A Mediterranean diet improves glycation markers in healthy people and in those with chronic diseases: a systematic review of clinical trials.

CONTEXT: Consumption of the Mediterranean diet (MedDiet) has beneficial effects on cardiometabolic health and aging. OBJECTIVE: This systematic review aimed to critically investigate the effect of the MedDiet on glycation markers in healthy or overweight individuals with type 2 diabetes or cardiovascular disease. DATA SOURCES: MEDLINE, EMBASE, Web of Science, and the Cochrane Library were searched, using the terms "Mediterranean diet" AND "glycation end products, advanced". DATA EXTRACTION: Three randomized and 3 nonrandomized clinical trials, containing data on 2935 adult and elderly individuals with normal weight or overweight, were included. All extracted data were compiled, compared, and critically analyzed. DATA ANALYSIS: The authors of most of the studies demonstrated a reduction in serum concentrations of advanced glycation end products (AGEs), such as εN-carboxymethyllysine and methylglyoxal, and in skin autofluorescence levels after at least 4 weeks of adherence to the MedDiet. The MedDiet also led to positive effects on gene expression of receptors for AGEs, as RAGE and AGER1, and an enzyme involved in detoxification (glyoxalase I). There is no evidence that short-term adherence affects glycation markers. CONCLUSIONS: Glycation markers improved in response to the MedDiet. The possible mechanisms involved may be related to the low AGE and refined sugars content of the diet, as well as its high monounsaturated fatty acid, phenolic compound, and dietary fiber contents. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42021284006.

Neourethra creation using autologous vascularized intestinal graft in cats.

The objective of this study was to assess the application of a urethrostomy technique that utilizes an autologous vascularized intestinal graft as a "neourethra" and to analyze its short- and long-term feasibilities. Six cats with urethral rupture and 8 cats with urethral stricture and a history of urethrostomy were included. The inclusion criteria were the indication for urethroplasty and limited urethral length for perineal urethrostomy. A segment of intestine was prepared as a graft for urethral repair. The diameter of the aboral end was adjusted to facilitate anastomosis with the urethra or neck of the urinary bladder. An ostomy was created in the prepubic region using the oral end. The postoperative follow-up period was at least 1 y. Restoration of urinary flow was successful in all cases immediately after surgery. During postoperative follow-up, minimal complications were observed, with urinary incontinence being one of the most frequent, occurring in 28.5% (4/14) of the cases. Urine culture, carried out at different times during the follow-up period, was positive in 72.7% (8/11) of the cats. The autologous graft from the vascularized intestinal segment was an appropriate urethral substitute and this urethroplasty technique therefore proved to be feasible in cats. The postoperative complications observed were not exclusive to this technique and generally could either be corrected or tolerated. Periodic clinical follow-up examinations are recommended. This procedure allows the reestablishment of urinary flow and should be considered a favorable option, particularly when there is insufficient urethral tissue to allow repair using conventional techniques.

L'objectif de cette étude était d'évaluer l'application d'une technique d'urétrostomie qui utilise une greffe intestinale vascularisée autologue comme « néo-urètre ¼ et d'analyser ses faisabilités à court et à long terme. Six chats avec rupture urétrale et huit chats avec rétrécissement urétral et antécédents d'urétrostomie ont été inclus. Les critères d'inclusion étaient l'indication d'urétroplastie et la longueur urétrale limitée pour l'urétrostomie périnéale. Un segment d'intestin a été préparé comme greffon pour la réparation urétrale. Le diamètre de l'extrémité aborale était ajusté pour faciliter l'anastomose avec l'urètre ou le col de la vessie. Une stomie a été créée dans la région prépubienne en utilisant l'extrémité orale. La période de suivi postopératoire était d'au moins 1 an. La restauration du flux urinaire a réussi dans tous les cas immédiatement après la chirurgie. Au cours du suivi postopératoire, des complications minimes ont été observées, l'incontinence urinaire étant l'une des plus fréquentes, survenant dans 28,5 % (4/14) des cas. La culture urinaire, réalisée à différents moments de la période de suivi, était positive chez 72,7 % (8/11) des chats. La greffe autologue du segment intestinal vascularisé était un substitut urétral approprié et cette technique d'urétroplastie s'est donc avérée réalisable chez le chat. Les complications postopératoires observées n'étaient pas exclusives à cette technique et pouvaient généralement être soit corrigées soit tolérées. Des examens de suivi clinique périodiques sont recommandés. Cette procédure permet le rétablissement du flux urinaire et doit être considérée comme une option favorable, en particulier lorsque le tissu urétral est insuffisant pour permettre une réparation à l'aide de techniques conventionnelles.(Traduit par Docteur Serge Messier).

