Vasile Marinca, Bogdan Gafton, Daniela Constantinescu, Petru Cianga and Mariana Pavel-Tanasa
Int. J. Mol. Sci. 2025, 26(19), 9332; https://doi.org/10.3390/ijms26199332 - 24 Sep 2025
Viewed by 1504
Abstract
Aberrant activation of proangiogenic signaling pathways, particularly the vascular endothelial growth factor (VEGF) axis, drives neovascularization and tumor progression in colorectal cancer (CRC). Bevacizumab targets VEGF-A-mediated angiogenesis, but the lack of validated predictive biomarkers limits personalized treatment. In this prospective study, we evaluated [...] Read more.
Aberrant activation of proangiogenic signaling pathways, particularly the vascular endothelial growth factor (VEGF) axis, drives neovascularization and tumor progression in colorectal cancer (CRC). Bevacizumab targets VEGF-A-mediated angiogenesis, but the lack of validated predictive biomarkers limits personalized treatment. In this prospective study, we evaluated a panel of circulating angiogenic biomarkers combined with clinical parameters, using mathematical models to predict survival in metastatic CRC patients treated with bevacizumab and chemotherapy. Low VEGF-A and VEGF-D levels, together with high bFGF, were associated with improved overall survival (OS). A logistic regression model incorporating these biomarkers, regional lymph node invasion, and primary tumor resection status showed significant prognostic accuracy (p < 0.001). Incorporating CypA further refined the model, identifying patients with low VEGF-A, VEGF-D, and CypA, and high VEGF-C and PlGF, as having the most favorable OS. These findings demonstrate that integrating clinical and circulating biomarker data can improve individualized risk assessment and support personalized therapeutic strategies for CRC patients receiving bevacizumab. Full article
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24 pages, 640 KB  
Article
How Talent Management Drives Sustainability in Hospitality Enterprises: The Mediating Role of Green Knowledge Sharing and Employee Voice
by Abdullah Hamoud Seraj, Ahmed Mohamed Hasanein, Bassam Samir Al-Romeedy and Eman Hassanien Taha
Tour. Hosp. 2025, 6(4), 176; https://doi.org/10.3390/tourhosp6040176 - 12 Sep 2025
Viewed by 1724
Abstract
The issue of organizational sustainability is pivotal in the hospitality industry in the face of increasing environmental and societal pressures. This research investigates the mediating roles of green knowledge sharing (GKS) and green employee voice (GEV) on talent management (TM) strategic contribution to [...] Read more.
The issue of organizational sustainability is pivotal in the hospitality industry in the face of increasing environmental and societal pressures. This research investigates the mediating roles of green knowledge sharing (GKS) and green employee voice (GEV) on talent management (TM) strategic contribution to strengthen organizational sustainability (OS). Based on the Social Exchange Theory, TM is conceptualized as the consequence of employee engagement in sustainability behaviors in relational processes. the data were collected from 268 employees working at five-star hotels in the Eastern Region, Saudi Arabia. The Partial Least Squares Structural Equation Modeling (PLS-SEM) was used to evaluate the hypotheses. The results indicate that TM has direct positive influence on OS, GKS, and GEV, which determines its central position in development of environmentally friendly workforce. GEV and GKS also have direct influences on OS, and therefore marketplace advocacy and knowledge exchange are essential to embedding sustainable practices. Mediation analyses show GKS and GEV can partially mediate the TM and OS relationship, proving that the impact TM has on sustainability is further facilitated by the green sharing of knowledge and proactive voice by the employees. Both theoretical and practical implications for both academics and practitioners have been addressed. Full article
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17 pages, 4423 KB  
Article
Multivariate Framework of Metabolism in Advanced Prostate Cancer Using Whole Abdominal and Pelvic Hyperpolarized 13C MRI—A Correlative Study with Clinical Outcomes
by Hsin-Yu Chen, Ivan de Kouchkovsky, Robert A. Bok, Michael A. Ohliger, Zhen J. Wang, Daniel Gebrezgiabhier, Tanner Nickles, Lucas Carvajal, Jeremy W. Gordon, Peder E. Z. Larson, John Kurhanewicz, Rahul Aggarwal and Daniel B. Vigneron
Cancers 2025, 17(13), 2211; https://doi.org/10.3390/cancers17132211 - 1 Jul 2025
Cited by 1 | Viewed by 1634 | Correction
Abstract
Background: Most of the existing hyperpolarized (HP) 13C MRI analyses use univariate rate maps of pyruvate-to-lactate conversion (kPL), and radiomic-style multiparametric models extracting complex, higher-order features remain unexplored. Purpose: To establish a multivariate framework based on whole abdomen/pelvis HP 13 [...] Read more.
