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19 pages, 2981 KiB  
Article
Evaluating the Effect of Fresh and Aged Antioxidant Formulations in Skin Protection Against UV Damage
by John Ivarsson, Patricia Brieva, Hina Choudhary and Giuseppe Valacchi
Cosmetics 2025, 12(4), 166; https://doi.org/10.3390/cosmetics12040166 (registering DOI) - 7 Aug 2025
Abstract
Introduction: Extrinsic skin damage is often a result of oxidative stress caused by exposure to environmental factors such as ultraviolet (UV) radiation, ozone (O3), and various pollutants. As a result, topical antioxidants have been evaluated for their effectiveness in mitigating [...] Read more.
Introduction: Extrinsic skin damage is often a result of oxidative stress caused by exposure to environmental factors such as ultraviolet (UV) radiation, ozone (O3), and various pollutants. As a result, topical antioxidants have been evaluated for their effectiveness in mitigating or reversing skin damage caused by environmental factors. Topical antioxidants containing a combination of l-ascorbic acid, tocopherol, and ferulic acid have significantly improved markers of skin health after exposure to environment-induced skin damage. However, research suggests that l-ascorbic acid and tocopherol tend to be relatively unstable, possibly affecting their efficacy against outdoor stressor damage. It has been shown that ferulic acid significantly improves the stability of both l-ascorbic acid and tocopherol, but its long-term stabilization effects on these antioxidants are relatively unknown. Material and Methods: This study evaluated the time-dependent effectiveness of a topical antioxidant mix containing 15% l-ascorbic acid, 1% tocopherol, and 0.5% ferulic acid (AOX) on UV-induced skin damage. Skin biopsies (12 mm, n = 60) were placed in a 6-well plate with medium and incubated at 37 °C and 5% CO2 overnight. The day after, skin samples were pretreated with 10 µL of differently aged AOX (0-, 6-, 12-, and 36-month-old) and then exposed to different doses of UV light (100, 200, 400 mJ/cm2) daily over four days. AOX formulations were stored in a cool, dry, and dark place at approximately 20–22 °C during the whole study. This study evaluated 4-hydroxynonenal (4-HNE) and 8-hydroxy-2′-deoxyguanosine (8-OHdG) as oxidative damage and skin DNA damage markers, Collagen1 and Filaggrin as skin structure, and IL-8 and Nrf2 as inflammatory and defensive response. Results: UV exposure significantly increased oxidative and inflammatory markers in human skin explants affecting also filaggrin and collagen levels. However, pre-treatment with the antioxidant formulation, particularly in its younger formulations (0-, 6-, and 12-month-old), significantly reduced the damaging effect of UV. Additionally, all antioxidant formulations effectively mitigated UV-induced damage across all doses. Conclusions: Our results indicate that pre-treatment with this formulation consistently reduces UV-induced oxidative damage and DNA damage in human skin explants, regardless of the formulation age and the discoloration state. Although effective, the protective capacity of aged formulations may be reduced only when extreme UV exposure is tested, a condition that is unlikely to occur under typical environmental conditions. These results support ferulic acid as a stabilization agent for topical antioxidant mixtures. Full article
(This article belongs to the Section Cosmetic Formulations)
16 pages, 611 KiB  
Article
Effects of Increasing Dietary Inclusion of White Lupin on Growth Performance, Meat Quality, and Fatty Acid Profile on Growing-Fattening Pigs
by Georgeta Ciurescu, Mihaela Dumitru, Nicoleta Aurelia Lefter and Dan-Traian Râmbu
Agriculture 2025, 15(15), 1709; https://doi.org/10.3390/agriculture15151709 (registering DOI) - 7 Aug 2025
Abstract
This study investigated the possibility of partial replacement of genetically modified soybean meal (SBM) with raw white lupin (WL) seeds in growing pigs’ diets and determined its impact on performance [body weight (BW), average daily gain (ADG), and average daily feed intake (ADFI)], [...] Read more.