Tumor-derived GCSF Alters Tumor and Systemic Immune System Cell Subset Composition and Signaling.

While immunotherapies such as immune checkpoint blockade and adoptive T-cell therapy improve survival for a subset of human malignancies, many patients fail to respond. Phagocytes including dendritic cells (DC), monocytes, and macrophages (MF) orchestrate innate and adaptive immune responses against tumors. However, tumor-derived factors may limit immunotherapy effectiveness by altering phagocyte signal transduction, development, and activity. Using Cytometry by Time-of-Flight, we found that tumor-derived GCSF altered myeloid cell distribution both locally and systemically. We distinguished a large number of GCSF-induced immune cell subset and signal transduction pathway perturbations in tumor-bearing mice, including a prominent increase in immature neutrophil/myeloid-derived suppressor cell (Neut/MDSC) subsets and tumor-resident PD-L1+ Neut/MDSCs. GCSF expression was also linked to distinct tumor-associated MF populations, decreased conventional DCs, and splenomegaly characterized by increased splenic progenitors with diminished DC differentiation potential. GCSF-dependent dysregulation of DC development was recapitulated in bone marrow cultures in vitro, using medium derived from GCSF-expressing tumor cell cultures. Importantly, tumor-derived GCSF impaired T-cell adoptive cell therapy effectiveness and was associated with increased tumor volume and diminished survival of mice with mammary cancer. Treatment with neutralizing anti-GCSF antibodies reduced colonic and circulatory Neut/MDSCs, normalized colonic immune cell composition and diminished tumor burden in a spontaneous model of mouse colon cancer. Analysis of human colorectal cancer patient gene expression data revealed a significant correlation between survival and low GCSF and Neut/MDSC gene expression. Our data suggest that normalizing GCSF bioactivity may improve immunotherapy in cancers associated with GCSF overexpression. Significance: Tumor-derived GCSF leads to systemic immune population changes. GCSF blockade restores immune populations, improves immunotherapy, and reduces tumor size, paralleling human colorectal cancer data. GCSF inhibition may synergize with current immunotherapies to treat GCSF-secreting tumors.

Proposal for the zoning of the industrial Brachyplatystoma vaillantii fisheries of the North Coast of Brazil and the influence of climatic factors on the fluctuations in the abundance of the species.

The present study was based on the analysis of 10,467 trawls of the industrial piramutaba (Brachyplatystoma vaillantii) fishing fleet of the Brazilian state of Pará, which were mapped by onboard GPS loggers (between February 2008 and September 2011) and the PREPS data from 40 vessels which were tracked by this system between 2008 and 2011. The variation in the mean monthly CPUE, based on Lomb's periodogram, revealed a well-defined and constant cycle with a duration of approximately one year. Three environmental factors influenced this cycle. The El Niño 3.4 index had a negative correlation with the CPUE of the piramutaba fishery, with a time lag of 15 months, while monthly rainfall and the mean discharge of the Amazon River correlated strongly (r=0.89 and 0.87, respectively; p<0.001) with the CPUE, with time lags of 12 and 11 months, respectively. The spatiotemporal analysis of the distribution of the activity of the piramutaba fishing fleet indicated that the most intense area of operation of the fleet lies between latitudes 00º N and 02° N, and longitudes 047º40' W and 049º40' W. This area was divided into four geographic quadrants, although fishery operations were concentrated in only three of these quadrants. The study proposed a quadrimester fishing cycle with zoning in three of the quadrants, where fishing would be permitted for four months (occupation period), followed by an 8-month rest period for the recuperation of stocks, aiming at the sustainability of this fishing exploration.

Deep Phenotyping by Mass Cytometry and Single-Cell RNA-Sequencing Reveals LYN-Regulated Signaling Profiles Underlying Monocyte Subset Heterogeneity and Lifespan.

