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19 pages, 949 KB  
Article
Differences in Uterine Fluid-Induced Endometrial Cell Responses and Uterine Microbiota in Repeat Breeder Cows
by Sayoko Oishi, Yui Kitagawa, Karen Koshimizu, Shiki Nakatsuji, Shigeki Morikawa, Yujiro Hagita, Hisataka Iwata, Ryotaro Miura, Seizo Hamano and Koumei Shirasuna
Dairy 2026, 7(3), 35; https://doi.org/10.3390/dairy7030035 - 1 May 2026
Abstract
Repeat breeder (RB) cows fail to conceive after three or more breeding attempts, yet the uterine factors contributing to this condition remain unclear. Here, we compared uterine fluid composition, endometrial cell responses to uterine fluid, and uterine microbiota between normal pregnant (Normal) and [...] Read more.
Repeat breeder (RB) cows fail to conceive after three or more breeding attempts, yet the uterine factors contributing to this condition remain unclear. Here, we compared uterine fluid composition, endometrial cell responses to uterine fluid, and uterine microbiota between normal pregnant (Normal) and RB cows. Uterine fluid was collected from multiparous Holstein cows classified as Normal (n = 5; conception within three breeding attempts) or RB (no conception after four attempts); RB cows were classified as RB-Rec (n = 4; conceived after uterine lavage) or RB-NoRec (n = 3; did not conceive after uterine lavage). Uterine fluids were applied to bovine endometrial cells, and microbiota composition was analyzed. Concentrations of lipopolysaccharide in the uterine fluid did not differ between the three groups, and uterine fluid from both RB groups significantly increased C-X-C motif chemokine ligand 8 secretion relative to the Normal group. RNA-seq revealed distinct endometrial cell responses to RB-NoRec uterine fluid, with enrichment of immune-related pathways including phagosome, ferroptosis, and cellular senescence. Uterine microbiota profiles differed among groups, with short-chain fatty acid-producing genera (e.g., Fusicatenibacter and Dorea) predominant in Normal cows and inflammation-associated genera (e.g., Trueperella and Helicobacter) predominant in RB-NoRec cows. These data indicate that uterine fluid properties and microbiota composition vary with reproductive status and may modulate endometrial immune activation associated with fertility outcomes. Full article
(This article belongs to the Section Reproduction)
19 pages, 2486 KB  
Article
Chemical Composition, Antioxidant Potential, and Standardized Antimicrobial Activity of Lavandula angustifolia Mill. Essential Oil: An In Vitro and In Silico Study
by Vesna Antunović, Željka Marjanović-Balaban, Žarko Gagić, Nebojša Kladar, Vesna Gojković Cvjetković, Vesna Kalaba and Dragica Đurđević-Milošević
Sci 2026, 8(5), 102; https://doi.org/10.3390/sci8050102 - 30 Apr 2026
Abstract
Lavandula angustifolia essential oil (LEO) was obtained by hydrodistillation of air-dried flowers collected in the Mostar region (Bosnia and Herzegovina). Its chemical composition was analyzed by gas chromatography-mass spectrometry, revealing a camphor content of 16.96%, substantially higher than the maximum value specified in [...] Read more.
Lavandula angustifolia essential oil (LEO) was obtained by hydrodistillation of air-dried flowers collected in the Mostar region (Bosnia and Herzegovina). Its chemical composition was analyzed by gas chromatography-mass spectrometry, revealing a camphor content of 16.96%, substantially higher than the maximum value specified in the European Pharmacopoeia. Antimicrobial activity was evaluated using quantitative suspension tests according to EN 1276 and EN 1650 under simulated “dirty” conditions with organic load (bovine albumin, 3 g/L) and a 5 min contact time. High-concentration LEO (80% w/v) exhibited strong bactericidal activity against Escherichia coli ATCC 10536 and Staphylococcus aureus ATCC 6538, and yeasticidal activity against Candida albicans ATCC 10231 (>5 log10 CFU/mL reduction for bacteria, >4 log10 CFU/mL reduction for yeast), but was ineffective against Pseudomonas aeruginosa ATCC 15442 and Enterococcus hirae ATCC 10541. Lower concentrations (1.0% and 0.1% w/v) showed no bactericidal and yeasticidal activity, highlighting LEO’s efficacy limits. Antioxidant activity, assessed by DPPH radical scavenging, was dose- and time-dependent. Molecular docking provided insight into the interaction of major constituents with selected microbial and antioxidant-related targets. These findings highlight both the potential and limitations of LEO as a renewable bio-based resource for sustainable disinfectant formulations while emphasizing the importance of chemical composition and regulatory compliance. Full article
(This article belongs to the Section Biology Research and Life Sciences)
25 pages, 2846 KB  
Article
Copper (Cu2+) Inhibits Voltage-Dependent Ionic Currents While Enhancing Neurotransmitter Release in Bovine Chromaffin Cells
by Víctor Varea-Tierno, Victoria Jiménez Carretero, Minerva Reyes Almodóvar, Javier Hernández Campano, María Arribas Tejedor, Ricardo de Pascual and Jesús M. Hernández-Guijo
Pharmaceuticals 2026, 19(5), 716; https://doi.org/10.3390/ph19050716 - 30 Apr 2026
Abstract
Background/Objectives: Copper (Cu2+) is an essential trace element that participates as a cofactor in key metabolic enzymes such as cytochrome c oxidase and superoxide dismutase. However, excessive copper exposure can be toxic and disturbances in copper homeostasis have been associated [...] Read more.
