-
Microbial Genomics Jul 2024Several hundred ciliate species live in animals' guts as a part of their microbiome. Among them, (Trichostomatia, Pycnotrichidae), the largest described ciliate, is...
Several hundred ciliate species live in animals' guts as a part of their microbiome. Among them, (Trichostomatia, Pycnotrichidae), the largest described ciliate, is found exclusively associated with (capybara), the largest known rodent reaching up to 90 kg. Here, we present the sequence, structural and functional annotation of this giant microeukaryote macronuclear genome and discuss its phylogenetic placement. The 85 Mb genome is highly AT rich (GC content 25.71 %) and encodes a total of 11 397 protein-coding genes, of which 2793 could have their functions predicted with automated functional assignments. Functional annotation showed that can digest recalcitrant structural carbohydrates, non-structural carbohydrates, and microbial cell walls, suggesting a role in diet metabolization and in microbial population control in the capybara's intestine. Moreover, the phylogenetic placement of provides insights on the origins of gigantism in the subclass Trichostomatia.
Topics: Phylogeny; Animals; Ciliophora; Rodentia; Genome, Protozoan; Base Composition; Molecular Sequence Annotation
PubMed: 38953769
DOI: 10.1099/mgen.0.001263 -
Asian Journal of Andrology Jul 2024Platelet-rich plasma (PRP) shows promise as a regenerative modality for mild-to-moderate erectile dysfunction (ED). However, its efficacy in treating severe ED remains...
Platelet-rich plasma (PRP) shows promise as a regenerative modality for mild-to-moderate erectile dysfunction (ED). However, its efficacy in treating severe ED remains unknown. Blood samples from 8-week-old male rats were used to prepare PRP through a two-step centrifugation procedure, followed by chitosan activation and freeze‒thaw cycle. A hyperhomocysteinemia (HHcy)-related ED model was established using a methionine-enriched diet, and an apomorphine (APO) test was conducted during the 4th week. APO-negative rats were divided into two groups and were injected with PRP or saline every 2 weeks. Erectile function and histological analyses of the corpus cavernosum were performed during the 16th week. The results revealed that erectile function was significantly impaired in rats with HHcy-related ED compared to that in age-matched rats but was improved by repeated PRP injections. Immunofluorescence staining revealed a reduction in reactive oxygen species and additional benefits on the recovery of structures within the corpus cavernosum in rats that received PRP treatment compared to those in the saline-injected control group. Therefore, PRP could enhance functional and structural recovery in a severe HHcy-related ED model. A notable strength of the present study lies in the use of a repeated intracavernous injection method, mirroring protocols used in human studies, which offers more reliable results for translating the findings to humans.
PubMed: 38953713
DOI: 10.4103/aja202418 -
Journal of the Science of Food and... Jul 2024Rice is considered a high estimated glycemic index (eGI) food because of its higher starch digestibility, which leads to type II diabetes and obesity as a result of a...
BACKGROUND
Rice is considered a high estimated glycemic index (eGI) food because of its higher starch digestibility, which leads to type II diabetes and obesity as a result of a sedentary life style. Furthermore, the incresaing diabetes cases in rice-consuming populations worldwide need alternative methods to reduce the glycemic impact of rice, with dietary prescriptions based on the eGI value of food being an attractive and practical concept. Rice is often paired with vegetables, pulses, tubers and roots, a staple food group in Africa, Latin America and Asia, which are rich in fibre and health-promoting compounds.
RESULTS
Rice from four categories (high protein, scented, general and pigmented) was analyzed for eGI and resistant starch (RS) content. Among the genotypes, Improved Lalat had the lowest eGI (53.12) with a relatively higher RS content (2.17%), whereas Hue showed the lowest RS (0.19%) with the highest eGI (76.3) value. The addition of tuber crops to rice caused a significant lowering of eGI where the maximum beneficial effect was shown by elephant foot yam (49.37) followed by yam bean (53.07) and taro (54.43).
CONCLUSION
The present study suggests that combining rice with suitable tuber crops can significantly reduce its eGI value, potentially reducing the burden of diet-associated lifestyle diseases particularly diabetics. © 2024 Society of Chemical Industry.
PubMed: 38953558
DOI: 10.1002/jsfa.13679 -
Journal of Human Nutrition and... Jul 2024Schools and early years settings provide an opportunity to promote healthy and sustainable food, but standards and guidance in England focus predominantly on nutritional...
