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Background Patients with moyamoya disease (MMD) have a high risk of stroke or death. We investigated whether extracranial to intracranial bypass surgery can reduce mortality by preventing strokes in patients with MMD. Methods and Results This nationwide retrospective cohort study encompassed patients with MMD registered under the Rare Intractable Diseases program via the Relieved Co-Payment Policy between 2006 and 2019, using the Korean National Health Insurance Service database. Following a 4-year washout period, landmark analyses were employed to assess mortality and stroke occurrence between the bypass surgery group and the nonsurgical control group at specific time points postindex date (1 month and 3, 6, 12, and 36 months). The study included 18 480 patients with MMD (mean age, 40.7 years; male to female ratio, 1:1.86) with a median follow-up of 5.6 years (interquartile range, 2.5-9.3; mean, 6.1 years [SD, 4.0 years]). During 111 775 person-years of follow-up, 265 patients in the bypass surgery group and 1144 patients in the nonsurgical control group died (incidence mortality rate of 618.1 events versus 1660.3 events, respectively, per 105 person-years). The overall adjusted hazard ratio (HR) revealed significantly lower all-cause mortality in the bypass surgery group from the 36-month landmark time point, for any stroke mortality from 3- and 6-month landmark time points, and for hemorrhagic stroke mortality from the 6-month landmark time point. Furthermore, the overall adjusted HRs for hemorrhagic stroke occurrence were beneficially maintained from all 5 landmark time points in the bypass surgery group. Conclusions Bypass surgery in patients with MMD was associated with a lower risk of all-cause and hemorrhagic stroke mortality and hemorrhagic stroke occurrence compared with nonsurgical control.
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Purpose: To assess normal CT scans with quantitative CT (QCT) analysis based on smoking habits and chronic obstructive pulmonary disease (COPD). Materials and Methods: From January 2013 to December 2014, 90 male patients with normal chest CT and quantification analysis results were enrolled in our study [non-COPD never-smokers (n = 38) and smokers (n = 45), COPD smokers (n = 7)]. In addition, an age-matched cohort study was performed for seven smokers with COPD. The square root of the wall area of a hypothetical bronchus of internal perimeter 10 mm (Pi10), skewness, kurtosis, mean lung attenuation (MLA), and percentage of low attenuation area (%LAA) were evaluated. Results: Among patients without COPD, the Pi10 of smokers (4.176 ± 0.282) was about 0.1 mm thicker than that of never-smokers (4.070 ± 0.191, p = 0.047), and skewness and kurtosis of smokers (2.628 ± 0.484 and 6.448 ± 3.427) were lower than never-smokers (2.884 ± 0.624, p = 0.038 and 8.594 ± 4.944, p = 0.02). The Pi10 of COPD smokers (4.429 ± 0.435, n = 7) was about 0.4 mm thicker than never-smokers without COPD (3.996 ± 0.115, n = 14, p = 0.005). There were no significant differences in MLA and %LAA between groups (p > 0.05). Conclusion: Even on normal CT scans, QCT showed that the airway walls of smokers are thicker than never-smokers regardless of COPD and it preceded lung parenchymal changes.
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Cinnamomum cassia (cassia) is a tropical aromatic evergreen tree of the Lauraceae family well known for its fragrance and spicy flavor and widely used in Asian traditional medicine. It has recently garnered attention for its diverse potential health benefits, including anti-inflammatory, anti-cancer, and anti-diabetic properties. However, the gastroprotective effect of C. cassia, particularly against ethanol-induced gastric damage, remains unclear. We investigated the potential gastroprotective property of C. cassia and the underlying mechanisms of action in a rat model of ethanol-induced gastric injury. To assess its effectiveness, rats were fed C. cassia for a 14-day period prior to inducing gastric damage by oral administration of ethanol. Our results indicated that pre-treatment with C. cassia mitigated ethanol-induced gastric mucosal lesions and bleeding. Reduced gastric acid secretion and expression of acid secretion-linked receptors were also observed. Additionally, pretreatment with C. cassia led to decreased levels of inflammatory factors, including TNF-α, p-p65, and IκBα. Notably, C. cassia upregulated the expressions of HO1 and HSP90, with particular emphasis on the enhanced expression of PAS and MUC, the crucial gastric mucosa defense molecules. These findings suggest that C. cassia has protective effects on the gastric mucosa and can effectively reduce oxidative stress and inflammation.