This study investigated the possibility of partial replacement of genetically modified soybean meal (SBM) with raw white lupin (WL) seeds in growing pigs’ diets and determined its impact on performance [body weight (BW), average daily gain (ADG), and average daily feed intake (ADFI)], meat quality, and fatty acid profile (FA). A total of 54 male crossbred pigs [(Topigs Large White × Norsvin Landrace) × Duroc], aged 12 weeks, with an initial average BW of 30.30 ± 0.77 kg, were divided into three dietary groups of 18 piglets each. The control group (CON) was fed a standardized SBM-based complete feed. In the experimental groups (WL1 and WL2) the SBM was replaced with increasing levels of WL seeds [WL1-5.0% and WL2-10.0% (grower period, 30–60 kg BW), and WL1-7.0% and WL2-14.0% (finisher period, 61–110 kg BW)]. All diets were formulated to be isocaloric and isonitrogenous with similar content of total lysine and sulphur amino acids, calcium, and available phosphorus. At the end of 83 days’ fattening trial, the animals were slaughtered. Longissimus dorsi muscle (LD) was sampled for analyses of the physicochemical traits. The results show that increasing the dietary raw WL concentration decreased final BW (p = 0.039), ADG (p < 0.0001), and ADFI (p = 0.004) throughout the experimental period, especially in the second phase of feeding. Dietary treatments did not affect the pigs’ blood biochemical constituents. Concerning LD muscle characteristics, the redness color (a*) and collagen content was higher (p < 0.0001) in the WL1/WL2 vs. CON group. Beneficial decrease in the values of some textural attributes (hardness, gumminess, chewiness, and resilience) of LD in the WL1/WL2 vs. CON group was registered. The use of WL had a significant effect on the content of FAs, especially for eicosapentaenoic (p = 0.014) and n-3 PUFA (p = 0.045), which were higher than those fed the CON diet. In conclusion, WL could be used as a replacement of SBM in growing–finishing pigs’ diets, with significant improvements in the meat fatty acid profile and technological properties. Full article
24 pages, 5480 KiB  
Article
Liposomal Co-Delivery of Acteoside, CBD, and Naringenin: A Synergistic Strategy Against Gliomas
by Jagoda Szkudlarek, Ludwika Piwowarczyk, Violetta Krajka-Kuźniak, Aleksandra Majchrzak-Celińska, Szymon Tomczak, Mikołaj Baranowski, Rafał Pietrzyk, Aneta Woźniak-Braszak and Anna Jelińska
Pharmaceutics 2025, 17(8), 1026; https://doi.org/10.3390/pharmaceutics17081026 - 7 Aug 2025
Abstract
Background/Objectives: Adult-type diffuse gliomas, including astrocytoma and glioblastoma multiforme (GBM), are brain tumors with a very poor prognosis. While current treatment options for glioma patients are not providing satisfactory outcomes, research indicates that natural compounds could serve as alternative treatments. However, their [...] Read more.
Background/Objectives: Adult-type diffuse gliomas, including astrocytoma and glioblastoma multiforme (GBM), are brain tumors with a very poor prognosis. While current treatment options for glioma patients are not providing satisfactory outcomes, research indicates that natural compounds could serve as alternative treatments. However, their low bioavailability requires nanotechnology solutions, such as liposomes. Methods: In this study, we propose the co-encapsulation of acteoside (ACT) with other natural compounds, cannabidiol (CBD) or naringenin (NG), in a cationic liposomal nanoformulation consisting of DOTAP and POPC lipids, which were prepared using the dry lipid film method. The liposomes were characterized by their physicochemical properties, including particle size, zeta potential, and polydispersity index (PDI), with additional analyses performed using 1H Nuclear Magnetic Resonance (NMR). Furthermore, biological experiments were performed with U-87 MG astrocytoma and U-138 MG GBM cell lines and non-cancerous MRC-5 lung fibroblasts using the MTT assay and evaluating the expression of Bax and Bcl-xL to evaluate their potential as anticancer agents. Conclusions: The IC50 values for the nanoformulations in U-138 MG cells at 48 h were 6 µM for ACT + CBD and 5 µM for ACT + NG. ACT and CBD or NG demonstrated a potential synergistic effect against GBM in a liposomal formulation. Notably, treatment with ACT + CBD (5 µM) and ACT + NG (5 µM) liposomal formulations significantly upregulated Bax protein level in U-138 cells at both 24 and 48 h. In parallel, ACT + CBD (5 µM) also modulated Bcl-xL protein level in both U-138 MG and U-87 MG cell lines at the same time points. The obtained nanoformulations were homogeneous and stable for 21 days, evidenced by a narrow particle size distribution, a low polydispersity index (PDI) < 0.3, and a positive zeta potential. Full article
(This article belongs to the Special Issue PLGA Micro/Nanoparticles in Drug Delivery)
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24 pages, 1967 KiB  
Article
Water Stress Promotes Secondary Sexual Dimorphism in Ecophysiological Traits of Papaya Seedlings
by Ingrid Trancoso, Guilherme A. R. de Souza, João Vitor Paravidini de Souza, Rosana Maria dos Santos Nani de Miranda, Diesily de Andrade Neves, Miroslava Rakocevic and Eliemar Campostrini
Plants 2025, 14(15), 2445; https://doi.org/10.3390/plants14152445 - 7 Aug 2025
Abstract
Plant genders could express different functional strategies to compensate for different reproductive costs, as females have an additional role in fruit and seed production. Secondary sexual dimorphism (SSD) expression is frequently greater under stress than under optimal growth conditions. The early gender identification [...] Read more.
