Life

16 pages, 1373 KiB

Open AccessArticle

Potential Effect of Root Exudates from Ten Crops on Promoting Stress Tolerance in Alfalfa (Medicago sativa) Seedlings

by Xiaoyan Zhang, Shangli Shi, Xiaolong Li, Changning Li and Qian Li

Life 2025, 15(4), 600; https://doi.org/10.3390/life15040600 (registering DOI) - 4 Apr 2025

Allelopathy plays a major role in agricultural production, influencing plant protection, crop yield, and crop rotation systems. This study investigated the effects of root exudates on 3105c alfalfa (Medicago sativa) seeds and seedlings to identify crops with strong and weak allelopathic [...] Read more.

Allelopathy plays a major role in agricultural production, influencing plant protection, crop yield, and crop rotation systems. This study investigated the effects of root exudates on 3105c alfalfa (Medicago sativa) seeds and seedlings to identify crops with strong and weak allelopathic potential. The results revealed that corn (Zea mays L.) (T1) exhibited the strongest allelopathic effects, whereas soybean (Glycine max (Linn.) Merr.) (T10) exhibited the weakest effects. T1 promoted seed germination by increasing radicle length and the simple vitality index. Both T1 and T10 promoted 3105c seedling growth and enhanced antioxidant capacity, albeit through different mechanisms. T1 primarily increased antioxidant capacity by elevating ascorbate and dehydroascorbate levels while reducing malondialdehyde content. In contrast, T10 enhanced antioxidant capacity by increasing soluble sugar and protein levels via hydroxyl free radical inhibition. These findings demonstrate that the allelopathic properties of corn effectively promote alfalfa growth by enhancing seed germination and improving physiological stress resistance. Full article

(This article belongs to the Special Issue Plant Biotic and Abiotic Stresses 2024)

18 pages, 2490 KiB

Open AccessArticle

Comparison of Three DNA Isolation Methods and Two Sequencing Techniques for the Study of the Human Microbiota

by Julio Plaza-Díaz, Mariana F. Fernández, Federico García, Natalia Chueca, Luis Fontana and Ana I. Álvarez-Mercado

Life 2025, 15(4), 599; https://doi.org/10.3390/life15040599 (registering DOI) - 4 Apr 2025

Abstract

Breast cancer is the most commonly diagnosed cancer in women and the second leading cause of female death. Altered interactions between the host and the gut microbiota appear to play an influential role in carcinogenesis. Several studies have shown different signatures of the [...] Read more.

Breast cancer is the most commonly diagnosed cancer in women and the second leading cause of female death. Altered interactions between the host and the gut microbiota appear to play an influential role in carcinogenesis. Several studies have shown different signatures of the gut microbiota in patients with breast cancer compared to healthy women. Currently, there is disagreement regarding the different DNA isolation and sequencing methodologies for studies on the human microbiota, given that they can influence the interpretation of the results obtained. The goal of this work was to compare (1) three different DNA extraction strategies to minimize the impact of human DNA, and (2) two sequencing strategies (16S rRNA and shotgun) to identify discrepancies in microbiome results. We made use of breast tissue and fecal samples from both healthy women and breast cancer patients who participated in the MICROMA study (reference NCT03885648). DNA was isolated by means of mechanical lysis, trypsin, or saponin. The amount of eukaryotic DNA isolated using the trypsin and saponin methods was lower compared to the mechanical lysis method (mechanical lysis, 89.11 ± 2.32%; trypsin method, 82.63 ± 1.23%; saponin method, 80.53 ± 4.09%). In samples with a predominance of prokaryotic cells, such as feces, 16S rRNA sequencing was the most advantageous approach. For other tissues, which are expected to have a more complex microbial composition, the need for an in-depth evaluation of the multifactorial interaction between the various components of the microbiota makes shotgun sequencing the most appropriate method. As for the three extraction methods evaluated, when sequencing samples other than stool, the trypsin method is the most convenient. For fecal samples, where contamination by host DNA is low, no prior treatment is necessary. Full article

(This article belongs to the Special Issue Microbiota in Health and Disease)

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15 pages, 649 KiB

Open AccessArticle

A Prospective Clinical Study of Ferric Citrate Hydrate for Chronic Heart Failure with Iron Deficiency Anemia

by Akira Sezai, Hisakuni Sekino, Makoto Taoka, Kazuaki Obata, Sakie Kanno and Masashi Tanaka

Life 2025, 15(4), 598; https://doi.org/10.3390/life15040598 (registering DOI) - 3 Apr 2025

Abstract

Background: The efficacy of intravenous iron preparations for chronic heart failure with iron deficiency has been reported, but the efficacy of oral iron preparations has not been demonstrated. In this study, we conducted a prospective clinical study using ferric citrate hydrate tablets in [...] Read more.