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Cinnamomum aromaticum , Animais , Ratos , Mucosa Gástrica , Estômago , Administração Oral , Etanol/toxicidadeRESUMO
OBJECTIVES: To investigate the diagnostic accuracy of using 3D polylines (3DPs) to improve cone-beam CT (CBCT) virtual navigation (VN)-guided percutaneous transthoracic needle biopsies (PTNB) of pulmonary lesions. METHODS: From May 2021 to November 2021, patients (81 males and 41 females; age, 65 ± 12 years) who underwent CBCT VN with 3DPs for PTNB of pulmonary lesions were retrospectively reviewed. Fluoroscopic visibility of target lesions was evaluated using captured images from a Bull's eye view. Diagnostic accuracy was calculated, and complications were assessed. RESULTS: The mean size of biopsied lesions was 23 ± 13 mm (range: 6-75 mm). Overall, 13.9% (17/122) were small pulmonary nodules (diameter ≤1 cm), and 68.0% (83/122) of biopsied lesions were fluoroscopic visible. The overall diagnostic accuracy was 94.3%. The diagnostic accuracy for visible and invisible lesions was 94.0 and 94.9%, respectively (p = 0.843), and 100% for small pulmonary nodules. Major complications occurred in 8.2% (10/122; eight pneumothorax with chest tube insertion, one hemoptysis with transfusion, and one air embolism) of patients. CONCLUSION: CBCT VN with 3DP guidance provide a real-time outline of pulmonary lesions, thus enabling a reliable and accurate PTNB. ADVANCES IN KNOWLEDGE: 3DP guidance could be useful technique for CBCT-guided PTNB, especially in small pulmonary nodules.
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Neoplasias Pulmonares , Nódulos Pulmonares Múltiplos , Masculino , Feminino , Humanos , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Radiografia Intervencionista/métodos , Biópsia Guiada por Imagem/métodos , Nódulos Pulmonares Múltiplos/patologia , Biópsia por Agulha/métodos , Tomografia Computadorizada de Feixe Cônico/métodos , Pulmão/patologia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologiaRESUMO
Purpose: The aim of this study was to evaluate the role of Pi10 in patients with fibrotic interstitial lung abnormality (fibrotic ILA) in a chest CT, according to cumulative cigarette smoking. Methods: We retrospectively assessed 54 fibrotic ILA patients and 18 healthy non-smokers (control) who underwent non-enhanced CT and pulmonary function tests. We quantitatively analyzed airway changes (the inner luminal area, airway inner parameter, airway wall thickness, Pi10, skewness, and kurtosis) in the chest CT of fibrotic ILA patients, and the fibrotic ILA patients were categorized into groups based on pack-years: light, moderate, heavy. Airway change data and pulmonary function tests among the three groups of fibrotic ILA patients were compared with those of the control group by one-way ANOVA. Results: Mean skewness (2.58 ± 0.36) and kurtosis (7.64 ± 2.36) in the control group were significantly different from those of the fibrotic ILA patients (1.89 ± 0.37 and 3.62 ± 1.70, respectively, p < 0.001). In fibrotic ILA group, only heavy smokers had significantly increased Pi10 (mean increase 0.04, p = 0.013), increased airway wall thickness of the segmental bronchi (mean increase 0.06 mm, p = 0.005), and decreased lung diffusing capacity for carbon monoxide (p = 0.023). Conclusion: Pi10, as a biomaker of quantitative CT in fibrotic ILA patients, can reveal that smoking affects airway remodeling.
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Fumar Cigarros , Doenças Pulmonares Intersticiais , Humanos , Pulmão/diagnóstico por imagem , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Estudos Retrospectivos , Tomografia Computadorizada por Raios XRESUMO
AIMS: Until recently, the pluripotency factor Octamer (ATGCAAAT)-binding transcriptional factor 4 (OCT4) was believed to be dispensable in adult somatic cells. However, our recent studies provided clear evidence that OCT4 has a critical atheroprotective role in smooth muscle cells. Here, we asked if OCT4 might play a functional role in regulating endothelial cell (EC) phenotypic modulations in atherosclerosis. METHODS AND RESULTS: Specifically, we show that EC-specific Oct4 knockout resulted in increased lipid, LGALS3+ cell accumulation, and altered plaque characteristics consistent with decreased plaque stability. A combination of single-cell RNA sequencing and EC-lineage-tracing studies revealed increased EC activation, endothelial-to-mesenchymal transitions, plaque neovascularization, and mitochondrial dysfunction in the absence of OCT4. Furthermore, we show that the adenosine triphosphate (ATP) transporter, ATP-binding cassette (ABC) transporter G2 (ABCG2), is a direct target of OCT4 in EC and establish for the first time that the OCT4/ABCG2 axis maintains EC metabolic homeostasis by regulating intracellular heme accumulation and related reactive oxygen species production, which, in turn, contributes to atherogenesis. CONCLUSIONS: These results provide the first direct evidence that OCT4 has a protective metabolic function in EC and identifies vascular OCT4 and its signalling axis as a potential target for novel therapeutics.
