Search Results (8,047)

To develop sustainable strategies for mitigating ruminal methanogenesis and improving nitrogen efficiency in dairy systems, this study investigated how low-dose tannic acid (T), tea polyphenols (TP), and their combination (T+TP; 50:50) modulate rumen microbiota and function. A sample of Holstein cows were given four dietary treatments: (1) control (basal diet); (2) T (basal diet + 0.4% DM tannic acid); (3) TP (basal diet + 0.4% DM tea polyphenols); and (4) T+TP (basal diet + 0.2% DM tannic acid + 0.2% DM tea polyphenols). We comprehensively analyzed rumen fermentation, methane production, nutrient digestibility, milk parameters, and microbiota dynamics. Compared with the control group, all diets supplemented with additives significantly reduced enteric methane production (13.68% for T, 11.40% for TP, and 10.89% for T+TP) and significantly increased milk protein yield. The crude protein digestibility significantly increased in the T group versus control. The results did not impair rumen health or fiber digestion. Critically, microbiota analysis revealed treatment-specific modulation: the T group showed decreased Ruminococcus flavefaciens abundance, while all tannin treatments reduced abundances of Ruminococcus albus and total methanogens. These microbial shifts corresponded with functional outcomes—most notably, the T+TP synergy drove the largest reductions in rumen ammonia-N (34.5%) and milk urea nitrogen (21.1%). Supplementation at 0.4% DM, particularly the T+TP combination, effectively enhances nitrogen efficiency and milk protein synthesis while reducing methane emissions through targeted modulation of key rumen microbiota populations, suggesting potential sustainability benefits linked to altered rumen fermentation. Full article

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

(1) Background: The goal of the present study was to evaluate whether the supplementation with a multi-species probiotic in the diet of laying hens can change the microbiota and health status of the oviduct. (2) Methods: A total of 60 cages housing lightweight laying hens (36 weeks old) were randomly assigned to the following two different treatments: a control group fed a diet without probiotic, and a treatment group receiving diets supplemented with 50 g/ton of probiotics. The trial lasted for 26 weeks, after which five layers were slaughtered per treatment for oviduct (magnum) assessment, focusing on microbiome composition, oxidant and antioxidant status, and morphological analyses. Additionally, intestinal (jejunum) samples were collected to determine oxidant and antioxidant status. (3) Results: Probiotic supplementation resulted in lower counts of organisms from the RB41 order (p = 0.039) and Burkholderia genus (p = 0.017), and a total reduction in Bacillus and Corynebacterium (p = 0.050) compared to the control treatment. Genera Burkholderia (p = 0.017), Corynebacterium (p = 0.050), and Bacillus (p = 0.050) were also lower with the probiotic supplementation in relation to the control. Genera Epulopiscium (p = 0.089), Flavobacterium (p = 0.100), Ruminococcus (p = 0.089), and Staphylococcus (p = 0.100) tended to be lower in the probiotic group compared to the control. No significant differences were found between treatments for oviduct lesions. Probiotic treatment resulted in a higher protein thiol level in the intestine compared to the control (p < 0.001). However, the use of probiotics tended to reduce glutathione S-transferase levels in the oviduct compared to the control (p = 0.068). (4) Conclusions: These results suggest that dietary supplementation with probiotics can modulate the oviduct microbiota and improve the antioxidant status of laying hens, without causing tissue damage. Further research is warranted to explore the long-term implications of these changes on reproductive performance and egg quality. Full article

