Modulatory Effects of Lactobacillus paracasei-Fermented Turmeric on Metabolic Dysregulation and Gut Microbiota in High-Fat Diet-Induced Obesity in Mice.

Turmeric, derived from Curcuma longa, and Lactobacillus paracasei, a lactic acid bacteria, have been studied for their potential antiobesity effects. To date, the antiobesity effects of turmeric fermented with L. paracasei have not been sufficiently investigated. This study was conducted via oral administration of 5% L. paracasei-fermented (FT) and unfermented turmeric (UT) in diet over 16 weeks using high-fat diet (HFD)-induced obese C57BL/6J mice. Results showed that the curcuminoid content of turmeric decreased following fermentation. Furthermore, FT significantly suppressed weight gain and liver and visceral adipose tissue weight and reduced plasma metabolic parameters in both the UT and FT experimental groups. The effects of FT were more noticeable than those of the unfermented form. Moreover, FT downregulated the expression of adipogenesis, lipogenesis, and inflammatory-related protein, but upregulated liver ß-oxidation protein SIRT 1, PPARα, and PGC-1α in perigonadal adipose tissue. Additionally, FT ameliorated insulin resistance by activating insulin receptor pathway protein expressions in visceral adipose tissues. FT also modulated gut microbiota composition, particularly in two beneficial bacteria, Akkermansia muciniphila and Desulfovibrio, as well as two short-chain fatty acid-producing bacteria: Muribaculum intestinale and Deltaproteobacteria. Our findings indicate that the modulation effect of FT may be an important pathway for its antiobesity mechanisms.

Lactobacillus rhamnosus 069 and Lactobacillus brevis 031: Unraveling Strain-Specific Pathways for Modulating Lipid Metabolism and Attenuating High-Fat-Diet-Induced Obesity in Mice.

Obesity is a global health crisis, marked by excessive fat in tissues that function as immune organs, linked to microbiota dysregulation and adipose inflammation. Investigating the effects of Lactobacillus rhamnosus SG069 (LR069) and Lactobacillus brevis SG031 (LB031) on obesity and lipid metabolism, this research highlights adipose tissue's critical immune-metabolic role and the probiotics' potential against diet-induced obesity. Mice fed a high-fat diet were treated with either LR069 or LB031 for 12 weeks. Administration of LB031 boosted lipid metabolism, indicated by higher AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) phosphorylation, and increased the M2/M1 macrophage ratio, indicating LB031's anti-inflammatory effect. Meanwhile, LR069 administration not only led to significant weight loss by enhancing lipolysis which evidenced by increased phosphorylation of hormone-sensitive lipase (HSL) and adipose triglyceride lipase (ATGL) but also elevated Akkermansia and fecal acetic acid levels, showing the gut microbiota's pivotal role in its antiobesity effects. LR069 and LB031 exhibit distinct effects on lipid metabolism and obesity, underscoring their potential for precise interventions. This research elucidates the unique impacts of these strains on metabolic health and highlights the intricate relationship between gut microbiota and obesity, advancing our knowledge of probiotics' therapeutic potential.

Structural Variances in Curcumin Degradants: Impact on Obesity in Mice.

Some thermal degradants of curcuminoids have demonstrated moderate health benefits in previous studies. Feruloyl acetone (FER), recently identified as a thermal degradant of curcumin, has been previously associated with anticancer and antioxidative effects, yet its other capabilities remain unexplored. Moreover, earlier reports suggest that methoxy groups on the aromatic ring may influence the functionality of the curcuminoids. To address these gaps, an animal study was conducted to investigate the antiobesity effects of both FER and its demethoxy counterpart (DFER) on mice subjected to a high-fat diet. The results demonstrated the significant prevention of weight gain and enlargement of the liver and various adipose tissues by both samples. Furthermore, these supplements exhibited a lipid regulatory effect in the liver through the adiponectin/AMPK/SIRT1 pathway, promoted thermogenesis via AMPK/PGC-1α activation, and positively influenced gut-microbial-produced short-chain fatty acid (SCFA) levels. Notably, DFER demonstrated superior overall efficacy in combating obesity, while FER displayed a significant effect in modulating inflammatory responses. It is considered that SCFA may be responsible for the distinct effects of FER and DFER in the animal study. Future studies are anticipated to delve into the efficacy of curcuminoid degradants, encompassing toxicity and pharmacokinetic evaluations.