Background: Most of the existing hyperpolarized (HP) 13C MRI analyses use univariate rate maps of pyruvate-to-lactate conversion (kPL), and radiomic-style multiparametric models extracting complex, higher-order features remain unexplored. Purpose: To establish a multivariate framework based on whole abdomen/pelvis HP 13C-pyruvate MRI and evaluate the association between multiparametric features of metabolism (MFM) and clinical outcome measures in advanced and metastatic prostate cancer. Methods: Retrospective statistical analysis was performed on 16 participants with metastatic or local-regionally advanced prostate cancer prospectively enrolled in a tertiary center who underwent HP-pyruvate MRI of abdomen or pelvis between November 2020 and May 2023. Five patients were hormone-sensitive and eleven were castration-resistant. GMP-grade [1-13C]pyruvate was polarized using a 5T clinical-research DNP polarizer, and HP MRI used a set of flexible vest-transmit, array-receive coils, and echo-planar imaging sequences. Three basic metabolic maps (kPL, pyruvate summed-over-time, and mean pyruvate time) were created by semi-automatic segmentation, from which 316 MFMs were extracted using an open-source, radiomic-compliant software package. Univariate risk classifier was constructed using a biologically meaningful feature (kPL,median), and the multivariate classifier used a two-step feature selection process (ranking and clustering). Both were correlated with progression-free survival (PFS) and overall survival (OS) (median follow-up = 22.0 months) using Cox proportional hazards model. Results: In the univariate analysis, patients harboring tumors with lower-kPL,median had longer PFS (11.2 vs. 0.5 months, p < 0.01) and OS (NR vs. 18.4 months, p < 0.05) than their higher-kPL,median counterparts. Using a hypothesis-generating, age-adjusted multivariate risk classifier, the lower-risk subgroup also had longer PFS (NR vs. 2.4 months, p < 0.002) and OS (NR vs. 18.4 months, p < 0.05). By contrast, established laboratory markers, including PSA, lactate dehydrogenase, and alkaline phosphatase, were not significantly associated with PFS or OS (p > 0.05). Key limitations of this study include small sample size, retrospective study design, and referral bias. Conclusions: Risk classifiers derived from select multiparametric HP features were significantly associated with clinically meaningful outcome measures in this small, heterogeneous patient cohort, strongly supporting further investigation into their prognostic values. Full article
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27 pages, 3732 KB  
Review
Occurrence, Biosynthesis, and Health Benefits of Anthocyanins in Rice and Barley
by Essam A. ElShamey, Xiaomeng Yang, Jiazhen Yang, Xiaoying Pu, Li’E Yang, Changjiao Ke and Yawen Zeng
Int. J. Mol. Sci. 2025, 26(13), 6225; https://doi.org/10.3390/ijms26136225 - 27 Jun 2025
Cited by 4 | Viewed by 3761
Abstract
The occurrence of anthocyanins in rice (Oryza sativa) and barley (Hordeum vulgare) varies among cultivars, with pigmented varieties (e.g., black rice and purple barley) accumulating higher concentrations due to genetic and environmental factors. The biosynthesis of anthocyanins is regulated [...] Read more.
The occurrence of anthocyanins in rice (Oryza sativa) and barley (Hordeum vulgare) varies among cultivars, with pigmented varieties (e.g., black rice and purple barley) accumulating higher concentrations due to genetic and environmental factors. The biosynthesis of anthocyanins is regulated by a complex network of structural and regulatory genes. Key enzymes in the pathway include chalcone synthase (CHS), chalcone isomerase (CHI), flavanone 3-hydroxylase (F3H), dihydroflavonol 4-reductase (DFR), anthocyanidin synthase (ANS), and UDP-glucose flavonoid 3-O-glucosyltransferase (UFGT). These genes are tightly controlled by transcription factors (TFs) from the MYB, bHLH (basic helix–loop–helix), and WD40 repeat families, which form the MBW (MYB-bHLH-WD40) regulatory complex. In rice, OsMYB transcription factors such as OsMYB3, OsC1, and OsPL (Purple Leaf) interact with OsbHLH partners (e.g., OsB1, OsB2) to activate anthocyanin biosynthesis. Similarly, in barley, HvMYB genes (e.g., HvMYB10) coordinate with HvbHLH TFs to regulate pigment accumulation. Environmental cues, such as light, temperature, and nutrient availability, further modulate these TFs, influencing the production of anthocyanin. Understanding the genetic and molecular mechanisms behind the biosynthesis of anthocyanins in rice and barley provides opportunities for the development of biofortification strategies that enhance their nutritional value. Full article
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15 pages, 11937 KB  
Article
Long-Term Quality of Life and Functional Outcomes in Patients with Total Laryngectomy
by Maria Octavia Murariu, Eugen Radu Boia, Adrian Mihail Sitaru, Cristian Ion Mot, Mihaela Cristina Negru, Alexandru Cristian Brici, Delia Elena Zahoi and Nicolae Constantin Balica
Cancers 2025, 17(6), 1011; https://doi.org/10.3390/cancers17061011 - 17 Mar 2025
Cited by 4 | Viewed by 2930
Abstract
Background: Laryngeal cancer affects quality of life (QoL), speech, and swallowing. Total laryngectomy (TL) causes severe impairments, while partial laryngectomy (PL) and chemoradiotherapy (CRT) preserve the organ but yield variable outcomes. This study assesses QoL, speech rehabilitation, swallowing, and social reintegration across these [...] Read more.
