Body Mass Research Articles

Abstract PR008: Cross-talk between metastatic cells and host systems: Neutrophil metabolic adaptation, immune profiling, and systemic metabolic shifts in tumor progression and cachexia

Abstract Oral squamous cell carcinoma (OSCC) is a prevalent type of head and neck cancer with a high mortality rate, partly due to late diagnosis often accompanied by metastasis. Cachexia, a complex syndrome marked by severe weight loss and muscle wasting, frequently accompanies advanced cancers including OSCC. Notably, 50-70% of OSCC patients exhibit cachexia at diagnosis, which persists post-treatment, hinting at a metastatic contribution to this syndrome. One significant challenge in studying cancer cachexia is the lack of well-characterized pre-clinical models that accurately reflect human disease. Traditional mouse models often involve subcutaneously transplanted cells, which fail to mimic the natural tumor-host interactions and metastatic progression seen in patients. These models do not typically exhibit metastasis and differ significantly from the genetic and molecular landscape of human cancers. To address these limitations, we developed a syngeneic mouse model by orthotopically transplanting MOC2 murine OSCC cells into the tongues of B6J mice, thereby closely mimicking the tumor microenvironment and metastatic behavior of human OSCC. By enhancing metastasis with a palm-enriched high-fat diet, we observed progressive tumor growth, metastasis, and body weight loss, independent of food intake reduction, indicating metabolic dysregulation rather than anorexia. Comprehensive analyses, including single-cell RNA sequencing (scRNAseq) of immune cells and transcriptomic and metabolomic profiling of tumor and host tissues, identified significant gene expression changes associated with metastasis and cachexia. Enhanced metastasis correlated with lipid metabolism changes in lung metastases, suggesting that metastatic cells exploit lipids for growth. Further, immune profiling revealed neutrophils' metabolic adaptation in metastasis, with implications for both tumor progression and cachexia. Targeting key metabolic and inflammatory pathways in tumor and immune cells holds potential for mitigating metastasis and cachexia. Early-stage serum metabolomics indicated systemic metabolic shifts, emphasizing the need to understand the interplay between tumor metastasis and host metabolism. These findings underscore the complex mechanisms underlying OSCC-induced cachexia, and the need for new targeted therapeutic strategies to disrupt this lethal synergy between cancer progression and metabolic deterioration of the host. Citation Format: Blanca Majem, Josefina Martin, Liudmila Shevkova, Claudia Bigas, Gloria Pascual, Salvador Aznar-Benitah. Cross-talk between metastatic cells and host systems: Neutrophil metabolic adaptation, immune profiling, and systemic metabolic shifts in tumor progression and cachexia [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr PR008.

The effect of processing or concentration of dried distillers grain with solubles (DDGS) on the growth of finishing lambs

Abstract Dried distiller’s grains with solubles (DDGS) are a popular by-product used in the livestock feed industry as it is a cost-effective feedstuff that is rich in crude protein and minerals. However, a common concern related to the use of DDGS in livestock diets is the negative impact that affect animal dry matter intake (DMI) and growth. To further investigate this challenge, the experiments aimed to evaluate the effect of feeding 1) two different diets, control versus heat processed DDGS or 2) increasing the concentration of DDGS and its effect on body weight (BW), average daily gain (ADG), DMI, and gain to feed ratio (G:F) in finishing lambs. In Experiment 1, both diets were the same except for heat processing of DDGS; the control diet used a commercial DDGS source directly from the supplier and the processed diet contained the same commercial DDGS source that differed through additional heat processing. For DDGS heat processing, 40% moisture was added to the DDGS and heated at 150°C for 70 minutes. After the heating process, the DDGS was placed in a second oven at 56°C for two days to allow for humidity evaporation. Lambs (n = 34), blocked by sex and BW, were housed in pens (2 to 3 lambs/pen, 6 pens/treatment) and were fed for 42 days. Lamb DMI was measured daily, and BW was measured every 14 days. In Experiment 2, lambs (n = 75) were blocked by BW (5 lambs/ pen, 5 pens/treatment) and fed diets differing in inclusion rates of DDGS (10%, 20%, and 30%). The feeding period lasted for 56 days, and lamb DMI and BW were measured daily or every 28 days, respectively. In both experiments, diets were isonitrogenous, and the feeding procedure utilized slick bunk management. Data were analyzed in SAS using a mixed model considering the treatments as fixed effect and pen and block as random effects. In Experiment 1, there were no treatment differences (P ≥ 0.13) in ADG, DMI, and G:F in finishing lambs. In Experiment 2, a linear and quadratic contrast were used to separate the mean and demonstrated that increasing the concentration of DDGS decreased lamb DMI (linear P < 0.01; quadratic P = 0.05), but did not affect lamb BW, ADG, or G:F (P ≥ 0.26). Despite that previous research shows differences in animal growth because of an increase in DDGS concentration, our experiments illustrated that heat processing or increased concentrations of DDGS up to 30% in finishing lamb diets are not responsible for a decrease in lamb performance.

