Metabolic Responses Research Articles

Effectiveness of a novel compound microbial agent for water quality and the gut microbiota of Micropterus salmoides

The cultivation of largemouth bass (Micropterus salmoides), a species of significant economic value in aquaculture, has experienced notable growth recently. However, the deterioration of water quality seriously affects the metabolic responses of M. salmoides. While compound microbial agent (CMA) is widely utilized for ecological rehabilitation and water filtration, its application in M. salmoides has not been reported. Here, based on physio-biochemical tests and 16S rRNA sequencing, we investigated the effects of CMA (yeast, Bacillus subtilis, and lactic acid bacteria) on the water quality within the recirculating aquaculture system, along with physiological indices and gut microbiota of M. salmoides. Compared to the control and single microbial agent (yeast), CMA treatment improved the water quality by improving the dissolved oxygen and delaying the increase of pH, total nitrogen, total phosphorus, ammonia nitrogen, and nitrite. The 16s rRNA gene sequencing revealed that the water treated with CMA exhibited elevated levels of chao1, Shannon, Pd, and a larger population of dominant bacterial. Besides, higher values of ACE, chao1, Shannon, and OTU level, and lower Simpson index were found in CMA treated M. salmoides samples, suggesting that CMA treatment enhanced the species richness and diversity of gut microbiota of M. salmoides. Furthermore, CMA treatment hindered the generation and proliferation of harmful bacteria, such as the Mycoplasma mobile 163K species and the Erysipelotrichaceae family, which was associated with enhanced antioxidant enzymatic activity and decreased MDA level in both the serum and liver. These findings shed light on the essential roles of CMA in M. salmoides culturing and introduce an innovative approach to enhance the aquatic environment.

Exercise-induced changes in myocardial glucose utilization during periods of active cardiac growth

Exercise training can promote physiological cardiac growth, which has been suggested to involve changes in glucose metabolism to facilitate hypertrophy of cardiomyocytes. In this study, we used a dietary, in vivo isotope labeling approach to examine how exercise training influences the metabolic fate of carbon derived from dietary glucose in the heart during acute, active, and established phases of exercise-induced cardiac growth. Male and female FVB/NJ mice were subjected to treadmill running for up to 4 weeks and cardiac growth was assessed by gravimetry. Cardiac metabolic responses to exercise were assessed via in vivo tracing of [13C6]-glucose via mass spectrometry and nuclear magnetic resonance. We found that the half-maximal cardiac growth response was achieved by approximately 1 week of daily exercise training, with near maximal growth observed in male mice with 2 weeks of training; however, female mice were recalcitrant to exercise-induced cardiac growth and required a higher daily intensity of exercise training to achieve significant, albeit modest, increases in cardiac mass. We also found that increases in the energy charge of adenylate and guanylate nucleotide pools precede exercise-induced changes in cardiac size and were associated with higher glucose tracer enrichment in the TCA pool and in amino acids (aspartate, glutamate) sourced by TCA intermediates. Our data also indicate that the activity of collateral biosynthetic pathways of glucose metabolism may not be markedly altered by exercise. Overall, this study provides evidence that metabolic remodeling in the form of heightened energy charge and increased TCA cycle activity and cataplerosis precedes cardiac growth caused by exercise training in male mice.

Abstract PO1-01-03: Pathological response according to early metabolic remission in an interim FDG-PET scan and to tumor infiltrating lymphocytes - A secondary analysis of the phase II trial ABCSG 52/ATHENE investigating atezolizumab in early HER2+ BC

