Explore the vast range of titles available.

In the last years, mesenchymal stem cell (MSC)-based therapies have become an interesting therapeutic opportunity for the treatment of rheumatoid arthritis (RA) due to their capacity to potently modulate the immune response. RA is a chronic autoimmune inflammatory disorder with an incompletely understood etiology. However, it has been well described that peripheral tolerance defects and the subsequent abnormal infiltration and activation of diverse immune cells into the synovial membrane, are critical for RA development and progression. Moreover, the imbalance between the immune response of pro-inflammatory and anti-inflammatory cells, in particular between memory Th17 and memory regulatory T cells (Treg), respectively, is well admitted to be associated to RA immunopathogenesis. In this context, MSCs, which are able to alter the frequency and function of memory lymphocytes including Th17, follicular helper T (Tfh) cells and gamma delta (γδ) T cells while promoting Treg cell generation, have been proposed as a candidate of choice for RA cell therapy. Indeed, given the plasticity of memory CD4 T cells, it is reasonable to think that MSCs will restore the balance between pro-inflammatory and anti-inflammatory memory T cells populations deregulated in RA leading to prompt their therapeutic function. In the present review, we will discuss the role of memory T cells implicated in RA pathogenesis and the beneficial effects exerted by MSCs on the phenotype and functions of these immune cells abnormally regulated in RA and how this regulation could impact RA progression.

All stages of winemaking can present problems, but alcoholic fermentation is, in particular, the stage with most complications. During wine fermentation some conditions can result in sluggish or stuck fermentations. The information provided by routine measurements has not been sufficient to detect and diagnose the state of the fermentation, and in case of paralization, rescue it on time. Hence, real-time monitoring of key variables, using advanced instrumentation, would anticipate problematic situations. Nitrogen is one of the most studied variables for sluggish or stuck fermentations. However, only a fraction of the available nitrogen is assimilated by the yeasts, constituted by ammonium ions and free α-amino acids. Nitrogen compounds have also been associated to be key factors in volatile compounds formation, including hydrogen sulfide (H2S). Sulfide release during winemaking is a longstanding and serious problem. H2S is a malodorous compound with a low sensory threshold. It’s produced as metabolic requirement of yeast for synthesizing sulphur compounds. Its formation is carried out by the sulfate reduction pathway starting from organic and inorganic sources, such as sulfites, cysteine, and glutathione. The role of amino acids and ammonium on H2S formation has shown a high variability. Individual yeast nitrogen requirements, as well as its assimilation capacity of nitrogen compounds, together with the time nitrogen is supplemented during fermentation, are oenological factors that influence sulfide formation. Furthermore, yeast variability in sulfide metabolic regulation has also a major impact on H2S formation. Genetic variability, in the form of differential allelic expression controlling sulfide reduction pathway or adjacent routes, has been found to be a decisive trait that affects yeast capacity to produce H2S. However, this information hasn’t been able to help predict and control sulfide formation through alcoholic fermentation. Considering the above, in this research nitrogen, specifically its organic sources, is studied, as regulator of H2S formation. For this, the evolution of amino acids profile during wine fermentation of Cabernet Sauvignon must was measured. Two problematic fermentations conditions were evaluated, high initial sugar concentration and low initial assimilable nitrogen content, besides the standard winery condition, with four commercial wine yeast. Samples were collected at 24 hours intervals until the maximum amount of H2S was produced. Amino acids were evaluated by HPLC (High Performance Liquid Chromatography), allowing their quantification. A colorimetric method was exclusively developed to accurately quantify H2S production. Depending on the initial condition of the fermentation some amino acid showed a characteristic evolution profile, distinctive to each yeast. Most importantly, a unique H2S release patron was established for each wine yeast in relation to the starting conditions of the must fermentation.