Background/Objectives: Copper (Cu2+) is an essential trace element that participates as a cofactor in key metabolic enzymes such as cytochrome c oxidase and superoxide dismutase. However, excessive copper exposure can be toxic and disturbances in copper homeostasis have been associated with neurodegenerative diseases including Alzheimer’s and Parkinson’s disease. Despite growing evidence linking copper to neuronal dysfunction, the cellular mechanisms by which Cu2+ affects neuronal excitability and neurotransmission remain poorly understood. The aim of this study was to investigate the effects of acute Cu2+ exposure on ionic currents involved in cellular excitability and neurotransmitter release in bovine chromaffin cells. Methods: Primary cultures of bovine chromaffin cells were used as a neuroendocrine model to study cellular excitability. Voltage-dependent ionic currents were recorded using the whole-cell patch-clamp technique in voltage-clamp configuration. Catecholamine secretion was monitored by amperometry, and cytosolic Ca2+ dynamics were measured in fluo-4-loaded cells during depolarization induced by high K+ stimulation. Results: Acute Cu2+ exposure produced a concentration-dependent enhancement of depolarization-evoked catecholamine release. In parallel, Cu2+ inhibited voltage-dependent calcium (ICa), sodium (INa), potassium (IKv), and calcium/voltage-dependent potassium (IKCa-v) currents in a concentration-dependent and partially reversible manner. In addition, Cu2+ increased basal cytosolic Ca2+ levels while reducing the amplitude of depolarization-evoked Ca2+ transients. Conclusions: Acute Cu2+ exposure exerts a dual effect in bovine chromaffin cells, inhibiting the ionic currents that support cellular excitability while potentiating catecholamine secretion. This apparent paradox is consistent with a disruption of intracellular Ca2+ homeostasis, in which elevated basal cytosolic Ca2+ may facilitate exocytosis despite reduced depolarization-evoked Ca2+ entry. These findings provide new insight into the mechanisms by which copper may alter neuronal signaling and contribute to neurotoxicity. Full article
(This article belongs to the Section Medicinal Chemistry)
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10 pages, 2106 KB  
Article
Identification and Characterization of a Novel Bovine Adenovirus Which Represents a Distinct Evolutionary Branch
by Jinyu Sui, Suchun Wang, Zihao Pan and Kaicheng Wang
Viruses 2026, 18(5), 522; https://doi.org/10.3390/v18050522 - 30 Apr 2026
Abstract
Bovine adenovirus (BAdV) is associated with respiratory and enteric diseases in cattle. In this study, the complete genomic sequence of a novel BAdV strain (named BAdV/LN/CHN/2023) was sequenced and annotated using the next-generation sequencing (NGS) technology. The viral genome comprises 32,391 base pairs [...] Read more.
Bovine adenovirus (BAdV) is associated with respiratory and enteric diseases in cattle. In this study, the complete genomic sequence of a novel BAdV strain (named BAdV/LN/CHN/2023) was sequenced and annotated using the next-generation sequencing (NGS) technology. The viral genome comprises 32,391 base pairs with a GC content of 44.93%, encoding 33 predicted open reading frames (ORFs), consistent with the genomic organization of mastadenoviruses. Comparative genomic analysis confirmed that BAdV/LN/CHN/2023 contains conserved structural and functional motifs characteristic of the genus Mastadenovirus. Phylogenetic analysis revealed that BAdV/LN/CHN/2023 shares low similarity with all currently recognized bovine mastadenoviruses classified by the International Committee on Taxonomy of Viruses (ICTV). In addition, an open reading frame (ORF) encoding the 146R protein was annotated in this strain; this feature has not been identified in any previously recognized bovine mastadenoviruses. This study presents the first full-length genomic sequence of a putative BAdV-11 strain, and based on ICTV criteria, we propose that this strain represents a novel mastadenovirus species, supported by phylogenetic distance and genomic divergence. Our findings expand the known genetic diversity of BAdVs and contribute to a better understanding of their evolutionary relationships. Full article
(This article belongs to the Section Animal Viruses)
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17 pages, 1280 KB  
Article
Risk Assessment of Lead and Cadmium Exposure Through Raw Milk Consumption from Small-Scale Dairy Systems in the Central Peruvian Andes
by Doris Chirinos-Peinado, Jorge Castro-Bedriñana, Elva Ríos-Ríos, Gianfranco Castro-Chirinos and Mery Baquerizo-Canchumanya
Toxics 2026, 14(5), 385; https://doi.org/10.3390/toxics14050385 - 30 Apr 2026
Abstract
Bovine milk is a primary dietary source of nutrients and bioactive compounds. However, its safety is increasingly under threat due to contamination from mining and intensive agriculture. In the Peruvian Andes, where small-scale dairy farming coexists with historical environmental liabilities, identifying the transfer [...] Read more.