RATIONALE: Monocytes are key effectors of the mononuclear phagocyte system, playing critical roles in regulating tissue homeostasis and coordinating inflammatory reactions, including those involved in chronic inflammatory diseases such as atherosclerosis. Monocytes have traditionally been divided into 2 major subsets termed conventional monocytes and patrolling monocytes (pMo) but recent systems immunology approaches have identified marked heterogeneity within these cells, and much of what regulates monocyte population homeostasis remains unknown. We and others have previously identified LYN tyrosine kinase as a key negative regulator of myeloid cell biology; however, LYN's role in regulating specific monocyte subset homeostasis has not been investigated. OBJECTIVE: We sought to comprehensively profile monocytes to elucidate the underlying heterogeneity within monocytes and dissect how Lyn deficiency affects monocyte subset composition, signaling, and gene expression. We further tested the biological significance of these findings in a model of atherosclerosis. METHODS AND RESULTS: Mass cytometric analysis of monocyte subsets and signaling pathway activation patterns in conventional monocytes and pMos revealed distinct baseline signaling profiles and far greater heterogeneity than previously described. Lyn deficiency led to a selective expansion of pMos and alterations in specific signaling pathways within these cells, revealing a critical role for LYN in pMo physiology. LYN's role in regulating pMos was cell-intrinsic and correlated with an increased circulating half-life of Lyn-deficient pMos. Furthermore, single-cell RNA sequencing revealed marked perturbations in the gene expression profiles of Lyn-/- monocytes with upregulation of genes involved in pMo development, survival, and function. Lyn deficiency also led to a significant increase in aorta-associated pMos and protected Ldlr-/- mice from high-fat diet-induced atherosclerosis. CONCLUSIONS: Together our data identify LYN as a key regulator of pMo development and a potential therapeutic target in inflammatory diseases regulated by pMos.

Survival of Beneficial Vaginal Lactobacilli (BVL) to Different Gastrointestinal Tract Conditions.

BACKGROUND: Lactobacilli are the dominant bacteria in the healthy vaginal tract, preventing the income of pathogenic microorganisms, either sexually or not transmitted. Probiotics are used to restore the vaginal microbiome by local administration. However, the ascendant colonization is proposed as a way to restore the vaginal balance, and to exert some complementary effects on the host, situation that requires that probiotic strains resist the gastrointestinal tract passage. OBJECTIVE: To determine which probiotic vaginal strains were able to resist different gastrointestinal factors (pH, bile salts, and enzymes) to advance in the design of oral formulas. METHODS: Different protocols were applied to evaluate the growth of 24 beneficial vaginal lactic bacteria (BVL) strains at low pH and high bile salts (individually evaluated) and in combined protocols. The viability of the strains in simulated gastrointestinal tract conditions was studied to select the most resistant strains. RESULTS: A low number of BVL was able to grow at low pH. Most of the strains did not survive at high bile salts concentration. The passage through pH first and bile salts later showed that only three strains were able to survive. In the simulated intestinal conditions, only Lactobacillus gasseri CRL1290, L. jensenii CRL1313, and L. jensenii CRL1349 decrease one or two logarithmic growth units (UFC/ml) at the end of the assay, maintaining their beneficial properties. CONCLUSION: The behavior of BVL in the conditions assayed is not related to specific strain or metabolic group, because the resistance is strain-specific. The results highlight the importance of the screening performed in a way to select the most adequate strains to be included in the oral designed formula for the restoration of the vaginal tract microbiome.

Nesting materials for does: Effect on nest building and performance at first parturition / Materiales de nido para conejas: Efecto sobre la construcción del nido y desempeño al primer parto / Materiais de ninho para coelhas: Efeito sobre a construção do ninho e desempenho na primeira parição

Abstract Background: The material placed into the nest should provide comfort to both does and their kits. Objective: To evaluate the effect of different nesting materials on rabbit doe performance and nest building. Methods: Thirty primiparous rabbit does were randomized allotted in a block design with three treatments and ten replicates each. The treatments consisted of nest bedding with wood shavings (280 g, control), Tifton hay (220 g), and thin strips of newspaper (200 g). The state of the nest was assessed to evaluate mixing of the material with doe's hair and preservation of the original material. Kit body weight, daily weight gain, and survival rate were evaluated from birth to weaning. Results: The nesting material did not affect the mixing level of material and hair, amount of hair in the nest, body weight, daily weight gain, or survival rate of rabbits from birth to 35 d of age (p>0.05). However, preservation of original material in the nest was lower when Tifton hay was used (p<0.05). Correlations between material type and total number of born alive and the amount of hair, mixture level between hair and material, and material preservation in the nest were not significant (p>0.05). No correlation (p>0.05) was observed between material preservation and hair presence or mixture level between both. Positive correlation between hair presence and mixture level (p<0.001) was observed. Conclusion: Tifton hay and cut newspaper can be used as nest bedding for pregnant does in replacement of wood shavings, with no negative effects on nest building behavior or kit performance.