The present study evaluated the effect of adding 0% (control), 30%, 40% and 50% SPMs (small-peptide chelating trace minerals) to replace ITMs (inorganic trace minerals) in the diets of Litopenaeus vannamei; 720 shrimp were randomly assigned to four treatments (six replicates per group, 30 shrimp per replicate) in a 42-day feeding trial. There were no significant differences (p > 0.05) among the control, 40% SPM and 50% SPM groups in terms of the survival rate, weight gain rate, specific growth rate, hepatosomatic index, condition factor, feed intake, feed conversion ratio, or protein efficiency ratio; however, protein efficiency ratio was reduced in the 30% SPM group (p < 0.05). Glucose, triglyceride, and aspartate aminotransferase levels in the hemolymph of the 30% SPM group were significantly increased (p < 0.05), while the glucose and aspartate aminotransferase levels were also significantly increased in the 40% SPM group (p < 0.05). In the 50% SPM group, the glucose and triglyceride levels were also significantly increased (p < 0.05). Hepatopancreatic alkaline phosphatase activity was elevated at 40% SPM, and alkaline phosphatase, acid phosphatase, glutathione peroxidase, and total antioxidant capacity activities were significantly increased in the 50% SPM group (p < 0.05). The moisture content and drip loss were reduced in both the 40% and 50% SPM groups (p < 0.05). Therefore, replacing 40–50% ITMs with SPMs can maintain growth performance while enhancing physiological functions. In conclusion, the results of this study demonstrate that the incorporation of 30–50% SPMs into one’s diet constitutes a viable alternative to 100% ITMs. Full article

This study investigated the effects of reducing organic trace minerals below commercial inclusion levels and compared them with both low-dose and commercial levels of inorganic trace minerals, focusing on growth performance, carcass traits, tibia characteristics, oxidative stress (superoxide dismutase [SOD] and malondialdehyde [MDA]), and immune response (serum IgG) in broilers. A total of 384 one-day-old Ross 308 chicks were randomly assigned to three dietary treatments: (1) commercial-level inorganic trace minerals (ILI; Zn 100 ppm; Cu 15 ppm; Fe 100 ppm; Mn 80 ppm; Se 0.2 ppm; I 3 ppm); (2) low-level organic trace minerals (LLO; Zn 30 ppm; Cu 4 ppm; Fe 11 ppm; Mn 30 ppm; Se 0.225 ppm; I 3 ppm), and (3) low-level inorganic trace minerals (LLI; Zn 30 ppm; Cu 4 ppm; Fe 11 ppm; Mn 30 ppm; Se 0.2 ppm; I 3 ppm). Each treatment consisted of eight replicates with 16 birds per replicate, and diets were provided in two phases: starter (days 1–21) and grower (days 22–35). The results showed that the LLO group demonstrated a significantly improved feed conversion ratio (FCR) during the starter phase, 2.4% better than that of the ILI and LLI groups (p = 0.02). Additionally, filet and thigh muscle yields in the LLO group were higher by 11.9% (p = 0.03) and 13.9% (p = 0.02), respectively, compared to the ILI group. Other carcass traits, as well as pH and drip loss, were not significantly affected. However, tibia breaking strength at day 35 was 15.1% lower in the LLO group compared to the ILI group (p = 0.02). No significant differences were observed in oxidative stress markers or IgG levels among groups. This study demonstrated that reducing the inclusion level of inorganic trace minerals did not negatively affect broiler growth performance, whereas supplementation with low levels of organic trace minerals improved both growth performance and carcass quality. Full article

The kallikrein–kinin system and its B1 and B2 receptors are key regulators in metabolic disorders such as obesity, diabetes, and insulin resistance. Obesity, a chronic and multifactorial condition often associated with comorbidities like type 2 diabetes and dyslipidemia, remains poorly understood at the metabolic level. The kinin B2 receptor (B2R) is involved in blood pressure regulation and glucose metabolism, promoting glucose uptake in skeletal muscle via bradykinin. Studies in B2R-KO mice demonstrate that the absence of this receptor predisposes animals to glucose intolerance under a high-fat diet and impairs adaptive thermogenesis, indicating a protective role for B2R in metabolic homeostasis and insulin sensitivity. In contrast, the kinin B1 receptor (B1R) is inducible under pathological conditions and is activated by kinin metabolites. Mouse models lacking B1R exhibit improved metabolic profiles, including protection against high-fat diet-induced obesity and insulin resistance, enhanced energy expenditure, and increased leptin sensitivity. B1R inactivation in adipocytes enhances insulin responsiveness and glucose tolerance, supporting its role in the development of insulin resistance. Moreover, B1R deficiency improves energy metabolism and thermogenic responses to adrenergic and cold stimuli, promoting the activation of brown adipose tissue and the browning of white adipose tissue. Collectively, these findings suggest that B1R and B2R represent promising therapeutic targets for the treatment of metabolic disorders. Full article