Bovine milk is a primary dietary source of nutrients and bioactive compounds. However, its safety is increasingly under threat due to contamination from mining and intensive agriculture. In the Peruvian Andes, where small-scale dairy farming coexists with historical environmental liabilities, identifying the transfer of metals into the food chain is essential for public health. This study quantifies the concentrations of lead (Pb) and cadmium (Cd) in raw milk from small-scale producers in rural districts in the province of Huancayo. Non-carcinogenic risks for populations aged 2–85 years were assessed under three consumption scenarios. Forty-five samples were analyzed using microwave plasma atomic emission spectrometry (MP-AES). The mean concentrations of Pb and Cd were 11.30 ± 18.94 µg/kg and 7.85 ± 18.11 µg/kg, respectively, which are below the maximum permissible limits (MPL). However, spatial analysis identified critical hotspots near smelters, where Pb levels reached 103 µg/kg, which is a significant exceedance of the MPL of 20 µg/kg. Toxicological modelling showed that the Hazard Index (HI) remained below the unity threshold (HI < 1) for all scenarios, ruling out immediate systemic risks. Nevertheless, the highest HI (0.78) was observed in two-year-old children in the high-consumption scenario, highlighting a localized neurodevelopmental concern. These findings emphasize the importance of georeferenced environmental monitoring and differentiated public health policies to mitigate the chronic low-level exposure to metals in vulnerable, high-altitude populations. Full article
(This article belongs to the Section Exposome Analysis and Risk Assessment)
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16 pages, 293 KB  
Article
Animal Welfare, Carcass-Processing Practices and Post-Mortem Lesions in Nigerian Municipal Slaughterhouses: Implications for Meat Quality and Public Health Security
by Emmanuel O. Njoga, Jameslove I. Kperegbeyi, Onyinye S. Onwumere-Idolor, Uzezi G. Imonikebe, Chidiebere O. Anyaoha, Lynda O. Majesty-Alukagberie, Joel C. Ugwunwarua, Nnaedozie E. Onah and James W. Oguttu
Vet. Sci. 2026, 13(5), 439; https://doi.org/10.3390/vetsci13050439 - 30 Apr 2026
Abstract
This five-month epidemiological investigation evaluated pre-slaughter welfare, carcass-processing practices, and post-mortem lesion prevalence in 1012 cattle and 413 pigs slaughtered in Enugu State, Nigeria. Direct observations and post-mortem inspections were conducted following OIE standards. Animal welfare was markedly compromised. Cattle were dragged from [...] Read more.
This five-month epidemiological investigation evaluated pre-slaughter welfare, carcass-processing practices, and post-mortem lesion prevalence in 1012 cattle and 413 pigs slaughtered in Enugu State, Nigeria. Direct observations and post-mortem inspections were conducted following OIE standards. Animal welfare was markedly compromised. Cattle were dragged from the lairage to kill floor, restrained in lateral recumbency for over 30 min before bleeding, and slaughtered without stunning. Pigs were transported tied to motorcycles and processed on unsanitary floors. The lairages lacked roofing, clean water, and adequate drainage. Carcass handling was unhygienic, with meat processed near maggot-infested drains and transported in open vans or motorized tricycles used to commute passengers and cement. Of all cattle examined, 45.3% (458/1012) exhibited gross lesions attributable to contagious bovine pleuropneumonia (CBPP, 15.5%), fasciolosis (18%), liver abscessation (6.6%), ascariasis (4.6%), and bovine tuberculosis (0.5%). No lesions were detected in pigs. Lesion occurrence differed significantly (p < 0.05) by sex (males = 44.1%, females = 66.7%), age (<4 years = 54.1%, ≥4 years = 45.4%), breed (White Fulani = 45.5%, others = 36.7%), slaughterhouse location, and season (rainy = 45.2%, dry = 45.5%). Temporal analysis showed the highest lesion rate in April (68.3%), declining to 37.7% in May. Lesions of CBPP and fasciolosis were significantly more frequent in young cattle and during the rainy months (p < 0.05). These findings reveal systemic welfare violations and disease endemicity within the municipal abattoirs surveyed. The combination of poor pre-slaughter welfare, unhygienic meat handling, and high prevalence of zoonotic and economically important livestock disease lesions highlights urgent public health concerns. Strengthening abattoir infrastructure, enforcing pre-slaughter animal welfare and hygiene regulations, mechanizing slaughter processes, and instituting continuous surveillance within the One Health framework are essential for ensuring meat safety and public health security in Nigeria and beyond. Full article
15 pages, 3326 KB  
Article
Age-Related Expression and Localization of HIF-1α and HIF-2α in Different Tissues of Yak
by Qin Wu, Huan Yang, Junyu Chen, Zhixin Chai, Hongwen Zhao and Zhijuan Wu
Oxygen 2026, 6(2), 10; https://doi.org/10.3390/oxygen6020010 - 29 Apr 2026
Abstract
The yak (Bos grunniens), a unique bovine species that is endemic to the Qinghai–Tibet Plateau and adjacent mountainous regions, exhibits remarkable adaptations to chronic high-altitude hypoxia. However, the molecular mechanisms underlying yaks’ adaptation to this extreme environment remain poorly understood. This [...] Read more.