Mesenchymal Stem/Stromal Cells (MSC) are promising therapeutic tools for inflammatory diseases due to their potent immunoregulatory capacities. Their suppressive activity mainly depends on inflammatory cues that have been recently associated with changes in MSC bioenergetic status towards a glycolytic metabolism. However, the molecular mechanisms behind this metabolic reprogramming and its impact on MSC therapeutic properties have not been investigated. Human and murine-derived MSC were metabolically reprogramed using pro-inflammatory cytokines, an inhibitor of ATP synthase (oligomycin), or 2-deoxy-D-glucose (2DG). The immunosuppressive activity of these cells was tested using co-culture experiments with pro-inflammatory T cells and with the Delayed-Type Hypersensitivity (DTH) and the Graph versus Host Disease (GVHD) murine models. We found that the oligomycin-mediated pro-glycolytic switch of MSC significantly enhanced their immunosuppressive properties . Conversely, glycolysis inhibition using 2DG significantly reduced MSC immunoregulatory effects. Moreover, , MSC glycolytic reprogramming significantly increased their therapeutic benefit in the DTH and GVHD mouse models. Finally, we demonstrated that the MSC glycolytic switch effect partly depends on the activation of the AMPK signaling pathway. Altogether, our findings show that AMPK-dependent glycolytic reprogramming of MSC using an ATP synthase inhibitor contributes to their immunosuppressive and therapeutic functions, and suggest that pro-glycolytic drugs might be used to improve MSC-based therapy.

This study evaluated leukocyte and immune parameters in female rabbits and their kits from three genetic lines (R, RF, and RFLP) during their first reproductive cycle. The R line was selected for growth rate over 37 generations, the RF line was derived from elite R animals, and the RFLP was obtained by backcrossing the RF line with a maternal line (LP). In females, the total lymphocyte percentage decreased from the first AI to weaning (−15.8 percentage points; p  < 0.001; MIXED model); granulocytes peaked at weaning (+12.4 percentage points greater than the AI and +4.4 percentage points greater than parturition; p  < 0.01; MIXED model). The CD4 +  /CD8 +  ratio increased 53.4% ( p  < 0.001; MIXED model), and the haptoglobin concentration doubled ( p  < 0.001; MIXED model). RF and RFLP had higher total lymphocyte percentages than R did (+6.4 and +4.6 percentage points; p  < 0.05; MIXED model). R females had lower CD4 +  percentages and CD4 +  /CD8 +  ratios than RLFP females did (−3.4 percentage points and −24.4%; p  < 0.05; MIXED model) but higher monocyte and granulocyte percentages (on average +0.9 and +4.1 percentage points; p  < 0.05; MIXED model). At weaning, R kits had fewer T lymphocytes and CD4 +  T lymphocytes than RF kits did (−8.1 and −6.1 percentage points; p  < 0.05; GLM) and lower CD25 +  and phagocytosis of heterophils than RFLP kits did (−0.8 and −1.2 percentage points; p  < 0.05; GLM). The results suggest that creating a paternal line via elite animals (RFs) and backcrossing it with a robust line could improve immune status and stayability, offering insights into the impacts of rabbit breeding on immune health and reproductive success.

As a consequence of the genetic selection process in growing rabbits, there are currently fast-growing animals exhibiting an average daily gain that may exceed 45 g/d. The protein requirements of these animals, namely amino acid requirements, may differ from animals with low growth rates. The objective of this work was to evaluate growth performance, the coefficient of total tract apparent digestibility (CTTAD), the apparent ileal digestibility (AID) of amino acids and nutrient retention of fast-growing rabbits when they had access to a diet with high levels of amino acids and/or a diet formulated with current nutritional recommendations in a choice-feeding trial. To this end, two diets were formulated: the M diet following current nutritional recommendations for growing rabbits (including 8.1, 5.8 and 6.9 g/kg dry matter (DM) of total lysine, sulphur amino acids and threonine, respectively) and the H diet with higher levels of total lysine, sulphur amino acids and threonine (9.4, 6.6 and 7.8 g/kg DM, respectively). A total of 220 weaned rabbits, from a paternal line selected for the growth rate, had free access to the M diet, the H diet or both (MH) diets from 28 to 63 days of age. The CTTAD of DM, crude protein and gross energy from 49 to 53 days of age as well as the AID of amino acids of the diets at 63 days of age were determined. Protein, amino acids and energy retained in the empty body from 28 to 63 days of age were also registered. No significant differences in growth performance, CTTAD, AID and nutrient retention between dietary treatments were observed. However, animals fed the H diet showed a higher AID of cysteine (p < 0.05) and higher threonine retention (p < 0.05) compared to the M diet. As regards the choice-feeding trial, MH animals showed a higher feed intake of the M diet compared to the H diet (+8.61%; p < 0.001), and furthermore, more than 50% of the animals preferred the M diet throughout the experimental period (p < 0.05). Our results suggest that animals with high growth rates do not show significantly higher productive traits when fed the H diet compared to the M diet. As regards choice feeding, MH animals were capable of choosing their preferred diet, showing high intra-individual repeatability in preference for the M diet. It would be interesting to continue studying this behaviour of choice based on amino acid levels.