Resumen Antecedentes: El material ubicado en el nido debe proporcionar confort a la coneja y a su camada. Objetivo: Evaluar el efecto de nidos forrados con diferentes materiales sobre el desempeño de la coneja y sobre la construcción del nido. Métodos: Treinta conejas primíparas fueron usadas en un diseño en bloques al azar con tres tratamientos y 10 repeticiones cada uno. Los tratamientos consistieron en forrar el nido con viruta (280 g), heno de Tifton (220 g) y periódico cortado en tiras (200 g). El estado del nido fue determinado para evaluar la mezcla del material y los vellos de la coneja, la preservación del material original, y el peso corporal, la ganancia de peso diaria y la tasa de supervivencia fueron evaluados desde el nacimiento hasta el destete. Resultados: El tipo de material no afectó el nivel de mezcla entre el material y los vellos, cantidad de vello en el nido, peso corporal, ganancia de peso diaria, o tasa de supervivencia de las crías desde el nacimiento hasta el d 35 de edad (p>0,05); sin embargo, la preservación del material original en el nido fue menor cuando el heno de Tifton fue usado (p<0,05). Las correlaciones del tipo de material y número total de nacidos vivos, y la cantidad de vello, nivel de mezcla entre vello y material, y preservación de material en el nido no fueron significativas (p>0,05). No hubo correlación (p>0,05) entre preservación del material en el nido con presencia de vello o nivel de mezcla en los nidos. Hubo una correlación positive entre la presencia de vello en el nido y el nivel de mezcla (p<0,001). Conclusión: El heno de Tifton y el periódico cortado en tiras puede ser usado como revestimiento de nidos para conejas gestantes, sustituyendo la viruta de madera sin efectos negativos sobre el comportamiento de construcción del nido de la coneja ni sobre el desempeño de las crías desde el nacimiento hasta el destete, considerando el primer parto.

Resumo Antecedentes: O material colocado no ninho deve proporcionar conforto à coelha e sua ninhada. Objetivo: Avaliar o efeito de ninhos forrados com diferentes materiais sobre o desempenho da coelha e sobre a construção do ninho. Métodos: Trinta coelhas primíparas foram usadas em delineamento em blocos ao acaso com três tratamentos e dez repetições cada. Foram avaliados três tipos de material para forrar o piso do ninho com maravalha (280 g), feno de Tifton (220 g) e jornal cortado em tiras (200 g). O estado do ninho foi determinado para avaliar a mistura do material com os pelos da coelha, a preservação do material original. Peso corporal, ganho de peso diário e a taxa de sobrevivência foram avaliados desde o nascimento até o desmame. Resultados: Nenhum efeito foi observado do tipo de material sobre o nível de mistura do material e pelos, quantidade de pelos no ninho, peso corporal, ganho de peso diário ou taxa de sobrevivência dos láparos do nascimento até 35 d de idade (p>0,05), entretanto, a preservação do material original no ninho foi menor quando o feno de Tifton foi usado (p<0,05). As correlacões de tipo de material e número total de nascidos vivos com a presença de pelo, nível de mistura entre pelo e material, e preservação de material no ninho não foram significativas (p>0,05). Não houve correlação (p>0,05) entre preservação do material no ninho com presença de pelo ou nível de mistura nos ninhos. Houve correlação positiva entre a presença de pelo no ninho com nível de mistura (p<0,001). Conclusão: Feno de Tifton e jornal cortado em tiras podem ser usados como revestimento de ninhos para coelhas gestantes, substituindo a maravalha sem efeitos negativos sobre o comportamento de construção do ninho da coelha nem sobre o desempenho dos láparos do nascimento até o desmame, considerando-se o primeiro parto.