Investigation on the Effect of Sacoglottis gabonensis on Blood Glucose, Body Weight and Behavioural Changes of Mice Exposed to Non-nutritive Sweeteners during Gestation Period

Aim: Aim of this research was to investigate the role of Sacoglotts gabonensis on blood sugar, body weight and behavioural changes of mice exposed to artificial sweeteners. Study Design: A total of 16 female mice (mean weight 18.6±2.32g) divided into four groups were used in this study. Methodology: Group A received no sweeteners or S. gabonensis, B received 50mg of sweeteners only, C received 50mg of sweeteners and 250mg/kg/bw of S. gabonensis, D received 250mg/kg/bw of S. gabonensis only for 8weeks. Results: show that group A and D had significant (p<0.05) decrease in blood glucose concentration with 7.27±3.53 mmol/L and 8.22±1.87 mmol/L respectively compared to group B and C with 9.12±1.03 mmol/L and 8.22±1.87 mmol/L. There was a significant (p<0.05) increase in body weight in groups A 32.60±7.34g and B 31.38±4.53g compared to groups C, 22.45±15.49g and D, 24.00±14.71g. Gestation length was between 19 and 20 days for the different groups and behavioural changes such as climbing, running, nesting and restlessness were observed in all the groups. Conclusion: The administration of S. gabonensis did not alter gestation length and behavioural changes during gravid period in experimental animals but altered the blood glucose concentrations However, administration of S. gabonensis is recommended for individuals who are at risk of developing high blood glucose concentration and increased body weight as it has shown modulatory effect on blood glucose and body weight gain.

Threonine attenuates lipopolysaccharide-induced intestinal inflammatory responses in rabbits.

Threonine (Thr) can be involved in the synthesis of immunoglobulins, which play the role of immune regulation, Thr also has to improve intestinal morphology, adjust the sticky protein synthesis, maintain the intestinal barrier function, etc. The experiment aimed to investigate the effects of diets supplemented with different levels of Thr on growth performance and intestinal health of rabbits under lipopolysaccharide (LPS) stress conditions. A total of 180 healthy 35-day-old weaned New Zealand White rabbits were randomly assigned in a 2 × 3 factorial design to receive an intraperitoneal injection of 100µg/kg BW LPS or saline and three diets with different levels of digestible threonine (0.43%, 0.54%, and 0.64%). The LPS challenge resulted in a reduction in body weight in rabbits at day 22, as well as a decrease in the serum d-lactic acid (D-LA) content and the number of goblet cells (GCs) in the jejunum. Additionally, the duodenum JAM2 and JAM3 were down-regulated. The expression of OCLN, ZO-1, and IL-2 in the jejunum, and CLDN, nuclear factor-κB (NF-κB) and ZO-1 mRNA in the ileum were also down-regulated. Furthermore, the duodenum TLR4 and IL-1β mRNA expression, while the jejunum exhibited an elevation in CLDN, TNF-α, and ileum TNF-α mRNA expression (P < 0.05). In the context of LPS challenge condition, dietary Thr addition was found to down-regulate the duodenum ZO-1 and jejunum CLDN mRNA expression of rabbits (P < 0.05). This was accompanied by an increase in ileum sIgA content and GCs number (P < 0.05). Additionally, dietary Thr addition resulted in a downregulation of duodenum TLR4, MyD88, NF-κB, TNF-α and IL-1β, jejunum MyD88, and IL-1β mRNA expression, as well as an up-regulation of ileum IL-10 mRNA expression in rabbits (P < 0.05). In conclusion, the LPS challenge can result in intestinal inflammation and damage the integrity of the intestinal barrier in rabbits. Nevertheless, dietary Thr supplementation can alleviate the intestinal inflammatory response in rabbits challenged with LPS.