Abstract Background: ABCSG-52/ATHENE investigated a neoadjuvant chemotherapy de-escalation/immunotherapy escalation approach with trastuzumab, pertuzumab, atezolizumab and epirubicin for early-stage HER2-positive breast cancer. The pathological complete response rate (pCR; ypT0/Tis, ypN0) - the primary endpoint of the trial - was 60.3% (95% CI 47.5% - 71.9%), and was higher than the predefined threshold for positivity (≥ 40%). Interestingly, higher pCR rates were observed in PD-L1 immune cell (IC) negative tumors (pCR 69.2%) as compared to PD-L1 IC positive tumors (pCR 55.2%). No new safety concerns were observed. Primary outcome data were reported at the ESMO Breast Cancer Conference 2023. Here, we present the correlation of pathological outcome according to early metabolic response in an interim fluorodeoxyglucose F18 positron emission tomography (FDG-PET) scan, and according to stromal tumor infiltrating lymphocytes (TILs) at baseline. Methods: Patients (pts) with previously untreated, histologically confirmed HER2-positive early breast cancer (EBC; clinical prognostic stage cT1c-4a-d, N0–3, M0) were randomized 1:1 to two 3-weekly cycles of a chemotherapy-free induction phase (Part 1) with trastuzumab and pertuzumab (TP) plus 1200 mg atezolizumab (TP+A), or TP alone. Subsequently, all pts received 4 cycles of TP+A in combination with epirubicin 90 mg/m² (Part 2). Randomization was stratified according to baseline TILs (< 5% vs ≥ 5%), hormone receptor status (positive vs. negative), and prognostic stage (≤ IIA vs. ≥ IIB; AJCC v.8.0). An FDG-PET assessment was performed at baseline and after 2 cycles of study treatment. According to PERCIST, early metabolic responses were classified as metabolic complete response (mCR) and metabolic partial response (mPR) and association with outcome was tested with Fisher’s exact test. TIL assessment in pretreatment biopsy specimen were performed according to the recommendations from the International TILs Working Group. Lymphocytic predominant phenotype was defined as a TIL proportion of ≥ 50%. Correlation of TILs and pCR was modeled with logistic regression. Results: Overall, 58 pts were randomized to TP-A (n=29) or TP (n=29) at 9 sites. In 45 patients, a protocol predefined PERCIST assessment was available. An early mCR was achieved in 14 pts (n=14/45, 31.1%): 5 pts (n=5/21, 23.8%) in the TP group and 9 pts (n=9/24, 37.5%) in the TP-A group. Pts with and without an early mCR achieved a pCR in 92.9% (n=13/14) and 54.8% (n=17/31) of cases (p=0.016), respectively. An early mCR/mPR was achieved in 37 pts (n=37/45, 82.2%). Pts with and without an early mCR/mPR achieved a Residual Cancer Burden (RCB) class 0 or I in 89.2% (n=33/37) and 50.0% (n=4/8) of cases (p=0.024), respectively. The mean stromal TIL proportion was 23.9% in the overall population, with 22.8% in TP group and 25.0% in TP-A group. A lymphocytic predominant phenotype was seen in 10.3% of pts treated in the TP group, and 17.2% of pts treated in the TP-A group. No association between TIL proportion at baseline and pCR could be detected (OR for a 10%-point increase = 1.02, 95% CI 0.78-1.34). A moderate positive correlation between numeric values of TILs and PD-L1 ICs was observed (spearman r=0.57, P< 0.0001). Exploratory correlation analyses of PD-L1 status, TIL proportion and metabolic responses in interim FDG-PET scans will be presented at the meeting. Conclusions: In ABCSG-52, chemotherapy de-escalation with intensified immunotherapy was effective and safe. Early metabolic response assessment was feasible and predicted pathologic response; therefore, incorporation of interim FDG-PET results into de-escalation trials merits further investigation. In contrast to regimens without immune-checkpoint inhibitors, TIL proportion at baseline did not correlate with pathological outcome. Funding: Provision of IMP and financial support by Roche Austria GmbH Citation Format: Gabriel Rinnerthaler, Daniel Egle, Rupert Bartsch, Clemens Schmitt, Andreas Petzer, Marija Balic, Edgar Petru, Ursula Denison, Christian F. Singer, Vesna Bjelic-Radisic, Simon Gampenrieder, Michael Knauer, Karl Sotlar, Christine Brunner, Florian Posch, Dominik Hlauschek, Lidija Sölkner, Zsuzsanna Bago-Horvath, Martin Filipits, Manuela Gili, Michael Gnant, Richard Greil. Pathological response according to early metabolic remission in an interim FDG-PET scan and to tumor infiltrating lymphocytes - A secondary analysis of the phase II trial ABCSG 52/ATHENE investigating atezolizumab in early HER2+ BC [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-01-03.

Abstract PO4-13-06: Effect of neoadjuvant dose-dense dose-intense chemotherapy timing infusion on complete histological response rate among patients with triple negative breast cancer (SIMCLOCK)

Abstract Background: Triple-negative breast cancers (TNBC) exhibit major responses to dose-dense, dose-intense (DD-DI) neoadjuvant chemotherapy (NAC) (1). Although chronomodulated chemotherapy has shown efficacy and reducing toxicity in other cancers, there are no data in breast cancers (2). We report here a series of patients with TNBC treated with DD-DI NAC and analyzed the association between chemotherapy time infusion and pathological complete response rate (pCR) and residual tumor burden (RCB). Patients and Methods: Patients with non-metastatic TNBC treated at breast cancer disease center, St Louis hospital (Paris, France), with neoadjuvant DD-DI cyclophosphamide (1200 mg/m2 d1) – epirubicin (75 mg/m2 d1) q2w (SIM regimen) followed by 12 injections of paclitaxel (80 mg/m2) qw were included. Starting time of each chemotherapy infusion were systematically recorded. Primary endpoint was pCR defined as no residual invasive tumor in breast and in lymph nodes. Patients were dichotomized into “morning” and “afternoon” infusion groups, independently for “SIM” and “paclitaxel” regimens. Two timing cut-offs were defined according to: 1) median time of all infusions 2) cut-off maximizing morning/afternoon differences of RCB. Statistical differences between the two patient groups were assessed for metabolic response at 2 courses at Pet scan (breast delta SUVmax), RCB class (0-1 vs 2-3), pCR, dose reduction rate and 24-months event-free survival (24-months EFS). Results: Between January 2018 and January 2022, 93 patients were included. Median age was 51 (28-74). Majority of SIM administrations occurred between 12:00 and 15:00 and Paclitaxel administrations between 11:20 and 14:30. Median follow-up was 32.4 months. Main characteristics between “morning group” or “afternoon” groups in the SIM or paclitaxel were similar. pCR was obtained in 48.9% of the whole population. Regardless of cut-offs defined, no difference in pCR rate was observed. Similarly, no differences were observed between morning and afternoon groups in terms of either metabolic response, dose reduction rate or 24-months EFS (table 1). Conclusion: Time of DD-DI NAC infusion is not associated with differences in pCR rate nor in RCB, toxicity and EFS in patients with early TNBC. As immunotherapy combined with NAC is a new standard in TNBC, the impact of immunotherapy infusion time combined with NAC is under evaluation.