Nudibranchs have garnered increasing interest in biomedical research due to their complex chemical defense mechanisms, many of which are derived from their diet, including sponges, cnidarians, tunicates, and algae. Their remarkable ability to sequester dietary toxins and synthesize secondary metabolites positions them as a promising source of biologically active compounds with potential therapeutic applications, particularly in oncology. This study aimed to review and summarize the available literature on the bioactive potential of nudibranch-derived compounds, focusing mainly on their antitumor properties. Although research in this area is still limited, recent studies have identified alkaloids and terpenoids isolated from species such as Dolabella auricularia, Jorunna funebris, Dendrodoris fumata, and members of the genus Phyllidia. These compounds exhibit notable cytotoxic activity against human cancer cell lines, including those from colon (HCT-116, HT-29, SW-480), lung (A549), and breast (MCF7) cancer. These findings suggest that compounds derived from nudibranchs could serve as scaffolds for the development of more effective and selective anticancer therapies. In conclusion, nudibranchs represent a valuable yet underexplored resource for antitumor drug discovery, with significant potential to contribute to the development of novel cancer treatments. Full article

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder marked by amyloid-β (Aβ) plaques, neurofibrillary tangles, blood–brain barrier dysfunction, oxidative stress (OS), and neuroinflammation. Current treatments provide symptomatic relief, but do not halt the disease’s progression. OS plays a crucial role in AD pathogenesis by promoting Aβ accumulation. Nuclear factor erythroid 2-related factor 2 (NRF2) is a key regulator of the antioxidant response, influencing genes involved in OS mitigation, mitochondrial function, and inflammation. Dysregulation of NRF2 is implicated in AD, making it a promising therapeutic target. Emerging evidence suggests that adherence to a Mediterranean diet (MD), which is particularly rich in polyphenols from extra virgin olive oil (EVOO), is associated with improved cognitive function and a reduced risk of mild cognitive impairment. Polyphenols can activate NRF2, enhancing endogenous antioxidant defenses. This study employs a computational approach to explore the potential of bioactive compounds in EVOO to modulate NRF2-related pathways in AD. We analyzed transcriptomic data from AD and EVOO-treated samples to identify NRF2-associated genes, and used chemical structure-based analysis to compare EVOO’s bioactive compounds with known NRF2 activators. Enrichment analysis was performed to identify common biological functions between NRF2-, EVOO-, and AD-related pathways. Our findings highlight important factors and biological functions that provide new insight into the molecular mechanisms through which EVOO consumption might influence cellular pathways associated with AD via modulation of the NRF2 pathway. The presented approach provides a different perspective in the discovery of compounds that may contribute to neuroprotective mechanisms in the context of AD. Full article

Glioblastoma (GBM) is the most aggressive primary brain tumor, characterized by rapid progression, profound heterogeneity, and resistance to conventional therapies. This review provides an integrated overview of GBM’s pathophysiology, highlighting key mechanisms such as neuroinflammation, genetic alterations (e.g., EGFR, PDGFRA), the tumor microenvironment, microbiome interactions, and molecular dysregulations involving gangliosides and sphingolipids. Current diagnostic strategies, including imaging, histopathology, immunohistochemistry, and emerging liquid biopsy techniques, are explored for their role in improving early detection and monitoring. Treatment remains challenging, with standard therapies—surgery, radiotherapy, and temozolomide—offering limited survival benefits. Innovative therapies are increasingly being explored and implemented, including immune checkpoint inhibitors, CAR-T cell therapy, dendritic and peptide vaccines, and oncolytic virotherapy. Advances in nanotechnology and personalized medicine, such as individualized multimodal immunotherapy and NanoTherm therapy, are also discussed as strategies to overcome the blood–brain barrier and tumor heterogeneity. Additionally, stem cell-based approaches show promise in targeted drug delivery and immune modulation. Non-conventional strategies such as ketogenic diets and palliative care are also evaluated for their adjunctive potential. While novel therapies hold promise, GBM’s complexity demands continued interdisciplinary research to improve prognosis, treatment response, and patient quality of life. This review underscores the urgent need for personalized, multimodal strategies in combating this devastating malignancy. Full article