Silymarin attenuates oxidative stress and pathological changes induced by salinomycin in adult male rabbits

AbstractFeed additives are used in animal husbandry to prevent diseases and enhance growth rates. Salinomycin sodium (SAL) is an approved feed additive for rabbit fattening diets, typically administered at a dosage of 20–25 mg/kg feed with a 5-day withdrawal period. However, the misuse or abuse of SAL can result in toxicity in rabbits. This study aimed to evaluate the adverse effects of SAL administration in different organs for the first time and the protective role of silymarin in rabbits. Seven groups of rabbits were randomly allocated. The control group received no additives. The second and third groups received rations with 20 mg SAL/kg and 40 mg SAL/kg, respectively. The fourth and fifth groups received the same SAL doses with silymarin at 6.5 mg/kg body weight (bw) and 13 mg/kg bw, respectively. The sixth and seventh groups were administered silymarin alone at 6.5 mg/kg bw and 13 mg/kg bw, respectively. Rabbits were euthanized and slaughtered on day 29 following the Halal method. SAL at 20 mg/kg ration caused mild to moderate pathological changes compared to the control group, while 40 mg SAL/kg ration induced severe pathological changes. However, silymarin supplementation, alone or with SAL, improved organs histology. Both silymarin doses (6.5 mg/kg bw and 13 mg/kg bw) mitigated SAL's harmful effects. In conclusion, this study highlights the potential detrimental effects of SAL toxicity on different organs in rabbits. The supplementation of silymarin reduced and prevented these hazardous effects. These findings emphasize the promising role of silymarin as a protective agent against SAL-induced toxicity in rabbits.

Effects of dietary Brassica rapa L. polysaccharide on growth performance, immune and antioxidant functions and intestinal flora of yellow-feathered quail.

This study aimed to explore the impact of Brassica rapa L. polysaccharides (BRP) on the growth, immune response, antioxidant capacity, and cecal microbiota in yellow-feathered quails. A total of 250 one-day-old yellow-feathered quails, evenly divided by sex, were randomly assigned to five groups, with each group comprising ten replicates of five quails each. The control group (CON) received a basic diet, while the antibiotic control group (CTC) was fed a basic diet supplemented with chlortetracycline (0.05g/kg). BRP was administered at concentrations of 0.25g/kg (Low dose BRP, LBRP), 0.5g/kg (Medium dose BRP, MBRP), and 1g/kg (High dose BRP, HBRP). The duration of the experiment was 42 days. The results indicated that, compared to the CON group, the final body weight of quails in the MBRP group significantly increased (P < 0.05), and there was a significant difference in body weight between the LBRP group and the CTC group (P < 0.05). At 21 days of age, the average weights of the thymus and bursa of Fabricius in the MBRP group were significantly greater than those in the CON group (P < 0.05), with no significant difference observed when compared to the CTC group (P > 0.05); at 42 days of age, the average weight of the thymus in the MBRP group was significantly greater than that in the CON group (P < 0.05), with no significant difference observed compared to the CTC group (P > 0.05). At 21 days of age, the levels of IgA and IgG in the MBRP group were significantly elevated compared to the CON group (P < 0.05), with no significant difference noted compared to the CTC group (P > 0.05). Additionally, the MBRP group showed significant increases in CAT, T-SOD, and GSH-Px levels (P < 0.05) compared to the CON group; the levels of IL-1β and TNF-α were significantly reduced (P < 0.05), and the level of IL-10 was significantly elevated (P < 0.05) compared to the CON group. Furthermore, 16S rRNA sequencing revealed that BRP supplementation increased the populations of beneficial cecal bacteria such as Lactococcus, Weissella, Parabacteroides, and norank_f_Ruminococcaceae, and decreased the population of the harmful bacterium Campylobacter, indicating that BRP modulates the microbial community structure in the cecum of yellow-feathered quails. In summary, BRP enhanced the growth performance, serum immunoglobulin levels, antioxidant functions, and improved the intestinal microbiota in yellow-feathered quails.