Abstract PO2-09-05: Building genomic and transcriptomic data among African American and Black patients with triple-negative inflammatory breast cancer

Abstract Background: Inflammatory breast cancer (IBC) is an aggressive breast cancer associated with poor response and early metastases. It represents a health disparity, with higher incidence and worse outcomes in Black compared to White patients. Further, IBC is enriched for the more aggressive triple-negative receptor subtype, TN-IBC, and this subtype is more prevalent among Black IBC patients. It is critical to identify genetic and molecular features that may guide better treatments for these aggressive cancers across races, and thus imperative to identify and increase racial representation among bioinformatics datasets. We previously performed comprehensive genomic and transcriptomic analyses for TN-IBC patient samples and here examine the differences among self-identified African American or Black (AA/B) and other races among IBC patients. Methods: As previously described, we collected matched blood and baseline tumor samples before treatment from 19 patients with primary TN-IBC. We performed whole exome and RNA sequencing (RNA-Seq) on these samples and compared mutations and differentially expressed genes (DEGs). Results were compared between 3 AA/B patient tissues vs the remaining 16 (Other) cases. Results: Mutations shared by all AA/B patients included amplification of the five most commonly mutated hallmark genes in the complete cohort, ARNT, BCL9, DDR2, FCGR2B and LMNA (all 100% in AA/B patients versus all 50% in the Other cohort). All AA/B patients had a Notch1 mutation (two deletions and one missense mutation, 100% AA/B vs 6% Other (one deletion)). Comparing differentially expressed genes and gene set enrichment analyses of the Broad molecular signatures database (MSigDB) demonstrates the majority of DEGs are downregulated in these AA/B patients. Six of the top 20 downregulated gene sets from the MSigDB C2 group relate to breast cancer subtype and among this TNIBC cohort AA/B tumor expression was downregulated for luminal and normal subtype related genes in multiple gene sets and enriched in the Lien metaplastic related genes. In the MSigDB C5 sets, over half of the top 20 enriched gene ontology sets among AA/B patients related to chromosomes, chromatin, spindle assembly or histone binding, while 16 of the top 20 downregulated enriched sets related to immune function. Multiple KEGG pathways enriched in AA/B cases related to RNA processing and expression and DNA replication and repair. Lastly, hallmark gene sets enriched in AA/B patients were cell cycle related, and targets of Myc, Hedgehog, B-catenin, TGFb, and TNFa via NFKb, while top significantly downregulated sets related to metabolism and immune response. Conclusion: While findings from a small sample size can only be considered hypothesis generating, some patterns emerge from the data among this rare cohort of AA/B TN IBC patients. These tumors appear to be devoid of luminal signals, characterized by cell cycle and chromatin remodeling signals, enriched for signaling typical of stem cell self-renewal, and perhaps more immune-deprived than other TN-IBC. Additional work to build racially diverse IBC transcriptomic data are needed to develop strategies to understand and improve outcomes for these patients. Citation Format: Wencai Ma, Li Zhao, Gayathri Devi, Savitri Krishnamurthy, Larry Coffer, Angela Alexander, Megumi Kai, Xiaoping Wang, Huong Le-Petross, Miral Patel, Bisrat Debeb, Chandra Bartholomeusz, Jianhua Zhang, Xingzhi Song, Andrew Futreal, Naoto Ueno, Rachel Layman, Anthony Lucci, Jing Wang, Wendy Woodward. Building genomic and transcriptomic data among African American and Black patients with triple-negative inflammatory breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-09-05.

FBXO28 reduces high-fat diet-induced hyperlipidemia in mice by alleviating abnormal lipid metabolism and inflammatory responses.