Background/Objectives: Celiac disease (CD) is an autoimmune disorder characterized by small intestinal enteropathy triggered by gluten ingestion, often associated with gut dysbiosis. The most effective treatment is strict adherence to a gluten-free diet (GFD), which alleviates symptoms. This study uniquely integrates taxonomic, functional, and resistance profiling to evaluate the gut microbiota of women with CD on a GFD. Methods: To evaluate the long-term impact of a GFD, this study analyzed the gut microbiota of 10 women with CD on a GFD for over a year compared to 10 healthy controls with unrestricted diets. Taxonomic diversity (16S rRNA gene sequencing and the analysis of α and β-diversity), metabolic functionality (Biolog EcoPlates^®), and antibiotic resistance profiles (Cenoantibiogram) were assessed. Results: Metagenomic analysis revealed no significant differences in taxonomic diversity but highlighted variations in the abundance of specific bacterial genera. Women with CD showed increased proportions of Bacteroides, Streptococcus, and Clostridium, associated with inflammation, but also elevated levels of beneficial genera such as Roseburia, Oxalobacter, and Paraprevotella. Despite no significant differences in metabolic diversity, higher minimum inhibitory concentrations (MICs) in women in the healthy control group suggest that dietary substrates in unrestricted diets may promote the proliferation of fast-growing bacteria capable of rapidly developing and disseminating antibiotic resistance mechanisms. Conclusions: These findings indicate that prolonged adherence to a GFD in CD supports remission of gut dysbiosis, enhances microbiota functionality, and may reduce the risk of antibiotic resistance, emphasizing the importance of dietary management in CD. Full article

Background: Diabetes mellitus is associated with worse outcomes after cardiac arrest. Hyperglycemia, diabetes treatments and other long-term sequalae may contribute to this association. We sought to determine the acute effect of diabetes on the return of spontaneous circulation (ROSC) and post-arrest cardiac function in a rat cardiac arrest model. Methods: Eighteen male Wistar rats were utilized, and 12 underwent the induction of type II diabetes for 10 weeks through a high-fat diet and the injection of streptozotocin. The carotid artery flow and femoral arterial pressure were measured. Seven minutes of asphyxial cardiac arrest was induced. An external cardiac compression was performed via an automated piston. Post-ROSC, epinephrine was titrated to a mean arterial pressure (MAP) of 70 mmHg. Data was analyzed using the Mann–Whitney test. The significance was set at p ≤ 0.05. Results: The rate of the ROSC was significantly lower in animals with diabetes, 50% compared to 100% in non-diabetics. Additionally, it took significantly longer to achieve the ROSC in diabetics, p = 0.034. In animals who survived, the cardiac function was reduced, as indicated by an increased epinephrine requirement, p = 0.041, and a decreased cardiac output at the end of the experiment, p = 0.017. The lactate, venous and arterial pressures, heart rate and carotid flow did not differ between groups at 2 h. Conclusions: Diabetes negatively affects the survival from cardiac arrest. Here, the critical difference was the rate of the conversion to a life-sustaining rhythm and the achievement of the ROSC. The post-ROSC cardiac function was depressed in diabetic animals. Interventions targeted at improving defibrillation success may be important in diabetics. Full article