Background: Laryngeal cancer affects quality of life (QoL), speech, and swallowing. Total laryngectomy (TL) causes severe impairments, while partial laryngectomy (PL) and chemoradiotherapy (CRT) preserve the organ but yield variable outcomes. This study assesses QoL, speech rehabilitation, swallowing, and social reintegration across these treatments. Methods: This prospective observational cohort study was conducted at the ENT Clinic, Victor Babeș University of Medicine and Pharmacy, Timișoara; recruitment was conducted between October 2019 and January 2024. Seventy-five patients diagnosed with laryngeal squamous cell carcinoma (LSCC) were initially enrolled but only 15 patients (20%) completed the 12-month follow-up, with an attrition rate of 80%. Tumor stages ranged from T1 to T4a, with TL patients having a higher proportion of advanced-stage disease (Stage III–IV: 76%) compared to PL (45%) and CRT (50%). Validated instruments, including the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Head and Neck Cancer (EORTC QLQ-H&N35), the Voice Handicap Index-30 (VHI-30), the Hospital Anxiety and Depression Scale (HADS), and the Dysphagia Outcome and Severity Scale (DOSS), were used to assess QoL, voice function, swallowing function, and psychological impact. Results: At 12 months, the global QoL score from the EORTC QLQ-H&N35 was lowest in TL patients (49.8 ± 10.9), significantly lower than both PL (61.2 ± 9.6, p = 0.002) and CRT (64.1 ± 7.8, p < 0.001). Post hoc Bonferroni analysis confirmed significant pairwise differences between TL vs. PL (p = 0.002) and TL vs. CRT (p < 0.001), while the difference between PL and CRT was non-significant (p = 0.14). TL patients had higher speech-related disability (VHI: 88.3 ± 12.6) and dysphagia prevalence (DOSS: 4.0 ± 1.2), with 16% remaining enteral feeding-dependent. Anxiety (HADS-A: 7.5 ± 2.9) and depression (HADS-D: 9.0 ± 3.2) were highest in TL patients, with 36% meeting clinical depression criteria at 12 months. Multivariable regression identified TL (OR = 3.92, 95% CI: 2.14–5.79, p < 0.001) and advanced tumor stage (OR = 2.85, 95% CI: 1.79–4.21, p = 0.002) as strong predictors of poor QoL. Kaplan–Meier analysis showed no significant OS differences (p = 0.12), but CRT patients had lower DFS (78%) compared to TL (82%) and PL (85%) (p = 0.048). Conclusions: TL patients experience the most significant impairments in QoL, speech, and social reintegration despite rehabilitation. CRT patients show higher recurrence rates but better QoL, while PL offers the best balance of function and survival. These findings highlight the need for long-term survivorship support tailored to treatment type. Full article
(This article belongs to the Special Issue Cancer Survivorship: During and After Treatment)
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15 pages, 1293 KB  
Article
Distribution of EGFR and KRAS Mutations in Patients with Surgically Resected Non-Small Cell Lung Cancer from Southern Italy: Real-Life Data from a Single Institution and Literature Review
by Michele Piazzolla, Paola Parente, Flavia Centra, Federico Pio Fabrizio, Marco Donatello Delcuratolo, Antonella Centonza, Concetta Martina Di Micco, Mario Mastroianno, Francesco Delli Muti, Fabiola Fiordelisi, Gianmaria Ferretti, Paolo Graziano and Lucia Anna Muscarella
Cancers 2025, 17(5), 730; https://doi.org/10.3390/cancers17050730 - 21 Feb 2025
Cited by 1 | Viewed by 3221
Abstract
Background/Objectives: The identification of driver mutations in NSCLC such as those in the EGFR and KRAS genes has revolutionized the understanding and management of many lung cancer patients and has opened up a new scenario in the early disease stages in terms of [...] Read more.