Background: The efficacy of intravenous iron preparations for chronic heart failure with iron deficiency has been reported, but the efficacy of oral iron preparations has not been demonstrated. In this study, we conducted a prospective clinical study using ferric citrate hydrate tablets in patients with chronic heart failure complicated by iron deficiency anemia. Methods and Results: A prospective study was conducted using ferric citrate hydrate in patients with chronic heart failure complicated by iron deficiency anemia. The registered patients were divided into two groups: those administered ferric citrate hydrate and those switched from iron sulfate sustained-release to ferric citrate hydrate. The primary endpoint was hemoglobin level. The secondary endpoints included hematocrit, serum iron, saturation, ferritin, and cardiac-, renal-, and hepatic-related biomarkers. A total of 141 patients were enrolled in this study, including 95 patients who were newly administered ferric citrate hydrate and 46 patients who were switched from iron sulfate sustained-release to ferric citrate hydrate. Conclusions: Ferric citrate hydrate significantly increased hemoglobin, serum iron, transferrin saturation (TSAT), and ferritin levels, and decreased atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels. Ferric citrate hydrate could be continued without side effects such as gastrointestinal symptoms. Improvement in iron metabolism and anemia due to iron supplementation with ferric citrate hydrate led to improvement in heart failure biomarkers. Full article

(This article belongs to the Special Issue Advancements in Heart Failure Research)

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35 pages, 2271 KiB

Open AccessReview

Coronary Artery Spasm: From Physiopathology to Diagnosis

by Ilinca Savulescu-Fiedler, Radu Octavian Baz, Radu Andrei Baz, Cristian Scheau and Andrei Gegiu

Life 2025, 15(4), 597; https://doi.org/10.3390/life15040597 (registering DOI) - 3 Apr 2025

Abstract

Coronary artery spasm (CAS) is a reversible vasoconstriction of normal or atherosclerotic epicardial coronary arteries with a subsequent reduction in myocardial blood flow, leading to myocardial ischemia, myocardial infarction, severe arrhythmias, or even sudden death. It is an entity that should be recognized [...] Read more.

Coronary artery spasm (CAS) is a reversible vasoconstriction of normal or atherosclerotic epicardial coronary arteries with a subsequent reduction in myocardial blood flow, leading to myocardial ischemia, myocardial infarction, severe arrhythmias, or even sudden death. It is an entity that should be recognized based on a particular clinical presentation. Numerous differences exist between CAS and obstructive coronary disease in terms of mechanisms, risk factors, and therapeutic solutions. The gold standard for CAS diagnosis is represented by transitory and reversible occlusion of the coronary arteries at spasm provocation test, which consists of an intracoronary administration of Ach, ergonovine, or methylergonovine during angiography. The pathophysiology of CAS is not fully understood. However, the core of CAS is represented by vascular smooth muscle cell contraction, with a circadian pattern. The initiating event of this contraction may be represented by endothelial dysfunction, inflammation, or autonomic nervous system unbalance. Our study explores the intricate balance of these factors and their clinical relevance in the management of CAS. Full article

(This article belongs to the Special Issue Coronary Artery Disease: Pathophysiological Mechanisms, Imaging Modalities and Therapeutic Implications)

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12 pages, 1425 KiB

Open AccessArticle

Comparative Analysis of the ELISIO-HX and Xevonta-Hi Dialyzers in Standard Hemodialysis

by Blanca Villacorta Linaza, Mario Román Cabezas, María Cristina Sánchez-Pozo, María Paz Alcaide Lara, Rocío Cabra-Rodríguez and Francisco Javier Toro Prieto

Life 2025, 15(4), 596; https://doi.org/10.3390/life15040596 (registering DOI) - 3 Apr 2025

Abstract

As chronic kidney disease (CKD) prevalence rises, optimizing hemodialysis remains essential. While online hemodiafiltration (OL-HDF) is the gold standard, expanded hemodialysis (HDx), i.e., using high-performance dialyzers in standard hemodialysis, remains the most common clinical practice. Medium cutoff (MCO) membranes aim to enhance middle-molecule [...] Read more.

As chronic kidney disease (CKD) prevalence rises, optimizing hemodialysis remains essential. While online hemodiafiltration (OL-HDF) is the gold standard, expanded hemodialysis (HDx), i.e., using high-performance dialyzers in standard hemodialysis, remains the most common clinical practice. Medium cutoff (MCO) membranes aim to enhance middle-molecule removal while preserving protein selectivity, although most studies evaluate them in OL-HDF. To this end, this study aims to compare the Xevonta-Hi (B. Braun), a high-flux (HF) polysulfone dialyzer, and the ELISIO-HX (Nipro), an MCO polyethersulfone dialyzer, in standard hemodialysis. In a prospective, observational study, seven stable patients sequentially received treatment with each dialyzer over four weeks. Pre- and post-dialysis levels of small and middle uremic molecules and inflammatory markers—including procalcitonin, prolactin, serum amyloid A, placental growth factor, interleukin-6, haptoglobin, ceruloplasmin, transferrin, prealbumin, and C-reactive protein—were measured. Both dialyzers demonstrated excellent clearance of small and middle molecules, with no significant differences in efficacy. Albumin and total protein losses remained minimal. Moderate reductions in serum amyloid A, placental growth factor, and interleukin-6 were observed, while no significant reductions occurred in the remaining inflammatory markers. These findings support the safety and effectiveness of both MCO and HF dialyzers in standard hemodialysis. Full article

(This article belongs to the Special Issue Dialysis)

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23 pages, 1916 KiB

Open AccessSystematic Review

Air Pollution and Endurance Exercise: A Systematic Review of the Potential Effects on Cardiopulmonary Health

by Sofía González-Rojas, Rodrigo Yáñez-Sepúlveda, Marcelo Tuesta, Braulio Sánchez-Ureña, José Trejos-Montoya, Jorge Olivares-Arancibia, José Francisco López-Gil and Daniel Rojas-Valverde

Life 2025, 15(4), 595; https://doi.org/10.3390/life15040595 (registering DOI) - 3 Apr 2025

Abstract

This systematic review aimed to analyze the implications of endurance exercise in environments with certain levels of air pollution. This study was developed on the basis of the consensus of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The present review [...] Read more.