The therapeutic efficacy of adipose mesenchymal stem cell-derived microvesicles versus infliximab in a dextran sodium sulfate induced ulcerative colitis rat model

ABSTRACT Ulcerative colitis (UC) is a chronic relapsing intestinal inflammation that is becoming of increasing incidence worldwide and has insufficient treatment. Therefore, finding effective therapies remains a priority. A dextran sodium sulfate colitis model was established to elucidate colonic layers alterations and compare adipose mesenchymal stem cell-derived microvesicles (MSC-MVs) versus infliximab (IFX) efficacy through biochemical, light, and electron microscope studies. Fifty-four rats were allocated to 4 groups: Control (Con), UC, UC+IFX, and UC+MSC-MVs groups. End body weights (BW) and serum malondialdehyde (MDA) levels were recorded. Colitis severity was estimated by disease activity index (DAI). Colonic specimens were processed to evaluate the histological structure, collagen content, surface mucous and goblet cells, CD44, TNF-α, and GFAP immune expression. Morphometric and statistical analyses were performed. The UC group revealed congested, stenosed colons, a significant decline in end BW, and a significant increase in serum MDA and DAI. Furthermore, disturbed histoarchitecture, inflammatory infiltration, depletion of surface mucous and goblet cells, increased collagen, and TNF-α expression and decreased GFAP expression were observed. Alterations were partially attenuated by IFX therapy, whereas MSC-MVs significantly improved all parameters. In conclusion, MSC-MVs were a superior therapeutic option, via attenuating oxidative stress and inflammatory infiltration, in addition to restoring intestinal epithelial integrity and mucosal barrier.

Late-gestation maternal undernutrition induces circulatory redistribution while preserving uteroplacental function independent of fetal glycaemic state.

Programming effects of maternal undernutrition on fetal metabolic and cardiovascular systems are well elucidated, yet a detailed characterization of maternal haemodynamics is not available. This study used comprehensive cardiovascular magnetic resonance (CMR) imaging to quantify maternal haemodynamics after 29days (111-140 days) of late-gestation undernutrition (LGUN) in pregnant sheep. Control ewes received 100% of metabolizable energy requirements (MERs, n=15), whereas LGUN ewes were globally nutrient restricted to 50% MER (n=18), with a subset of fetuses undergoing continuous glucose infusion (LGUN+G, n=6/18). Ewes underwent CMR (138-140 days' gestation), and placental tissue was collected the next day. Ewes in both LGUN groups had reduced body weight and mean blood glucose concentration across gestation. Ventricular dimensions were lower in both LGUN groups. Uterine artery blood flow (QUtA) was elevated in the LGUN group compared with controls, whereas peripheral blood flow was reduced and further diminished in LGUN+G. Maternal weight change correlated with all haemodynamic parameters across all groups. Uteroplacental oxygen and glucose delivery were increased in LGUN compared to control ewes, whereas uteroplacental oxygen consumption was preserved. LGUN did not impact placental or fetal weight, and markers of brain-sparing physiology were absent. Placental expression of insulin-like growth factors (IGF-1 and IGF-2) and their receptors, glucose, fatty acid (FA) or amino acid transporters and markers of angiogenesis was not impacted. FA transporter expression was positively correlated with QUtA, and FA binding protein correlated negatively with maternal weight change. Maternal cardiovascular adaptations in response to LGUN manifest as preservation of placental growth and function, thereby preserving fetal growth. KEY POINTS: Maternal undernutrition during pregnancy alters fetal metabolic and cardiovascular physiology, but little is known about alterations in maternal haemodynamics. Late-gestation undernutrition (LGUN) and LGUN+G redirected maternal blood flow from the periphery to the uteroplacental unit, concomitantly increasing the delivery of glucose and oxygen to the uteroplacental unit. Substrate transporter expression and uteroplacental oxygen consumption were preserved in LGUN and LGUN+G, suggesting prioritization of the placenta. This study is the first to report detailed maternal haemodynamics in the setting of maternal undernutrition, where placental growth and function were maintained, ultimately preserving fetal oxygen metabolism and growth.

Valproate Administration to Adult 5xFAD Mice Upregulates Expression of Neprilysin and Improves Olfaction and Memory.