The yak (Bos grunniens), a unique bovine species that is endemic to the Qinghai–Tibet Plateau and adjacent mountainous regions, exhibits remarkable adaptations to chronic high-altitude hypoxia. However, the molecular mechanisms underlying yaks’ adaptation to this extreme environment remain poorly understood. This study aimed to elucidate the spatiotemporal expression dynamics of hypoxia-inducible factor 1α (HIF-1α) and 2α (HIF-2α) in major tissues of yaks across developmental stages (0.5, 1.5, 2.5, and 4.5 years; n = 3 per group). The tissues (heart, liver, spleen, lungs, kidneys, blood vessels and skeletal muscles) were analyzed using hematoxylin and eosin (H&E) staining and immunohistochemistry. The results revealed significant differences in the expression levels of HIF-1α and HIF-2α between tissues and at different ages. In cardiac tissue, both HIF-1α and HIF-2α are localized to the myocardial interstitium, with HIF-1α expression peaking at 1.5–2.5 years and HIF-2α expression reaching its maximum at 2.5 years. Hepatic HIF-1α showed perivenous hepatocytes enrichment and peaked at 2.5 years (p < 0.01 vs. other ages), while HIF-2α was uniformly distributed across lobules without age-related changes. Splenic HIF-1α and HIF-2α levels increased progressively with age, both peaking at 4.5 years (p < 0.01), and age was strongly correlated with expression levels (HIF-1α: r = 0.430; HIF-2α: r = 0.493). In pulmonary tissues, HIF-1α in bronchial smooth muscle peaked at 2.5 years, whereas alveolar septal HIF-2α peaked at 1.5 years (p < 0.05). In the kidney, HIF-1α was primarily localized to tubular epithelial cells and HIF-2α was diffusely distributed in the glomerular interstitium; neither factor showed significant variation across ages. In vascular tissues, HIF-1α expression remained stable across all ages and was predominantly observed in the smooth muscle layer, while HIF-2α exhibited a significant peak in endothelial cells at 2.5 years (p < 0.01). These findings suggest that HIF-1α predominates during early development stages, while HIF-2α becomes dominant as yaks approach maturity. Full article
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17 pages, 1371 KB  
Article
Growth Enhancement of Salmonella by Tungstate Treatment
by Robin C. Anderson, Delila D. Dominguez, Megan R. Shaw, Casey N. Johnson, Samat Amat, Jackie M. Kotzur, Merritt L. Drewery, Patricia J. Baynham, Ken J. Genovese, Tawni L. Crippen and Ryan J. Arsenault
Pathogens 2026, 15(5), 478; https://doi.org/10.3390/pathogens15050478 - 29 Apr 2026
Abstract
Salmonella in gut habitats have traditionally been thought to conserve energy for growth via fermentation. However, recent reports indicate that ingested Salmonella can stimulate host-derived nitrate accumulation in the mucosal microenvironment, thereby enabling growth through nitrate respiration. Sodium tungstate is an effective treatment [...] Read more.