Soil warming-induced reduction in water content enhanced methane uptake at different soil depths in a subtropical forest.

Global warming can significantly impact soil CH4 uptake in subtropical forests due to changes in soil moisture, temperature sensitivity of methane-oxidizing bacteria (MOB), and shifts in microbial communities. However, the specific effects of climate warming and the underlying mechanisms on soil CH4 uptake at different soil depths remain poorly understood. To address this knowledge gap, we conducted a soil warming experiment (+4 °C) in a natural forest. From August 2020 to October 2021, we measured soil temperature, soil moisture, and CH4 uptake rates at four different soil depths: 0-10 cm, 10-20 cm, 20-40 cm, and 40-60 cm. Additionally, we assessed the soil MOB community structure and pmoA gene (with qPCR) at the 0-10 and 10-20 cm depths. Our findings revealed that warming significantly enhanced soil net CH4 uptake rate by 12.28 %, 29.51 %, and 61.05 % in the 0-10, 20-40, and 40-60 cm soil layers, respectively. The warming also led to reduced soil moisture levels, with more pronounced reductions observed at the 20-40 cm depth compared to the 0-20 cm depth. At the 0-10 cm depth, warming increased the relative abundance of upland soil cluster α (a type of MOB) and decreased the relative abundance of Methylocystis, but it did not significantly increase the pmoA gene copies. Our structural equation model analysis indicated that warming directly regulated soil CH4 uptake rate through the decrease in soil moisture, rather than through changes in the pmoA gene and MOB community structure at the 0-20 cm depth. In summary, our results demonstrate that warming enhances soil CH4 uptake at different depths, with soil moisture playing a crucial role in this process. Under warming conditions, the drier soil pores allow for better CH4 penetration, thereby promoting more efficient activity of MOB.

L-Glutamine Substantially Improves 5-Fluorouracil-Induced Intestinal Mucositis by Modulating Gut Microbiota and Maintaining the Integrity of the Gut Barrier in Mice.

SCOPE: This study investigates the potential of glutamine to mitigate intestinal mucositis and dysbiosis caused by the chemotherapeutic agent 5-fluorouracil (5-FU). METHODS AND RESULTS: Over twelve days, Institute of Cancer Research (ICR) mice are given low (0.5 mg kg-1) or high (2 mg kg-1) doses of L-Glutamine daily, with 5-FU (50 mg kg-1) administered between days six and nine. Mice receiving only 5-FU exhibited weight loss, diarrhea, abnormal cell growth, and colonic inflammation, correlated with decreased mucin proteins, increased endotoxins, reduced fecal short-chain fatty acids, and altered gut microbiota. Glutamine supplementation counteracted these effects by inhibiting the Toll-like receptor 4/nuclear factor kappa B (TLR4/NF-κB) pathway, modulating nuclear factor erythroid 2-related factor 2/heme oxygenase 1 (Nrf2/HO-1) oxidative stress proteins, and increasing mammalian target of rapamycin (mTOR) levels, thereby enhancing microbial diversity and protecting intestinal mucosa. CONCLUSIONS: These findings underscore glutamine's potential in preventing 5-FU-induced mucositis by modulating gut microbiota and inflammation pathways.

Trans-2-nonadecyl-4-(hydroxymethyl)-1,3-dioxolane (TNHD) purified from freshwater clams markedly alleviates dimethylnitrosamine-induced hepatic fibrosis.

Liver fibrosis occurs due to injury or inflammation, which results in the excessive production of collagen and the formation of fibrotic scar tissue that impairs liver function. Despite the limited treatment options available, freshwater clams may hold promise in the treatment of liver fibrosis. In this study, we demonstrated the effects of ethanol extract of freshwater clam (FCE), ethyl acetate extract of FCE (EA-FCE), and trans-2-nonadecyl-4-(hydroxymethyl)-1,3-dioxolane (TNHD) on liver fibrosis induced by dimethylnitrosamine (DMN). Administration of FCE and TNHD alleviated liver injury, including tissue damage, necrosis, inflammation scores, fibrosis scores, serum enzymes, and triglyceride levels. Furthermore, we analyzed the expression of fibrosis-related proteins, such as α-smooth muscle actin (α-SMA) and transforming growth factor (TGF-ß), as well as the hydroxyproline content, which decreased after treatment with FCE and TNHD. Animal experiments revealed that FCE and TNHD can reduce liver fibrosis by inhibiting cytokines that activate stellate cells and decreasing extracellular matrix (ECM) secretion. Cell experiments have shown that TNHD inhibits the MAPK/Smad signaling pathway and TGF-ß1 activation, resulting in a reduction in the expression of fibrosis-related proteins. Therefore, freshwater clam extracts, particularly TNHD, may have potential therapeutic and preventive effects for the amelioration of liver fibrosis.