Background/Objectives: The identification of driver mutations in NSCLC such as those in the EGFR and KRAS genes has revolutionized the understanding and management of many lung cancer patients and has opened up a new scenario in the early disease stages in terms of therapeutic options (EGFR) and prognosis (KRAS). Data on prevalence rates and disease stage distributions of EGFR and KRAS mutations in surgically resected NSCLC are growing, but in Southern Italy, estimation is limited, since upfront EGFR testing in early-stage adenocarcinoma has been only recently introduced according to the current guidelines in clinical practice, whereas KRAS screening is usually uninvestigated in resected NSCLC. In this real-life study of a single institution in the Apulia Region, we provide an overview of the epidemiological distribution of EGFR and KRAS mutations in patients in Southern Italy with resected NSCLC, highlighting their prevalence, clinical significance, and correlation with demographic and pathological factors. A literature review was also performed to compare our findings with the most recent available data from the screening of Italian cohorts of advanced and surgically resected NSCLC patients. Methods: Data from 149 patients coming from Southern Italy with surgically resected NSCLC were retrospectively collected over a period of 16 years. EGFR and KRAS mutation screenings were performed and correlated with clinical and pathological data. Results: In total, 24 out of 149 NSCLC (16%) patients harbored an EGFR mutation. Exon 19 deletions and missense p.L858R mutations of the EGFR gene have quite similar frequencies (46%) and were more observed in never smokers (p < 0.001) and female (p < 0.001) patients with the adenocarcinoma histotype. KRAS gene mutations were detected in 31.5% of cases, with missense p.G12C (32%), p.G12V (28%), and p.G12D (17%) mutations as the most frequent ones. Neither EGFR nor KRAS mutational status were found to impact overall survival (OS) in our study cohort. Conclusions: Our findings improve the understanding of lung cancer genetics in a small and homogeneous area of Southern Italy and guide future research. The EGFR and KRAS mutations in NSCLC resected patients from Southern Italy showed a global similar incidence compared to other recently described Italian cohorts of advanced and early-stage NSCLC, with a higher frequency of exon19 EGFR deletions. No prognostic impact was observed for both EGFR and KRAS status, but additional investigations on a larger cohort are needed. Full article
(This article belongs to the Special Issue Modern Surgical Treatments for Thoracic Malignancies)
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12 pages, 1705 KB  
Article
Preeclampsia Treatment Aspirin/Clampsilin: Oxidative Stress, sFlt-1/PIGF Soluble Tyrosine Kinase 1, and Placental Growth Factor Monitoring
by Denitsa Kostadinova-Slavova, Kamelia Petkova-Parlapanska, Irina Koleva, Mariya Angelova, Rafaah Sadi J. Al-Dahwi, Ekaterina Georgieva, Yanka Karamalakova and Galina Nikolova
Int. J. Mol. Sci. 2024, 25(24), 13497; https://doi.org/10.3390/ijms252413497 - 17 Dec 2024
Cited by 3 | Viewed by 2649
Abstract
The present study aimed to investigate and compare oxidative stress biomarkers and antioxidant enzyme activity in the serum of women at risk of developing preeclampsia (PE) to prevent adverse pregnancy outcomes through early intervention. Changes in soluble fms-like tyrosine kinase-1 (sFlt-1) and placental [...] Read more.
The present study aimed to investigate and compare oxidative stress biomarkers and antioxidant enzyme activity in the serum of women at risk of developing preeclampsia (PE) to prevent adverse pregnancy outcomes through early intervention. Changes in soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) levels were measured between 11 and 13 gestational weeks (gw.) before the onset of preeclampsia and its associated complications. This study evaluated the feasibility of the sFlt-1/PlGF biomarker ratio in predicting preeclampsia and adverse pregnancy outcomes, with the goal of preventive therapy with acetylsalicylic acid (150 mg daily), with acetylsalicylic acid (75 mg daily) and Clampsilin. For this purpose, the following were evaluated: (1) the levels of reactive oxygen species (ROS) and reactive nitrogen species (RNS) as parameters of oxidative stress; (2) lipid oxidation; (3) antioxidant enzyme activity; and (4) cytokine production. Analysis of the results showed that pregnant women at risk of preeclampsia had significantly higher levels of ROS, lipid oxidation, and superoxide anion radical (•O2) levels compared to normal pregnancies. In PE, depleted levels of nitric oxide (NO), impaired NO synthase system (NOS), and reduced antioxidant enzyme activity (p < 0.03) suggest that PE patients cannot compensate for oxidative stress (OS). In conclusion, oxidative stress in PE plays a key role, which arises from placental problems and affects both mother and baby. The groups with acetylsalicylic acid therapy (150 mg and 75 mg) were better affected compared to those on Clampsillin. Full article
(This article belongs to the Special Issue Oxidation in Human Health and Disease)
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35 pages, 3354 KB  
Review
Oxidative Stress and Placental Pathogenesis: A Contemporary Overview of Potential Biomarkers and Emerging Therapeutics
by Ioana Vornic, Victor Buciu, Cristian George Furau, Pusa Nela Gaje, Raluca Amalia Ceausu, Cristina-Stefania Dumitru, Alina Cristina Barb, Dorin Novacescu, Alin Adrian Cumpanas, Silviu Constantin Latcu, Talida Georgiana Cut and Flavia Zara
Int. J. Mol. Sci. 2024, 25(22), 12195; https://doi.org/10.3390/ijms252212195 - 13 Nov 2024
Cited by 40 | Viewed by 9255
Abstract
Oxidative stress (OS) plays a crucial role in placental pathogenesis and pregnancy-related complications. This review explores OS’s impact on placental development and function, focusing on novel biomarkers for the early detection of at-risk pregnancies and emerging therapeutic strategies. We analyzed recent research on [...] Read more.