Hyperlipidemia is a lipid metabolism disorder with increasing incidence and prevalence worldwide. Abnormal lipid metabolism and inflammation are two significant characteristics of hyperlipidemia. The purpose of this study was to explore the role and mechanism of F-box only protein 28 (FBXO28) in hyperlipidemia. Mice were fed with high-fat diet (HFD) to elicit obesity, and 3T3-L1 preadipocytes were stimulated with MDI cocktail (IBMX, DEX and insulin) to evoke differentiation. In vivo and in vitro role of FBXO28 in hyperlipidemia was investigated by hematoxylin-eosin and oil Red O staining, the lipid biochemistry measurement, enzyme-linked immunosorbent assay, reverse transcription quantitative polymerase chain reaction and western blotting assays. The mechanism of FBXO28 explored by co-immunoprecipitation, immunofluorescence, ubiquitination and cycloheximide assays. Low expression of FBXO28 was found in hyperlipidemia in silico, in vivo and in vitro. Upregulation of FBXO28 declined the body weight, fat accumulation, and serum lipid content in HFD-fed mice. Abnormal lipid accumulation, and the level of liposynthetic genes and beta-oxidation related genes were improved by overexpression of FBXO28 both in HFD-elicited mice and MDI-treated 3T3-L1 preadipocytes. Besides, overexpression of FBXO28 declined HFD-induced the level of proinflammatory factors and F4/80. Mechanically, FBXO28 directly bound RAB27A and promoted its ubiquitinated degradation. Thus, upregulation of RAB27A inverted the improved role of FBXO28 in abnormal lipid metabolism and inflammation in vivo and in vitro. FBXO28 ameliorated abnormal lipid metabolism and inflammation through the ubiquitinated degradation of RAB27A, thereby attenuating HFD-induced hyperlipidemia. The results could promote the treatment of hyperlipidemia, and the relevant diseases.

Succinylation of Park 7 Activates a Protective Metabolic Response to Acute Kidney Injury.

Acute Kidney Injury (AKI) is extremely prevalent among hospitalizations and presents a significant risk for the development of chronic kidney disease and increased mortality. Ischemia caused by shock, trauma, and transplant are common causes of AKI. To attenuate ischemic AKI therapeutically, we need a better understanding of the physiological and cellular mechanisms underlying damage. Instances of ischemia are most damaging in Proximal Tubule Epithelial Cells (PTECs) where hypoxic signaling cascades, and perhaps more rapidly, posttranslational modifications (PTMs), act in concert to change cellular metabolism. Here we focus on the effects of the understudied PTM, lysine succinylation. We have previously shown a protective effect of protein hypersuccinylation on PTECs after depletion of the desuccinylase Sirtuin 5. General trends in the results suggested that hypersuccinylation led to upregulation of peroxisomal activity and was protective against kidney injury. Included in the list of changes was the Parkinson's-related deglycase Park7. There is little known about any links between peroxisome activity and Park7. In this study we show in vitro and in vivo that Park7 has a crucial role in protection from AKI, and upregulated peroxisome activity. These data in combination with published results of Park7's protective role in cardiovascular damage and chronic kidney disease lead us to hypothesize that succinylation of Park7 may ameliorate oxidative damage resulting from AKI and prevent disease progression. This novel mechanism provides a potential therapeutic mechanism that can be targeted.

The effects of dietary macronutrient composition on resting energy expenditure following active weight loss: A systematic review and meta-analysis.

A systematic review and meta-analysis was conducted to evaluate the relative effectiveness of different dietary macronutrient patterns on changes in resting energy expenditure (REE) in relation to weight loss, categorized as minimal (<5%) and moderate to high (>5%). Changes in REE were assessed using a DerSimonian and Laird random-effects meta-analysis. A diet lower in carbohydrates (CHO) or higher in fat and protein was associated with smaller reductions in REE, with these trends being more pronounced among participants who experienced moderate to high weight loss. Adjusted meta-regression analysis indicated that, within the participants who experienced moderate to high weight loss, each 1% increase in CHO intake was associated with a reduction of 2.30 kcal/day in REE (95% CI: -4.11 to -0.47, p = 0.013). In contrast, a 1% increase in protein and fat intake was correlated with an increase in REE by 3.00 (95% confidence interval [CI] [1.02, 5.07], p = 0.003) and 0.5 (95% CI [-2.43, 3.41], p = 0.740) kcal/day, respectively. No significant associations were found among participants who experienced minimal weight loss. These findings indicate that, under a caloric deficit, the impact of dietary macronutrient composition on REE may vary depending on the degree of weight loss and individual metabolic responses.

Resistance Exercise Sessions Comprising Multijoint vs. Single-Joint Exercises Result in Similar Metabolic and Hormonal Responses, But Distinct Levels of Muscle Damage in Trained Men.

Barbosa, PH, Bueno de Camargo, JB, Jonas de Oliveira, J, Reis Barbosa, CG, Santos da Silva, A, Dos-Santos, JW, Verlengia, R, Barreira, J, Braz, TV, and Lopes, CR. Resistance exercise sessions comprising multijoint vs. single-joint exercises result in similar metabolic and hormonal responses, but distinct levels of muscle damage in trained men. J Strength Cond Res 38(5): 842-847, 2024-Resistance-type exercise (RE) elicits distinct acute metabolic and hormonal responses, which can be modulated by the manipulation of training variables. The purpose of this study was to compare the metabolic (blood lactate and estimated lactic anaerobic system energy expenditure) and hormonal (growth hormone [GH]) responses to RE sessions composed exclusively of multijoint (MULTI) or single-joint (SINGLE) exercises. Assessments of creatine kinase (CK) levels were also performed. In a crossover design, 10 recreationally resistance-trained men (age: 26.9 ± 3.0 years, total body mass: 83.2 ± 13.8 kg; height: 176 ± 7.0 cm; training experience: 5.5 ± 2.4 years) were randomly submitted to both protocols. Blood collections were made pre, 3 minutes after, and 36 hours after each experimental session. No significant difference between MULTI vs. SINGLE was observed for the rises in blood lactate (p = 0.057) and GH (p = 0.285) levels. For CK, a significant difference between the protocols was noted, in which MULTI resulted in significant rises after 3 minutes (p = 0.017) and 36 hours (p = 0.043) compared with SINGLE. In conclusion, the findings of this study suggest that resistance-trained individuals display similar metabolic and hormonal responses when performing MULTI and SINGLE exercise protocols. Also, RE sessions comprising MULTI exercises induce a higher magnitude of muscle damage, which may require a longer recovery period compared with SINGLE.