It is well known that the development of neurodegeneration, and especially Alzheimer's disease (AD), is often accompanied by impaired olfaction which precedes memory loss. A neuropeptidase neprilysin (NEP)-a principal amyloid-degrading enzyme in the brain-was also shown to be involved in olfactory signalling. Previously we have demonstrated that 5xFAD mice develop olfactory deficit by the age of 6months which correlated with reduced NEP expression in the brain areas involved in olfactory signalling. The aim of this study was to analyse the effect of administration of a histone deacetylase inhibitor, valproic acid (VA), to adult 5xFAD mice on their olfaction and memory as well as on brain morphology and NEP expression in the parietal cortex (PC) and hippocampus (Hip). The data obtained demonstrated that administration of VA to 7-month-old mice (200mg/kg of body weight) for 28days resulted in improvement of their memory in the Morris water maze as well as olfaction in the odor preference and food search tests. This correlated with increased expression of NEP in the PC and Hip as well as a reduced number of amyloid plaques in these brain areas. This strongly suggests that NEP can be considered an important therapeutic target not only in AD but also in olfactory loss.

Syringin ameliorates dextran sulphate colitis via alteration oxidative stress, inflammation NF-κB signalling pathway and gut microbiota.

The objective of the current study was to investigate the potential effects of syringin against dextran sulphate colitis (DSS)-induced ulcerative colitis (UC) in mice. In vitro study was performed on the RAW 264.7 cells and cytokines and inflammatory level were estimated. The oxidative stress, inflammatory cytokines, apoptosis and inflammatory parameters were estimated. The mRNA expression and faecal samples were estimated in the colon tissue. Syringin treatment enhanced the body weight, colon length and reduced the disease activity index (DAI), spleen index. Syringin treatment remarkably suppressed the level of nitric oxide (NO), myeloperoxidase (MPO), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) along with alteration of antioxidant parameters. Syringin treatment also altered level of cytokines in the serum and colon tissue; inflammatory parameters viz., platelet-activating factor (PAF), cyclooxygenase-2 (COX-2), prostaglandin (PGE2), inducible nitric oxide synthetase (iNOS), nuclear factor κ-B (NF-κB); matrix metalloproteinases (MMP) level. Syringin significantly (p < 0.001) enhanced the level of nuclear factor erythroid 2-related factor (Nrf2) and heme oxygenase-1 (HO-1). Syringin remarkably altered the relative abundance of gut microbiota like Firmicutes, Bacteroidetes, F/B ratio, Verrucomicrobia and Actinobacteria. Syringin exhibited the protective effect against DSS-induced UC in mice via alteration of NF-κB signalling pathway.

Rotating Spacetime: Theory or Reality? A Concise Journey of General Relativity

The paper reviews the theoretical formulae of different astrophysical conditions to describe spacetime and connects theory with observational evidence. The spacetime is governed by gravity, which is well-explained by the theory of General Relativity. The paper starts from the simplest version of spacetime, that is, flat spacetime which has no gravitational influence. This spacetime is described by the Minkowski metric. Then the paper goes to the properties of spacetime in the presence of gravity, which creates curved spacetime. The Schwarzschild metric defines this spacetime. Although these phenomena are well-established by experimental proof, the most intricate characteristic of spacetime has not been discovered until very recently. That is the spacetime around a rotating massive body. The paper will present the mathematical expressions for describing such spacetime, the Kerr metric, and finally will end with the observational evidence of the effect of a spinning heavy body around it. Some particular exotic effects such as “frame-dragging" and “ergosphere" will be presented in brief.

Identifying slow-growing commercial pigs using growth performance and health indicators.

This study aimed to evaluate the growth performance and health status of commercial pigs in different body weight (BW) groups and develop methods for identifying slow-growing pigs. The research observed 79 commercial pigs grouped from 104 to 202 days of age, collecting data on BW, feed intake, and body condition score (BCS) from caliper. Results showed that BCS were highly correlated with BW (r > 0.85, P < 0.001), providing a simple method for assessing commercial pig BW. Commercial pigs with slaughter BWs below 114kg at approximately 200 days old were identified as slow-growing individuals. White blood cell count, insulin-like growth factor binding protein-3, and blood urea nitrogen were identified as potential biomarkers for identifying slow-growing pigs. Economic analysis revealed that profitability across all BW groups was highly sensitive to market conditions, with feed costs being the most significant factor. Low BW groups performed better in low-price markets but reach break-even points later under medium to high-price scenarios.

Evaluation of laboratory findings indicating pancreatitis in healthy lean, obese, and diabetic cats.