Plant genders could express different functional strategies to compensate for different reproductive costs, as females have an additional role in fruit and seed production. Secondary sexual dimorphism (SSD) expression is frequently greater under stress than under optimal growth conditions. The early gender identification in papaya may help to reduce orchard costs because the most desirable fruit shape is formed by hermaphrodite plants. We hypothesized that (a) gender ecophysiological phenotyping can be an alternative to make gender segregations in papaya seedlings, and (b) such gender segregation will be more efficient after a short drought exposure than under adequate water conditions. To test such hypotheses, seedlings of two papaya varieties (‘Candy’ and ‘THB’) were exposed to two kind of treatments: (1) water shortage (WS) for 45 h, after which they were well watered, and (2) continuously well-watered (WW). Study assessed the ecophysiological responses, such as stomatal conductance (gs), SPAD index, optical reflectance indices, morphological traits, and biomass accumulation in females (F) and hermaphrodites (H). In WS treatment, the SSD was expressed in 14 of 18 traits investigated, while in WW treatment, the SSD was expressed only in 7 of 18 traits. As tools for SSD expression, gs and simple ratio pigment index (SRPI) must be measured on the first or second day after the imposed WS was interrupted, respectively, while the other parameters must be measured after a period of four days. In some traits, the SSD was expressed in only one variety, or the response of H and F plants were of opposite values for two varieties. The choice of the clearest responses of gender segregation in WS treatment will be greenness index, combination of normalized difference vegetation index (CNDVI), photochemical reflectance index (PRI), water band index (WBI), SRPI, leaf number, leaf dry mass, and leaf mass ratio. If the WW conditions are maintained for papaya seedling production, the recommendation in gender segregation will be the analysis of CNDVI, carotenoid reflectance index 2 (CRI2), WBI, and SRPI. The non-destructive optical leaf indices segregated papaya hermaphrodites from females under both water conditions and eventually could be adjusted for wide-scale platform evaluations, with planned space arrangements of seedlings, and sensor’s set. Full article
(This article belongs to the Section Horticultural Science and Ornamental Plants)
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20 pages, 4401 KiB  
Article
Effect of Slightly Acidic Electrolyzed Water Combined with Nano-Bubble Sterilization on Quality of Larimichthys crocea During Refrigerated Storage
by Jiehui Zhong, Hongjin Deng, Na Lin, Mengyao Zheng, Junjie Wu, Quanyou Guo and Saikun Pan
Foods 2025, 14(15), 2754; https://doi.org/10.3390/foods14152754 - 7 Aug 2025
Abstract
The large yellow croaker (Larimichthys crocea) is susceptible to microbial contamination during storage due to its high protein and moisture contents. This study was designed to find a new way to reduce bacteria in large yellow croakers by combining slightly acidic [...] Read more.
The large yellow croaker (Larimichthys crocea) is susceptible to microbial contamination during storage due to its high protein and moisture contents. This study was designed to find a new way to reduce bacteria in large yellow croakers by combining slightly acidic electrolyzed water (SAEW) with nano-bubble (NB) technology. Exploring the effects of available chlorine concentration (ACC), processing time, and water temperature on the bacteria reduction effect of the SAEW-NB treatment for large yellow croakers. Also, the effects of the SAEW-NB combined treatment on sensory evaluation, total viable counts (TVCs), total volatile basic nitrogen (TVB-N), texture, taste profile, and volatile flavor compounds of large yellow croakers were analyzed during the storage period at 4 °C. The results show that the SAEW-NB treatment achieved significantly enhanced microbial reduction compared to individual treatments. Under the conditions of a 4 °C water temperature, 40 mg/L ACC, and 15 min treatment, the SAEW-NB treatment inhibited the increases in physical and chemical indexes such as TVC and TVB-N, maintained the fish texture, and delayed the production of off-flavor volatiles such as aldehydes, alcohols, esters, and ketones, compared with the control group (CG) during storage at 4 °C. In conclusion, the SAEW-NB treatment could better retard fish spoilage, extending the shelf life by approximately 2 days. It might be a promising new industrial approach for large yellow croakers’ storage. Full article
(This article belongs to the Special Issue Innovative Muscle Foods Preservation and Packaging Technologies)
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20 pages, 3448 KiB  
Article
Fatty Acid-Rich Fraction of Hibiscus syriacus L. Alleviates Atopic Dermatitis-like Skin Lesions Mouse Model via Inflammatory Pathway Modulation: Integrative Docking and Experimental Validation
by Trang Thi Minh Nguyen, Bom Park, Xiangji Jin, Qiwen Zheng, Gyeong-Seon Yi, Su-Jin Yang and Tae-Hoo Yi
Plants 2025, 14(15), 2447; https://doi.org/10.3390/plants14152447 - 7 Aug 2025
Abstract
Atopic dermatitis (AD) remains a therapeutic challenge due to the limitations of current treatments, creating demand for safer multi-target alternatives to corticosteroids. Our integrated study establishes Hibiscus syriacus L. (H. syriacus) as a mechanistically validated solution through computational and biological validation. [...] Read more.