Impact of chickpea hummus on postprandial blood glucose, insulin and gut hormones in healthy humans combined with mechanistic studies of food structure, rheology and digestion kinetics

Slowing the rate of carbohydrate digestion leads to low postprandial glucose and insulin responses, which are associated with reduced risk of type 2 diabetes. There is increasing evidence that food structure plays a crucial role in influencing the bioaccessibility and digestion kinetics of macronutrients. The aims of this study were to compare the effects of two hummus meals, with different degrees of cell wall integrity, on postprandial metabolic responses in relation to the microstructural and rheological characteristics of the meals. A randomised crossover trial in 15 healthy participants was designed to compare the acute effect of 27 g of starch, provided as hummus made from either intact chickpea cells (ICC) or ruptured chickpea cells (RCC), on postprandial metabolic responses. In vitro starch digestibility, microstructural and rheological experiments were also conducted to evaluate differences between the two chickpea hummus meals. Blood insulin and GIP concentrations were significantly lower (P < 0.02, P < 0.03) after the consumption of the ICC meal than the meal containing RCC. In vitro starch digestion for 90 min was slower in ICC than in RCC. Microscopic examination of hummus samples digested in vitro for 90 min revealed more intact chickpea cells in ICC compared to the RCC sample. Rheological experiments showed that fracture for ICC hummus samples occurred at smaller strains compared to RCC samples. However, the storage modulus for ICC was higher than RCC, which may be explained by the presence of intact cells in ICC. Food structure can affect the rate and extent of starch bioaccessibility and digestion and may explain the difference in the time course of metabolic responses between meals. The rheological properties were measured on the two types of meals before ingestion, showing significant differences that may point to different breakdown mechanisms during subsequent digestion.This trial was registered at clinicaltrial.gov as NCT03424187.

The differential effects of palmitic acid and oleic acid on the metabolic response of hypothalamic astrocytes from male and female mice.

Diets rich in saturated fats are more detrimental to health than those containing mono- or unsaturated fats. Fatty acids are an important source of energy, but they also relay information regarding nutritional status to hypothalamic metabolic circuits and when in excess can be detrimental to these circuits. Astrocytes are the main site of central fatty acid β-oxidation, and hypothalamic astrocytes participate in energy homeostasis, in part by modulating hormonal and nutritional signals reaching metabolic neurons, as well as in the inflammatory response to high-fat diets. Thus, we hypothesized that how hypothalamic astrocytes process-specific fatty acids participates in determining the differential metabolic response and that this is sex dependent as males and females respond differently to high-fat diets. Male and female primary hypothalamic astrocyte cultures were treated with oleic acid (OA) or palmitic acid (PA) for 24 h, and an untargeted metabolomics study was performed. A clear predictive model for PA exposure was obtained, while the metabolome after OA exposure was not different from controls. The observed modifications in metabolites, as well as the expression levels of key metabolic enzymes, indicate a reduction in the activity of the Krebs and glutamate/glutamine cycles in response to PA. In addition, there were specific differences between the response of astrocytes from male and female mice, as well as between hypothalamic and cerebral cortical astrocytes. Thus, the response of hypothalamic astrocytes to specific fatty acids could result in differential impacts on surrounding metabolic neurons and resulting in varied systemic metabolic outcomes.

Nanoplastic contamination: Impact on zebrafish liver metabolism and implications for aquatic environmental health

Nanoplastics (NPs) are increasingly pervasive in the environment, raising concerns about their potential health implications, particularly within aquatic ecosystems. This study investigated the impact of polystyrene nanoparticles (PSN) on zebrafish liver metabolism using liquid chromatography hybrid quadrupole time of flight mass spectrometry (LC-QTOF-MS) based non-targeted metabolomics. Zebrafish were exposed to 50 nm PSN for 28 days at low (L-PSN) and high (H-PSN) concentrations (0.1 and 10 mg/L, respectively) via water. The results revealed significant alterations in key metabolic pathways in low and high exposure groups. The liver metabolites showed different metabolic responses with L-PSN and H-PSN. A total of 2078 metabolite features were identified from the raw data obtained in both positive and negative ion modes, with 190 metabolites deemed statistically significant in both L-PSN and H-PSN groups. Disruptions in lipid metabolism, inflammation, oxidative stress, DNA damage, and amino acid synthesis were identified. Notably, L-PSN exposure induced changes in DNA building blocks, membrane-associated biomarkers, and immune-related metabolites, while H-PSN exposure was associated with oxidative stress, altered antioxidant metabolites, and liver injury. For the first time, L-PSN was found depolymerized in the liver by cytochrome P450 enzymes. Utilizing an analytical approach to the adverse outcome pathway (AOP), impaired lipid metabolism and oxidative stress have been identified as potentially conserved key events (KEs) associated with PSN exposure. These KEs further induced liver inflammation, steatosis, and fibrosis at the tissue and organ level. Ultimately, this could significantly impact biological health. The study highlights the PSN-induced effects on zebrafish liver metabolism, emphasizing the need for a better understanding of the risks associated with NPs contamination in aquatic ecosystems.