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Aterosclerose , Placa Aterosclerótica , Aterosclerose/genética , Aterosclerose/metabolismo , Aterosclerose/prevenção & controle , Linhagem da Célula , Humanos , Miócitos de Músculo Liso/metabolismo , Placa Aterosclerótica/metabolismo , Transdução de SinaisRESUMO
In the bone marrow, classical and plasmacytoid dendritic cells (DC) develop from the macrophage-DC precursor (MDP) through a common DC precursor (CDP) step. This developmental process receives essential input from the niche in which it takes place, containing endothelial cells (EC) among other cell types. Here we show that targeted deletion of serine/threonine kinase 11 (Stk11) encoding tumor suppressor liver kinase b1 (Lkb1) in mouse ECs but not DCs, results in disrupted differentiation of MDPs to CDPs, severe reduction in mature DC numbers and spontaneous tumorigenesis. In wild type ECs, Lkb1 phosphorylates polypyrimidine tract binding protein 1 (Ptbp1) at threonine 138, which regulates stem cell factor (Scf) pre-mRNA splicing. In the absence of Lkb1, exon 6 of Scf is spliced out, leading to the loss of Scf secretion. Adeno-associated-virus-mediated delivery of genes encoding either soluble Scf or the phosphomimetic mutant Ptbp1T138E proteins rescued the defects of MDP to CDP differentiation and DC shortage in the endothelium specific Stk11 knockout mice. In summary, endothelial Stk11 expression regulates DC differentiation via modulation of Scf splicing, marking the Stk11-soluble-Scf axis as a potential cause of DC deficiency syndromes.
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Proteínas Quinases Ativadas por AMP/genética , Diferenciação Celular/genética , Transformação Celular Neoplásica/genética , Células Dendríticas/metabolismo , Células Endoteliais/metabolismo , Quinases Proteína-Quinases Ativadas por AMP/genética , Quinases Proteína-Quinases Ativadas por AMP/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Western Blotting , Células da Medula Óssea/metabolismo , Sobrevivência Celular/genética , Células Cultivadas , Imunofluorescência , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Camundongos Knockout , Camundongos Transgênicos , Interferência de RNA , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fator de Células-Tronco/genética , Fator de Células-Tronco/metabolismoRESUMO
Fibrosis has various biological processes and affects almost every organ, especially in patients with inflammatory bowel disease, including Crohn's disease, who experience discomfort caused by intestinal fibrosis, which is a problem that needs to be resolved. TGF-ß signaling is known to act as a key regulator of intestinal fibrosis, and its modulation could be an excellent candidate for fibrosis therapy. Xanthohumol (XN) has various effects, including anti-inflammation and anti-cancer; however, the detailed mechanism of TGF-ß signaling has not yet been studied. The purpose of this study was to investigate the mechanism underlying the anti-fibrotic effect of XN on TGF-ß1-induced intestinal fibrosis using primary human intestinal fibroblasts (HIFs). In this study, to check the anti-fibrotic effects of XN on intestinal fibrosis, we assessed the expression of fibrosis-related genes in TGF-ß1-stimulated HIFs by qPCR, immunoblotting, and immunofluorescence staining. As a result, XN showed the ability to reduce the expression of fibrosis-associated genes increased by TGF-ß1 treatment in HIFs and restored the cell shape altered by TGF-ß1. In particular, XN repressed both NF-κB- and Smad-binding regions in the α-SMA promoter, which is important in fibrosis. In addition, XN inhibited NF-κB signaling, including phosphorylated-IkBα and cyclooxygenase-2 expression, and TNF-α-stimulated transcriptional activity of NF-κB. XN attenuated TGF-ß1-induced phosphorylation of Smad2 and Smad3, and the transcriptional activity of CAGA. Particularly, XN interfered with the binding of TGF-Receptor I (TßRI) and Smad3 by binding to the kinase domain of the L45 loop of TßRI, thereby confirming that the fibrosis mechanism did not proceed further. In conclusion, XN has an inhibitory effect on TGF-ß1-induced intestinal fibrosis in HIFs, significantly affecting TGF-ß/Smad signaling.