The objective of this work was to ascertain the nutritive value of six concentrate feedstuffs commonly used in guinea pig feed manufacturing through the substitution method. Six test diets were obtained by replacing the corresponding basal mixture with 40% corn, 50% barley, 45% wheat bran, 35% soybean meal, 30% pigeon pea, or 30% Leucaena leaf meal. Sixty-three guinea pigs were randomly assigned to one of the nine experimental diets (three basal diets and six test diets, with seven animals per diet). The animals were housed in individual cages and provided with feed and water ad libitum. Following a ten-day adaptation period, the feed intake and faeces excretion were monitored for a further five days. The digestible energy content, expressed as kcal/kg dry matter (±standard error), was 3857 ± 83 for corn, 3454 ± 68 for barley, 2911 ± 110 for wheat bran, 3855 ± 81 for soybean meal, 3105 ± 79 for pigeon pea, and 2972 ± 72 for Leucaena leaf meal. The apparent total tract digestibility of crude protein, expressed as % (±standard error) was 73.8 ± 4.9 for corn, 69.5 ± 4.6 for barley, 76.4 ± 3.6 for wheat bran, 88.4 ± 1.0 for soybean meal, 62.1 ± 1.9 for pigeon pea, and 68.0 ± 1.8 for Leucaena leaf meal. Further research is required to increase knowledge about these and other feedstuffs for guinea pigs.

The main aim of this work was to evaluate a novel combination of the first limiting amino acids (lysine, methionine, and threonine) in fast-growing rabbits (combination MHL, shown to minimise levels of plasmatic urea nitrogen in previous research, medium level of lysine, high level of methionine, and low level of threonine) and compare it with current recommendations (combination MMM, medium level of all amino acids). A total of 165 weaned rabbits (28 d old) from a paternal line selected for growth rate were used in the growth trial. The effect of the diet on apparent fecal digestibility, as well as the apparent and true ileal digestibility, were studied. Nutrient retention was also determined. Although no differences in digestibility between diets were observed, animals fed with Diet MHL improved the global average daily gain (+2.3 g/d; p = 0.0482) and feed conversion ratio (−0.10; p = 0.0229). Animals fed with Diet MMM reduced the protein-to-energy ratio retained (p = 0.0086). In conclusion, Diet MHL promoted an improvement in growth traits in a paternal line. Consequently, we propose its levels of 6.4, 5.4, and 5.0 g/kg DM of true ileal digestible lysine, methionine, and threonine, respectively.

