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Adipose tissues serve as an energy reservoir and endocrine organ, yet the mechanisms that coordinate these functions remain elusive. Here, we show that the transcriptional coregulators, YAP and TAZ, uncouple fat mass from leptin levels and regulate adipocyte plasticity to maintain metabolic homeostasis. Activating YAP/TAZ signalling in adipocytes by deletion of the upstream regulators Lats1 and Lats2 results in a profound reduction in fat mass by converting mature adipocytes into delipidated progenitor-like cells, but does not cause lipodystrophy-related metabolic dysfunction, due to a paradoxical increase in circulating leptin levels. Mechanistically, we demonstrate that YAP/TAZ-TEAD signalling upregulates leptin expression by directly binding to an upstream enhancer site of the leptin gene. We further show that YAP/TAZ activity is associated with, and functionally required for, leptin regulation during fasting and refeeding. These results suggest that adipocyte Hippo-YAP/TAZ signalling constitutes a nexus for coordinating adipose tissue lipid storage capacity and systemic energy balance through the regulation of adipocyte plasticity and leptin gene transcription.
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Proteínas Adaptadoras de Transdução de Sinal , Adipócitos , Tecido Adiposo , Metabolismo Energético , Via de Sinalização Hippo , Leptina , Proteínas Serina-Treonina Quinases , Transdução de Sinais , Proteínas de Sinalização YAP , Animais , Leptina/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Camundongos , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas de Sinalização YAP/metabolismo , Tecido Adiposo/metabolismo , Adipócitos/metabolismo , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/genética , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Proteínas com Motivo de Ligação a PDZ com Coativador Transcricional/metabolismo , Fosfoproteínas/metabolismo , Fosfoproteínas/genética , Proteínas Supressoras de Tumor/metabolismo , Proteínas Supressoras de Tumor/genética , Transativadores/metabolismo , Transativadores/genéticaRESUMO
Heat-treated Lactiplantibacillus plantarum nF1 (HT-nF1) increases immune cell activation and the production of various immunomodulators (e.g., interleukin (IL)-12) as well as immunoglobulin (Ig) G, which plays an important role in humoral immunity, and IgA, which activates mucosal immunity. To determine the effect of HT-nF1 intake on improving immune function, a randomized, double-blind, placebo-controlled study was conducted on 100 subjects with normal white blood cell counts. The HT-nF1 group was administered capsules containing 5 × 1011 cells of HT-nF1 once a day for 8 weeks. After 8 weeks of HT-nF1 intake, significant changes in IL-12 were observed in the HT-nF1 group (p = 0.045). In particular, the change in natural killer (NK) cell activity significantly increased in subjects with low secretory (s) IgA (≤49.61 µg/mL) and low NK activity (E:T = 10:1) (≤3.59%). These results suggest that HT-nF1 has no safety issues and improves the innate immune function by regulating T helper (Th)1-related immune factors. Therefore, we confirmed that HT-nF1 not only has a positive effect on regulating the body's immunity, but it is also a safe material for the human body, which confirms its potential as a functional health food ingredient.
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Interleucina-12 , Células Matadoras Naturais , Probióticos , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Método Duplo-Cego , Temperatura Alta , Sistema Imunitário , Imunidade Inata , Imunoglobulina A/sangue , Células Matadoras Naturais/imunologia , Lactobacillus plantarum , Probióticos/administração & dosagemRESUMO
Background: Imbalance of the gut microbiome and decrease in the number of short-chain fatty acid (SCFA)-producing bacteria often affect human health by altering intestinal and immune homeostasis. The use of probiotics has been shown to be an attractive method to modulate gut microbiota to prevent or treat intestinal dysbiosis. Likewise, this study aimed to determine whether the oral consumption of heat-treated Lactiplantibacillus plantarum nF1 (HLp-nF1) induces changes in the gut environment in healthy infants by measuring changes in fecal SCFAs. Methods: The study enrolled 43 infants aged under 2 months, with 30 infants in the HLp-nF1 group receiving HLp-nF1 orally (2.5 × 1010 cells/g/pack, daily dose of two packs) for 8 weeks. The fecal samples were collected and the questionnaires were administered at weeks 0 and 8. Results: The concentrations of the total SCFAs, acetate, propionate, and butyrate significantly increased following HLp-nF1 supplementation (P < 0.0001, P < 0.0001, P < 0.0001, and P=0.028, respectively). Conclusions: Supplementation of HLp-nF1 has a positive effect on SCFA production and could be a potentially useful and straightforward method to manipulate SCFA formation.