Atopic dermatitis (AD) remains a therapeutic challenge due to the limitations of current treatments, creating demand for safer multi-target alternatives to corticosteroids. Our integrated study establishes Hibiscus syriacus L. (H. syriacus) as a mechanistically validated solution through computational and biological validation. The fraction’s two main compounds, linoleic acid and palmitic acid, exhibit favorable drug-like properties including high lipophilicity (LogP 5.2) and 87% oral absorption. Molecular docking collectively predicts comprehensive NF-κB pathway blockade. Experimental validation showed that the fraction (100 μg/mL) inhibited LPS-induced nitric oxide (NO) by 78% and TNF-α/IFN-γ-induced reactive oxygen species (ROS) by 40%, while significantly downregulating the chemokines TARC (73%) and MDC (71%). In DNCB-induced AD mice, the treatment (200 mg/kg/day) produced a 62% improvement in clinical severity scores, reduced serum IgE by 27%, decreased transepidermal water loss by 36%, and doubled skin hydration while normalizing pH levels from the alkaline to physiological range. While both treatments reduced DNCB-induced epidermal hyperplasia, H. syriacus (62.9% reduction) restored the normal thickness without pathological thinning, a critical advantage over corticosteroids that cause atrophy. This dual-action therapeutic achieves corticosteroid-level anti-inflammatory effects while restoring skin barrier integrity to normal levels and avoiding corticosteroid-associated atrophy, positioning it as a next-generation AD treatment. Full article
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11 pages, 1581 KiB  
Article
Combining Topical Oxygen and Negative-Pressure Wound Therapy: New Insights from a Pilot Study on Chronic Wound Treatment
by Bartosz Molasy, Mateusz Frydrych, Rafał Kuchciński and Stanisław Głuszek
J. Clin. Med. 2025, 14(15), 5564; https://doi.org/10.3390/jcm14155564 - 7 Aug 2025
Abstract
Background: Chronic wounds are a growing clinical challenge due to their prolonged healing time and associated healthcare burden. Combined therapeutic approaches, including topical oxygen therapy (TOT) and negative-pressure wound therapy (NPWT), have shown promise in enhancing wound healing. This pilot exploratory study aimed [...] Read more.
Background: Chronic wounds are a growing clinical challenge due to their prolonged healing time and associated healthcare burden. Combined therapeutic approaches, including topical oxygen therapy (TOT) and negative-pressure wound therapy (NPWT), have shown promise in enhancing wound healing. This pilot exploratory study aimed to assess the clinical effectiveness of combined TOT and NPWT in chronic wound treatment and to explore the prognostic value of selected laboratory and thermographic markers. Methods: Eighteen patients with chronic wounds due to type 2 diabetes mellitus or chronic venous insufficiency were treated with either TOT alone (control group) or TOT combined with NPWT (intervention group). Wound characteristics, thermographic data, and laboratory parameters (NLR, MLR, PLR, CRP, and total protein) were collected at baseline and during therapy. The primary endpoints were the total treatment duration and complete wound closure. Statistical analyses were exploratory and used non-parametric tests, correlation analyses, and simple linear regression. Results: Ulcer duration was significantly associated with the wound surface area. Lower serum total protein levels correlated negatively with ulcer duration, wound size, and granulation tissue area. A significant reduction in treatment duration was observed in the intervention group compared to the controls. One strong correlation was found between MLR and peripheral wound temperature on day 7 in the control group. No significant group differences were observed in wound size or thermographic measures after one week of treatment. Conclusions: Combining TOT and NPWT may reduce treatment duration in chronic wound management. Selected laboratory and thermographic markers show promise as prognostic tools. These exploratory findings require confirmation in larger, randomized trials. Full article
(This article belongs to the Special Issue New Advances in Wound Healing and Skin Wound Treatment)
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19 pages, 1684 KiB  
Article
Effectiveness of Implementing Hospital Wastewater Treatment Systems as a Measure to Mitigate the Microbial and Antimicrobial Burden on the Environment
by Takashi Azuma, Miwa Katagiri, Takatoshi Yamamoto, Makoto Kuroda and Manabu Watanabe
Antibiotics 2025, 14(8), 807; https://doi.org/10.3390/antibiotics14080807 - 7 Aug 2025
Abstract
Background: The emergence and spread of antimicrobial-resistant bacteria (ARB) has become an urgent global concern as a silent pandemic. When taking measures to reduce the impact of antimicrobial resistance (AMR) on the environment, it is important to consider appropriate treatment of wastewater from [...] Read more.