Salmonella in gut habitats have traditionally been thought to conserve energy for growth via fermentation. However, recent reports indicate that ingested Salmonella can stimulate host-derived nitrate accumulation in the mucosal microenvironment, thereby enabling growth through nitrate respiration. Sodium tungstate is an effective treatment that inhibits the growth of certain nitrate-respiring bacteria, including Escherichia coli, Paracoccus and Proteus, when cultured under gut simulating conditions or within the gut of experimentally treated mice. This inhibitory effect is hypothesized to occur by inactivation of molybdenum-containing enzymes required for nitrate metabolism. Information is lacking on whether tungstate can inhibit the growth of Salmonella, particularly in the presence of culturable gut microbiota. Therefore, the objectives of this study were to evaluate the effects of sodium tungstate on Salmonella during pure culture or when cultured with freshly collected bovine rumen microbiota and to assess its impact on fermentation as well as nitrate and nitrite metabolism within the rumen microbial cultures. Our results indicate that 50 mM sodium tungstate treatment, whether alone or in combination with 5 mM nitrate, markedly increased the growth of Salmonella serovars Newport, Dublin and Typhimurium during pure culture. Moreover, during in vitro incubation, increased growth of experimentally inoculated S. Newport as well as wildtype E. coli and lactic acid bacteria was observed with ruminal microbiota treated with 100 mM tungstate when compared to non-tungstate-treated controls. Effects of tungstate on nitrate and nitrite metabolism were as expected during pure and mixed culture. When cultured with reduced tungsten rather than tungstate, the latter being bound to four oxygen atoms, an inhibitory effect on the growth of S. Newport was observed and effects on nitrate and nitrite metabolism were consistent with those observed with tungstate. These results suggest that, under conditions used in the present experiments, tungstate may have served as a source of oxygen for respiration above that achieved with nitrate alone. While this hypothesis has yet to be proven, it is supported by an adverse effect of tungstate, whether alone or in combination with 5 mM nitrate, on methane and volatile fatty acid production by the ruminal microbiota when compared to untreated or nitrate-only-treated microbiota. Full article
(This article belongs to the Special Issue Zoonotic Salmonella Infections: Transmission Dynamics and Control)
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14 pages, 348 KB  
Article
Effects of Sex and a Diet Containing Bovine Ruminal Content on Performance, Ruminal Fermentation, Digestibility, Carcass Traits, and Meat Quality in Lambs
by Adrián Muñoz-Cuautle, María Esther Ortega-Cerrilla, Jorge Hernández-Bautista, Javier Suárez-Espinosa, José Vian, Ricardo García-Barojas and Pedro Zetina-Córdoba
Ruminants 2026, 6(2), 30; https://doi.org/10.3390/ruminants6020030 - 29 Apr 2026
Abstract
The objective of this study was to evaluate the productive performance, ruminal fermentation, in vivo digestibility, carcass yield, and physicochemical variables of meat when bovine rumen content (BRC) was included in the diet of lambs. Thirty-six Pelibuey-Dorper crossbred lambs of both sexes, with [...] Read more.
The objective of this study was to evaluate the productive performance, ruminal fermentation, in vivo digestibility, carcass yield, and physicochemical variables of meat when bovine rumen content (BRC) was included in the diet of lambs. Thirty-six Pelibuey-Dorper crossbred lambs of both sexes, with an average weight of 19.5 ± 1.5 kg, were used in a generalized randomized block design with the sex of the lambs as a blocking factor with four treatments: BRC0, BRC15, BRC30, and BRC45, corresponding to 0%, 15%, 30%, and 45% BRC inclusion in the diet, respectively. The results indicate that the dietary effect was not significant for any of the evaluated variables, whereas sex showed significant differences in final body weight, average daily gain, dry matter intake, and hot and cold carcass yield. Although specific treatment-sex combinations significantly influenced productive performance variables such as average daily gain, dry matter intake and ruminal fermentation parameters, such as propionic acid, there is no consistent evidence that the inclusion of bovine rumen content promotes superior productive performance or carcass quality in fattening lambs. Full article
(This article belongs to the Special Issue Nutrients and Feed Additives in Sheep and Goats)
8 pages, 199 KB  
Communication
Serological Investigation of Infectious Bovine Rhinotracheitis in Dromedary Camels and Dairy Herds in Tunisia: Preliminary Results
by Stefano Petrini, Mohamed Methnani, Cecilia Righi, Khaled El Hicheri, Cristina Casciari, Aida Tatli, Ben Smida Boubaker, Elena Tinelli, Sana Kacem, Claudia Pellegrini, Roberto Sabato, Francesco Feliziani and Giovanni Pezzotti
Microbiol. Res. 2026, 17(5), 88; https://doi.org/10.3390/microbiolres17050088 - 29 Apr 2026
Abstract
Livestock farming represents a key economic activity in the Tataouine Governorate of southern Tunisia, where cattle and dromedary camels coexist. Varicellovirus bovinealpha1 (BoAHV-1), the etiological agent of infectious bovine rhinotracheitis (IBR), primarily affects cattle, while its circulation in camelids remains poorly understood. Following [...] Read more.