Oxidative stress (OS) plays a crucial role in placental pathogenesis and pregnancy-related complications. This review explores OS’s impact on placental development and function, focusing on novel biomarkers for the early detection of at-risk pregnancies and emerging therapeutic strategies. We analyzed recent research on OS in placental pathophysiology, examining its sources, mechanisms, and effects. While trophoblast invasion under low-oxygen conditions and hypoxia-induced OS regulate physiological placental development, excessive OS can lead to complications like miscarriage, preeclampsia, and intrauterine growth restriction. Promising OS biomarkers, including malondialdehyde, 8-isoprostane, and the sFlt-1/PlGF ratio, show potential for the early detection of pregnancy complications. Therapeutic strategies targeting OS, such as mitochondria-targeted antioxidants, Nrf2 activators, and gasotransmitter therapies, demonstrate encouraging preclinical results. However, clinical translation remains challenging. Future research should focus on validating these biomarkers in large-scale studies and developing personalized therapies to modulate placental OS. Emerging approaches like extracellular vesicle-based therapies and nanomedicine warrant further investigation for both diagnostic and therapeutic applications in pregnancy-related complications. Integrating OS biomarkers with other molecular and cellular markers offers improved potential for the early identification of at-risk pregnancies. Full article
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20 pages, 2118 KB  
Communication
Preliminary Study on the Restoration of the Phospholipid Profile in Serum from Patients with COVID-19 by Treatment with Vitamin E
by María Elena Soto, Linaloe Manzano-Pech, Verónica Guarner-Lans, Adrían Palacios-Chavarría, Rafael Ricardo Valdez-Vázquez, Raúl Martínez-Memije, Mohammed El-Hafidi, Félix Leao Rodríguez-Fierros and Israel Pérez-Torres
Curr. Issues Mol. Biol. 2024, 46(7), 7219-7238; https://doi.org/10.3390/cimb46070429 - 8 Jul 2024
Viewed by 1914
Abstract
SARS-CoV-2 is an obligatory intracellular pathogen that requires a lipid bilayer membrane for its transport to build its nucleocapsid envelope and fuse with the host cell. The biological membranes are constituted by phospholipids (PLs), and vitamin E (Vit E) protects them from oxidative [...] Read more.
SARS-CoV-2 is an obligatory intracellular pathogen that requires a lipid bilayer membrane for its transport to build its nucleocapsid envelope and fuse with the host cell. The biological membranes are constituted by phospholipids (PLs), and vitamin E (Vit E) protects them from oxidative stress (OS). The aim of this study was to demonstrate if treatment with Vit E restores the modified profile of the FA in PLs in serum from patients with coronavirus disease-19 (COVID-19). We evaluated Vit E, total fatty acids (TFAs), fatty acids of the phospholipids (FAPLs), total phospholipids (TPLs), 8-isoprostane, thromboxane B2 (TXB2), prostaglandins (PGE2 and 6-keto-PGF1α), interleukin-6 (IL-6), and C-reactive protein (CRP) in serum from 22 COVID-19 patients before and after treatment with Vit E and compared the values with those from 23 healthy subjects (HSs). COVID-19 patients showed a decrease in Vit E, TPLs, FAPLs, and TFAs in serum in comparison to HSs (p ≤ 0.01), and Vit E treatment restored their levels (p ≤ 0.04). Likewise, there was an increase in IL-6 and CRP in COVID-19 patients in comparison with HSs (p ≤ 0.001), and treatment with Vit E decreased their levels (p ≤ 0.001). Treatment with Vit E as monotherapy can contribute to restoring the modified FA profile of the PLs in the SARS-CoV-2 infection, and this leads to a decrease in lipid peroxidation, OS, and the inflammatory process. Full article
(This article belongs to the Section Molecular Medicine)
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19 pages, 4833 KB  
Article
OsCAMTA3 Negatively Regulates Disease Resistance to Magnaporthe oryzae by Associating with OsCAMTAPL in Rice
by Shibo Yu, Shengping Li, Wei Wang and Dingzhong Tang
Int. J. Mol. Sci. 2024, 25(9), 5049; https://doi.org/10.3390/ijms25095049 - 6 May 2024
Cited by 5 | Viewed by 2617
Abstract
Rice (Oryza sativa) is one of the most important staple foods worldwide. However, rice blast disease, caused by the ascomycete fungus Magnaporthe oryzae, seriously affects the yield and quality of rice. Calmodulin-binding transcriptional activators (CAMTAs) play vital roles in the [...] Read more.