Background: The emergence and spread of antimicrobial-resistant bacteria (ARB) has become an urgent global concern as a silent pandemic. When taking measures to reduce the impact of antimicrobial resistance (AMR) on the environment, it is important to consider appropriate treatment of wastewater from medical facilities. Methods: In this study, a continuous-flow wastewater treatment system using ozone and ultraviolet light, which has excellent inactivation effects, was implemented in a hospital in an urban area of Japan. Results: The results showed that 99% (2 log10) of Gram-negative rods and more than 99.99% (>99.99%) of ARB comprising ESBL-producing Enterobacterales were reduced by ozone treatment from the first day after treatment, and ultraviolet light-emitting diode (UV-LED) irradiation after ozone treatment; UV-LED irradiation after ozonation further inactivated the bacteria to below the detection limit. Inactivation effects were maintained throughout the treatment period in this study. Metagenomic analysis showed that the removal of these microorganisms at the DNA level tended to be gradual in ozone treatment; however, the treated water after ozone/UV-LED treatment showed a 2 log10 (>99%) removal rate at the end of the treatment. The residual antimicrobials in the effluent were benzylpenicillin, cefpodoxime, ciprofloxacin, levofloxacin, azithromycin, clarithromycin, doxycycline, minocycline, and vancomycin, which were removed by ozone treatment on day 1. In contrast, the removal of ampicillin and cefdinir ranged from 19% to 64% even when combined with UV-LED treatment. Conclusions: Our findings will help to reduce the discharge of ARB and antimicrobials into rivers and maintain the safety of aquatic environments. Full article
(This article belongs to the Special Issue Antibiotic Resistance in Wastewater Treatment Plants)
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17 pages, 1005 KiB  
Case Report
Management of Acute Kidney Injury Using Peritoneal Dialysis in a Bottlenose Dolphin (Tursiops truncatus) with Bilateral Ureteral Obstruction
by Todd L. Schmitt, Thomas H. Reidarson, James F. McBain, Hendrik H. Nollens, Amber P. Sanchez and David M. Ward
J. Zool. Bot. Gard. 2025, 6(3), 40; https://doi.org/10.3390/jzbg6030040 - 7 Aug 2025
Abstract
An adult female bottlenose dolphin (Tursiops truncatus) housed at a public oceanarium presented with acute anorexia and lethargy. A blood analysis demonstrated mild leukocytosis, marked azotemia, hyperkalemia, and hyperphosphatemia suggestive of acute kidney injury or renal insufficiency. Ultrasound examination of the [...] Read more.
An adult female bottlenose dolphin (Tursiops truncatus) housed at a public oceanarium presented with acute anorexia and lethargy. A blood analysis demonstrated mild leukocytosis, marked azotemia, hyperkalemia, and hyperphosphatemia suggestive of acute kidney injury or renal insufficiency. Ultrasound examination of the dolphin revealed ascites, pleural effusion, bilateral nephrolithiasis, mild hydronephrosis, and bilateral hydroureter consistent with bilateral post-renal obstruction. Initial treatment consisted of antibiotics, oral fluids, and anti-inflammatory treatment. Further imaging diagnosed bilateral obstructing ureteroliths at both ureteral orifice junctions of the urinary bladder. The dolphin’s azotemia and hyperkalemia were nonresponsive to traditional medical management; therefore, peritoneal dialysis was performed for emergent clinical stabilization. Peritoneal dialysis was conducted over 3 days and facilitated the patient to undergo laser lithotripsy of the offending ureteral obstruction. The dolphin made a full recovery following months of intensive medical treatment for complications from peritoneal dialysis and secondary peritonitis. This is the first documented case of successful, though complicated, peritoneal dialysis in a cetacean. Full article
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18 pages, 3212 KiB  
Article
Supplementation with Live and Heat-Treated Lacticaseibacillus paracasei NB23 Enhances Endurance and Attenuates Exercise-Induced Fatigue in Mice
by Mon-Chien Lee, Ting-Yin Cheng, Ping-Jui Lin, Ting-Chun Lin, Chia-Hsuan Chou, Chao-Yuan Chen and Chi-Chang Huang
Nutrients 2025, 17(15), 2568; https://doi.org/10.3390/nu17152568 - 7 Aug 2025
Abstract
Background: Exercise-induced fatigue arises primarily from energy substrate depletion and the accumulation of metabolites such as lactate and ammonia, which impair performance and delay recovery. Emerging evidence implicates gut microbiota modulation—particularly via probiotics—as a means to optimize host energy metabolism and accelerate [...] Read more.
Background: Exercise-induced fatigue arises primarily from energy substrate depletion and the accumulation of metabolites such as lactate and ammonia, which impair performance and delay recovery. Emerging evidence implicates gut microbiota modulation—particularly via probiotics—as a means to optimize host energy metabolism and accelerate clearance of fatigue-associated by-products. Objective: This study aimed to determine whether live or heat-inactivated Lacticaseibacillus paracasei NB23 can enhance exercise endurance and attenuate fatigue biomarkers in a murine model. Methods: Forty male Institute of Cancer Research (ICR) mice were randomized into four groups (n = 10 each) receiving daily gavage for six weeks with vehicle, heat-killed NB23 (3 × 1010 cells/mouse/day), low-dose live NB23 (1 × 1010 CFU/mouse/day), or high-dose live NB23 (3 × 1010 CFU/mouse/day). Forelimb grip strength and weight-loaded swim-to-exhaustion tests assessed performance. Blood was collected post-exercise to measure serum lactate, ammonia, blood urea nitrogen (BUN), and creatine kinase (CK). Liver and muscle glycogen content was also quantified, and safety was confirmed by clinical-chemistry panels and histological examination. Results: NB23 treatment produced dose-dependent improvements in grip strength (p < 0.01) and swim endurance (p < 0.001). All NB23 groups exhibited significant reductions in post-exercise lactate (p < 0.0001), ammonia (p < 0.001), BUN (p < 0.001), and CK (p < 0.0001). Hepatic and muscle glycogen stores rose by 41–59% and 65–142%, respectively (p < 0.001). No changes in food or water intake, serum clinical-chemistry parameters, or tissue histology were observed. Conclusions: Our findings suggest that both live and heat-treated L. paracasei NB23 may contribute to improved endurance performance, increased energy reserves, and faster clearance of fatigue-related metabolites in our experimental model. However, these results should be interpreted cautiously given the exploratory nature and limitations of our study. Full article
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9 pages, 235 KiB  
Article
Ceftazidime-Avibactam Plus Aztreonam for the Treatment of Blood Stream Infection Caused by Klebsiella pneumoniae Resistant to All Beta-Lactame/Beta-Lactamase Inhibitor Combinations
by Konstantinos Mantzarlis, Efstratios Manoulakas, Dimitrios Papadopoulos, Konstantina Katseli, Athanasia Makrygianni, Vassiliki Leontopoulou, Periklis Katsiafylloudis, Stelios Xitsas, Panagiotis Papamichalis, Achilleas Chovas, Demosthenes Makris and George Dimopoulos
Antibiotics 2025, 14(8), 806; https://doi.org/10.3390/antibiotics14080806 - 7 Aug 2025
Abstract
Introduction: The combination of ceftazidime−avibactam (CAZ-AVI) with aztreonam (ATM) may be an option for the treatment of infections due to metallo-β-lactamases (MBLs) producing bacteria, as recommended by current guidelines. MBLs protect the pathogen from any available β-lactam/β-lactamase inhibitor (BL/BLI). Moreover, in vitro and [...] Read more.