Obesity is a risk factor for diabetes mellitus, which commonly coexists with pancreatitis in cats. However, obesity has not previously been associated with pancreatitis in cats. To evaluate factors affecting serum concentrations of pancreatic lipase immunoreactivity (fPLI), trypsin-like immunoreactivity (fTLI), cobalamin and folate in clinically healthy lean, overweight and obese, or diabetic cats. Seventy-nine client-owned cats (27 healthy lean [LN, BCS 4-5/9], 30 healthy overweight and obese [OW, BCS 7-9/9], and 22 diabetic [DM]) were included. Cross-sectional study. The cats underwent physical examination, and blood tests. Linear regression models compared differences in fPLI, fTLI, cobalamin, and folate concentrations. Fisher's exact test assessed the proportions of cats with fPLI and fTLI indicative of pancreatitis, and hypocobalaminemia. A random forest algorithm identified explanatory variables for cats having fPLI levels indicative of pancreatitis. No LN cats, while 6/30 (20%) of OW and 10/22 (45%) of DM cats had fPLI concentrations indicative of pancreatitis. Body condition score (P = .02) and body weight (P = .002) were positively associated with fPLI levels in LN and OW cats. Higher fPLI, and lower cobalamin concentrations were associated with higher age across groups. Body condition score and body weight were associated with higher fPLI levels in nondiabetic cats. A larger proportion of OW and DM cats had fPLI concentrations indicative of pancreatitis compared to LN cats. Whether this indicates subclinical pancreatitis remains to be determined. Hypocobalaminemia was less frequent in OW compared to DM cats.

An in vivo and in silico probing of the protective potential of betaine against sodium fluoride-induced neurotoxicity.

Excessive fluoride exposure beyond the tolerable limit may adversely impacts brain functionality. Betaine (BET), a trimethyl glycine, possesses antioxidant, anti-inflammatory and anti-apoptotic functions, although the underlying mechanisms of the role of BET on fluoride-induced neurotoxicity remain unelucidated. To assess the mechanism involved in the neuro-restorative role of BET on behavioural, neurochemical, and histological changes, we employed a rat model of sodium fluoride (NaF) exposure. Animals were treated with NaF (9mg/kg) body weight (bw) only or co-treated with BET (50 and 100mg/kg bw) orally uninterrupted for 28 days. We obtained behavioural phenotypes in an open field, performed negative geotaxis, and a forelimb grip test, followed by oxido-inflammatory, apoptotic, and histological assessment. Behavioural endpoints indicated lessened locomotive and motor and heightened anxiety-like performance and upregulated oxidative, inflammatory, and apoptotic biomarkers in NaF-exposed rats. Co-treatment with BET significantly enhanced locomotive, motor, and anxiolytic performance, increased the antioxidant signalling mechanisms and demurred oxidative, inflammatory, and apoptotic biomarkers and histoarchitectural damage in the cerebrum and cerebellum cortices mediated by NaF. The in-silico analysis suggests that multiple hydrogen bonds and hydrophobic interactions of BET with critical amino acid residues, including arginine (ARG380 and ARG415) in the Keap1 Kelch domain, which may disrupt Keap1-Nrf2 complex and activate Nrf2. This may account for the observed increased in the Nrf2 levels, elevated antioxidant response and enhanced anti-inflammatory response. The BET-Keap1 complex was also observed to exhibit structural stability and conformational flexibility in solvated biomolecular systems, as indicated by the thermodynamic parameters computed from the trajectories obtained from a 100 ns full atomistic molecular dynamics simulation. Therefore, BET mediates neuroprotection against NaF-induced cerebro-cerebellar damage through rats' antioxidant, anti-inflammatory, and anti-apoptotic activity, which molecular interactions with Keap1-Nrf2 may drive.

Tiliroside protects against diabetic nephropathy in streptozotocin-induced diabetes rats by attenuating oxidative stress and inflammation

BACKGROUND Diabetic nephropathy (DN), affecting half of diabetic patients and contributing significantly to end-stage kidney disease, poses a substantial medical challenge requiring dialysis or transplantation. The nuanced onset and clinical progression of kidney disease in diabetes involve consistent renal function decline and persistent albuminuria. AIM To investigate Tiliroside's (Til) protective effect against diabetic nephropathy (DN) in rats under diabetic conditions. METHODS Five groups of six rats each were included in this study: Rats treated with DMSO by intraperitoneal injection as controls, those treated with STZ by intraperitoneal injection, those treated with STZ + Til (25 mg/kg body weight [bwt]) or Til (50 mg/kg bwt), and those treated with anti-diabetic medication glibenclamide (600 μg/kg bwt). Biochemical markers, fasting blood glucose, food intake, kidney weight, antioxidant enzymes, inflammatory and fibrotic markers, and renal injury were monitored in different groups. Molecular docking analysis was performed to identify the interactions between Til and its targeted biomarkers. RESULTS Til significantly reduced biochemical markers, fasting blood glucose, food intake, and kidney weight and elevated antioxidant enzymes in diabetic rats. It also mitigated inflammatory and fibrotic markers, lessened renal injury, and displayed inhibitory potential against crucial markers associated with DN as demonstrated by molecular docking analysis. CONCLUSION These findings suggest Til's potential as a therapeutic agent for DN treatment, highlighting its promise for future drug development.