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This study aimed to determine the alleviating effect of broccoli grown with deep sea water mineral (DSWM) fertilizer extracted from deep sea water on the development of colorectal cancer in C57BL/6N mice treated with AOM/DSS. Naturaldream Fertilizer Broccoli (NFB) cultured with deep sea water minerals (DSWM) showed a higher antioxidant effect and mineral content. In addition, orally administered NFB, showed a level of recovery in the colon and spleen tissues of mice compared with those in normal mice through hematoxylin and eosin (H&E) staining. Orally administered NFB showed the inhibition of the expression of inflammatory cytokine factors IL-1ß, IL-6, TNF, IFN-γ, and IL-12 while increasing the expression of IL-10. Furthermore, the expression of inflammatory cytokines and NF-κB in the liver tissue was inhibited, and that of inflammatory enzymes, such as COX-2 and iNOS, was reduced. In the colon tissue, the expression of p53 and p21 associated with cell cycle arrest increased, and that of Bcl-2 associated with apoptosis decreased. Additionally, the expression of Bax, Bad, Bim, Bak, caspase 9, and caspase 3 increased, indicating enhanced activation of apoptosis-related factors. These results demonstrate that oral administration of broccoli cultivated using DSWM significantly restores spleen and colon tissues and simultaneously inhibits the NF-κB pathway while significantly decreasing cytokine expression. Moreover, by inducing cell cycle arrest and activating cell apoptosis, they also suggest alleviating AOM/DSS-induced colon cancer symptoms in C57BL/6N mice.
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Brassica , Colite , Neoplasias do Colo , Camundongos , Animais , Colite/metabolismo , NF-kappa B/metabolismo , Fertilizantes/efeitos adversos , Brassica/metabolismo , Camundongos Endogâmicos C57BL , Neoplasias do Colo/metabolismo , Citocinas/metabolismo , Camundongos Endogâmicos , Minerais/metabolismo , Anti-Inflamatórios/efeitos adversos , Água do Mar , Sulfato de Dextrana/efeitos adversos , Colo/metabolismo , Modelos Animais de DoençasRESUMO
The antiobesity effects of kimchi with catechin and lactic acid bacteria as starters were studied in C57BL/6 mice with high-fat diet (HFD)-induced obesity. We prepared four types of kimchi: commercial kimchi, standard kimchi, green tea functional kimchi, and catechin functional kimchi (CFK). Body weight and weight of adipose tissue were significantly lower in the kimchi-treated groups than in the HFD and Salt (HFD +1.5% NaCl) groups. In addition, in the CFK group, the serum levels of triglycerides, total cholesterol, and low-density lipoprotein cholesterol were significantly lower and those of high-density lipoprotein cholesterol were markedly higher than the corresponding levels in the HFD and Salt groups. Moreover, CFK reduced fat cells and crown-like structures in the liver and epididymal fat tissues. The protein expression of adipo/lipogenesis-related genes in the liver and epididymal fat tissues was significantly lower (1.90-7.48-fold) in the CFK group than in the HFD and Salt groups, concurrent with upregulation of lipolysis-related genes (1.71-3.38-fold) and downregulation of inflammation-related genes (3.17-5.06-fold) in epididymal fat tissues. In addition, CFK modulated the gut microbiomes of obese mice by increasing the abundance of Bacteroidetes (7.61%), while in contrast, Firmicutes (82.21%) decreased. In addition, the presence of the Erysipelotrichaceae (8.37%) family in the CFK group decreased, while the number of beneficial bacteria of the families, Akkermansiaceae (6.74%), Lachnospiraceae (14.95%), and Lactobacillaceae (38.41%), increased. Thus, CFK exhibited an antiobesity effect through its modulation of lipid metabolism and the microbiome.