Introduction: The combination of ceftazidime−avibactam (CAZ-AVI) with aztreonam (ATM) may be an option for the treatment of infections due to metallo-β-lactamases (MBLs) producing bacteria, as recommended by current guidelines. MBLs protect the pathogen from any available β-lactam/β-lactamase inhibitor (BL/BLI). Moreover, in vitro and clinical data suggest that double carbapenem therapy (DCT) may be an option for such infections. Materials and Methods: This retrospective study was conducted in two mixed intensive care units (ICUs) at the University Hospital of Larissa, Thessaly, Greece, and the General Hospital of Larissa, Thessaly, Greece, during a three-year period (2022−2024). Mechanically ventilated patients with bloodstream infection (BSI) caused by K. pneumoniae resistant to all BL/BLI combinations were studied. Patients were divided into three groups: in the first, patients were treated with CAZ-AVI + ATM; in the second, with DCT; and in the third, with antibiotics other than BL/BLIs that presented in vitro susceptibility. The primary outcome of the study was the change in Sequential Organ Failure Assessment (SOFA) score between the onset of infection and the fourth day of antibiotic treatment. Secondary outcomes were SOFA score evolution during the treatment period, total duration of mechanical ventilation (MV), ICU length of stay (LOS), and ICU mortality. Results: A total of 95 patients were recruited. Among them, 23 patients received CAZ-AVI + AZT, 22 received DCT, and 50 patients received another antibiotic regimen which was in vitro active against the pathogen. The baseline characteristics were similar. The mean (SE) overall age was 63.2 (1.3) years. Mean (SE) Acute Physiology and Chronic Health Evaluation II (APACHE II) and SOFA scores were 16.3 (0.6) and 7.6 (0.3), respectively. The Charlson Index was similar between groups. The control group presented a statistically lower SOFA score on day 4 compared to the other two groups [mean (SE) 8.9 (1) vs. 7.4 (0.9) vs. 6.4 (0.5) for CAZ-AVI + ATM, DCT and control group, respectively (p = 0.045)]. The duration of mechanical ventilation, ICU LOS, and mortality were similar between the groups (p > 0.05). Comparison between survivors and non-survivors revealed that survivors had a lower SOFA score on the day of BSI, higher PaO2/FiO2 ratio, higher platelet counts, and lower lactate levels (p < 0.05). Septic shock was more frequent among non-survivors (60.3%) in comparison to survivors (27%) (p = 0.0015). Independent factors for mortality were PaO2/FiO2 ratio and lactate levels (p < 0.05). None of the antibiotic regimens received by the patients was independently associated with survival. Conclusions: Treatment with CAZ-AVI + ATM or DCT may offer similar clinical outcomes for patients suffering from BSI caused by K. pneumoniae strains resistant to all available BL/BLIs. However, larger studies are required to confirm the findings. Full article
20 pages, 2823 KiB  
Article
Pro-Reparative Effects of KvLQT1 Potassium Channel Activation in a Mouse Model of Acute Lung Injury Induced by Bleomycin
by Tom Voisin, Alban Girault, Mélissa Aubin Vega, Émilie Meunier, Jasmine Chebli, Anik Privé, Damien Adam and Emmanuelle Brochiero
Int. J. Mol. Sci. 2025, 26(15), 7632; https://doi.org/10.3390/ijms26157632 - 7 Aug 2025
Abstract
Acute Respiratory Distress Syndrome (ARDS) is a complex and devastating form of respiratory failure, with high mortality rates, for which there is no pharmacological treatment. The acute exudative phase of ARDS is characterized by severe damage to the alveolar–capillary barrier, infiltration of protein-rich [...] Read more.