This systematic review aimed to analyze the implications of endurance exercise in environments with certain levels of air pollution. This study was developed on the basis of the consensus of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The present review is supported by articles containing the main databases PubMed, Elsevier, and Web of Science (WoS), including scientific articles published in the last 20 years. This study highlights that exposure to air pollution during endurance activities, such as cycling and outdoor running, significantly affects cardiopulmonary health. In conclusion, while physical exercise in environments with high air pollution presents significant risks to cardiopulmonary health, implementing preventive measures and adopting public policies are crucial to minimizing these impacts and promoting safe exercise practices. Likewise, on the basis of these results, it is possible to motivate the creation of safe and natural spaces for sports practice. Full article

(This article belongs to the Special Issue Effects of Exercise on Susceptibility to Environmental and Disease Stressors)

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15 pages, 1859 KiB

Open AccessArticle

Prediction of Early Diagnosis in Ovarian Cancer Patients Using Machine Learning Approaches with Boruta and Advanced Feature Selection

by Tuğçe Öznacar and Tunç Güler

Life 2025, 15(4), 594; https://doi.org/10.3390/life15040594 (registering DOI) - 3 Apr 2025

Abstract

Objectives: Ovarian cancer continues to be one of the most prevalent gynecological cancers diagnosed. Early detection is highly critical for increasing survival chances. This research aims to assess the feature extraction process from various machine learning techniques for better modelling of ovarian cancer [...] Read more.

Objectives: Ovarian cancer continues to be one of the most prevalent gynecological cancers diagnosed. Early detection is highly critical for increasing survival chances. This research aims to assess the feature extraction process from various machine learning techniques for better modelling of ovarian cancer and the selection process in ovarian cancer analysis. By eliminating irrelevant features, this approach could guide clinicians towards more accurate results and optimize diagnostic precision. Methods: This study included both patients with and without ovarian cancer, creating a dataset containing 50 independent variables/features. Eight machine learning algorithms: Random Forest, XGBoost, CatBoost, Decision Tree, K-Nearest Neighbors, Naive Bayes, Gradient Boosting, and Support Vector Machine, were evaluated alongside four feature selection techniques: Boruta, PCA, RFE, and MI. Metrics performance has been evaluated to obtain the best possible combination for diagnosis. Results: These results were obtained using these methods with a significantly reduced number of features. Random Forest and CatBoost’s performances demonstrated significant differences in contrast to other algorithms (respectively, AUC 0.94% and 0.95%). On the other hand, feature selection methods such as Boruta and RFE consistently reflected higher AUC and accuracy scores than the others. Conclusions: This study highlights the importance of choosing appropriate machine learning algorithms and feature selection techniques for ovarian cancer diagnosis. Boruta and RFE showed high accuracy. By reducing the number of features from 50 to the most relevant ones, clinicians can make more precise diagnoses, enhance patient outcomes, and reduce unnecessary tests. Full article

(This article belongs to the Section Medical Research)

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30 pages, 1880 KiB

Open AccessReview

Gut Microbiota: A New Challenge in Mood Disorder Research

by Giuseppe Marano, Sara Rossi, Greta Sfratta, Gianandrea Traversi, Francesco Maria Lisci, Maria Benedetta Anesini, Roberto Pola, Antonio Gasbarrini, Eleonora Gaetani and Marianna Mazza

Life 2025, 15(4), 593; https://doi.org/10.3390/life15040593 (registering DOI) - 3 Apr 2025

Abstract

The gut microbiome has emerged as a novel and intriguing focus in mood disorder research. Emerging evidence demonstrates the significant role of the gut microbiome in influencing mental health, suggesting a bidirectional communication between the gut and the brain. This review examines the [...] Read more.

The gut microbiome has emerged as a novel and intriguing focus in mood disorder research. Emerging evidence demonstrates the significant role of the gut microbiome in influencing mental health, suggesting a bidirectional communication between the gut and the brain. This review examines the latest findings on the gut–microbiota–brain axis and elucidates how alterations in gut microbiota composition can influence this axis, leading to changes in brain function and behavior. Although dietary interventions, prebiotics, probiotics, and fecal microbiota transplantation have yielded encouraging results, significant advances are needed to establish next-generation approaches that precisely target the neurobiological mechanisms of mood disorders. Future research must focus on developing personalized treatments, facilitated by innovative therapies and technological progress, which account for individual variables such as age, sex, drug history, and lifestyle. Highlighting the potential therapeutic implications of targeting the gut microbiota, this review emphasizes the importance of integrating microbiota research into psychiatric studies to develop more effective and personalized treatment strategies for mood disorders. Full article

(This article belongs to the Special Issue Microbiota in Health and Disease)

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13 pages, 3572 KiB

Open AccessArticle

Metabolic and Microcirculatory Changes in Severe Renal Ischemia–Reperfusion and Ischemic Preconditioning in the Rat: Are They Detectable in the First Hour of Reperfusion?

by David Martin Adorjan, Laszlo Adam Fazekas, Adam Varga, Adam Attila Matrai, Laszlo Bidiga, Tamas Lesznyak, Adam Deak, Katalin Peto and Norbert Nemeth

Life 2025, 15(4), 592; https://doi.org/10.3390/life15040592 (registering DOI) - 3 Apr 2025

Abstract

Ischemia–reperfusion (I/R) strongly affects a graft’s function and survival and modulates microcirculatory and hemorheological parameters. However, the boundary between the reversibility and irreversibility of damage is unclear. This study compared the effects of renal I/R and ischemic preconditioning (IPC) to determine whether metabolic, [...] Read more.