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Fármacos Antiobesidade , Catequina , Alimentos Fermentados , Lactobacillales , Animais , Camundongos , Catequina/farmacologia , Catequina/metabolismo , Lactobacillales/metabolismo , Camundongos Endogâmicos C57BL , Fármacos Antiobesidade/farmacologia , Fígado/metabolismo , Dieta Hiperlipídica/efeitos adversos , ColesterolRESUMO
This study researched the mineral composition of Korean washed-dehydrated solar salt (WDS) without bittern. It also evaluated the anticancer effects of doenjang (WDSD) prepared using WDS on azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced colon cancer in C57BL/6 mice. The mineral composition of WDS showed lower Mg (11.71 ± 1.89 g/kg) and S (9.77 ± 2.88 g/kg) contents, and it was confirmed that mice in the WDSD group (AOM/DSS+WDSD) displayed significantly lower weight loss, colon length reduction, and tumor formation compared with the control (Con) group. In addition, pathologically, it was confirmed that the extent of epithelial cell damage and inflammation in the colon tissue of the WDSD group was restored to a state similar to that of the Nor group. Besides, WDSD regulated the protein expression of apoptosis (Bcl-2-associated X protein [Bax], B cell lymphoma-2 [Bcl-2], B cell lymphoma-extra large [Bcl-xL], and caspase 9, caspase 3), and p53, p21, and proinflammatory cytokines (interleukin [IL]-6, tumor necrosis factor [TNF]-α), thereby inducing the apoptosis and cell cycle arrest of cancer cells and suppressing inflammation. In addition, the intestinal microbiota of the mice treated with WDSD were more diverse, with an abundance of Bifidobacterium, a lactic acid bacterium beneficial to colon health, was also a greater presence of Faecalibaculum, which showed antitumor effects. These results indicate that solar salts and their different processing methods affect their functional health-promoting properties. In addition, the inhibitory effect on colon cancer was further enhanced when doenjang was prepared with WDS with low Mg and S content.
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Colite , Neoplasias do Colo , Animais , Camundongos , Camundongos Endogâmicos C57BL , Neoplasias do Colo/induzido quimicamente , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/metabolismo , Colo , Citocinas/metabolismo , Interleucina-6/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Cloreto de Sódio na Dieta/metabolismo , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Azoximetano/efeitos adversos , Sulfato de Dextrana/efeitos adversos , Colite/induzido quimicamente , Colite/tratamento farmacológicoRESUMO
Brown adipose tissue (BAT) has abundant mitochondria with the unique capability of generating heat via uncoupled respiration. Mitochondrial uncoupling protein 1 (UCP1) is activated in BAT during cold stress and dissipates mitochondrial proton motive force generated by the electron transport chain to generate heat. However, other mitochondrial factors required for brown adipocyte respiration and thermogenesis under cold stress are largely unknown. Here, we show LETM1 domain-containing protein 1 (LETMD1) is a BAT-enriched and cold-induced protein required for cold-stimulated respiration and thermogenesis of BAT. Proximity labeling studies reveal that LETMD1 is a mitochondrial matrix protein. Letmd1 knockout male mice display aberrant BAT mitochondria and fail to carry out adaptive thermogenesis under cold stress. Letmd1 knockout BAT is deficient in oxidative phosphorylation (OXPHOS) complex proteins and has impaired mitochondrial respiration. In addition, BAT-specific Letmd1 deficient mice exhibit phenotypes identical to those observed in Letmd1 knockout mice. Collectively, we demonstrate that the BAT-enriched mitochondrial matrix protein LETMD1 plays a tissue-autonomous role that is essential for BAT mitochondrial function and thermogenesis.
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Tecido Adiposo Marrom , Proteínas Mitocondriais , Termogênese , Animais , Masculino , Camundongos , Adipócitos Marrons/metabolismo , Tecido Adiposo Marrom/metabolismo , Camundongos Knockout , Mitocôndrias/metabolismo , Proteínas Mitocondriais/genética , Proteínas Mitocondriais/metabolismo , Termogênese/genética , Proteína Desacopladora 1/genética , Proteína Desacopladora 1/metabolismoRESUMO
Pears are ancient functional foods for modern times. Particularly, Korean pears (Pyrus pyrifolia cv.) have been used as folk medicine for respiratory diseases and have strong potential for the treatment of hazardous aerosol-related diseases. Thus, the effects of pear ethanol extracts on air pollution-related respiratory hypersensitivity were studied by toxicokinetics, pro-inflammatory cytokines, and microbiomics in preclinical and randomized double-blind clinical studies. The mild-asthma subjects, who lived in the same city, Seoul, Korea, were separated into the placebo and the treatment (pear extracts, as brix 55; arbutin 5.01 mg and chlorogenic acid 0.18 mg/3 mL per day) groups for 4 weeks (n = 20). As results, there were positive associations between urinary 2-naphthol (NT) or 1-hydroxypyrene (OHP), exposure biomarkers for polyaromatic hydrocarbons in PM2.5, and pro-inflammatory cytokines, interleukin (IL)-4 or IgE, respectively, in the human subjects. The pear extracts somewhat reduced 2-NT and 1-OHP levels. The proportions of fiber-degrading bacteria that stimulate growth of beneficial microflora for immune defense, that is, Bifidobacterium and Eubacterium, were significantly higher in the pear consuming group than in the placebo group. Moreover, pro-inflammatory cytokines, including IgE, IL-4, IL-5, and IL-13, were significantly suppressed by the pear extracts in the preclinical tests of the ovalbumin-induced asthma mice. Thus, we suggest that air pollution-related respiratory hypersensitivity can be alleviated by Korean pear extracts by modulation of microbiome and immunocytokines.