Associations Between Microsatellites Markers and Growth Traits in Goat

The rapid progress in the field of biotechnology gives us a great chance to improve the productivity of our native animals in short time, relatively. The situation in Saudi Arabia not differ in compare with other country in our region which have a big challenge to increase the meat production for food security purposes. The situation in goat is very far from the point which other farm animals like cattle reached today, where a complete QTLs maps for most important traits is available. But by the same way, long time ago we have a complete comparative map between goat and both sheep and cattle. According to that in the previous investigation in both sheep and cattle we collected a total of 19 loci distributed in goat different chromosomes along with a total of 1050 records from 525 individual of a crossbred of Aradi and Damascus Goat were used to perform the linkage analysis. The studied traits were body weight at birth, 4, 8, 12, 16, 20, and 24 weeks of age. The association between microsatellite markers and body weights traits were estimated by stepwise partial regression. Twelve markers (BMS2325, BMS332, BM17132, BMS1316, BM1827, BM1225, BMS2142, BM1558, BMS2809, BMS1348, BMC4216 and BM1329) successfully linked to studied traits. These markers are. In general, our work design and plan successfully worked and could explained some of genetic vitiation by using microsatellites markers. Further work to build a complete QTLs map for meat production traits is necessary to make a complete view about this important species.

Mesenchymal Stem Cell-Derived Extracellular Vesicles Carrying Circ-Tulp4 Attenuate Diabetes Mellitus with Nonalcoholic Fatty Liver Disease by Inhibiting Cell Pyroptosis through the HNRNPC/ABHD6 Axis.

Diabetes mellitus with nonalcoholic fatty liver disease (DM-NAFLD) represents a complex metabolic syndrome with significant clinical challenges. This study explores the therapeutic potential and underlying mechanisms of umbilical cord-derived mesenchymal stem cells (UCMSCs)-derived extracellular vesicles (EVs) in DM-NAFLD. UCMSCs-EVs were isolated and characterized. DM-NAFLD mouse model was developed through high-energy diet and streptozotocin injection. Additionally, primary mouse hepatocytes were exposed to high glucose to simulate cellular conditions. Hepatic tissue damage, body weight changes, lipid levels, glucose and insulin homeostasis, and hepatic lipid accumulation were evaluated. The interaction between UCMSCs-EVs and hepatocytes was assessed, focusing on the localization and function of circ-Tulp4. The study also investigated the expression of circularRNA TUB-like protein 4 (circ-Tulp4), heterogeneous nuclear ribonucleoprotein C (HNRNPC), abhydrolase domain containing 6 (ABHD6), cleaved Caspase-1, NLR family pyrin domain containing 3 (NLRP3) and cleaved N-terminal gasdermin D (GSDMD-N). The binding of circ-Tulp4 to lysine demethylase 6B (KDM6B) and the subsequent epigenetic regulation of ABHD6 by H3K27me3 were analyzed. Circ-Tulp4 was reduced, while HNRNPC and ABHD6 were elevated in DM-NAFLD models. UCMSCs-EVs attenuated hepatic steatosis and inhibited the NLRP3/cleaved Caspase-1/GSDMD-N pathway. EVs delivered circ-Tulp4 into hepatocytes, thereby restoring circ-Tulp4 expression. Elevated circ-Tulp4 enhanced the recruitment of H3K27me3 to the HNRNPC promoter through interaction with KDM6B, thus suppressing HNRNPC and ABHD6. Overexpression of HNRNPC or ABHD6 counteracted the protective effects of UCMSCs-EVs, exacerbating pyroptosis and hepatic steatosis in DM-NAFLD. UCMSCs-EVs deliver circ-Tulp4 into hepatocytes, where circ-Tulp4 inhibits the HNRNPC/ABHD6 axis, thereby reducing pyroptosis and alleviating DM-NAFLD. These findings provide a novel therapeutic avenue for targeting DM-NAFLD through modulation of cell pyroptosis.