Ischemia–reperfusion (I/R) strongly affects a graft’s function and survival and modulates microcirculatory and hemorheological parameters. However, the boundary between the reversibility and irreversibility of damage is unclear. This study compared the effects of renal I/R and ischemic preconditioning (IPC) to determine whether metabolic, microcirculatory, and micro-rheological changes are already detectable in the first hour of reperfusion. Wistar rats were divided into control (n = 6), I/R (n = 7) and IPC (n = 7) groups. In the ischemic groups the left kidney was subjected to 120 min of ischemia followed by 60 min of reperfusion. In the IPC group, a 3 × 5 min protocol was used prior to the manifest ischemia. Parenchymal microcirculation and renal artery blood flow were measured before ischemia (base) and during reperfusion (R-30, R-60). Hematological, micro-rheological parameters, electrolytes, and metabolites were tested at base and at R-60. Both ischemic groups showed micro-rheological impairment. An increase in potassium, lactate, and creatinine concentrations and a decrease in pH were observed. The blood flow of the IPC group deteriorated less, and microcirculation recordings indicated better values. The 120 min ischemia and the 60 min reperfusion resulted in micro-rheological and metabolic alterations, together with decreased renal blood flow and parenchymal microcirculation. Although the applied IPC protocol showed minor protective effects, its impact was limited in the first hour of reperfusion. Full article

(This article belongs to the Special Issue Microvascular Dynamics: Insights and Applications)

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20 pages, 3088 KiB

Open AccessArticle

Comparative Analysis of Physiological Parameters, Antioxidant Defense, Ion Regulation, and Gene Expression in Two Distinct Maize Hybrids Under Salt Stress at Seedling Stage

by Medhat Rehan, Mohamed M. Kamara and Hassan Barakat

Life 2025, 15(4), 591; https://doi.org/10.3390/life15040591 (registering DOI) - 3 Apr 2025

Abstract

Salinity significantly impacts maize production globally, requiring a deeper understanding of maize response mechanisms to salt stress. This study assessed the response of two Egyptian maize hybrids, SC-10 and TWC-321, under salt stress (200 mM NaCl) and non-stressed conditions to identify traits and [...] Read more.

Salinity significantly impacts maize production globally, requiring a deeper understanding of maize response mechanisms to salt stress. This study assessed the response of two Egyptian maize hybrids, SC-10 and TWC-321, under salt stress (200 mM NaCl) and non-stressed conditions to identify traits and mechanisms linked to enhanced salinity tolerance. Both hybrids accumulated similar Na⁺ levels in leaves, but TWC-321 exhibited better ion regulation, with lower Na⁺ concentrations and Na⁺ to K⁺ ratio in roots. While SC-10 showed a reduction in leaf K⁺ levels, TWC-321 maintained stable K⁺ levels, highlighting its superior salinity tolerance. TWC-321 also demonstrated better oxidative stress management, as evidenced by lower malondialdehyde levels and significantly higher total chlorophyll content, relative water content, and stomatal conductance. Proline accumulation was more pronounced in TWC-321, and it showed higher antioxidant enzyme activities (SOD, CAT, and POD) compared to SC-10, which exhibited lower SOD and POD activities. Gene expression analysis demonstrated distinct responses to salt stress between the hybrids. Although zmHKT1;5 was similarly induced in both hybrids, TWC-321 exhibited higher expression levels of zmHKT2 (1.96-fold compared to 1.42-fold in SC-10) and upregulated zmNHX1 (1.92-fold), whereas zmNHX1 expression was slightly reduced in SC-10 (0.8-fold). Additionally, TWC-321 achieved a greater total dry weight than SC-10 under salinity stress, highlighting its superior performance and resilience. These findings indicate that enhanced Na⁺ exclusion and sequestration mechanisms mediate the salinity tolerance of TWC-321. Correlation analysis under salinity stress identified key indicators of salinity tolerance, including increased activity of CAT and SOD, elevated proline accumulation, and higher K⁺ content. Consequently, the salinity tolerance of TWC-321 can be attributed to its effective ion regulation, stable photosynthetic pigment levels, improved osmotic adjustment, enhanced water retention, and potent antioxidant defense system. These insights are highly valuable for breeding programs focused on developing salt-tolerant maize hybrids. Full article

(This article belongs to the Special Issue Unravelling the Molecular Mechanisms of Different Stress Responses in Plants)

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14 pages, 1180 KiB

Open AccessArticle

Effect of Intraoperative Nefopam on Postoperative Analgesia in Living Liver Donors Undergoing Laparoscopic Hepatectomy with Transversus Abdominis Plane Block: A Propensity Score-Matched Study

by Min Suk Chae, Jin-Oh Jeong, Kyung Kwan Lee, Wonwoo Jeong, Young Wook Moon and Ji Young Min

Life 2025, 15(4), 590; https://doi.org/10.3390/life15040590 - 3 Apr 2025

Abstract

Laparoscopic surgery reduces tissue trauma and accelerates recovery, but postoperative pain remains a concern. Opioids are effective but have adverse effects, highlighting the need for multimodal analgesia. Nefopam, a non-opioid analgesic, provides pain relief without respiratory depression or dependence. This study aims to [...] Read more.