Acute Respiratory Distress Syndrome (ARDS) is a complex and devastating form of respiratory failure, with high mortality rates, for which there is no pharmacological treatment. The acute exudative phase of ARDS is characterized by severe damage to the alveolar–capillary barrier, infiltration of protein-rich fluid into the lungs, neutrophil recruitment, and high levels of inflammatory mediators. Rapid resolution of this reversible acute phase, with efficient restoration of alveolar functional integrity, is essential before the establishment of irreversible fibrosis and respiratory failure. Several lines of in vitro and in vivo evidence support the involvement of potassium (K+) channels—particularly KvLQT1, expressed in alveolar cells—in key cellular mechanisms for ARDS resolution, by promoting alveolar fluid clearance and epithelial repair processes. The aim of our study was to investigate whether pharmacological activation of KvLQT1 channels could elicit beneficial effects on ARDS parameters in an animal model of acute lung injury. We used the well-established bleomycin model, which mimics (at day 7) the key features of the exudative phase of ARDS. Our data demonstrate that treatments with the KvLQT1 activator R-L3, delivered to the lungs, failed to improve endothelial permeability and lung edema in bleomycin mice. However, KvLQT1 activation significantly reduced neutrophil recruitment and tended to decrease levels of pro-inflammatory cytokines/chemokines in bronchoalveolar lavages after bleomycin administration. Importantly, R-L3 treatment was associated with significantly lower injury scores, higher levels of alveolar type I (HTI-56, AQP5) and II (pro-SPC) cell markers, and improved alveolar epithelial repair capacity in the presence of bleomycin. Together, these results suggest that the KvLQT1 K+ channel may be a potential target for the resolution of the acute phase of ARDS. Full article
(This article belongs to the Special Issue Lung Diseases Molecular Pathogenesis and Therapy)
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14 pages, 759 KiB  
Article
Vitamin D Deficiency and Exocrine Pancreatic Insufficiency: An Analysis Carried Out in Orthogeriatric Patients (VIDEP.org)
by Pavol Mikula, Matthias Unseld and Hans Jürgen Heppner
J. Clin. Med. 2025, 14(15), 5558; https://doi.org/10.3390/jcm14155558 - 7 Aug 2025
Abstract
Introduction: Vitamin D deficiency, a reversible cause of osteoporosis, is increasingly prevalent, showing varying degrees of severity that are notably pronounced among the growing population of multimorbid elderly patients. Given that the aging pancreas undergoes senescent processes leading to impaired function—which negatively impacts [...] Read more.
Introduction: Vitamin D deficiency, a reversible cause of osteoporosis, is increasingly prevalent, showing varying degrees of severity that are notably pronounced among the growing population of multimorbid elderly patients. Given that the aging pancreas undergoes senescent processes leading to impaired function—which negatively impacts enteral vitamin D absorption and, consequently, elderly bone metabolism—a specific diagnostic and treatment approach is crucial. Our study aimed to determine the prevalence of vitamin D deficiency and exocrine pancreatic insufficiency (EPI) in orthogeriatric patients. We also evaluated differences in vitamin D deficiency severity between patients with normal and impaired pancreatic function. Furthermore, a short-term monitoring of vitamin D level increases after 12 days of substitution therapy in both groups aimed to inform osteoanabolic therapy for specific high-fracture-risk patients, assessing the influence of pancreatic function on substitution efficacy. Methods: We conducted a retrospective, monocentric cohort study, evaluating data from all patients hospitalized with manifest osteoporosis in an orthogeriatric department during a six-month spring/summer period. Demographic data, relevant comorbidities, the type of fracture, the amount of faecal elastase 1 (CALEX® Cap Bühlmann), and the serum levels of 25-hydroxyvitamin D (25(OH)D) were assessed. Results: We found a high prevalence (70.6%) of vitamin D deficiency (25(OH)D < 30 µg/L) among all orthogeriatric patients. Of these, 16% met the criteria for mild to severe EPI. The group with normal exocrine pancreatic function showed a higher average vitamin D value, and their increase in vitamin D levels following short-term substitution was up to 100% greater compared to the group with impaired pancreatic function. Notably, 69% of women and 20% of men met the therapeutic threshold for specific osteoanabolic osteoporosis therapy, even without a T-score. Conclusions: Our findings reveal a very high prevalence of vitamin D deficiency and a high prevalence of EPI in orthogeriatric patients. Those with impaired exocrine pancreatic function exhibit lower baseline vitamin D levels and a diminished capacity for vitamin D absorption during short-term monitoring. These results have significant clinical implications for osteoporotic therapy, given that a substantial proportion of patients, particularly women, meet the criteria for specific osteoanabolic treatment. Full article
(This article belongs to the Special Issue The “Orthogeriatric Fracture Syndrome”—Issues and Perspectives)
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10 pages, 485 KiB  
Article
Factors Associated with Functional Outcome Following Acute Ischemic Stroke Due to M1 MCA/ICA Occlusion in the Extended Time Window
by John Constantakis, Quinn Steiner, Thomas Reher, Timothy Choi, Fauzia Hollnagel, Qianqian Zhao, Nicole Bennett, Veena A. Nair, Eric E. Adelman, Vivek Prabhakaran, Beverly Aagard-Kienitz and Bolanle Famakin
J. Clin. Med. 2025, 14(15), 5556; https://doi.org/10.3390/jcm14155556 - 6 Aug 2025
Abstract
Introduction: A validated clinical decision tool predictive of favorable functional outcomes following endovascular thrombectomy (EVT) in acute ischemic stroke (AIS) remains elusive. We performed a retrospective case series of patients at our regional Comprehensive Stroke Center, over a four-year period, who have undergone [...] Read more.