Morphological traits, allometric relationship and competition of two seed-feeding species of beetles in infested pods

Abstract Pair-wise competition produces asymmetric consequences for the interacting species, resulting in reduction of species fitness at the individual scale; however, little is known of the effects of competition on the allometric patterns of insects. In this study, we explored how competition, by means of pod infestation, affects the development of female and male individuals in the co-occurring bruchine beetles Merobruchus terani and Stator maculatopygus. We found differences between M. terani and S. maculatopygus in all morphometric traits, but no significant differences between males and females in either species. We also found, with an increasing degree of pod infestation, a positive trend in the pronotum, elytron and body weight of M. terani and a negative trend in morphological traits and body weight of S. maculatopygus. A negative allometry was maintained, suggesting that with increasing body weight, the body structures did not increase proportionally. On the other hand, we found that increasing the degree of pod infestation produced a wider variation in the individuals' body size than in low levels of infestation. Finally, we discuss how pod infestation can trigger competition between species, with both positive and negative impacts, even though the species function similarly in resource exploitation.

Insulin temporal sensitivity and its signaling pathway in the rat pineal gland.

AIMS: In our previous work, we reported that the insulin potentiating effect on melatonin synthesis is regulated by a post-transcriptional mechanism. However, the major proteins of the insulin signaling pathway (ISP) and the possible pathway component recruited on the potentiating effect of insulin had not been characterized. A second question raised was whether windows of sensitivity to insulin exist in the pineal gland due to insulin rhythmic secretion pattern. MAIN METHODS: Melatonin content from norepinephrine(NE)-synchronized pineal gland cultures was quantified by high performance liquid chromatography with electrochemical detection and arylalkylamine-N-acetyltransferase (AANAT) activity was assayed by radiometry. Immunoblotting and immunoprecipitation techniques were performed to establish the ISP proteins expression and the formation of 14-3-3:AANAT complex, respectively. KEY FINDINGS: The temporal insulin susceptibility protocol revealed two periods of insulin potentiating effect, one at the beginning and another one at the end of the in vitro induced "night". In some Timed-insulin Stimulation (TSs), insulin also promoted a reduction on melatonin synthesis, showing its dual action in cultured pineal glands. The major ISP components, such as IRbeta, IGF-1R, IRS-1, IRS-2 and PI3K(p85), as well tyrosine phosphorylation of pp85 were characterized within pineal glands. Insulin is not involved in the 14-3-3:AANAT complex formation. The blockage of PI3K by LY 294002 reduced melatonin synthesis and AANAT activity. SIGNIFICANCE: The present study demonstrated windows of differential insulin sensitivity, a functional ISP and the PI3K-dependent insulin potentiating effect on NE-mediated melatonin synthesis, supporting the hypothesis of a crosstalk between noradrenergic and insulin pathways in the rat pineal gland.

Insulin temporal sensitivity and its signaling pathway in the rat pineal gland

In our previous work, we reported that the insulin potentiating effect on melatonin synthesis is regulated by a post-transcriptional mechanism. However, the major proteins of the insulin signalingpathway (ISP) and the possible pathway component recruited on the potentiating effect of insulin had not been characterized. A second question raised was whether windows of sensitivity to insulin exist in the pineal gland due to insulin rhythmic secretion pattern. Melatonin content from norepinephrine(NE)-synchronized pineal gland cultures was quantified by high performance liquid chromatography with electrochemical detection and arylalkylamine-N-acetyltransferase (AANAT) activity was assayed by radiometry. Immunoblotting and immunoprecipitation techniques were performed to establish the ISP proteins expression and the formation of 14-3-3: AANAT complex, respectively. The temporal insulin susceptibility protocol revealed two periods of insulin potentiating effect, one at the beginning and another one at the end of the in vitro induced “night”. In some Timed-insulin Stimulation (TSs), insulin also promoted a reduction on melatonin synthesis, showing its dual action in cultured pineal glands. The major ISP components, such as IRâ, IGF-1R, IRS-1, IRS-2 and PI3K(p85), as well tyrosine phosphorylation of pp85 were characterized within pineal glands. Insulin is not involved in the 14- 3-3:AANAT complex formation. The blockage of PI3K by LY 294002 reduced melatonin synthesis and AANAT activity.The present study demonstrated windows of differential insulin sensitivity, a functional ISP and the PI3K-dependent insulin potentiating effect on NE-mediated melatonin synthesis, supporting thehypothesis of a crosstalk between noradrenergic and insulin pathways in the rat pineal gland.