Efficacy and Mechanism of the Action of Live and Heat-Killed Bacillus coagulans BC198 as Potential Probiotic in Ameliorating Dextran Sulfate Sodium-Induced Colitis in Mice.

Inflammatory bowel disease alters the gut microbiota, causes defects in mucosal barrier function, and leads to dysregulation of the immune response to microbial stimulation. This study investigated and compared the efficacy of a candidate probiotic strain, Bacillus coagulans BC198, and its heat-killed form in treating dextran sulfate sodium-induced colitis. Both live and heat-killed B. coagulans BC198 increased gut barrier-associated protein expression, reduced neutrophil and M1 macrophage infiltration of colon tissue, and corrected gut microbial dysbiosis induced by colitis. However, only live B. coagulans BC198 could alleviate the general symptoms of colitis, prevent colon shortening, and suppress inflammation and tissue damage. At the molecular level, live B. coagulans BC198 was able to inhibit Th17 cells while promoting Treg cells in mice with colitis, reduce pro-inflammatory MCP-1 production, and increase anti-inflammatory IL-10 expression in the colonic mucosa. The live form of B. coagulans BC198 functioned more effectively than the heat-killed form in ameliorating colitis by enhancing the anti-inflammatory response and promoting Treg cell accumulation in the colon.

Revisiting the roles of glucose transporters in skeletal muscle physiology: is GLUT10 a novel player?

Skeletal muscle is the largest metabolic tissue responsible for systemic glucose handling. Glucose uptake into skeletal tissue is highly dynamic and delicately regulated, in part through the controlled expression and subcellular trafficking of multiple types of glucose transporters. Although the roles of GLUT4 in skeletal muscle metabolism are well established, the physiological significance of other, seemingly redundant, glucose transporters remain incompletely understood. Nonetheless, recent studies have shed light on the roles of several glucose transporters, such as GLUT1 and GLUT10, in skeletal muscle. Mice experiments suggest that GLUT10 could be a novel player in skeletal muscle metabolism in the context of mechanical overload, which is in line with the meta-analytical results of gene expression changes after resistance exercise in humans. Herein we discuss the knowns, unknowns, and implications of these recent findings.

Virofree Associates with the Modulation of Gut Microbiomes and Alleviation of DSS-Induced IBD Symptoms in Mice.

Inflammatory bowel disease (IBD) is a chronic, nonspecific inflammation of the intestines that primarily comprises Crohn's disease and ulcerative colitis. The incidence and prevalence of IBD have been increasing globally, highlighting the significance of research and prophylactic interventions. Virofree, a mixture of various botanical extracts (including grapes, cherries, olive leaves, marigolds, green tea, and others), has shown significant potential in disease prevention. This study examined the effects of Virofree on intestinal inflammation and the gut microbiota in mice using a dextran sulfate sodium (DSS)-induced model. The mice showed no adverse reactions when administered Virofree. Virofree administration reduced the disease activity index as indicated by amelioration of DSS-induced symptoms in the mice, including weight loss, diarrhea, and rectal bleeding. Regarding the gut microbiota, Virofree intervention modulated the DSS-induced decrease in gut microbial diversity; the Virofree group showed no increase in the phyla Proteobacteria or Verrucomicrobia while displaying an increase in the genus Duncaniella, bacteria that may have protective properties. These findings suggest that Virofree may have a direct or indirect impact on the composition of the gut microbiota and that it can alleviate the imbalance of the microbiome and intestinal inflammation caused by DSS treatment.