Assuntos
Poluição do Ar , Asma , Microbiota , Pyrus , Humanos , Animais , Camundongos , Frutas , Poluição do Ar/efeitos adversos , Asma/tratamento farmacológico , Extratos Vegetais/farmacologia , Imunoglobulina ERESUMO
Adipocyte dedifferentiation has recently gained attention as a process underpinning adipocyte plasticity; however, a lack of suitable experimental platforms has hampered studies into the underlying mechanisms. Here, we developed a microscope-mountable ceiling culture chip that provides a stable yet tunable culture environment for long-term live-imaging of dedifferentiating adipocytes. A detailed spatiotemporal analysis of mature adipocyte dedifferentiation utilizing the culture platform and Cre-recombinase tracers revealed the involvement of dynamic actin remodeling for lipid droplet (LD) secretion during adipocyte dedifferentiation. Additionally, Hippo, Hedgehog, and PPARγ signaling pathways were identified as potent regulators of adipocyte dedifferentiation. Contrary to the belief that adult adipocytes are relatively static, we show that adipocytes are very dynamic, relying on actin-driven mechanical forces to execute LD extrusion and intercellular LD transfer processes.
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Actinas , Gotículas Lipídicas , Adipócitos/metabolismo , Desdiferenciação Celular , Gotículas Lipídicas/metabolismo , PPAR gama/metabolismo , Recombinases/metabolismoRESUMO
Background: Irritable bowel syndrome (IBS) can be caused by abnormal bowel movements, altered brain-gut axis, gut microbiota change, and low levels of inflammation or immune activation. The intake of food containing much fiber and lactic acid bacteria (LABs) can alleviate IBS. Objective: This study was undertaken to confirm the alleviative effect of kimchi on symptoms of IBS. Design: Three types of kimchi (standard kimchi, SK; dead nano-sized Lactobacillus plantarum nF1 (nLp) added to standard kimchi, nLpSK; or functional kimchi, FK) were given to 30 individuals in each of three groups, that is, the SK group (n = 30), the nLpSK group (n = 30), or the FK group (n = 30) at 210 g a day for 12 weeks. Food intake records, serum levels of inflammatory factors, fecal levels of harmful enzymes, and microbiome changes were investigated over the 12-week study period. Results: After intervention, dietary fiber intake was increased in all groups. Typical IBS symptoms (abdominal pain or inconvenience, desperation, incomplete evacuation, and bloating), defecation time, and stool type were also improved. In serum, all groups showed reductions in tumor necrosis factor (TNF)-α (P < 0.001) levels. In addition, serum IL-4 (P < 0.001), IL-10 (P < 0.001), and IL-12 (P < 0.01) were significantly reduced in the nLpSK and FK groups, and serum monocyte chemotactic protein (MCP)-1 (P < 0.05) was significantly reduced in the nLpSK group. Furthermore, activities of fecal ß-glucosidase and ß-glucuronidase were significantly decreased in all three groups, and these reductions were greatest in the nLpSK group. Gut microbiome analysis showed that kimchi consumption increased Firmicutes populations at the expense of Bacteroidetes and Tenericutes populations. In addition, the Bifidobacterium adolescentis population increased significantly in the FK group (P = 0.026). Conclusion: Kimchi intake helps alleviate IBS by increasing dietary fiber intake and reducing serum inflammatory cytokine levels and harmful fecal enzyme activities. Notably, nLp improved the immune system, and several functional ingredients in FK promoted the growth of Bifidobacterium adolescentis in gut.