DOES EXERCISE INFLUENCE CHRONIC INFLAMMATION IN BURNS &amp;gt;1 YEAR AFTER INJURY?

A burn is one of the most traumatic injuries a person can sustain, and along with mental and physical scars, trigger a greater and more persistent inflammatory and metabolic response than other trauma cases, with hypermetabolic and hyperinflammation being reported &amp;gt;3 years post-burn. Exercise has been shown to positively influence inflammatory and metabolic function in both healthy and diseased cohorts, however little is known about the influence of exercise on chronic inflammation and metabolism in burn survivors. The aim of this study was to determine the effects of an exercise intervention on inflammatory and metabolic markers in patients who had sustained a burn injury &amp;gt;1 year ago. In this study 15 participants were randomised in a cross over design into one of two conditions, either exercise-control, or control-exercise. The exercise condition comprised of six weeks of resistance and aerobic exercise, completed remotely or supervised in a hospital gym. A comprehensive battery of clinical and physiological assessments was completed at 0, 3 and 6 weeks of each exercise and control condition. The primary outcome measure for this study was TNF-alpha and how this changed in response to the exercise condition. Secondary measures included indirect calorimetry, metabolomic and lipidomic analysis, strength and aerobic fitness testing, body composition and questionnaires related to functional status and physical activity history. It is hoped that the results from this study will contribute to the future of post-burn rehabilitation and continue to develop the understanding surrounding the chronic post-response physiological response.

CARDIOVASCULAR RESPONSE AND COST OF DOWNHILL WALKING: A NOVEL EXERCISE MODALITY FOR PEOPLE WITH TYPE 2 DIABETES MELLITUS (T2DM)

INTRODUCTION &amp; AIMS Exercise is a cornerstone in managing T2DM, along with diet and medication. Walking is the easiest to perform and most widely recommended exercise for people with T2DM. However, people with T2DM appear to walk 1200 to 2500 less steps per day than healthy people as many find exercise or walking to be exhausting. Downhill walking may be an alternative to conventional exercise for people with T2DM. Little is known about the metabolic cost of incline walking in people with T2DM. This study determined the energy cost of walking downhill, uphill, and on a flat level surface in people with T2DM. METHODS Participants walked on a treadmill at 2.5 km/hr, starting at 0% grade for 4 minutes and progressing to 4%, 8%, 12%, and 16% for four minutes at each grade. After resting for 10 minutes, they walked downhill at -4%, -8%, -12%, and -16% grades. Borg’s 6-20 RPE scale measured perceived exertion, while VO2, pulmonary ventilation, and energy expenditure were measured using an automated gas analysis system. Expired gas was collected every 15 seconds, and the average of the four readings of the fourth minute of walking at each grade was used for analysis. RESULTS Compared to flat-level the 4%, 8%, 12% and 16% incline increased energy cost by 17.5%, 42.6%, 68.3% and 95.1% respectively. Compared to level walking, walking at -4%, -8%, -12% and -16% treadmill decline decreased the metabolic energy cost by 13.1%, 15.2%, 17.9% and 13.4% respectively. Similarly, cardiometabolic response (HR) and perceived effort during downhill walking were lower than walking uphill. CONCLUSION Health professionals wanting to promote exercise as part of a lifestyle approach to manage T2DM could consider downhill walking as an exercise option as it induces lower cardiovascular and metabolic responses and is perceived as easier than uphill walking.

Alpha-ketoglutarate supplementation in long-lived Drosophila melanogaster: Impact on lifespan and metabolic responses.

Studies on antiaging remedies in insect models sometimes show discrepancies in results. These discrepancies could be explained by different responses of short- and long-lived strains on the antiaging remedies. The purpose of the study was to test whether life-prolonging effects of alpha-ketoglutarate (AKG), observed in nematodes and fruit flies, would be reproduced in long-lived Drosophila melanogaster flies. Lifespan was assayed in flies kept in demographic cages. Fecundity, proportion of flies capable of negative geotaxis, starvation resistance, time of heat coma onset, levels of triacyglycerols, body glucose, glycogen, activities of glutamate dehydrogenase, catalase, glutathione-S-transferase, hexokinase, phosphofructokinase, pyruvate kinase, lactate, and glutamate dehydrogenases were assessed. Dietary AKG did not affect fly lifespan on the diet with 5% yeast and 5% sucrose (5Y:5S) and on the diet with 9% yeast and 1% sucrose (9Y:1S), but increased lifespan on the low-protein diet (1Y:9S). Twenty-five-day-old female flies fed a 5Y:5S diet with 10 mM AKG for 3 weeks, did not differ from the control group (without AKG) in climbing activity, resistance to heat stress, and starvation. The levels of glucose and glycogen were unaffected but the levels of triacylglycerols were lower in AKG-fed female flies. No differences in activities of glycolytic enzymes, NADPH-producing enzymes, glutamate dehydrogenase, oxygen consumption, and levels of oxidative stress markers were observed between the control and AKG-fed flies. However, AKG-fed flies had lower activities of catalase and glutathione-S-transferase. These results suggest that potential antiaging remedies, such as AKG, may not extend lifespan in long-living organisms despite influencing several metabolic parameters.