BACKGROUND
Schools and early years settings provide an opportunity to promote healthy and sustainable food, but standards and guidance in England focus predominantly on nutritional quality. The present study estimated greenhouse gas emissions (GHGE) of school lunches provided for children attending school nurseries, including comparison between meal options.
METHODS
Menus, recipes and portion weights for lunches provided for 3-4-year-old children attending nine school nurseries were collected daily for one week. GHGE for each food and recipe were calculated using Foodprint functionality of Nutritics software. GHGE were calculated for each menu option (main, vegetarian, jacket potato and sandwich) provided in each school, and for meals with and without meat/fish.
RESULTS
In total, 161 lunches including 273 foods were analysed. Median GHGE across all meals was 0.53 kgCOe (i.e. kilograms of carbon dioxide equivalent) per portion, with significantly higher GHGE associated with main meals (0.71 kgCOe per portion) compared to all other meal types (0.43-0.50 kgCOe per portion; p < 0.001) which remained after adjustment for meal size and energy density. Red meat-based meals were highest in GHGE (median 0.98 kgCOe per portion and 0.34 kgCOe per 100 g) and meals containing any meat/fish were significantly higher in GHGE (median 0.58 kgCOe per portion) than vegetarian meals (median 0.49 kgCOe per portion) (p = 0.014). Meals with higher adherence to the nutrient framework underpinning the early years guidelines had significantly higher GHGE than meals with lower adherence (p < 0.001).
CONCLUSIONS
The results were comparable to previous estimates of school lunch GHGE and highlight variation by meal option. Consideration of GHGE alongside the nutritional quality of lunches by caterers could support provision of healthy and sustainable lunches.
PubMed: 38953466
DOI: 10.1111/jhn.13345 -
Magnesium Research Jun 2024Pathogenic mechanisms implicated in the development of Parkinson disease (PD) are multifaceted and include alpha synuclein aggregation, oxidative stress due to... (Review)
Review
Pathogenic mechanisms implicated in the development of Parkinson disease (PD) are multifaceted and include alpha synuclein aggregation, oxidative stress due to generation of reactive oxygen species (ROS), mitochondrial dysfunction, apoptosis, imbalance of trace elements as well as endoplasmic reticulum stress, and inflammation. Alteration in the homeostasis of bivalent cations, such as iron, magnesium and calcium, has been implicated in the pathogenesis of PD. Low levels of magnesium have been associated with accelerated dopaminergic cell loss in animal PD models, and magnesium has been shown to have a neuroprotective effect in PD models. Evidence of a low magnesium level in the brain of PD individuals, with a low magnesium level in the diet, increasing the risk of PD, further strengthens the role of magnesium deficiency in the pathogenesis of PD. The presence of low-level magnesium in brain tissue and high level in CSF and serum support the possibility of dysfunctional magnesium transporters in PD. Indeed, variants in magnesium transport channels, such as TRPM7 and SLC41A1, have been recently detected in PD individuals. Magnesium, being an NMDA antagonist, could also have a therapeutic role in levodopa-induced dyskinesia. There are no clinical studies indicating a neuroprotective role of magnesium in PD, however, the Mediterranean diet and variants of the diet have been associated with a lower risk of PD, which may be due to the magnesium-rich constituents of the diet. Further clinical trials encompassing therapeutic models to optimize channel function, coupled with a high magnesium diet, may pave the way for promising neuroprotective intervention for PD.
Topics: Humans; Magnesium; Parkinson Disease; Neuroprotective Agents; Animals
PubMed: 38953416
DOI: 10.1684/mrh.2024.0523 -
Cell Biochemistry and Function Jul 2024β-Nicotinamide mononucleotide (NMN) is a biologically active nucleotide that regulates the physiological metabolism of the body by rapidly increasing nicotinamide...