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Serotonin (5-hydroxytryptophan) is a hormone that regulates emotions in the central nervous system. However, serotonin in the peripheral system is associated with obesity and fatty liver disease. Because serotonin cannot cross the blood-brain barrier (BBB), we focused on identifying new tryptophan hydroxylase type I (TPH1) inhibitors that act only in peripheral tissues for treating obesity and fatty liver disease without affecting the central nervous system. Structural optimization inspired by para-chlorophenylalanine (pCPA) resulted in the identification of a series of oxyphenylalanine and heterocyclic phenylalanine derivatives as TPH1 inhibitors. Among these compounds, compound 18i with an IC50 value of 37 nM was the most active in vitro. Additionally, compound 18i showed good liver microsomal stability and did not significantly inhibit CYP and Herg. Furthermore, this TPH1 inhibitor was able to actively interact with the peripheral system without penetrating the BBB. Compound 18i and its prodrug reduced body weight gain in mammals and decreased in vivo fat accumulation.
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Hepatopatias , Triptofano Hidroxilase , Animais , Barreira Hematoencefálica/metabolismo , Mamíferos/metabolismo , Obesidade/tratamento farmacológico , Serotonina , Triptofano Hidroxilase/metabolismoRESUMO
Inflammation is a characteristic of obesity. The rich compounds in lemon peel have anti-inflammatory effects. This study examined whether fermented lemon peel can have an anti-obesity effect on obese mice induced by a high-fat diet (HFD) by regulating inflammation. The lemon peel fermentation supernatant (LPFS) could inhibit the weight gain of mice and improve the lesions of the liver and epididymal adipose tissue. In addition, LPFS regulates blood lipids, liver function, and inflammation-related indicators in the serum of obese mice. LPFS plays a positive role in regulating the inflammation and obesity-related genes in liver tissue and adipose tissue of obese mice. High-performance liquid chromatography showed an increase in the contents of compounds with antioxidant or/and anti-inflammatory effects and compounds with anti-obesity effects. These results suggest that the LPFS could help reduce obesity in obese mice induced by an HFD by adjusting the balance of the inflammatory response. PRACTICAL APPLICATIONS: Obesity often increases the risk of chronic diseases, and mild inflammation is a feature of obesity. Therefore, timely suppression of inflammation in the body can help control the occurrence of obesity. This study clarified the anti-obesity effect of fermented lemon peel on a high-fat diet (HFD)-induced obese mice by regulating the body's inflammatory response and confirmed that fermentation improves the anti-inflammatory activity of lemon peel. This study provides important references for future investigation, prophylaxis, and treatment of inflammation and obesity-related diseases, as well as the advances in functional foods and fermented foods with anti-inflammatory and anti-obesity activities.
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Dieta Hiperlipídica , Obesidade , Animais , Dieta Hiperlipídica/efeitos adversos , Inflamação/tratamento farmacológico , Fígado , Camundongos , Camundongos Obesos , Obesidade/tratamento farmacológico , Obesidade/etiologiaRESUMO
BACKGROUND & AIMS: Mitochondrial dysfunction disrupts the synthesis and secretion of digestive enzymes in pancreatic acinar cells and plays a primary role in the etiology of exocrine pancreas disorders. However, the transcriptional mechanisms that regulate mitochondrial function to support acinar cell physiology are poorly understood. Here, we aim to elucidate the function of estrogen-related receptor γ (ERRγ) in pancreatic acinar cell mitochondrial homeostasis and energy production. METHODS: Two models of ERRγ inhibition, GSK5182-treated wild-type mice and ERRγ conditional knock-out (cKO) mice, were established to investigate ERRγ function in the exocrine pancreas. To identify the functional role of ERRγ in pancreatic acinar cells, we performed histologic and transcriptome analysis with the pancreas isolated from ERRγ cKO mice. To determine the relevance of these findings for human disease, we analyzed transcriptome data from multiple independent human cohorts and conducted genetic association studies for ESRRG variants in 2 distinct human pancreatitis cohorts. RESULTS: Blocking ERRγ function in mice by genetic deletion or inverse agonist treatment results in striking pancreatitis-like phenotypes accompanied by inflammation, fibrosis, and cell death. Mechanistically, loss of ERRγ in primary acini abrogates messenger RNA expression and protein levels of mitochondrial oxidative phosphorylation complex genes, resulting in defective acinar cell energetics. Mitochondrial dysfunction due to ERRγ deletion further triggers autophagy dysfunction, endoplasmic reticulum stress, and production of reactive oxygen species, ultimately leading to cell death. Interestingly, ERRγ-deficient acinar cells that escape cell death acquire ductal cell characteristics, indicating a role for ERRγ in acinar-to-ductal metaplasia. Consistent with our findings in ERRγ cKO mice, ERRγ expression was significantly reduced in patients with chronic pancreatitis compared with normal subjects. Furthermore, candidate locus region genetic association studies revealed multiple single nucleotide variants for ERRγ that are associated with chronic pancreatitis. CONCLUSIONS: Collectively, our findings highlight an essential role for ERRγ in maintaining the transcriptional program that supports acinar cell mitochondrial function and organellar homeostasis and provide a novel molecular link between ERRγ and exocrine pancreas disorders.