Rice (Oryza sativa) is one of the most important staple foods worldwide. However, rice blast disease, caused by the ascomycete fungus Magnaporthe oryzae, seriously affects the yield and quality of rice. Calmodulin-binding transcriptional activators (CAMTAs) play vital roles in the response to biotic stresses. In this study, we showed that OsCAMTA3 and CAMTA PROTEIN LIKE (OsCAMTAPL), an OsCAMTA3 homolog that lacks the DNA-binding domain, functioned together in negatively regulating disease resistance in rice. OsCAMTA3 associated with OsCAMTAPL. The oscamta3 and oscamtapl mutants showed enhanced resistance compared to wild-type plants, and oscamta3/pl double mutants showed more robust resistance to M. oryzae than oscamta3 or oscamtapl. An RNA-Seq analysis revealed that 59 and 73 genes, respectively, were differentially expressed in wild-type plants and oscamta3 before and after inoculation with M. oryzae, including OsALDH2B1, an acetaldehyde dehydrogenase that negatively regulates plant immunity. OsCAMTA3 could directly bind to the promoter of OsALDH2B1, and OsALDH2B1 expression was decreased in oscamta3, oscamtapl, and oscamta3/pl mutants. In conclusion, OsCAMTA3 associates with OsCAMTAPL to regulate disease resistance by binding and activating the expression of OsALDH2B1 in rice, which reveals a strategy by which rice controls rice blast disease and provides important genes for resistance breeding holding a certain positive impact on ensuring food security. Full article
(This article belongs to the Special Issue Advanced Research in Plant-Fungi Interactions)
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15 pages, 4367 KB  
Article
Mapping and Candidate Gene Prediction of qPL7-25: A Panicle Length QTL in Dongxiang Wild Rice
by Sanfeng Li, Yuchun Rao, Penggen Duan, Zhonghao Wang, Ping Hu, Ruoqian Yu, Chenxi Luo, Mengna Tang, Caolin Lu, Yuexing Wang and Yijian Mao
Agriculture 2023, 13(8), 1623; https://doi.org/10.3390/agriculture13081623 - 18 Aug 2023
Cited by 2 | Viewed by 2711
Abstract
Panicle length (PL) is an important trait closely related to rice yield. More than 200 quantitative trait loci (QTL) for PL have been identified, but only a few can be used for breeding. Dongxiang wild rice contains many excellent genes, and mining favorable [...] Read more.
Panicle length (PL) is an important trait closely related to rice yield. More than 200 quantitative trait loci (QTL) for PL have been identified, but only a few can be used for breeding. Dongxiang wild rice contains many excellent genes, and mining favorable PL-related QTL from DXWR is helpful for rice variety improvement. Here, we report a QTL analysis for PL using a recombinant inbred line population consisting of 143 individuals derived from a cross between Dongxiang wild rice and indica cultivar Guangluai 4. A total of four QTL (qPL1-37, qPL4-26, qPL7-25, and qPL8-4) for PL were identified and located on chromosomes 1, 4, 7, and 8. Among them, qPL7-25 showed the largest F-value of 32.32 and 16.80, and the QTL explained 18.66% and 13.06% of the phenotypic variation of Dongxiang wild rice in Hangzhou and Hainan, respectively. QTL mapping was performed using a population of 1800 individuals derived from the crossing of NIL-qPL7-25 and GLA4. qPL7-25 was located between two InDel markers, InDel-24591 and InDel-24710, in a 119 kb region containing 14 predicted genes. Using Sanger sequencing and qRT-PCR analysis, we propose that LOC_Os07g41200 is probably a new allele of the well-known GL7 gene, which affects grain length and appearance quality in rice. These results provide new insights into the use of molecular marker-assisted selection for breeding high-yielding and high-quality rice varieties. Full article
(This article belongs to the Special Issue Germplasm Resources Exploration and Genetic Breeding of Crops)
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17 pages, 5373 KB  
Article
Evaluation of Intratumoral Response Heterogeneity in Metastatic Colorectal Cancer and Its Impact on Patient Overall Survival: Findings from 10,551 Patients in the ARCAD Database
by Fang-Shu Ou, Daniel H. Ahn, Jesse G. Dixon, Axel Grothey, Yiyue Lou, Pashtoon M. Kasi, Joleen M. Hubbard, Eric Van Cutsem, Leonard B. Saltz, Hans-Joachim Schmoll, Richard M. Goldberg, Alan P. Venook, Paulo Hoff, Jean-Yves Douillard, J. Randolph Hecht, Herbert Hurwitz, Cornelis J. A. Punt, Miriam Koopman, Carsten Bokemeyer, Charles S. Fuchs, Eduardo Diaz-Rubio, Niall C. Tebbutt, Chiara Cremolini, Fairooz F. Kabbinavar, Tanios Bekaii-Saab, Benoist Chibaudel, Takayuki Yoshino, John Zalcberg, Richard A. Adams, Aimery de Gramont and Qian Shiadd Show full author list remove Hide full author list
Cancers 2023, 15(16), 4117; https://doi.org/10.3390/cancers15164117 - 15 Aug 2023
Cited by 4 | Viewed by 3815
Abstract
Metastatic colorectal cancer (mCRC) is a heterogeneous disease that can evoke discordant responses to therapy among different lesions in individual patients. The Response Evaluation Criteria in Solid Tumors (RECIST) criteria do not take into consideration response heterogeneity. We explored and developed lesion-based measurement [...] Read more.