Introduction: A validated clinical decision tool predictive of favorable functional outcomes following endovascular thrombectomy (EVT) in acute ischemic stroke (AIS) remains elusive. We performed a retrospective case series of patients at our regional Comprehensive Stroke Center, over a four-year period, who have undergone EVT to elucidate patient characteristics and factors associated with a favorable functional outcome after EVT. Methods: We reviewed all cases of EVT at our institution between February 2018 and February 2022 in the extended time window from 6–24 h. Demographic, clinical, imaging, and procedure co-variates were included. A favorable clinical outcome was defined as a modified Rankin scale of 0–2. We included patients with M1 or internal carotid artery occlusion treated with EVT within 6–24 h after symptom onset. We used a univariate and multivariate logistic regression analysis to identify patient factors associated with a favorable clinical outcome at 90 days. Results: Our study included evaluation of 121 patients who underwent EVT at our comprehensive stroke center. Our analysis demonstrates that a higher recanalization score based on the modified Thrombolysis In Cerebral Infarction (mTICI) scale (2B-3) was a strong indicator of a favorable outcome (OR 7.33; CI 2.06–26.07; p = 0.0021). Our data also showed that a higher baseline National Institutes of Health Stroke Scale (NIHSS) score (p = 0.0095) and the presence of pre-existing hypertension (p = 0.0035) may also be predictors of an unfavorable outcome (mRS > 2) per our multivariate analysis. Conclusion: Patients without pre-existing hypertension had more favorable outcomes following EVT in the expanded time window. This is consistent with other multicenter data in the expanded time window that demonstrates greater odds of a poor outcome with elevated pre-, peri-, and post-endovascular-treatment blood pressure. Our data also demonstrate that the mTICI score is a strong predictor of favorable outcome, even after controlling for other variables. A lower baseline NIHSS at the time of thrombectomy may also indicate a favorable outcome. Furthermore, the presence of clinical or radiographic mismatch based on the Alberta Stroke Program Early Computed Tomography Score (ASPECTS) and NIHSS per DAWN and DEFUSE-3 criteria did not emerge as a predictor of favorable outcome, which is congruent with recent randomized controlled trials and meta-analyses. Full article
(This article belongs to the Special Issue Ischemic Stroke: Diagnosis and Treatment)
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22 pages, 1215 KiB  
Article
Gas Atmosphere Innovation Applied to Prolong the Shelf Life of ‘Regina’ Sweet Cherries
by Rodrigo Neira-Ojeda, Sebastián Rodriguez, Cristian Hernández-Adasme, Violeta Muñoz, Dakary Delgadillo, Bo Sun, Xiao Yang and Victor Hugo Escalona
Plants 2025, 14(15), 2440; https://doi.org/10.3390/plants14152440 - 6 Aug 2025
Abstract
In this study, the impact of moderate and high CO2 and O2 levels was compared to low and moderate gas combinations during prolonged storage on the quality of Regina sweet cherries harvested in different maturity stages, particularly in terms of decreasing [...] Read more.
In this study, the impact of moderate and high CO2 and O2 levels was compared to low and moderate gas combinations during prolonged storage on the quality of Regina sweet cherries harvested in different maturity stages, particularly in terms of decreasing internal browning. Fruits were harvested in two different maturity stages (Light and Dark Mahogany skin color) and stored in CA of 15% CO2 + 10% O2; 10% CO2 + 10% O2; 10% CO2 + 5% O2; 5% CO2 + 5% O2 and MA of 4 to 5% CO2 + 16 to 17% O2 for 30 and 40 days at 0 °C and 90% RH, followed by a marketing period. After the storage, both maturity stages significantly reduced internal browning, decay, and visual quality losses in CA with 10–15% CO2 and 10% O2. In addition, it preserved luminosity, total soluble solids (TSSs), titratable acidity (TA), and bioactive compounds such as anthocyanins and phenols. This treatment also maintained the visual appearance of the sweet cherries, favoring their market acceptance. At the same time, the light red fruits showed a better general quality compared to darker color after the storage. In conclusion, a controlled atmosphere with optimized CO2 and O2 concentrations, together with harvesting with a Light Mahogany external color, represents an effective strategy to extend the shelf life of Regina sweet cherries up to 40 days plus the marketing period, maintaining their physical and sensory quality for export markets. Full article
(This article belongs to the Special Issue Postharvest Quality and Physiology of Vegetables and Fruits)
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