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Pâncreas Exócrino , Pancreatite Crônica , Células Acinares/patologia , Animais , Estrogênios/metabolismo , Humanos , Camundongos , Camundongos Knockout , Pâncreas/patologia , Pâncreas Exócrino/metabolismo , Pancreatite Crônica/patologiaRESUMO
STUDY DESIGN: A retrospective case control study. PURPOSE: This study aimed to assess the clinical significance of sagittal balance for predicting and managing the recollapse of cemented vertebra following percutaneous vertebroplasty (PVP) in patients with thoracolumbar osteoporotic vertebral fracture (OVF). OVERVIEW OF LITERATURE: Recently, the recollapse of cemented vertebra following PVP for OVF has been reported. Although the risk factors for recollapse have been determined, the association between sagittal spinopelvic parameters and sagittal imbalance with recollapse has not been established. METHODS: Ambulatory patients who underwent single-level PVP for thoracolumbar OVF with a follow-up of at least 24 months were retrospectively reviewed. The patients were divided into two groups depending on the presence of symptomatic recollapse at the cemented vertebra: (1) recollapsed (RC) group and (2) noncollapsed (NC) group. The patient characteristics and radiographic measurements associated with sagittal imbalance were analyzed at each follow-up visit. RESULTS: Overall, 134 patients (RC group, n=28; NC group, n=106) were enrolled. The mean fracture-free interval was 3.2 months (range, 1.2-25.1 months). The multivariate binary logistic regression analysis identified low bone mineral density (p =0.047), degree of dynamic mobility within the vertebra (p =0.025), and sagittal imbalance as significant risk factors for recollapse (p =0.013; odds ratio, 5.405). The progression of sagittal imbalance and thoracolumbar kyphosis (T10-L2) was more significant in the RC and sagittal imbalance groups than in the NC group (both p =0.000). CONCLUSIONS: Sagittal imbalance, lower bone mineral density, and dynamic mobility within the vertebra are associated with the recollapse of cemented vertebrae following PVP. Sagittal imbalance, rather than local kyphosis or thoracolumbar kyphosis, is particularly significant in that it results in more progressive collapse and sagittal deformity and is accompanied by substantial back pain and neurological deficits. Therefore, a stricter and more active management, including anti-osteoporosis medication, is required for the treatment of OVF with sagittal imbalance of the spine.