Livestock farming represents a key economic activity in the Tataouine Governorate of southern Tunisia, where cattle and dromedary camels coexist. Varicellovirus bovinealpha1 (BoAHV-1), the etiological agent of infectious bovine rhinotracheitis (IBR), primarily affects cattle, while its circulation in camelids remains poorly understood. Following recent European Union regulations requiring BoAHV-1 surveillance in multiple animal species, this short communication reports serological findings from dairy cattle and dromedary herds in southern Tunisia. In March 2024, serum samples were collected from four non-vaccinated farms, including two intensive Friesian dairy cattle herds and two extensive dromedary herds (50 animals each). Serum samples from all animals were tested for BoAHV-1 antibodies using competitive commercial gB- and gE-based enzyme-linked immunosorbent assays (c-ELISA) and confirmed by virus neutralization test (VNT). Antibodies against BoAHV-1 were detected in cattle from both dairy farms, with low seroprevalence and neutralizing antibody titers, indicating past or ongoing exposure. In contrast, all dromedary samples tested seronegative by both c-ELISA and VNT. These findings confirm BoAHV-1 circulation in cattle in the Tataouine region and its absence in dromedaries at sampling. Further studies involving larger sample sizes and molecular investigations are required to clarify the potential role of camelids in BoAHV-1 epidemiology in southern Tunisia. Full article
15 pages, 2186 KB  
Article
Mechanistic Insights into Glycine’s Regulation of Milk Protein Synthesis via PI3K-AKT-mTOR Signaling
by Xinyu Zhang, Yu Ding, Min Yang, Yuxin Zhou, Ruoshan Luo, Yang Yang, Hang Zhang, Wanping Ren, Liang Yang, Yong Wei, Yankun Zhao, Tongjun Guo and Wei Shao
Curr. Issues Mol. Biol. 2026, 48(5), 453; https://doi.org/10.3390/cimb48050453 - 27 Apr 2026
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Abstract
Amino acids play a dual role in milk protein synthesis, functioning as both metabolic precursors and signaling molecules. This study aimed to elucidate the molecular mechanism by which glycine regulates α-casein production in bovine mammary epithelial cells (MAC-T). Under serum-free conditions, MAC-T cells [...] Read more.
Amino acids play a dual role in milk protein synthesis, functioning as both metabolic precursors and signaling molecules. This study aimed to elucidate the molecular mechanism by which glycine regulates α-casein production in bovine mammary epithelial cells (MAC-T). Under serum-free conditions, MAC-T cells were exposed to graded concentrations of glycine (1.105, 2.209, 4.418, 8.836, 17.673, and 35.345 mM) for 24 h. α-Casein levels in cell lysates and culture supernatants were quantified by ELISA. Transcriptional activity of casein-encoding genes (CSN1S1, CSN1S2) and PI3K-AKT-mTOR pathway components was assessed by RT-qPCR. Phosphorylation status of pathway proteins was analyzed by Western blot. The functional involvement of the PI3K-AKT-mTOR pathway was validated using the specific inhibitor LY294002. Glycine stimulated α-casein synthesis and secretion in a concentration-dependent manner, with maximal efficacy at 4.418 mM. At this concentration, glycine upregulated CSN1S1, CSN1S2, and PI3K-AKT-mTOR pathway gene expression, and enhanced phosphorylation of the corresponding proteins. Inhibition of PI3K-AKT-mTOR signaling by LY294002 abolished glycine-induced α-casein synthesis, and this effect was reversed by glycine co-treatment. These findings demonstrate that glycine enhances α-casein synthesis through activation of the PI3K-AKT-mTOR pathway. Full article
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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18 pages, 2220 KB  
Article
Heat Shock Affects Amino Acid Metabolism in Bovine Cumulus Cells and Denuded Oocytes During In Vitro Maturation
by Hayder Radhi Hussein Mzedawee, Rasoul Kowsar, Golnaz Manian and Mehdi Hajian
Biology 2026, 15(9), 682; https://doi.org/10.3390/biology15090682 - 27 Apr 2026
Viewed by 221
Abstract
Increased heat levels can affect follicle development, oocyte maturation, and bovine fertility by disrupting amino acid (AA) metabolism and oocyte competence. This study aimed to explore the effect of heat shock on AA metabolism in bovine cumulus cells (CCs) or denuded oocytes (DOs). [...] Read more.