Metastatic colorectal cancer (mCRC) is a heterogeneous disease that can evoke discordant responses to therapy among different lesions in individual patients. The Response Evaluation Criteria in Solid Tumors (RECIST) criteria do not take into consideration response heterogeneity. We explored and developed lesion-based measurement response criteria to evaluate their prognostic effect on overall survival (OS). Patients and Methods: Patients enrolled in 17 first-line clinical trials, who had mCRC with ≥ 2 lesions at baseline, and a restaging scan by 12 weeks were included. For each patient, lesions were categorized as a progressing lesion (PL: > 20% increase in the longest diameter (LD)), responding lesion (RL: > 30% decrease in LD), or stable lesion (SL: neither PL nor RL) based on the 12-week scan. Lesion-based response criteria were defined for each patient as follows: PL only, SL only, RL only, and varied responses (mixture of RL, SL, and PL). Lesion-based response criteria and OS were correlated using stratified multivariable Cox models. The concordance between OS and classifications was measured using the C statistic. Results: Among 10,551 patients with mCRC from 17 first-line studies, varied responses were noted in 51.6% of patients, among whom, 3.3% had RL/PL at 12 weeks. Among patients with RL/SL, 52% had stable disease (SD) by RECIST 1.1, and they had a longer OS (median OS (mOS) = 19.9 months) than those with SL only (mOS = 16.8 months, HR (95% CI) = 0.81 (0.76, 0.85), p < 0.001), although a shorter OS than those with RL only (mOS = 25.8 months, HR (95% CI) = 1.42 (1.32, 1.53), p < 0.001). Among patients with SL/PL, 74% had SD by RECIST 1.1, and they had a longer OS (mOS = 9.0 months) than those with PL only (mOS = 8.0 months, HR (95% CI) = 0.75 (0.57, 0.98), p = 0.040), yet a shorter OS than those with SL only (mOS = 16.8 months, HR (95% CI) = 1.98 (1.80, 2.18), p < 0.001). These associations were consistent across treatment regimen subgroups. The lesion-based response criteria showed slightly higher concordance than RECIST 1.1, although it was not statistically significant. Conclusion: Varied responses at first restaging are common among patients receiving first-line therapy for mCRC. Our lesion-based measurement criteria allowed for better mortality discrimination, which could potentially be informative for treatment decision-making and influence patient outcomes. Full article
(This article belongs to the Special Issue Colorectal Cancer: Epidemiology and Prevention)
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19 pages, 5174 KB  
Article
Necroptosis-Related Prognostic Model for Pancreatic Carcinoma Reveals Its Invasion and Metastasis Potential through Hybrid EMT and Immune Escape
by Haichuan Liu, Zhenghang Li, La Zhang, Mi Zhang, Shanshan Liu, Jianwei Wang, Changhong Yang, Qiling Peng, Chengyou Du and Ning Jiang
Biomedicines 2023, 11(6), 1738; https://doi.org/10.3390/biomedicines11061738 - 16 Jun 2023
Cited by 8 | Viewed by 3317
Abstract
Necroptosis, pro-inflammatory programmed necrosis, has been reported to exert momentous roles in pancreatic cancer (PC). Herein, the objective of this study is to construct a necroptosis-related prognostic model for detecting pancreatic cancer. In this study, the intersection between necroptosis-related genes and differentially expressed [...] Read more.