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NF-kappa B , Fator de Crescimento Transformador beta1 , Humanos , Fator de Crescimento Transformador beta1/metabolismo , NF-kappa B/metabolismo , Fibrose , Transdução de SinaisRESUMO
Dietary intervention to prevent Helicobacter pylori (H. pylori)-gastric cancer might be ideal by long-term intervention, rejuvenating action, and no risk of bacterial resistance. Stimulated with finding that kimchi prevented H. pylori-gastric cancer, we compared the efficacy of cancer preventive kimchi (cpkimchi) and standard recipe kimchi (skimchi) and the efficacy between fermented kimchi and non-fermented kimchi (kimuchi) in H. pylori-initiated gastric cancer model and explored novel mechanisms hinted from RNAseq transcriptome analysis. Animal models assessing gastric pathology on 24 and 36 weeks after H. pylori initiated, salt diet-promoted gastric mutagenesis model showed fermented cpkimchi afforded the best outcome of either rejuvenating atrophic gastritis or inhibiting tumorigenesis compared to skimchi and kimuchi. Highest inhibition of atrophic gastritis was achieved with cpkimchi, while significantly lower in kimuchi. Transcriptomic analysis showed ameliorated-endoplasmic reticulum (ER) stress, -oxidative stress, and -apoptosis as major rejuvenating action of cpkimchi. Homogenates from animal model showed that elevated expressions of p-PERK, IRE, ATF6, p-elf, and XBP1 in control group, while significantly decreased with dietary intake of only cpkimchi. Significantly increased expressions of HO-1 and γ-GCS were only noted with cpkimchi. Conclusively, long-term dietary intervention of fermented cpkimchi can be potential way preventing H. pylori-associated carcinogenesis via rejuvenation of atrophic gastritis.
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Supported with significant rejuvenating and regenerating actions of mesenchymal stem cells (MSCs) in various gastrointestinal diseases including Helicobacter pylori (H. pylori)-associated gastric diseases, we have compared these actions among placenta derived-MSCs (PD-MSCs), umbilical cord derived-MSCs (UC-MSCs), and adipose tissue derived-MSCs (AD-MSCs) and explored contributing genes implicated in rejuvenation of H. pylori-chronic atrophic gastritis (CAG) and tumorigenesis. In this study adopting H. pylori-initiated, high salt diet-promoted gastric carcinogenesis model, we have administered three kinds of MSCs around 15-18 weeks in H. pylori infected C57BL/6 mice and sacrificed at 24 and 48 weeks, respectively, in order to either assess the rejuvenating capability or anti-tumorigenesis. At 24 weeks, MSCs all led to significantly mitigated atrophic gastritis, for which significant inductions of autophagy, preservation of tumor suppressive 15-PGDH, attenuated apoptosis, and efficient efferocytosis was imposed with MSCs administration during atrophic gastritis. At 48 weeks, MSCs administered during H. pylori-associated atrophic gastritis afforded significant blocking the progression of CAG, as evidenced with statistically significant reduction in H. pylori-associated gastric tumor (p<0.05) accompanied with significant decreases in IL-1ß, COX-2, STAT3, and NF-κB. Combined together with the changes of stanniocalcin-1 (STC-1), thrombospondin-1 (TSP-1), and IL-10 known as biomarkers reflecting stem cell activities at 48 weeks after H. pylori, PD-MSCs among MSCs afforded the best rejuvenating action against H. pylori-associated CAG via additional actions of efferocytosis, autophagy, and anti-apoptosis at 24 weeks. In conclusion, MSCs, especially PD-MSCs, exerted rejuvenating actions against H. pylori-associated CAG via anti-mutagenesis of IL-10, CD-36, ATG5 and cancer suppressive influences of STC-1, TSP-1, and 15-PGDH.
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Dietary intervention to prevent Helicobacter pylori (H. pylori)-gastric cancer might be ideal because of no risk of bacterial resistance, safety, and rejuvenating action of atrophic gastritis. We have published data about the potential of fermented kimchi as nutritional approach for H. pylori. Hence recent advances in RNAseq analysis lead us to investigate the transcriptome analysis to explain these beneficiary actions of kimchi. gastric cells were infected with either H. pylori or H. pylori plus kimchi. 943 genes were identified as significantly increased or decreased genes according to H. pylori infection and 68 genes as significantly changed between H. pylori infection and H. pylori plus kimchi (p<0.05). Gene classification and Medline database showed DLL4, FGF18, PTPRN, SLC7A11, CHAC1, FGF21, ASAN, CTH, and CREBRF were identified as significantly increased after H. pylori, but significantly decreased with kimchi and NEO1, CLDN8, KLRG1, and IGFBP1 were identified as significantly decreased after H. pylori, but increased with kimchi. After KEGG and STRING-GO analysis, oxidative stress, ER stress, cell adhesion, and apoptosis genes were up-regulated with H. pylori infection but down-regulated with kimchi, whereas tissue regeneration, cellular anti-oxidative response, and anti-inflammation genes were reversely regulated with kimchi (p<0.01). Conclusively, transcriptomes of H. pylori plus kimchi showed significant biological actions.