Increased heat levels can affect follicle development, oocyte maturation, and bovine fertility by disrupting amino acid (AA) metabolism and oocyte competence. This study aimed to explore the effect of heat shock on AA metabolism in bovine cumulus cells (CCs) or denuded oocytes (DOs). CCs and DOs were separately cultured for 24 h in vitro at 38.5 °C (control group), 39.5 °C (moderate heat shock-CC, MHS-CC group), or 40.5 °C (high heat shock-CC, HHS-CC group). AA levels were analyzed in 24-h in vitro maturation media using high-performance liquid chromatography. The findings indicated that the HHS-CC group consumed more AAs than the control (p = 0.04) or MHS-CC group (p = 0.03). Compared with the control and HHS-CC groups, the MHS-CC group exhibited elevated alanine levels (p = 0.02). The MHS-CC (p = 0.03) and HHS-CC (p = 0.03) groups exhibited significantly greater glutamine depletion than the control group. The HHS-DO group exhibited significant lysine depletion (p < 0.01) but produced more tryptophan than the control and MHS-DO groups (p = 0.02). In contrast to the control and MHS-DO groups, the HHS-DO group displayed a notably elevated level of appearance (p = 0.005) and net balance (p = 0.005) for all AAs. The findings imply that heat shock may alter the metabolism of certain AAs in CCs and DOs, thereby affecting the developmental competence of bovine oocytes. Full article
(This article belongs to the Section Developmental and Reproductive Biology)
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16 pages, 1470 KB  
Article
YAP-TEAD Inhibition Impairs Interferon Tau-Induced Gene Expression and Reduces Integrin β1 Abundance in Primary Bovine Luteal Cells
by Suzana Rossato Feltrin, Karine de Vargas Aires, Amanda Luiza Prante, Ana Paula da Silva, Carlos Miguel Staudt, Manuela Brauner Freitas, Carolina dos Santos Amaral, Luis Fernando Schütz, Valério Marques Portela and Alfredo Quites Antoniazzi
Ruminants 2026, 6(2), 28; https://doi.org/10.3390/ruminants6020028 - 27 Apr 2026
Viewed by 105
Abstract
The Hippo pathway effector Yes-associated protein (YAP), acting through TEA domain (TEAD) transcription factors, regulates transcriptional programs in ovarian tissues; however, its role in interferon tau (IFNT) signaling within bovine luteal cells has not been investigated. This study aimed to determine whether YAP-TEAD [...] Read more.
The Hippo pathway effector Yes-associated protein (YAP), acting through TEA domain (TEAD) transcription factors, regulates transcriptional programs in ovarian tissues; however, its role in interferon tau (IFNT) signaling within bovine luteal cells has not been investigated. This study aimed to determine whether YAP-TEAD interaction is required for IFNT-induced interferon-stimulated gene (ISG) expression in primary bovine luteal cells and to perform an exploratory assessment of selected receptor genes (ITGB1, GRP78, VEGFR2). Primary luteal cells were treated with recombinant ovine IFNT (roIFNT; 1 ng/mL) in the presence or absence of verteporfin (VP; 0.1, 0.5, or 1.0 µM), a pharmacological YAP-TEAD inhibitor, and mRNA expression was quantified by RT-qPCR. VP dose-dependently suppressed YAP target genes (YAP1, CTGF, ANKRD1) and reduced roIFNT-induced expression of MX1, MX2, and OAS1, whereas ISG15 was unaffected. Steroidogenic gene expression (3β-HSD, P450scc, StAR) remained unchanged across treatments, indicating preserved cell viability. Among the exploratory receptor endpoints, VP decreased ITGB1 and increased GRP78 at the highest concentration, while VEGFR2 was unaffected. These findings indicate that YAP-TEAD activity contributes to IFNT-induced ISG responsiveness in bovine luteal cells, with preliminary evidence of effects on integrin-mediated signaling pathways. Full article
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24 pages, 20745 KB  
Article
pH-Responsive Bovine Serum Albumin Nanoparticles Encapsulating Doxorubicin-Based Complexes Induce Cuproptosis in Lung Cancer Cells
by Haiying Zhang, Xuanjia Chen, Shihui Qiao, Huanfeng Meng, Hui Long, Huamin Zhong, Yiheng Liu, Yun Song, Yanan Gao, Yan Liu and Lujia Mao
Pharmaceutics 2026, 18(5), 526; https://doi.org/10.3390/pharmaceutics18050526 - 26 Apr 2026
Viewed by 534
Abstract
Background/Objectives: This study investigates the induction of cuproptosis in A549 lung cancer cells by doxorubicin (DOX) complexes and the development of pH-responsive bovine serum albumin (BSA)-based nanocarriers for their delivery. We successfully synthesized and characterized two novel complexes: DOX–Cu, where DOX acts [...] Read more.