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With the increasing incidence of type 2 diabetes, it is imperative to identify how to effectively prevent or treat this disease. Studies have shown that some lactic acid bacteria can improve type 2 diabetes with almost no side effects. Therefore, in this experimental study, we explored the preventive and therapeutic effects of Lactobacillus fermentum TKSN041 (L. fermentum TKSN041) on streptozotocin-induced type 2 diabetes in rats. The results showed that L. fermentum TKSN041 could reduce the amount of water intake, reduce weight loss, and control the increase in the fasting blood glucose level of diabetic rats. The organ index and tissue section results showed that L. fermentum TKSN041 could reduce the damage caused by diabetes to the liver, kidney, spleen, pancreatic, and brain tissue. Furthermore, L. fermentum TKSN041 decreased the levels of triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL), aminotransferase (AST), alanine aminotransferase (ALT), glycated serum proteins (GSP), malondialdehyde (MDA), interleukin 1 beta (IL-1ß), interleukin 6 (IL-6), and endothelin 1 (ET-1) in serum and increased the serum levels of high-density lipoprotein cholesterol (HDL) and interleukin 10 (IL-10). Finally, L. fermentum TKSN041 up-regulated the mRNA and protein expressions of NF-kappa-B inhibitor-α (IκB-α), AMP-activated protein kinase (AMPK), insulin receptor substrate-1 (IRS-1), liver kinase B1 (LKB1), and glucose transporter 4 (GLUT4) and down-regulated those of nuclear factor-κBp65 (NFκB-p65) and tumor necrosis factor alpha (TNF-α). Furthermore, LF-TKSN041 up-regulated the mRNA expressions of peroxisome proliferator-activated receptor γ (PPAR-γ) and down-regulated neuropeptide Y (NPY), sterol regulatory element-binding protein-1 (SREBF-1), and vascular endothelial growth factor (VEGF). These results suggest that L. fermentum TKSN041 may be a useful intervention factor for the prevention or treatment of type 2 diabetes induced by STZ. Clinical trials are needed to further demonstrate its effectiveness.
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Diabetes Mellitus Tipo 2/tratamento farmacológico , Limosilactobacillus fermentum/fisiologia , Probióticos/administração & dosagem , Proteínas Quinases Ativadas por AMP/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Alanina Transaminase/genética , Alanina Transaminase/metabolismo , Animais , Colesterol/metabolismo , Diabetes Mellitus Tipo 2/induzido quimicamente , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Transportador de Glucose Tipo 4/genética , Transportador de Glucose Tipo 4/metabolismo , Humanos , Proteínas Substratos do Receptor de Insulina/genética , Proteínas Substratos do Receptor de Insulina/metabolismo , Masculino , PPAR gama/genética , PPAR gama/metabolismo , Ratos , Ratos Sprague-Dawley , Estreptozocina , Triglicerídeos/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
BACKGROUD: The purpose of this study was to compare clinical outcomes and complications of primary and revision surgery in patients with adult spinal deformity (ASD) accompanied by sagittal imbalance. Revision surgery has been associated with poor clinical outcomes and increased risk of complications. Previous studies comparing primary versus revision surgery included data for a wide variety of diseases and ages, but few investigated patients with ASD with sagittal imbalance undergoing anterior and posterior combined surgery. METHODS: Retrospective cohort analysis of prospectively collected data. We identified 60 consecutive patients with ASD combined with sagittal imbalance who underwent primary or revision surgery; of these, 6 patients were excluded for lack of a minimal 2-year follow-up. Patients' surgical and radiological data, clinical outcomes, and complications were reviewed. RESULTS: There were 30 patients in the primary group and 24 patients in the revision group. Patient characteristics, including the prevalence of sarcopenia, were similar between the two groups. Pedicle subtraction osteotomy was performed more frequently in the revision group although there was no statistically significant difference between groups. The primary group had more proximal junctional problems, whereas the revision group had more rod breakage (p < 0.05). There were significant improvements in clinical outcomes in both groups when the preoperative and 2-year postoperative values were compared. The Oswestry disability index and visual analog scale score were similar in both groups 2 years postoperatively. CONCLUSIONS: Considering the greater pain and disability at the time of the revision procedure, revision patients benefited more from surgery at the 2-year follow-up than the primary surgery patients. Complication rates were similar between the groups except for proximal junctional problems and rod breakage. Therefore, revision surgery should not be avoided in the treatment of ASD patients with sagittal imbalance.