Regulation of Xenobiotic-Metabolizing Enzymes by 5-Demethylnobiletin and Nobiletin to Mitigate Benzo[a]pyrene-Induced DNA Damage In Vitro and In Vivo.

Benzo[a]pyrene (B[a]P) is a genotoxic polycyclic aromatic hydrocarbon that is metabolized by cytochrome P450 family 1 enzymes (CYP 1s) and can bind to DNA to form DNA adducts, leading to DNA damage and increased colorectal cancer risk. Previous studies have shown polymethoxyflavones to have a high potential for anticancer effects by regulating CYP 1s, especially nobiletin (NBT) and 5-demethylnobiletin (5-DMNB). However, the effects of NBT and 5-DMNB on B[a]P metabolism remain unclear. Therefore, this study aimed to clarify the effects of NBT and 5-DMNB on B[a]P-induced DNA damage in vitro and in vivo. In NCM460 cells, 5-DMNB and NBT appeared to reduce the metabolic conversion of B[a]P by regulating the aryl hydrocarbon receptor (AhR)/CYP 1s signaling pathway. This process protected NCM460 cells from B[a]P's cytotoxic effects by decreasing DNA damage and suppressing B[a]P diol-epoxide-DNA adduct formation. In BALB/c mice, 5-DMNB and NBT also protected against B[a]P-induced DNA damage. Altogether, these findings indicate that 5-DMNB and NBT attenuate B[a]P-induced DNA damage by modulating biotransformation, highlighting their chemopreventive potential against B[a]P-induced carcinogenesis. Therefore, 5-DMNB and NBT are promising agents for colorectal cancer chemoprevention in the future.

Translating Genetic Discovery into a Mechanistic Understanding of Pediatric Movement Disorders: Lessons from Genetic Dystonias and Related Disorders.

The era of next-generation sequencing has increased the pace of gene discovery in the field of pediatric movement disorders. Following the identification of novel disease-causing genes, several studies have aimed to link the molecular and clinical aspects of these disorders. This perspective presents the developing stories of several childhood-onset movement disorders, including paroxysmal kinesigenic dyskinesia, myoclonus-dystonia syndrome, and other monogenic dystonias. These stories illustrate how gene discovery helps focus the research efforts of scientists trying to understand the mechanisms of disease. The genetic diagnosis of these clinical syndromes also helps clarify the associated phenotypic spectra and aids the search for additional disease-causing genes. Collectively, the findings of previous studies have led to increased recognition of the role of the cerebellum in the physiology and pathophysiology of motor control-a common theme in many pediatric movement disorders. To fully exploit the genetic information garnered in the clinical and research arenas, it is crucial that corresponding multi-omics analyses and functional studies also be performed at scale. Hopefully, these integrated efforts will provide us with a more comprehensive understanding of the genetic and neurobiological bases of movement disorders in childhood.

Protective Effects of Piceatannol on DNA Damage in Benzo[a]pyrene-Induced Human Colon Epithelial Cells.

Evidence shows that the dietary intake of polycyclic aromatic hydrocarbons (PAHs) from food processing induces the cellular DNA damage response and leads to the development of colorectal cancer (CRC). Therefore, protecting from cellular DNA damage might be an effective strategy in preventing CRC. Benzo[a]pyrene (B[a]P) was used as a CRC initiator in the present study. Compared with other stilbenoids, piceatannol (PIC) showed the most effective inhibition of B[a]P-induced cytochrome P450 1B1 (CYP1B1) protein expression in NCM460 normal human colon epithelial cells. PIC treatment alleviated DNA migration and enhanced the expression of DNA-repair-related proteins, including histone 2AX (H2AX), checkpoint kinase 1 (Chk1), and p53, in B[a]P-induced NCM460 cells. The 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay, flow cytometry, and enzyme-linked immunosorbent assay (ELISA) revealed that PIC exerted antioxidative effects on NCM460 cells by increasing the glutathione (GSH) content and scavenging the excess intracellular reactive oxygen species (ROS) induced by B[a]P. Furthermore, PIC suppressed B[a]P-induced CYP1B1 protein expression and stimulated miR-27b-3p expression. The upregulation of phase II detoxification enzymes, such as nicotinamide adenine dinucleotide phosphate (NADPH) and quinone oxidoreductase 1 (NQO1), and the antioxidative enzyme, heme oxygenase 1 (HO-1), via the activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway was observed in the PIC-treated group. Our results suggest that PIC is a potential CRC-blocking agent due to its ability to alleviate DNA damage, decrease intracellular ROS production, modulate the metabolism and detoxification of B[a]P, and activate the Nrf2 signaling pathway in B[a]P-induced NCM460 cells.