β-Nicotinamide mononucleotide (NMN) is a biologically active nucleotide that regulates the physiological metabolism of the body by rapidly increasing nicotinamide adenine dinucleotide (NAD). To determine the safety and biological activity of NMN resources, we constructed a recombinant strain of P. pastoris that heterologously expresses nicotinamide-phosphate ribosyltransferase (NAMPT), and subsequently catalyzed and purified the expressed product to obtain NMN. Consequently, this study established a high-fat diet (HFD) obese model to investigate the lipid-lowering activity of NMN. The findings showed that NMN supplementation directly increased the NAD levels, and reduced HFD-induced liver injury and lipid deposition. NMN treatment significantly decreased total cholesterol (TC) and triglyceride (TG) in serum and liver, as well as alanine aminotransferase (ALT) and insulin levels in serum (p < .05 or p < .01). In conclusion, this study combined synthetic biology with nutritional evaluation to confirm that P. pastoris-generated NMN modulated lipid metabolism in HFD mice, offering a theoretical framework and evidence for the application of microbially created NMN.
Topics: Animals; Nicotinamide Mononucleotide; Lipid Metabolism; Diet, High-Fat; Mice; Liver; Male; Mice, Inbred C57BL; Nicotinamide Phosphoribosyltransferase
PubMed: 38953407
DOI: 10.1002/cbf.4087 -
MSphere Jul 2024Ticks, like other obligatory blood-feeding arthropods, rely on endosymbiotic bacteria to supplement their diet with B vitamins lacking in blood. It has been suggested...
UNLABELLED
Ticks, like other obligatory blood-feeding arthropods, rely on endosymbiotic bacteria to supplement their diet with B vitamins lacking in blood. It has been suggested that additional metabolites such as L-proline may be involved in this nutritional symbiosis, but this has yet to be tested. Here, we studied the metabolite-based interaction between the brown dog tick (Acari: Ixodidae) and its like endosymbionts (CLE). We measured amino acid titers and tested the effect of B vitamins and L-proline supplementation on the fitness of CLE-suppressed female ticks, displaying low titers of CLE. We found higher titers of L-proline in the symbiont-hosting organs of unfed ticks and in engorged blood-fed whole ticks. Supplementation of B vitamins increased the hatching rate of CLE-suppressed ticks; this effect appears to be stronger when L-proline is added. Our results indicate that L-proline is produced by CLE, and we suggest that CLE is essential in states of high metabolic demand that affects tick reproductive fitness, such as oogenesis and embryonic development. These findings demonstrate the broader effect of nutritional symbionts on their hosts and may potentially contribute to the control of ticks and tick-borne diseases.
IMPORTANCE
-like endosymbionts (CLE) are essential to the brown dog tick for feeding and reproduction. This symbiosis is based on the supplementation of B vitamins lacking in the blood diet. The involvement of additional metabolites has been suggested, but no experimental evidence is available as yet to confirm a metabolic interaction. Here, we show that B vitamins and L-proline, both of which contribute to tick reproductive fitness, are produced by CLE. These findings demonstrate the importance of symbiont-derived metabolites for the host's persistence and shed light on the complex bacteria-host metabolic interaction, which can be channeled to manipulate and control tick populations.
PubMed: 38953331
DOI: 10.1128/msphere.00693-23 -
ELife Jul 2024We studied lysosomal Ca in inflammasome. Lipopolysaccharide (LPS) + palmitic acid (PA) decreased lysosomal Ca ([Ca]) and increased [Ca] through mitochondrial ROS, which...
We studied lysosomal Ca in inflammasome. Lipopolysaccharide (LPS) + palmitic acid (PA) decreased lysosomal Ca ([Ca]) and increased [Ca] through mitochondrial ROS, which was suppressed in -KO macrophages. Inflammasome activation and metabolic inflammation in adipose tissue of high-fat diet (HFD)-fed mice were ameliorated by KO. ER→lysosome Ca refilling occurred after lysosomal Ca release whose blockade attenuated LPS + PA-induced inflammasome. Subsequently, store-operated Caentry (SOCE) was activated whose inhibition suppressed inflammasome. SOCE was coupled with K efflux whose inhibition reduced ER Ca content ([Ca]) and impaired [Ca] recovery. LPS + PA activated KCa3.1 channel, a Ca-activated K channel. Inhibitors of KCa3.1 channel or KO reduced [Ca], attenuated increase of [Ca] or inflammasome activation by LPS + PA, and ameliorated HFD-induced inflammasome or metabolic inflammation. Lysosomal Ca release induced delayed JNK and ASC phosphorylation through CAMKII-ASK1. These results suggest a novel role of lysosomal Ca release sustained by ERlysosome Ca refilling and K efflux through KCa3.1 channel in inflammasome activation and metabolic inflammation.