Growth performance, health status and flesh quality of striped catfish (Pangasianodon hypophthalmus) reared in variable stocking densities in biofloc system

Optimization of ideal stocking density in intensive aquaculture system is a challenging appraisal. Higher stocking density is inducing chronic stress, impacting negatively on physiology and increasing disease associated risks in fish. Hence, the study was designed to evaluate the water quality, growth performance, health status and flesh quality of striped catfish (Pangasianodon hypophthalmus). The fish (2.61–2.64 ± 0.01 g initial body weight) were reared in randomly designed variable stocking densities (SDs) including five treatments (30, 40, 50, 60 and 70 fish m−3) in triplicates at C:N ratio 15:1 in jaggery supplemented biofloc system for 120 days in 1000 –L experimental fiber-reinforced plastic tanks. SD30 acted as control treatment having low stocking density. During the culture, pH, alkalinity and dissolved oxygen level decreased and BOD increased with increased stocking density. TDS and TSS level increased upto SD50 treatment and further decreased in higher stocking density treatments. Higher population of heterotrophic, ammonifying and nitrifying bacteria significantly (p < 0.05) reduced TAN, NH3-N, NO2-N, and elevated NO3-Nas well as rate and potential of ammonification and nitrification in SD50 treatment than other treatments. Bacillariophyceae and protozoa were most dominant group in the biofloc microbiome in all the treatments. Highly elevated biofloc volume, floc microbiome, good floc characteristics and floc quality might have enhanced fish survival rate, body weight gain, SGR through improving FCR in SD50 than other SDs. Moreover, higher population of gut microbiota (TPC and probiotic) and elevated digestive enzymes activity in fish reared in SD50 treatment significantly (p < 0.05) enhanced PER, ANPU, and somatic indices (GSI and HSI) as well as enhanced colour (lightness, yellowness/blueness and whiteness), flesh quality and hardness. Fish reared in SD50 treatment showed significantly (p < 0.05) higher haematological (TEC, TLC and Hb), immunological (TSP, albumin, RBA and lysozyme), antioxidant responses (higher SOD and CAT) and lower metabolic stress enzymes responses (ALT, AST and glucose). Moreover, fish reared in SD50 treatment showed improved villi surface area and height in intestine and slightly vacuolated hepatocytes in liver. Overall, significantly (p < 0.05) better water quality, fish performance, health status and flesh quality were observed in SD50. Collectively, the findings suggest that farmers can be benefitted by fetching higher production through suitable stocking density (50fish m−3) of P. hypophthalmus in biofloc with improved water quality, growth performance, health status and flesh quality.

Solanum nigrum L. berries extract ameliorated the alcoholic liver injury by regulating gut microbiota, lipid metabolism, inflammation, and oxidative stress

Solanum nigrum L. (SN) berry is an edible berry containing abundant polyphenols and bioactive compounds, which possess antioxidant and antiinflammatory properties. However, the effects of SN on alcohol-induced biochemical changes in the enterohepatic axis remain unclear. In the current study, a chronic ethanol-fed mice ALD model was used to test the protective mechanisms of SN berries. Microbiota composition was determined via 16S rRNA sequencing, we found that SN berries extract (SNE) improved intestinal imbalance by reducing the Firmicutes to Bacteroides ratio, restoring the abundance of Akkermansia microbiota, and reducing the abundance of Allobaculum and Shigella. SNE restored the intestinal short-chain fatty acids content. In addition, liver transcriptome data analysis revealed that SNE primarily affected the genes involved in lipid metabolism and inflammatory responses. Furthermore, SNE ameliorated hepatic steatosis in alcohol-fed mice by activating AMP-activated protein kinase (AMPK), acetyl-CoA carboxylase (ACC), peroxisome proliferator-activated receptor α (PPAR-α). SNE reduced the expression of toll-like receptor 4 (TLR4), myeloid differentiation factor-88 (MyD88) nuclear factor kappa-B (NF-κB), which can indicate that SNE mainly adjusted LPS/TLR4/MyD88/NF-κB pathway to reduce liver inflammation. SNE enhanced hepatic antioxidant capacity by regulating NRF2-related protein expression. SNE alleviates alcoholic liver injury by regulating of gut microbiota, lipid metabolism, inflammation, and oxidative stress. This study may provide a reference for the development and utilization of SN resources.