Laparoscopic surgery reduces tissue trauma and accelerates recovery, but postoperative pain remains a concern. Opioids are effective but have adverse effects, highlighting the need for multimodal analgesia. Nefopam, a non-opioid analgesic, provides pain relief without respiratory depression or dependence. This study aims to investigate the efficacy of intravenous nefopam combined with a transversus abdominis plane (TAP) block in living liver donors undergoing laparoscopic hepatectomy. This retrospective cohort analysis was conducted on 452 adult living donors who underwent laparoscopic hepatectomy with a TAP block between August 2013 and August 2018 at a single tertiary medical center. After propensity score matching, 296 patients were included, with 148 in the nefopam group and 148 in the non-nefopam group. The primary outcomes assessed were pain scores using the Numeric Rating Scale (NRS) at 1, 4, 8, 12, and 24 h postoperatively, opioid consumption, postoperative nausea and vomiting, and nefopam-related adverse effects. Nefopam significantly reduced NRS at 1, 4, and 8 h postoperatively (p < 0.001) and decreased fentanyl use in the post-anesthesia care unit (26.0 ± 32.2 μg vs. 60.5 ± 37.9 μg, p < 0.001) and total intravenous patient-controlled analgesia volume (p < 0.001). The incidence of postoperative nausea and vomiting and severe opioid-related complications did not differ between groups. Nefopam-related side effects were mild and self-limiting. Nefopam combined with a TAP block effectively reduces postoperative pain and opioid consumption in living liver donors, supporting its role in multimodal analgesia. Further research is needed to explore its broader applications. Full article

(This article belongs to the Special Issue Trends in Clinical Research 2025)

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21 pages, 4173 KiB

Open AccessArticle

Eco-Spatial Modeling of Two Giant Flying Squirrels (Sciuridae: Petaurista): Navigating Climate Resilience and Conservation Roadmap in the Eastern Himalaya and Indo-Burma Biodiversity Hotspots

by Imon Abedin, Manokaran Kamalakannan, Tanoy Mukherjee, Hilloljyoti Singha, Dhriti Banerjee, Hyun-Woo Kim and Shantanu Kundu

Life 2025, 15(4), 589; https://doi.org/10.3390/life15040589 - 3 Apr 2025

Abstract

Global warming and anthropogenic threats are significant drivers of biodiversity loss, particularly impacting smaller mammalian species. Hence, this study assessed two overlooked giant flying squirrel species, Petaurista magnificus and Petaurista nobilis, distributed across the transboundary regions of the Eastern Himalayas and Indo-Burma [...] Read more.

Global warming and anthropogenic threats are significant drivers of biodiversity loss, particularly impacting smaller mammalian species. Hence, this study assessed two overlooked giant flying squirrel species, Petaurista magnificus and Petaurista nobilis, distributed across the transboundary regions of the Eastern Himalayas and Indo-Burma biodiversity hotspots. Utilizing a maximum entropy (MaxEnt) species distribution model, this study delineated suitable habitats within the IUCN-defined extent of both Petaurista species based on two modeling approaches: the habitat–climate model (HCM) and the climate-only model (COM). The models identified suitable habitat coverage of only 3.92% (HCM) and 3.75% (COM) for P. magnificus and 14.17% (HCM) and 10.04% (COM) for P. nobilis. However, as the HCM integrates both environmental and habitat variables, providing a more holistic assessment, it revealed limited biological corridor connectivity within the IUCN-defined extent for both species. Furthermore, the future projections based on the HCM indicate habitat loss of up to 81.90% for P. magnificus and 89.88% for P. nobilis due to climate change, alongside severe fragmentation, leading to the disappearance of viable habitat patches. These remaining suitable patches are expected to shrink and become increasingly isolated in the future due to climate change. Furthermore, centroid shift analyses based on the HCM predict a northwestward shift for P. magnificus and a westward shift for P. nobilis under different climate scenarios. Hence, to address these conservation challenges, the study underscores the necessity for extensive field surveys, genetic assessments, habitat corridor evaluations, and the establishment of transboundary conservation frameworks to formulate an evidence-based species management strategy for both Petaurista species. Full article

(This article belongs to the Special Issue Ecology and Conservation of Small Mammals: Exploring Biodiversity, Climate Resilience, and Ecosystem Dynamics Through Small Mammal Monitoring and Research: 2nd Edition)

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21 pages, 3292 KiB

Open AccessArticle

Frequency-Regulated Repeated Micro-Vibration Promotes Osteoblast Differentiation Through BMP Signaling in MC3T3-E1 Cells

by Ayumu Matsushita, Tada-aki Kudo, Kanako Tominami, Yohei Hayashi, Takuya Noguchi, Takakuni Tanaka, Satoshi Izumi, Keiko Gengyo-Ando, Atsushi Matsuzawa, Guang Hong and Junichi Nakai

Life 2025, 15(4), 588; https://doi.org/10.3390/life15040588 - 3 Apr 2025

Abstract

Physical stimulation, which is a key factor affecting the metabolism of osteoblasts and their precursor cells, plays an important role in bone remodeling; however, the role of micro-vibrations in osteoblast differentiation is unclear. In the present study, we determined the effects of frequency-regulated [...] Read more.