Topics: Animals; Inflammasomes; Mice; Lysosomes; Calcium; Potassium; Inflammation; Mice, Knockout; Endoplasmic Reticulum; Lipopolysaccharides; TRPM Cation Channels; Intermediate-Conductance Calcium-Activated Potassium Channels; Mice, Inbred C57BL; Macrophages; Male; Diet, High-Fat
PubMed: 38953285
DOI: 10.7554/eLife.87561 -
Endocrinology Jul 2024Neprilysin is a ubiquitous peptidase that can modulate glucose homeostasis by cleaving insulinotropic peptides. While global deletion of neprilysin protects mice against...
Neprilysin is a ubiquitous peptidase that can modulate glucose homeostasis by cleaving insulinotropic peptides. While global deletion of neprilysin protects mice against high fat diet (HFD)-induced insulin secretory dysfunction, strategies to ablate neprilysin in a tissue-specific manner are favored to limit off-target effects. Since insulinotropic peptides are produced in the gut, we sought to determine whether gut-specific neprilysin deletion confers beneficial effects on insulin secretion similar to that of global neprilysin deletion in mice fed HFD. Mice with conditional deletion of neprilysin in enterocytes (NEPGut-/-) were generated by crossing Vil-Cre and floxed neprilysin (NEPfl/fl) mice. Neprilysin activity was almost abolished throughout the gut in NEPGut-/- mice, and was similar in plasma, pancreas and kidney in NEPGut-/- vs control mice. An oral glucose tolerance test was performed at baseline and following 14 weeks of HFD feeding, during which glucose tolerance and glucose-stimulated insulin secretion (GSIS) were assessed. Despite similar body weight gain at 14 weeks, NEPGut-/- displayed lower fasting plasma glucose levels, improved glucose tolerance and increased GSIS compared to control mice. In conclusion, gut-specific neprilysin deletion recapitulates the enhanced GSIS seen with global neprilysin deletion in high-fat-fed mice. Thus, strategies to inhibit neprilysin specifically in the gut may protect against fat-induced glucose intolerance and beta-cell dysfunction.
PubMed: 38953181
DOI: 10.1210/endocr/bqae080 -
Frontiers in Pharmacology 2024Ezetimibe, which lowers cholesterol by blocking the intestinal cholesterol transporter Niemann-Pick C1 like 1, is reported to reduce hepatic steatosis in humans and...
BACKGROUND
Ezetimibe, which lowers cholesterol by blocking the intestinal cholesterol transporter Niemann-Pick C1 like 1, is reported to reduce hepatic steatosis in humans and animals. Here, we demonstrate the changes in hepatic metabolites and lipids and explain the underlying mechanism of ezetimibe in hepatic steatosis.
METHODS
We fed Otsuka Long-Evans Tokushima Fatty (OLETF) rats a high-fat diet (60 kcal % fat) with or vehicle (control) or ezetimibe (10 mg kg) via stomach gavage for 12 weeks and performed comprehensive metabolomic and lipidomic profiling of liver tissue. We used rat liver tissues, HepG2 hepatoma cell lines, and siRNA to explore the underlying mechanism.
RESULTS
In OLETF rats on a high-fat diet, ezetimibe showed improvements in metabolic parameters and reduction in hepatic fat accumulation. The comprehensive metabolomic and lipidomic profiling revealed significant changes in phospholipids, particularly phosphatidylcholines (PC), and alterations in the fatty acyl-chain composition in hepatic PCs. Further analyses involving gene expression and triglyceride assessments in rat liver tissues, HepG2 hepatoma cell lines, and siRNA experiments unveiled that ezetimibe's mechanism involves the upregulation of key phospholipid biosynthesis genes, CTP:phosphocholine cytidylyltransferase alpha and phosphatidylethanolamine N-methyl-transferase, and the phospholipid remodeling gene lysophosphatidylcholine acyltransferase 3.
CONCLUSION
This study demonstrate that ezetimibe improves metabolic parameters and reduces hepatic fat accumulation by influencing the composition and levels of phospholipids, specifically phosphatidylcholines, and by upregulating genes related to phospholipid biosynthesis and remodeling. These findings provide valuable insights into the molecular pathways through which ezetimibe mitigates hepatic fat accumulation, emphasizing the role of phospholipid metabolism.
PubMed: 38953111
DOI: 10.3389/fphar.2024.1406493