This study evaluated the effects of liquid oregano oil, chitosan nanoparticles with encapsulated liquid oregano oil, and a negative control of empty chitosan nanoparticles on in vitro ruminal fermentation. Three Boer goats were used as ruminal fluid donors, fed with a formulated ration for 21 d for inoculum adaptation. Treatments tested on in vitro assays were diet without oregano oil or nanoparticles (CON); diet with 100 ppm of oregano oil in nanoparticles (100N); diet with 300 ppm of liquid oregano oil (300L); diet with 300 ppm of oregano oil in nanoparticles (300N); and diet with 300 ppm of empty nanoparticles (300CHN). The variables studied were in vitro dry matter digestibility (ivDMD), in vitro neutral detergent fiber digestibility (ivNDFD_om), total gas production (TGP), ammonia nitrogen concentration (NH₃), and pH. The experimental design was a randomized complete block design. Linear and quadratic regressions were used to identify dependence and inflection points. The ivDMD increased at 12, 36, and 48 h, with 300N and with 300L exhibiting increased ivNDFD_om at 36 h. Ruminal pH was highest (p < 0.05) with 300CHN at 36 h. For first-order regression analysis of TGP, coefficients (β) were highest (p < 0.05) for 300N. In conclusion, 300N increased ruminal fermentation in vitro, as reflected by increases in ivDMD, ivNDFD_om, and TGP. Full article

Restaurants and open markets generate considerable quantities of organic waste. Converting these residues into poultry feed ingredients offers a sustainable disposal route. This study aimed to evaluate the nutritional and sensory viability of a novel feed complement formulated from Bonito fish meal (Sarda chiliensis chiliensis) and Única potato peel flour (Solanum tuberosum L. cv. Única). This study was conducted in three phases: (i) production and nutritional characterization of the two by-product flours; (ii) formulation of a 48:52 (w/w) blend, incorporated into broiler diets at 15%, 30%, and 45% replacement levels over a 7-week trial divided into starter (3 weeks), grower (3 weeks), and finisher (1 week) phases; and (iii) assessment of growth performance (weight gain, final weight, and feed conversion ratio), followed by a sensory evaluation of the resulting meat using a Check-All-That-Apply (CATA) analysis. The Bonito fish meal exhibited 50.78% protein, while the Única potato peel flour was rich in carbohydrates (74.08%). The final body weights of broiler chickens ranged from 1872.1 to 1886.4 g across treatments, and the average feed conversion ratio across all groups was 0.65. Replacing up to 45% of commercial feed with the formulated complement did not significantly affect growth performance (p > 0.05). Sensory analysis revealed that meat from chickens receiving 15% and 45% substitution levels was preferred in terms of aroma and taste, whereas the control group was rated higher in appearance. These findings suggest that the formulated feed complement may represent a viable poultry-feed alternative with potential sensory and economic benefits, supporting future circular-economy strategies. Full article