PERIPHERAL AND CENTRAL DEMANDS OF REPEATED-SPRINT EXERCISE WITH CONTINUOUS BLOOD FLOW RESTRICTION FOR TEAM-SPORT PLAYERS

INTRODUCTION &amp; AIMS Team-sport players’ repeated-sprint ability improves following repeated-sprint training with systemic hypoxia (reduced fraction of inspired oxygen) through enhanced metabolic demands compared to sea-level training. Localised hypoxia (i.e., blood flow restriction; BFR) presents a limb-specific alternative strategy, though central and peripheral demands during multiple-set repeated-sprint BFR exercise have not been quantified for team-sport players. Therefore, this study aimed to assess the impact of BFR during repeated-sprint exercise on performance, metabolic, neuromuscular, and perceptual responses for team-sport players. METHODS Twenty-six semi-professional and amateur team-sport players performed cycling repeated-sprint exercise (three sets of five 5-second sprints with 25 seconds of passive recovery) with continuous BFR at 45% arterial occlusion pressure or without. Power output, vastus lateralis muscle oxygenation, and cardiorespiratory responses were continuously monitored. Surface electromyography examined vastus lateralis, biceps femoris, and lateral gastrocnemius activation, and root mean square was calculated over eight consecutive cycle revolutions. Exercise-related sensations and blood lactate concentration were assessed following sets. Linear mixed models compared differences in dependent variable means between conditions and sets or repetitions. RESULTS Mean, peak power output, and oxygen consumption decreased (p &amp;lt; .01) with BFR (-5.0%, -4.5%, and -6.3%, respectively) compared to without. Vastus lateralis tissue saturation index reduced (p &amp;lt; .001) during sprints and recovery periods for BFR (-6.9% and -5.9%, respectively). Electromyography root mean square decreased (p &amp;lt; .01) for biceps femoris and lateral gastrocnemius muscles with BFR (-2.8% and -8.9%, respectively), but remained unchanged for the vastus lateralis. Perceived limb discomfort increased (p &amp;lt; .001) for BFR, though blood lactate concentration and rating of perceived exertion did not differ between conditions (p &amp;gt; .05). CONCLUSION Repeated-sprint exercise with BFR for team-sport players reduced performance and likely increased the physiological and perceptual stimulus for the periphery with greater reliance on anaerobic glycolysis, despite comparable or decreased central demands.

Holistic transcriptional responses of Cordyceps militaris to different culture temperatures

Cordyceps militaris is a medicinal entomopathogenic fungus containing valuable biometabolites for pharmaceutical applications. Its genetic inheritance and environmental factors play a crucial role in the production of biomass enriched with cordycepin. While temperature is a crucial controlled parameter for fungal cultivation, its impacts on growth and metabolite biosynthesis remains poorly characterized. This study aimed to investigate the metabolic responses and cordycepin production of C. militaris strain TBRC6039 under various temperature conditions through transcriptome analysis. Among 9,599 expressed genes, 576 genes were significantly differentially expressed at culture temperatures of 15 and 25 °C. The changes in the transcriptional responses induced by these temperatures were found in several metabolisms involved in nutrient assimilation and energy source, including amino acids metabolism (e.g., glycine, serine and threonine metabolism) and lipid metabolism (e.g., biosynthesis of unsaturated fatty acids and steroid biosynthesis). At the lower temperature (15 °C), the biosynthetic pathways of lipids, specifically ergosterol and squalene, were the target for maintaining membrane function by transcriptional upregulation. Our study revealed the responsive mechanisms of C. militaris in acclimatization to temperature conditions that provide an insight on physiological manipulation for the production of metabolites by C. militaris.

Structural insights on anti-biofilm mechanism of heated slightly acidic electrolyzed water technology against multi-resistant Staphylococcus aureus biofilm on food contact surface

Slightly acidic electrolyzed water (SAEW) has proven to be an efficient and novel sanitizer in food and agriculture field. This study assessed the efficacy of SAEW (30 mg/L) at 40 °C on the inactivation of foodborne pathogens and detachment of multi-resistant Staphylococcus aureus (MRSA) biofilm. Furthermore, the underlying mechanism of MRSA biofilm under heated SAEW at 40 °C treatment on metabolic profiles was investigated. The results showed that the heated SAEW at 40 °C significantly effectively against foodborne pathogens of 1.96–7.56 (lg (CFU/g)) reduction in pork, chicken, spinach, and lettuce. The heated SAEW at 40 °C treatment significantly reduced MRSA biofilm cells by 2.41 (lg (CFU/cm2)). The synergistic effect of SAEW treatment showed intense anti-biofilm activity in decreasing cell density and impairing biofilm cell membranes. Global metabolic response of MRSA biofilms, treated by SAEW at 40 °C, revealed the alterations of intracellular metabolites, including amino acids, organic acid, fatty acid, and lipid. Moreover, signaling pathways involved in amino acid metabolism, energy metabolism, nucleotide synthesis, carbohydrate metabolites, and lipid biosynthesis were functionally disrupted by the SAEW at 40 °C treatment. As per our knowledge, this is the first research to uncover the potential mechanism of heated SAEW treatment against MRSA biofilm on food contact surface.