Soil warming decreased dissolved organic carbon quantity and quality in subtropical forests.

Soil dissolved organic carbon (DOC) is the most active part in forest soil carbon pool, the responses of which to climate warming has profound effects on forest carbon cycling. Based on a manipulative soil warming experiment in subtropical evergreen broad-leaved forests, we collected soil solutions in situ and used ultraviolet-visible, infrared and three-dimensional fluorescence spectroscopy analyses to explore the effects of soil warming (+4 ℃, 1 year) on soil DOC quantity and quality along the soil profile. The results showed that soil DOC flux remained constant along the soil profile. Soil DOC mainly included two humic-like fractions and one microbial metabolite. Warming significantly decreased soil DOC flux and the abundance of aromatic and hydrophobic components, and increased the amount of low molecular weight carbohydrates. Furthermore, soil warming increased the relative proportion of humic-like fractions in the surface soil layer (0-10 cm) and microbial metabolite in the deep soil layer (30-40 cm), indicating that warming might accelerate microbial turnover in the deep layer. Overall, soil warming not only decreased soil DOC content, but also simplified the composition of soil DOC in subtropical evergreen broad-leaved forests.

Properties of Ni-Al2O3 composite coating by laser-assisted pulse electrodeposition.

To study the influence of laser process parameters on the surface properties of the coating, N i-A l 2 O 3 composite coatings on 304 stainless-steel sheets with laser-assisted pulsed electrodeposition was proposed in this paper. Laser single pulse energy and scanning speed were selected as research factors. Single-factor experiments were performed to investigate the effect of various factors on the surface morphology, particle mass fraction, microhardness, surface roughness, and corrosion resistance of the composite coating. The experimental results show that the surface properties of the composite coating first increase and then decrease with increasing laser single pulse energy. When the laser single pulse energy is 11 µJ, the minimum surface roughness value is 0.380 µm with a smooth and uniform coating surface and the best surface morphology. Moreover, as the scanning speed increases, the corrosion resistance of the composite coating initially increases and then decreases. The corrosion resistance of the composite coatings is best with a scanning speed of 1000 mm/s. When the scanning speed was 1500 mm/s, the particle mass fraction in the coating reached a maximum of 1.984%; meanwhile, the highest hardness of the composite coating was obtained with the value of 476.38 HV.

Piceatannol and 3'-Hydroxypterostilbene Alleviate Inflammatory Bowel Disease by Maintaining Intestinal Epithelial Integrity and Regulating Gut Microbiota in Mice.

Inflammatory bowel disease has become a significant health concern across the globe, causing frequent and long-term harm to the digestive system. This study evaluated the effect of piceatannol (PIC) and 3'-hydroxypterostilbene (HPSB) on dextran sulfate sodium (DSS)-induced colitis in mice and investigated whether their effects are exerted through the amelioration of gut barrier dysfunction to reduce the severity of colitis. The findings showed that both PIC and HPSB attenuated inflammation by inhibiting the TNF-α/NF-κB/MLC pathway and reducing NLRP3 inflammasome activation. However, PIC was comparably effective in modulating tight junctions. The results may be attributed to the effect of PIC on reducing cell apoptosis-associated protein expression, including Bax/Bcl-2 and caspase-3 activation. Furthermore, microbiota analysis revealed that both PIC and HPSB increased representative probiotic species, including Akkermansiaceae and Lactobacillus intestinalis, and exhibited inhibitory effects on several bacterial species (Spiroplasmataceae and Acholeplasmataceae). Based on linear discriminant analysis effect size, butyrate-producing bacteria were identified as a biomarker in the PIC group. Overall, the results demonstrated that PIC repressed inflammation, inhibited cell apoptosis, and regulated microbiota composition. Consequently, PIC is more effective in maintaining gut barrier integrity than HPSB, and it is a promising ingredient in the development of functional food for colitis prevention.