Physical stimulation, which is a key factor affecting the metabolism of osteoblasts and their precursor cells, plays an important role in bone remodeling; however, the role of micro-vibrations in osteoblast differentiation is unclear. In the present study, we determined the effects of frequency-regulated repeated micro-vibration (FRMV) on cell proliferation and established a method to induce osteoblast differentiation through FRMV using the mouse pre-osteoblast-like cell line MC3T3-E1, which is widely used in bone metabolism research. The results indicated that FRMV significantly influenced the proliferation of MC3T3-E1 cells in a normal growth medium. FRMV at 42.2 Hz significantly promoted proliferation, whereas FRMV at 92.1 Hz showed no effect on the proliferation rate. Moreover, FRMV at 42.2 Hz significantly increased alkaline phosphatase (ALP) enzyme activity and ALP gene expression in MC3T3-E1 cells. Treatment with LDN193189, a bone morphogenetic protein (BMP) signaling inhibitor, revealed that the FRMV-induced upregulation in ALP enzyme activity and ALP gene expression were significantly suppressed in MC3T3-E1 cells. The results suggest that the FRMV protocol developed in the present study induces osteoblast differentiation through the BMP signaling pathway. Thus, FRMV may contribute to the development of effective bone regeneration technologies. Full article

(This article belongs to the Special Issue Bone Remodeling)

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24 pages, 4652 KiB

Open AccessArticle

Anti-Inflammatory Effects of Hyeonggaeyeongyo-tang: Evidence from In Vitro and In Vivo Studies

by Keun Hee Lee, Min Hee Kim and Hae Jeong Nam

Life 2025, 15(4), 587; https://doi.org/10.3390/life15040587 - 2 Apr 2025

Abstract

Hyeonggaeyeongyo-tang (HGYGT), a traditional herbal formula, is used to treat inflammatory otorhinolaryngological diseases such as otitis media and sinusitis. In this study, we investigated the anti-inflammatory effects of HGYGT in LPS-stimulated RAW 264.7 cells (in vitro) and a carrageenan (CA)-induced rat paw edema [...] Read more.

Hyeonggaeyeongyo-tang (HGYGT), a traditional herbal formula, is used to treat inflammatory otorhinolaryngological diseases such as otitis media and sinusitis. In this study, we investigated the anti-inflammatory effects of HGYGT in LPS-stimulated RAW 264.7 cells (in vitro) and a carrageenan (CA)-induced rat paw edema model (in vivo). In LPS-stimulated RAW 264.7 cells, treatment with HGYGT (100 and 300 μg/mL) significantly reduced nitric oxide (NO) production by 24.5% and 51.3%, respectively (p < 0.05, p < 0.01). It also significantly suppressed the production of PGE2 (49.8%), IL-1β (42.7%), IL-6 (45.6%), and TNF-α (47.2%) at 300 μg/mL (p < 0.01). A Western blot analysis confirmed that HGYGT (300 μg/mL) significantly downregulated iNOS and COX-2 expression by 58.4% and 53.1%, respectively, while COX-1 remained unaffected. And HGYGT treatment at 300 μg/mL markedly inhibited NF-κB activation by 44.9% (p < 0.01). Furthermore, HGYGT selectively inhibited JNK phosphorylation by 46.7% (p < 0.01), without significantly affecting ERK1/2 or p38 MAPKs. In the CA-induced rat paw edema model, oral administration of HGYGT (1.0 g/kg) reduced paw swelling by 31.5% at 4 h post-injection (p < 0.01) and significantly decreased iNOS expression in inflamed paw tissues by 43.2% (p < 0.01). A histological analysis revealed that HGYGT (1.0 g/kg) reduced inflammatory cell infiltration by 39.6% in the affected tissue (p < 0.05), demonstrating its anti-inflammatory potential. Our findings demonstrate that HGYGT exerts anti-inflammatory effects by suppressing the JNK and NF-κB signaling pathways in LPS-stimulated RAW 264.7 cells, reducing the production of inflammatory mediators. Notably, HGYGT selectively inhibits COX-2 without affecting COX-1 and preferentially suppresses the JNK pathway. Moreover, its in vivo anti-inflammatory effects were confirmed through iNOS inhibition and histopathological analysis. These findings provide robust scientific evidence supporting the traditional use of HGYGT and its anti-inflammatory properties. Full article

(This article belongs to the Special Issue Therapeutic Effects of Natural Products on Human Diseases: 2nd Edition)

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18 pages, 800 KiB

Open AccessReview

Fluoroquinolones for the Prophylaxis of Spontaneous Bacterial Peritonitis in Patients with Liver Cirrhosis: Are They Losing Ground?

by Simona Juncu, Horia Minea, Andreea Lungu, Alina Jucan, Raluca Avram, Ana-Maria Buzuleac, Camelia Cojocariu, Laura Sorina Diaconu, Carol Stanciu, Anca Trifan and Ana-Maria Sîngeap

Life 2025, 15(4), 586; https://doi.org/10.3390/life15040586 - 2 Apr 2025

Abstract

Spontaneous bacterial peritonitis (SBP) is the most common bacterial infection in cirrhotic patients. Historically, the bacterial spectrum was dominated by Gram-negative bacteria. However, recent studies showed that fluoroquinolone (FQ)-based prophylaxis promotes the intestinal overgrowth of Gram-positive bacteria and contributes to the selection of [...] Read more.