Nephrogenic diabetes insipidus (NDI) is a rare hereditary disorder characterized by renal resistance to arginine vasopressin (AVP), resulting in the kidneys’ inability to concentrate urine. Approximately 90% of NDI cases follow an X-linked inheritance pattern and are associated with pathogenic variants in the AVPR2 gene, which encodes the vasopressin receptor type 2. The remaining 10% are attributed to mutations in the AQP2 gene, which encodes aquaporin-2, and may follow either autosomal dominant or recessive inheritance patterns. We present the case of a male infant, younger than nine months of age, who was clinically diagnosed with NDI at six months. The patient presented recurrent episodes of polydipsia, polyuria, dehydration, hypernatremia, and persistently low urine osmolality. Despite adjustments in pharmacologic treatment and strict monitoring of urinary output, the clinical response remained suboptimal. Given the lack of improvement and the radiological finding of an absent posterior pituitary (neurohypophysis), the possibility of coexistent central diabetes insipidus (CDI) was raised, prompting a therapeutic trial with desmopressin. Nevertheless, in the absence of clinical improvement, desmopressin was discontinued. The patient’s management was continued with hydrochlorothiazide, ibuprofen, and a high-calorie diet restricted in sodium and protein, resulting in progressive clinical stabilization. Whole-exome sequencing identified a novel homozygous missense variant in the AQP2 gene (c.398T > A; p.Val133Glu), classified as likely pathogenic according to the American College of Medical Genetics and Genomics (ACMG) criteria: PM2 (absent from population databases), PP2 (missense variant in a gene with a low rate of benign missense variation), and PP3 (multiple lines of computational evidence supporting a deleterious effect)]. NDI is typically diagnosed during early infancy due to the early onset of symptoms and the potential for severe complications if left untreated. In this case, although initial clinical suspicion included concomitant CDI, the timely initiation of supportive management and the subsequent incorporation of molecular diagnostics facilitated a definitive diagnosis. The identification of a previously unreported homozygous variant in AQP2 contributed to diagnostic confirmation and therapeutic decision-making. The diagnosis and comprehensive management of NDI within the context of polyuria-polydipsia syndrome necessitates a multidisciplinary approach, integrating clinical evaluation with advanced molecular diagnostics. The novel AQP2 c.398T > A (p.Val133Glu) variant described herein was associated with early and severe clinical manifestations, underscoring the importance of genetic testing in atypical or treatment-refractory presentations of diabetes insipidus. Full article

After the first release of synthalin B (dodecamethylenbiguanide) in 1928 and its later retraction in the 1940s in Germany, the retraction of phenformin (N-Phenethylbiguanide) and of Buformin in the USA (but not outside) because of the lethal complication of acidosis seemed to have put an end to the era of the biguanides as oral antidiabetics. The strongly hygroscopic metformin (1-1-dimethylbiguanide), first synthesized 1922 and resuscitated as an oral antidiabetic (type 2 of the elderly) compound first released in 1959 in France and in other European countries, was used in the first large multicenter prospective long-term trial in England in the UKPDS (1977–1997). It was then released in the USA after a short-term prospective trial in healthy overweight “young” type 2 diabetics (mean age 53 years) in 1995 for oral treatment of type 2 diabetes. It was, however, prescribed to mostly multimorbid older patients (above 60–65 years of age). Metformin is now the most used oral drug for type 2 diabetes worldwide. While intravenous administration of biguanides does not have any glucose-lowering effect, their oral administration leads to enormous increase in their intestinal concentration (up to 300-fold compared to that measured in the blood), to reduced absorption of glucose from the diet, to increased excretion of glucose through the stool, and to decrease in insulin serum level through increased hepatic uptake and decreased production. Intravenously injected F18-labeled glucose in metformin-treated type 2 diabetics accumulates in the small and even more in the large intestine. The densitometry picture observed in metformin-treated overweight diabetics is like that observed in patients after bowel-cleansing or chronically taking different types of laxatives, where the accumulated radioactivity can even reach values observed in colon cancer. The glucose-lowering mechanism of action of metformin is therefore not only due to inhibition of glucose uptake in the small intestine but also to “attraction” of glucose from the hepatocyte into the intestine, possibly through the insulin-mediated uptake in the hepatocyte and its secretion into the bile. Furthermore, these compounds have also a diuretic effect (loss of sodium and water in the urine) Acute gastrointestinal side effects accompanied by fluid loss often lead to the drugs’ dose reduction and strongly limit adherence to therapy. Main long-term consequences are “chronic” dehydration, deficiency of vitamin B12 and of iron, and, as observed for all the biguanides, to “chronic” increase in fasting and postprandial lactate plasma level as a laboratory marker of a clinical condition characterized by hypotension, oliguria, adynamia, and evident lactic acidosis. Metformin is not different from the other biguanides: synthalin B, buformin, and phenformin. The mechanism of action of the biguanides as antihyperglycemic substances and their side effects are comparable if not even stronger (abdominal pain, nausea, vomiting, diarrhea, fluid loss) to those of laxatives. Full article