Background/Objectives: This study investigates the induction of cuproptosis in A549 lung cancer cells by doxorubicin (DOX) complexes and the development of pH-responsive bovine serum albumin (BSA)-based nanocarriers for their delivery. We successfully synthesized and characterized two novel complexes: DOX–Cu, where DOX acts as a ligand for Cu(II), and DOX–BTZ, a conjugate formed between DOX and the proteasome inhibitor bortezomib (BTZ). Methods: Spectroscopic and NMR analyses were performed to confirm the formation of the complexes. In vitro assays were conducted to evaluate cytotoxicity in A549 cells, alongside assessment of DLAT aggregation as a marker of cuproptosis. The formulation of DOX into BSA nanoparticles (DOX–Cu@BSA NPs and DOX–BTZ@BSA NPs) was carried out to evaluate potential alleviation of DOX-induced cytotoxicity in cardiomyocytes in vitro. Fluorescence quenching and molecular docking studies were employed to investigate the binding interactions between the complexes and BSA. Cellular uptake experiments were performed to assess nanoparticle internalization into A549 cells. Results: Both complexes exhibited superior cytotoxicity against A549 cells compared to individual components. This enhanced cell death was associated with significant aggregation of dihydrolipoamide S-acetyltransferase (DLAT), a key marker of cuproptosis, suggesting the involvement of this copper-dependent cell death pathway. The BSA nanoparticles displayed favorable characteristics, including uniform size (~190 nm), high encapsulation efficiency (~75–79%), and colloidal stability. Crucially, they exhibited a pH-responsive drug release profile, with significantly accelerated release under acidic conditions (pH 5.7) mimicking the tumor microenvironment. Fluorescence quenching and molecular docking studies revealed strong, spontaneous binding between the complexes and BSA, primarily driven by hydrophobic interactions. Cellular uptake experiments confirmed efficient internalization of the nanoparticles into A549 cells. Conclusions: Collectively, this work offers a proof-of-concept for a strategy of utilizing BSA-based multidrug delivery systems for cuproptosis induction, offering a potential avenue to enhance therapeutic efficacy while reducing systemic toxicity in lung cancer treatment. Full article
(This article belongs to the Special Issue New Insights into Nanomaterials for Cancer Therapy and Drug Delivery)
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26 pages, 1923 KB  
Systematic Review
Systematic Review and Meta-Analysis of Extended-Spectrum Beta-Lactamase-Producing (ESBL) Escherichia coli in Food-Producing Animals and Animal Products in Nigeria
by Yusuf Yakubu, Mohammed Sani Gaddafi, Ummukulthum Lawal Hassan, Ibrahim Idris, Laura Felicioli and Kelvin Olutimilehin Jolayemi
Antibiotics 2026, 15(5), 432; https://doi.org/10.3390/antibiotics15050432 - 25 Apr 2026
Viewed by 226
Abstract
Background/Objectives: Extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli are priority antimicrobial-resistant pathogens with significant implications for food safety and public health. Food-producing animals and their derived products represent a key interface for zoonotic transmission, yet prevalence data across Nigeria remain fragmented and unsynthesized. This [...] Read more.
Background/Objectives: Extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli are priority antimicrobial-resistant pathogens with significant implications for food safety and public health. Food-producing animals and their derived products represent a key interface for zoonotic transmission, yet prevalence data across Nigeria remain fragmented and unsynthesized. This systematic review and meta-analysis assessed the prevalence, species distribution, geographical patterns, and detection methods of ESBL-producing E. coli in food-producing animals and animal-derived food products across Nigeria. Methods: A comprehensive search of PubMed, Web of Science, Scopus, and African journals online was conducted for studies published between January 2000 and January 2026, following PRISMA 2020 guidelines. Twenty eligible studies collectively analyzed 5104 samples, and 984 ESBL-positive isolates were included in the meta-analysis. Results: The overall pooled prevalence of ESBL-producing E. coli was 17.0% (95% CI: 13.0–21.0%; I2 = 89.4%). Subgroup analysis by animal species revealed the highest pooled prevalence among caprine (32.0%, 95% CI: 17.0–52.0%), bovine (24.0%, 95% CI: 17.0–33.0%), porcine (17.0%, 95% CI: 7.0–36.0%) and avian species (13.0%, 95% CI: 9.0–19.0%). Animal-derived food products showed a pooled prevalence of 19.0% (95% CI: 17.0–21.0%). Regional analysis showed the highest pooled prevalence in South-West (19.0%, 95% CI: 13.0–27.0%) and South-South (19.0%, 95% CI: 9.0–34.0%). Studies using combined culture and molecular methods reported higher pooled prevalence (19.0%, 95% CI: 14.0–25.0%) than culture alone (12.0%, 95% CI: 8.0–18.0%). However, the difference between subgroups was not statistically significant (test for subgroup differences: p = 0.0563). Conclusions: These findings confirm extensive ESBL-producing E. coli circulation in Nigerian food-producing animals and highlight critical gaps in antimicrobial stewardship, veterinary surveillance, and food safety infrastructure, underscoring the urgent need for coordinated One Health strategies to contain the spread of resistant strains through the food chain. Full article
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