Spontaneous bacterial peritonitis (SBP) is the most common bacterial infection in cirrhotic patients. Historically, the bacterial spectrum was dominated by Gram-negative bacteria. However, recent studies showed that fluoroquinolone (FQ)-based prophylaxis promotes the intestinal overgrowth of Gram-positive bacteria and contributes to the selection of quinolone-resistant Gram-negative bacteria, increasing multidrug-resistant (MDR) organism infections. FQ resistance rates reach up to nearly one-third in community-acquired cases and 50% in hospital-acquired cases, raising concerns about FQ efficacy. Moreover, rare but serious side effects further limit FQ use. Predictive factors of FQ treatment failure have been identified, guiding management strategies. Rifaximin has emerged as a promising alternative for SBP prophylaxis, with encouraging results. This review aims to explore the shifting role of FQ-based SBP prophylaxis, focusing on the emerging concerns, side effects, and alternative strategies. While norfloxacin remains a first-line prophylactic in cirrhotic patients with low ascitic protein levels, its efficacy appears to be reduced in those with advanced liver failure or additional risk factors for MDR organisms. In these subgroups, alternative prophylactics, such as trimethoprim–sulfamethoxazole or rifaximin, may be preferable. We propose a risk-stratification approach to guide treatment selection, with further studies needed to refine these criteria. Full article

(This article belongs to the Special Issue Diagnosis and Management of Microbial Infections)

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16 pages, 238 KiB

Open AccessReview

The Role of Resistin in Macrovascular and Microvascular Complications of Type 2 Diabetes

by Africa Samantha Reynoso-Roa, Susan Andrea Gutiérrez-Rubio, Ezequiel Magallón-Gastélum, Trinidad García-Iglesias, Daniel Osmar Suárez-Rico and Teresa Arcelia García-Cobián

Life 2025, 15(4), 585; https://doi.org/10.3390/life15040585 - 2 Apr 2025

Abstract

Resistin is an adipokine produced in adipose tissue with pro-inflammatory properties, whose elevation has been associated with insulin resistance and diabetes. Over the past years, significant research has explored the pathophysiological mechanisms involving resistin, utilizing various in vitro and in vivo models. Additionally, [...] Read more.

Resistin is an adipokine produced in adipose tissue with pro-inflammatory properties, whose elevation has been associated with insulin resistance and diabetes. Over the past years, significant research has explored the pathophysiological mechanisms involving resistin, utilizing various in vitro and in vivo models. Additionally, numerous clinical studies have aimed to establish a correlation between resistin and the development and progression of macrovascular and microvascular complications in type 2 diabetes. This narrative review summarizes in vitro, in vivo, and human studies published in English since the discovery of resistin in 2001 to the present, examining the role of this adipokine in the pathophysiology of macrovascular and microvascular complications in in vivo and in vitro T2D models, as well as the clinical evidence supporting its use as a biochemical marker in patients with these conditions. The results exhibit considerable heterogeneity and appear to be dependent on the experimental model or population studied. While experimental evidence supports resistin’s involvement at the cellular and molecular levels in the pathogenesis of these complications, current clinical evidence remains insufficient to justify its use as a biochemical marker for either diagnosis or prognosis. Therefore, further well-designed studies are required to elucidate resistin’s potential role in the clinical setting. Full article

(This article belongs to the Special Issue Advances in Vascular Health and Metabolism)

44 pages, 549 KiB

Open AccessOpinion

The PACE Trial’s GET Manual for Therapists Exposes the Fixed Incremental Nature of Graded Exercise Therapy for ME/CFS

by Mark Vink and Katarzyna Partyka-Vink

Life 2025, 15(4), 584; https://doi.org/10.3390/life15040584 - 2 Apr 2025

Abstract

The British National Institute for Health and Care Excellence (NICE) published its updated guidelines for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) in October 2021. NICE concluded, after an extensive review of the literature, that graded exercise therapy (GET) is harmful and should not be [...] Read more.

The British National Institute for Health and Care Excellence (NICE) published its updated guidelines for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) in October 2021. NICE concluded, after an extensive review of the literature, that graded exercise therapy (GET) is harmful and should not be used, and that cognitive behavioural therapy (CBT) is only an adjunctive and not a curative treatment. An article by White et al., which is written by 51 researchers, claims that there are eight anomalies in the review process and the interpretation of the evidence by NICE. In this article, we reviewed the evidence they used to support their claims. Their three most important claims are that NICE redefined the disease, that CBT and GET are effective, and that fixed incremental increases are not part of GET. However, our analysis shows that the disease was not redefined by NICE. Instead, it was redefined in the 1990s by a group of doctors, including a number of authors of White et al., when they erased the main characteristic of the disease (an abnormally delayed muscle recovery after trivial exertion, which, over the years, has evolved into post-exertional malaise) and replaced it with chronic disabling severe fatigue. Their own studies show that CBT and GET do not lead to a substantial improvement of the quality-of-life scores or a reduction in CFS symptom count, nor do they lead to objective improvement. Also, both treatments have a negative instead of a positive effect on work and disability status. Moreover, a recent systematic review, which included one of the authors of White et al., showed that ME/CFS patients remain severely disabled after treatment with CBT. Our analysis of, for example, the PACE trial’s GET manual for therapists exposes the fixed incremental nature of GET. Why the authors are not aware of that is unclear because eight of them were involved in the PACE trial. Three of them were centre leaders and its principal investigators, four others were also centre leaders, and another one was one of the three independent safety assessors of the trial. Moreover, many of these eight authors wrote, or were involved in writing, this manual. In conclusion, our analysis shows that the arguments that are used to claim that there are eight anomalies in the review process and the interpretation of the evidence by NICE are anomalous and highlight the absence of evidence for the claims that are made. Furthermore, our analysis not only exposes the fixed incremental nature of GET, but also of CBT for ME/CFS. Full article

(This article belongs to the Section Medical Research)