STUDIES OF ASTHMA CONTROL IN PATIENTS WITH METABOLIC SYNDROME

Every day, a practitioner is faced with the problem of patient comorbidity. Bronchial asthma is a common problem, as is metabolic syndrome. Due to the increase in allergic diseases and lifestyle changes, patients may have a combination of metabolic syndrome and bronchial asthma. This combination has been shown to aggravate the course of asthma. Therefore, we wanted to confirm or refute this with our study. The study design included 94 patients with a diagnosis of asthma. A comparative analysis of the spirographic study data revealed that patients with asthma + MetS had statistically significant differences (p&lt;0.05). The analysis of anthropometric data revealed that patients with the highest BMI and body weight had a significantly more severe course of asthma (p&lt;0,05), which is consistent with the data of available world studies [24, 25], and a positive correlation was found between BMI, percentage of body fat and lower percentage of body fat in patients with severe asthma (ρ=0,89, ρ=0,90, ρ=0,87; r=0,88, r=0,91, r=0,90, respectively). The data obtained indicate the need for individual management of patients with comorbidities, including MetS and asthma, to prevent severe asthma, which is associated with inadequate asthma control and poor quality of life.

Light conditions have a greater impact on leaf quality as food for emperor moth (Saturnia japonica) larvae than tree size

ABSTRACT Emperor moth (Saturnia japonica) outbreaks in Hokkaido’s deciduous forests have been happening since 2006. The susceptibility of monarch birch (Betula maximowicziana) leaves differs, with the specific mechanisms affecting their defensibility at the ontogenetic level remaining unknown. In this study, the first instar emperor moth larvae were fed monarch birch leaves from 32 individual trees (saplings to mature trees), and their body weights were compared. Various leaf characteristics (water content, toughness, leaf mass per area, total phenolics, condensed tannin, nitrogen content, carbon content, and carbon to nitrogen [C/N] ratio) were measured concurrently to identify the factors affecting larval growth. Structural equation model analysis indicated that the C/N ratio was the most important factor affecting larval weight and that light conditions have a greater effect on the C/N ratio. In conclusion, light conditions had a strong effect on the foliar C/N ratio which in turn had a significant impact on the weight of emperor moth larvae. This study provides insights into monarch birch management and proposes that maintaining a lighter canopy is important to reduce herbivore damage.

β-cryptoxanthin suppresses oxidative stress via activation of the Nrf2/HO-1 signaling pathway in diabetic kidney disease

ObjectivesThis study aims to explore the role and investigate mechanisms of β-Cryptoxanthin (BCX) in high glucose (HG)-induced podocyte injury and renal dysfunction.MethodsIn this study, db/db mice were orally treated with BCX. Blood glucose, body weight, urinary albumin creatinine ratio (ACR) were recorded to evaluate the mice renal function. The H&amp;amp;E, PAS staining, and transmission electron microscopy (TEM) were utilized to examine the effect of BCX on the morphological changes of glomeruli in db/db mice. In addition, reactive oxygen species (ROS) content, mitochondrial membrane potential (MMP) level, ATP level, and SA-β-gal staining were used to assess the podocyte oxidative damage, mitochondrial dysfunction and senescence. Furthermore, the effects of BCX on Nrf2/HO-1 signaling pathway were evaluated in vivo and in vitro through Western blotting, immunohistochemistry and immunofluorescence analysis.ResultsIn vivo, BCX reversed glomerular mesangial matrix expansion and reduced proteinuria in db/db mice, as well as decreased glomerular oxidative stress and kidney aging. Similarly, in vitro study showed that BCX effectively alleviated the oxidative stress, mitochondrial dysfunction, and senescence induced by HG in podocytes. Furthermore, we identified that the antioxidative effects of BCX are associated with the activation of Nrf2/HO-1 signaling pathway, and that Nrf2 knockdown partially abrogated the protective effects of BCX in vitro.ConclusionOur study demonstrated for the first time that BCX alleviates podocyte injury in DKD by promoting Nrf2/HO-1 signaling pathways. BCX may be a potential candidate compound for preventing Diabetic kidney disease (DKD).