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Osteotomia/métodos , Reoperação/métodos , Curvaturas da Coluna Vertebral/cirurgia , Fusão Vertebral/métodos , Idoso , Estudos de Coortes , Avaliação da Deficiência , Feminino , Humanos , Vértebras Lombares/cirurgia , Masculino , Pessoa de Meia-Idade , Medição da Dor , Complicações Pós-Operatórias , Radiografia , Estudos Retrospectivos , Curvaturas da Coluna Vertebral/diagnóstico por imagem , Vértebras Torácicas/cirurgiaRESUMO
Chinese Sichuan pickle is a fermented food rich in microorganisms. Microorganisms have the potential to become an important new form of potent future therapeutic capable of treating human disease. Selecting vitamin C as a positive control, a lactic acid bacteria (Lactobacillus plantarum CQPC02, LP-CQPC02) isolated from Sichuan pickle was given to mice over 4 weeks to investigate the effect of CQPC02 on fatigue levels and biochemical oxidation phenomena in exercise-exhausted Institute of Cancer Research (ICR) mice. The fatigue model was established by forced swimming of mice, the levels of hepatic glycogen, skeletal muscle glycogen, lactic acid, blood urea nitrogen and free fatty acid were measured by physicochemical methods, serum serum creatine kinase (CK), aspartate aminotransferase (AST) and alanine aminotransferase (ALT), superoxide dismutase (SOD), catalase (CAT) and malondialdehyde (MDA) levels were measured by kits, the histopathological changes in the livers of mice were observed by H&E slicing, and the mRNA changes in the livers and skeletal muscles were observed by quantitative polymerase chain reaction (qPCR). Both vitamin C and LP-CQPC02 increased swimming exhaustion time. The concentration of LP-CQPC02 and exhaustion time were positively correlated. LP-CQPC02 also increased liver glycogen, skeletal muscle glycogen and free fatty acid content in mice and reduced lactic acid and blood urea nitrogen content in a dose-dependent manner. As walnut albumin antioxidant peptide concentration increased, levels of mouse CK, AST, and AST gradually decreased. LP-CQPC02 increased SOD and CAT levels and decreased MDA levels in a dose-dependent fashion. LP-CQPC02 up-regulated expression of mRNA encoding copper/zinc-superoxide dismutase (Cu/Zn-SOD), manganese-superoxide dismutase (Mn-SOD), and CAT in swimming exhaustion mouse liver tissue. LP-CQPC02 also up-regulated alanine/serine/cysteine/threonine transporter 1 (ASCT1) expression while down-regulating syncytin-1, inducible nitric oxide synthase (iNOS), tumor necrosis factor-alpha (TNF-α) expression in swimming exhaustion mouse skeletal muscle. Overall, LP-CQPC02 had a clear anti-fatigue and anti-oxidation effect. This suggests that LP-CQPC02 can be developed as a microbiological therapeutic agent.
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The antioxidant effect of soymilk fermented by Lactobacillus plantarum HFY01 (screened from yak yogurt) was investigated on mice with premature aging induced by D-galactose. In vitro antioxidant results showed that L. plantarum HFY01-fermented soymilk (LP-HFY01-DR) had better ability to scavenge the free radicals 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azino-bis (3-ethylbenzthiazoline-6-sulphonic acid) diammonium salt (ABTS) than unfermented soymilk and Lactobacillus bulgaricus-fermented soymilk. Histopathological observation showed that LP-HFY01-DR could protect the skin, spleen and liver, reduce oxidative damage and inflammation. Biochemical results showed that LP-HFY01-DR could effectively upregulate glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) levels and decrease malondialdehyde (MDA) content in the liver, brain, and serum. Real-time quantitative reverse transcription polymerase chain reaction further showed that LP-HFY01-DR could promote the relative expression levels of the genes encoding for cuprozinc superoxide dismutase (Cu/Zn-SOD, SOD1), manganese superoxide dismutase (Mn-SOD, SOD2), CAT, GSH, and GSH-Px in the liver, spleen, and skin. High-performance liquid chromatography results revealed daidzin, glycitin, genistin, daidzein, glycitein, and genistein in LP-HFY01-DR. In conclusion, LP-HFY01-DR could improve the antioxidant capacity in mice with premature aging induced by D-galactose.
RESUMO
The anticancer effects of Shinan (Shinan-South Korea) sea salts on azoxymethane (AOM)/dextran sodium sulfate (DSS) with high fat diet (HFD)-induced colon cancer and obesity in C57BL/6N mice were studied. We prepared three types of sea salt: generally manufactured sea salt (GS), generally manufactured after filtering seawater (FS), and manufactured with only new seawater (NS). Sea salt intake increased colon length and reduced colon length/weight ratio, tumor number, and progression of colon cancer in colon tissue. The differently prepared sea salts also ameliorated liver injury. In addition, the mineral composition of each salt was different. Moreover, the sea salts enhanced activation of natural killer cell (CD56) expression in colon and spleen tissues. However, the mineral compositions of sea salts were not simply associated with anticancer effects in AOM/DSS+HFD induced mice. Thus, the anticolorectal cancer effects of sea salts may be mediated by different factors, which remain to be identified.