18 pages, 1596 KiB

Open AccessArticle

Metabolic Profile, Antioxidant, Antimicrobial, Contractile, and Anti-Inflammatory Potential of Moringa oleifera Leaves (India)

by Natalina Panova, Anelia Gerasimova, Yulian Tumbarski, Ivan Ivanov, Mina Todorova, Ivayla Dincheva, Galia Gentscheva, Vera Gledacheva, Valeri Slavchev, Iliyana Stefanova, Nadezhda Petkova, Stoyanka Nikolova and Krastena Nikolova

Life 2025, 15(4), 583; https://doi.org/10.3390/life15040583 - 1 Apr 2025

Abstract

Background: Moringa oleifera is one of the most famous plants used for medicinal purposes. Its leaf extracts have antimicrobial activity and antioxidant activities, and reduce swelling in ulcers. Objectives: The present article aimed to determine the metabolic profile of Moringa oleifera leaf extracts [...] Read more.

Background: Moringa oleifera is one of the most famous plants used for medicinal purposes. Its leaf extracts have antimicrobial activity and antioxidant activities, and reduce swelling in ulcers. Objectives: The present article aimed to determine the metabolic profile of Moringa oleifera leaf extracts from two samples originating from India and to evaluate in vitro and ex vivo their biological activities. Methods: The antioxidant properties of Moringa oleifera leaf extracts (methanol, 50% ethanol, and 70% ethanol) were studied in vitro for antimicrobial, anti-inflammatory, and antioxidant activities. The ex vivo contractile effects of the extracts were determined by assaying circularly isolated smooth muscle (SM) strips from a rat’s stomach. Results: The obtained results indicated that one of the samples had amino acid and organic acid content approximately twice that of the second sample. In all the tests, the 50% ethanol extract of both samples showed better antioxidant activity (209 mM TE 100 g⁻¹ for the DPPH method). The 70% ethanolic extract of Sample 1 exhibited the strongest antimicrobial activity, inhibiting Gram-positive Bacillus cereus, Bacillus subtilis, and Staphylococcus aureus. The 50% ethanolic extract of both samples exhibited the highest anti-inflammatory activity, demonstrating a twice better effect than the reference drug diclofenac. Finally, the pre-incubation of SM preparations with both samples significantly enhanced the ACh-induced contractile response, increasing it by 134% and 111%, respectively. Conclusions: The findings suggested potential applications of Moringa oleifera as a suitable candidate for antimicrobial, antioxidant, anti-inflammatory, and antispasmodic supplementation for alternative pharmaceutical and nutraceutical products. Full article

(This article belongs to the Special Issue Green Medicine: Unraveling the Medicinal Effects of Plant Extracts and Functional Foods)

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15 pages, 526 KiB

Open AccessReview

Advancements in Clinical Utilization of Recombinant Human Collagen: An Extensive Review

by Isaac Wong Kai Jie, Kar Wai Alvin Lee, Song Eun Yoon, Jong Keun Song, Lisa Kwin Wah Chan, Cheuk Hung Lee, Eunji Jeong, Jin-Hyun Kim and Kyu-Ho Yi

Life 2025, 15(4), 582; https://doi.org/10.3390/life15040582 - 1 Apr 2025

Abstract

Introduction: Recombinant human collagen, developed through advanced recombinant DNA technology, has emerged as a cutting-edge biomaterial with diverse applications in medicine. It addresses significant limitations of animal-derived collagens, such as immunogenicity and the risk of zoonotic diseases. Objective: This review evaluates the clinical [...] Read more.

Introduction: Recombinant human collagen, developed through advanced recombinant DNA technology, has emerged as a cutting-edge biomaterial with diverse applications in medicine. It addresses significant limitations of animal-derived collagens, such as immunogenicity and the risk of zoonotic diseases. Objective: This review evaluates the clinical applications, benefits, and challenges associated with recombinant human collagen, focusing on its potential to transform medical and surgical practices. Methods: A comprehensive search was conducted in MEDLINE, PubMed, and Ovid databases using keywords such as “Recombinant Human Collagen”, “Collagen-Based Biomaterials”, “Clinical Applications”, “Tissue Repair”, and “Wound Healing”. Relevant studies, including clinical trials and diagnostic applications, were analyzed and classified according to the Oxford Centre for Evidence-Based Medicine evidence hierarchy. Findings: Recombinant human collagen demonstrates superior mechanical properties and controlled degradation rates compared to traditional collagen sources. Clinical studies highlight its effectiveness in accelerating wound closure, promoting dermal regeneration, and minimizing scarring, making it particularly valuable in chronic wound management and surgical interventions. In tissue engineering, recombinant human collagen scaffolds have shown potential for regenerating cartilage, bone, and cardiovascular tissues by supporting cell proliferation, differentiation, and matrix deposition. Additionally, its adaptability for forming hydrogels and matrices enhances its suitability for drug delivery systems, enabling controlled and sustained release of therapeutic agents. Conclusion: Recombinant human collagen represents a transformative advancement in clinical practice, providing a safer and more effective alternative to traditional collagen sources. Its demonstrated success in wound healing, tissue engineering, and drug delivery highlights its potential to significantly improve patient outcomes. However, challenges such as high production costs, regulatory complexities, and long-term biocompatibility remain barriers to widespread clinical adoption. Further research and collaboration between biotechnology developers and regulatory authorities are essential to fully realize its clinical potential. Full article

(This article belongs to the Special Issue Advances in Bioprinting, Tissue Engineering, and Regenerative Medicine)

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