Necroptosis, pro-inflammatory programmed necrosis, has been reported to exert momentous roles in pancreatic cancer (PC). Herein, the objective of this study is to construct a necroptosis-related prognostic model for detecting pancreatic cancer. In this study, the intersection between necroptosis-related genes and differentially expressed genes (DEGs) of pancreatic ductal adenocarcinoma (PDAC) was obtained based on GeneCards database, GEO database (GSE28735 and GSE15471), and verified using The Cancer Genome Atlas (TCGA). Next, a prognostic model with Cox and LASSO regression analysis, and divided the patients into high-risk and low-risk groups. Subsequently, the Kaplan–Meier (KM) survival curve and the receiver operating characteristic (ROC) curves were generated to assess the predictive ability of overall survival (OS) of PC patients. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to predict the potential biofunction and possible mechanical pathways. The EMTome database and an immune analysis were applied to further explore underlying mechanism. Finally, clinical samples of PDAC patients were utilized to verify the expression of model genes via immunohistochemistry (IHC), and the normal human pancreatic ductal cell line, hTERT-HPNE as well as human pancreatic ductal carcinoma cell lines, PANC-1 and PL45, were used to identify the levels of model genes by Western blot (WB) and immunofluorescence (IF) in vitro. The results showed that 13 necroptosis-related DEGs (NRDEGs) were screened based on GEO database, and finally four of five prognostic genes, including KRT7, KRT19, IGF2BP3, CXCL5, were further identified by TCGA to successfully construct a prognostic model. Univariate and multivariate Cox analysis ultimately confirmed that this prognostic model has independent prognostic significance, KM curve suggested that the OS of low-risk group was longer than high-risk group, and the area under receiver (AUC) of ROC for 1, 3, 5 years was 0.733, 0.749 and 0.667, respectively. A GO analysis illustrated that model genes may participate in cell–cell junction, cadherin binding, cell adhesion molecule binding, and neutrophil migration and chemotaxis, while KEGG showed involvement in PI3K-Akt signaling pathway, ECMreceptor interaction, IL-17 signaling pathway, TNF signaling pathway, etc. Moreover, our results showed KRT7 and KRT19 were closely related to EMT markers, and EMTome database manifested that KRT7 and KRT19 are highly expressed in both primary and metastatic pancreatic cancer, declaring that model genes promoted invasion and metastasis potential through EMT. In addition, four model genes were positively correlated with Th2, which has been reported to take part in promoting immune escape, while model genes except CXCL5 were negatively correlated with TFH cells, indicating that model genes may participate in immunity. Additionally, IHC results showed that model genes were higher expressed in PC tissues than that in adjacent tumor tissues, and WB and IF also suggested that model genes were more highly expressed in PANC-1 and PL45 than in hTERT-HPNE. Tracing of a necroptosis-related prognostic model for pancreatic carcinoma reveals its invasion and metastasis potential through EMT and immunity. The construction of this model and the possible mechanism of necroptosis in PDAC was preliminarily explored to provide reliable new biomarkers for the early diagnosis, treatment, and prognosis for pancreatic cancer patients. Full article
(This article belongs to the Section Biomedical Engineering and Materials)
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18 pages, 3532 KB  
Article
Genome-Wide Association Mapping for Yield and Yield-Related Traits in Rice (Oryza Sativa L.) Using SNPs Markers
by Muhammad Ashfaq, Abdul Rasheed, Renshan Zhu, Muhammad Ali, Muhammad Arshad Javed, Alia Anwar, Javaria Tabassum, Shabnum Shaheen and Xianting Wu
Genes 2023, 14(5), 1089; https://doi.org/10.3390/genes14051089 - 15 May 2023
Cited by 10 | Viewed by 3941
Abstract
Rice (Oryza sativa L.) is a staple food for more than 50% of the world’s population. Rice cultivar improvement is critical in order to feed the world’s growing population. Improving yield is one of the main aims of rice breeders. However, yield [...] Read more.
Rice (Oryza sativa L.) is a staple food for more than 50% of the world’s population. Rice cultivar improvement is critical in order to feed the world’s growing population. Improving yield is one of the main aims of rice breeders. However, yield is a complex quantitative trait controlled by many genes. The presence of genetic diversity is the key factor to improve the yield hence, the presence of diversity in any germplasm is important for yield improvement. In the current study, the rice germplasm was collected from Pakistan and the United States of America and a panel of 100 diverse genotypes was utilized to identify important yield and yield-related traits. For this, a genome-wide association study (GWAS) was performed to identify the genetic loci related to yield. The GWAS on the diverse germplasm will lead to the identification of new genes which can be utilized in the breeding program for improvement of yield. For this reason, firstly, the germplasm was phenotypically evaluated in two growing seasons for yield and yield-related traits. The analysis of variance results showed significant differences among traits which showed the presence of diversity in the current germplasm. Secondly, the germplasm was also genotypically evaluated using 10K SNP. Genetic structure analysis showed the presence of four groups which showed that enough genetic diversity was present in the rice germplasm to be used for association mapping analysis. The results of GWAS identified 201 significant marker trait associations (MTAs. 16 MTAs were identified for plant height, 49 for days to flowering, three for days to maturity, four for tillers per plant, four for panicle length, eight for grains per panicle, 20 unfilled grains per panicle, 81 for seed setting %, four for thousand-grain weight, five for yield per plot and seven for yield per hectare. Apart from this, some pleiotropic loci were also identified. The results showed that panicle length (PL) and thousand-grain weight (TGW) were controlled by a pleiotropic locus OsGRb23906 on chromosome 1 at 10,116,371 cM. The loci OsGRb25803 and OsGRb15974 on chromosomes 4 and 8 at the position of 14,321,111 cM and 6,205,816 cM respectively, showed pleiotropic effects for seed setting % (SS) and unfilled grain per panicle (UG/P). A locus OsGRb09180 on chromosome 4 at 19,850,601 cM was significantly linked with SS and yield/ha. Furthermore, gene annotation was performed, and results indicated that the 190 candidate genes or QTLs that closely linked with studied traits. These candidate genes and novel significant markers could be useful in marker-assisted gene selection and QTL pyramiding to improve rice yield and the selection of potential parents, recombinants and MTAs which could be used in rice breeding programs to develop high-yielding rice varieties for sustainable food security. Full article
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