Systematic analysis of microbiota in pregnant Chinese women and its association with miscarriage.

Background: Miscarriage is the most common adverse pregnancy outcome and more than 50% of its incidence remains unexplained. Earlier studies have suggested that maternal microbiota might be associated with miscarriage, but the association is insufficiently understood. Methods: We used 16S ribosomal RNA (rRNA) amplicon sequencing and metagenomic sequencing technology to characterize the bacterial composition of three sites including the rectum, vagina, and cervix of a case group of 63 pregnant women who had miscarried compared to a control group of 24 pregnant women who underwent voluntary elective abortion. Results: The alpha-diversity from the rectum and cervix was significantly decreased in the case group relative to the control group. However, we did not find significant differences in microbial diversity of vaginal samples between the two groups. Lactobacillus was the most predominant genus in the cervix and vaginal samples. Gestational age at the time of surgery was positively associated with the rectum microbiota diversity, with an effect size of 10% (P=0.004). Host factors including gestational age and red blood count (RBC) were associated with the rectal microbiota diversity. Conclusions: We detected a significantly lower rectal microbiota diversity and a pro-inflammatory tendency in the miscarriage group. This is the first study to investigate the association of microbiota from samples collected from three sites and miscarriage. Further studies are warranted to explore further the role of microbiota in miscarriage.

Ulva prolifera polysaccharide exerts anti-obesity effects via upregulation of adiponectin expression and gut microbiota modulation in high-fat diet-fed C57BL/6 mice.

Obesity is characterized by metabolic disorder and accompanying an altered and less diverse gut microbiota composition during a fat-enriched diet. Recent studies indicated that sulphated polysaccharide prevents high-fat diet (HFD) induced obesity, reduces metabolic disorder, and restores the gut microbiota. However, there are few studies about Ulva prolifera polysaccharide (UPP) may induce anti-obesogenic effects. Therefore, the present study investigates the enzymatic extracted UPP effects in HFD-fed mice. The results showed that UPP considerably slowed down the HFD-induced weight gain and improved metabolic disorders in HFD-fed mice. Notably, the effects were associated with lower body weight gain, reduced adipose tissue hypertrophy, triglyceride concentration in liver and systemic low-grade inflammation, and improved fasting blood glucose. Moreover, our result reveals that UPP may elevate the expression of AMPK via adiponectin activation. Interestingly, we found that UPP may induce PPARα agonist to enhance ß-oxidation since the elevation of CPT-1 and PPARα expression simultaneously. Meanwhile, gut microbiota analysis revealed UPP promoted the growth of Parasutterella, Feacalibaculum, and Bifidobacterium, and reduced the abundance of Acetatifactor, Tyzerella, Ruminococcus_1, and Desulfovibrio. The changes in microbiota may have a positively correlated effect on improving obesity and metabolic abnormalities. UPP may prevent HFD-induced obesity and associated metabolic diseases, as well as modulate the composition of gut microbiota to facilitate the growth of probiotics.

Role of Ketogenic Diets in Multiple Sclerosis and Related Animal Models: An Updated Review.

Prescribing a ketogenic diet (KD) is a century-old dietary intervention mainly used in the context of intractable epilepsy. The classic KD and its variants regained popularity in recent decades, and they are considered potentially beneficial in a variety of neurological conditions other than epilepsy. Many patients with multiple sclerosis (MS) have attempted diet modification for better control of their disease, although evidence thus far remains insufficient to recommend a specific diet for these patients. The results of 3 pilot clinical trials of KD therapy for MS, as well as several related studies, have been reported in recent years. The preliminary findings suggest that KD is safe, feasible, and potentially neuroprotective and disease-modifying for patients with MS. Research on corresponding rodent models has also lent support to the efficacy of KD in the prevention and treatment of experimental autoimmune encephalomyelitis and toxin-induced inflammatory demyelinating conditions in the brain. Furthermore, the animal studies have yielded mechanistic insights into the molecular mechanisms of KD action in relevant situations, paving the way for precision nutrition. Herein we review and synthesize recent advances and also identify unresolved issues, such as the roles of adipokines and gut microbiota, in this field. Hopefully this panoramic view of current understanding can inform future research directions and clinical practice with regard to KD in MS and related conditions.