Organic acids (OAs) are employed in animal feed to regulate gastrointestinal disorders and diarrhoea thanks to their ability to modulate the gastrointestinal environment and their antimicrobial capacity. However, there is not enough evidence regarding the most adequate OA and its effectiveness in rabbit farming. Therefore, the aim of this study was to screen and evaluate the response of young rabbits to six OAs, administered via drinking water, at three different concentrations (pH levels). Organic acids (acetic, ACET; formic, FOR; propionic, PROP; lactic, LAC; citric, CIT; and butyric, BUT) were tested at three concentrations (pH 3, 4, and 5). A negative control (CON; non-acidified water) was also included. We used 240 weaned rabbits (28 days old) divided into 2 batches. In each batch, animals were randomly allocated to 1 of the 19 experimental treatments and were housed in group cages of 6 animals per cage, treatment, and batch. Among the 240 rabbits, an additional cage with 6 animals was included to determine the initial physiological state of the animals. All animals were fed with commercial pelleted feed throughout the whole experiment. The duration of the study was 7 days, until 35 days of age. At 31 and 35 days of age, in each batch, three animals per day and treatment were slaughtered. The pH of the digestive contents in the fundus, antrum, duodenum, jejunum, ileum, and cecum, as well as the gastric pepsin enzyme activity, was measured. Water and feed consumption per cage and individual body weight (BW) were recorded daily. The type and dosage of OAs affected water intake. ACET 3, PROP 3, and BUT 3 reduced water intake compared to CON, negatively impacting feed intake and weight gain. FOR and CIT acids led to the highest BW and weight gain at 35 days, compared to PROP, LAC, and BUT (p < 0.05); showing ACET intermediate values. While OAs had limited effects on gastric and small intestine pH, acidified water at pH 4 and 5 lowered ileum and caecum pH (p < 0.05) compared to pH 3. Acidified water at pH 4 showed the highest (p < 0.05) pepsin activity compared to pH 3 and pH 5. Considering the limited sample size and short-term assessment period of our screening test, the OAs with the highest potential for use in post-weaning rabbits were FOR, ACET, and CIT at pH 4. The selected combinations did not exhibit any early adverse effects in young rabbits. These results should be further confirmed in a broader population of animals. It would also be advisable to extend the application of OAs over longer periods to evaluate their effects throughout the entire growing period of rabbits.

A total of 338 weaned rabbits (from the R line, selected for post-weaning growth rate) were used to evaluate the response to 18 generations of selection for increased growth rate on rabbit performance. Animals were obtained from two vitrified populations of the R line: R19V, belonging to the 18th generation (n = 165), and R37V, belonging to the 36th generation (n = 173), were allocated in individual and collective pens (178 and 160, respectively). A fattening trial was conducted from weaning (28 d of age until 63 d of age). During the trial, the body weight (BW), daily feed intake (DFI), average daily gain (ADG) and feed conversion ratio (FCR) were weekly monitored. Additionally, mortality and morbidity were daily registered. On days 49 to 53, an apparent faecal digestibility trial was also performed (12 animals per generation). Our results indicate that the generation of selection for growth rate did not affect mortality and morbidity. There were no differences in the diet digestibility according to the generation of selection. Regarding performance traits, R37V animals showed higher global BW (+6.7%; p = 0.0011) than R19V animals. R37V animals showed the same BW at weaning; however, R37V animals showed higher BW values in the last three weeks compared with R19V animals. Animals from the R37V generation also showed a higher DFI from 56 to 63 d of age (+12%; p = 0.0152) than R19V animals. However, there were no differences in global ADG and FCR between generations. These results indicate that the selection for growth rate in growing rabbits has slowed down, suggesting a lack of effectiveness in the genetic progress.

Objective To assess clinical variables that may be useful in differentiating gynaecomastia from carcinoma and to analyse the contribution of mammography and ultrasound to the evaluation of male breast disease. Methods All men who underwent mammography and/or ultrasound between 1993 and 2006 in our hospital were retrospectively evaluated. Clinical characteristics in patients with gynaecomastia and those with carcinoma were compared. Radiological findings were classified according to the BI-RADS (Breast Imaging Reporting and Data System) criteria. The diagnostic performance of physical examination, mammography and ultrasound was determined and compared. Results A total of 628 patients with 518 mammograms and 423 ultrasounds were reviewed. The final diagnoses were: 19 carcinomas, 526 gynaecomastias, 84 other benign conditions and 25 normal. There were statistically significant differences in age, bilateral involvement, clinical presentation and physical examination between patients with carcinoma and those with gynaecomastia. The diagnostic performance of physical examination was lower than that of mammography and ultrasound ( p  < 0.05 for specificity). Mammography was the most sensitive (94.7%) and ultrasound the most specific (95.3%) for detection of malignancy ( p  > 0.05). We propose an algorithm for the use of mammography and ultrasound in men. Conclusions Mammography and ultrasound, with a negative predictive value close to 100%, make it possible to avoid very many unnecessary surgical procedures in men.