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Chronic Helicobacter pylori infection causes gastric cancer via the progression of precancerous chronic atrophic gastritis (CAG). Therefore, repairing gastric atrophy could be a useful strategy in preventing H. pylori-associated gastric carcinogenesis. Although eradication of the bacterial pathogen offers one solution to this association, this study was designed to evaluate an alternative approach using mesenchymal stem cells to treat CAG and prevent carcinogenesis. Here, we used human placenta-derived mesenchymal stem cells (PD-MSCs) and their conditioned medium (CM) to treat H. pylori-associated CAG in a mice/cell model to explore their therapeutic effects and elucidate their molecular mechanisms. We compared the changes in the fecal microbiomes in response to PD-MSC treatments, and chronic H. pylori-infected mice were given ten treatments with PD-MSCs before being sacrificed for end point assays at around 36 weeks of age. These animals presented with significant reductions in the mean body weights of the control group, which were eradicated following PD-MSC treatment (p < 0.01). Significant changes in various pathological parameters including inflammation, gastric atrophy, erosions/ulcers, and dysplastic changes were noted in the control group (p < 0.01), but these were all significantly reduced in the PD-MSC/CM-treated groups. Lgr5+, Ki-67, H+/K+-ATPase, and Musashi-1 expressions were all significantly increased in the treated animals, while inflammatory mediators, MMP, and apoptotic executors were significantly decreased in the PD-MSC group compared to the control group (p < 0.001). Our model showed that H. pylori-initiated, high-salt diet-promoted gastric atrophic gastritis resulted in significant changes in the fecal microbiome at the phylum/genus level and that PD-MSC/CM interventions facilitated a return to more normal microbial communities. In conclusion, administration of PD-MSCs or their conditioned medium may present a novel rejuvenating agent in preventing the progression of H. pylori-associated premalignant lesions.
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Nicotinamide riboside (NR), vitamin B3, is a substrate for nicotinamide adenine dinucleotide (NAD+)-consuming enzymes and is a coenzyme for hydride-transfer enzymes, including adenosine diphosphate (ADP)-ribose transferases, poly (ADP-ribose) polymerases, cADP-ribose synthases, and sirtuins, which play a central role in the aging process, neurodegenerative processes, and myopathy. Since cancer cachexia is a disease condition presenting with weight loss, skeletal muscle atrophy, and loss of adipose tissue in patients with advanced cancer, we hypothesized that NR intake could ameliorate sarcopenia. In this study, we investigated whether preemptive administration of NR ameliorated C26 adenocarcinoma-induced cancer cachexia and explored anti-cachexic mechanisms focused on the changes in muscle atrophy, cachexic inflammation, and catabolic catastrophe. Dietary intake of the NR-containing pellet diet significantly attenuated cancer cachexia in a mouse model. Starting with significant inhibition of cachexic factors, tumor necrosis factor alpha, and interleukin-6, NR significantly inhibited muscle-specific ubiquitin-proteasome ligases, such as atrogin-1, muscle RING-finger protein-1 (MuRF-1), mitofusin-2, and peroxisome proliferator-activated receptor gamma coactivator-1-alpha (PCG-1α). Significant inhibition of epididymal fat lipolysis was noted with significant inhibition of adipose triglyceride lipase (ATGL) gene. Furthermore, NR administration significantly increased the levels of crucial enzymes involved in the biosynthesis of NAD+ and nicotinamide phosphoribosyl transferase and significantly inhibited the NAD+-sensitive deacetylase sirtuin 1 (SIRT1). Preemptive intake of NR in patients vulnerable to cachexia can be a preemptive option to ameliorate cancer cachexia.
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Dietary intervention to prevent Helicobacter pylori (H. pylori)-associated gastric diseases seems to be ideal with no risk of bacterial resistance, safe long-term intervention, and correcting pathogenic mechanisms including rejuvenation of precancerous atrophic gastritis and anti-mutagenesis. A transcriptome as set of all RNAs transcribed by certain tissues or cells demonstrates gene functions and reveals the molecular mechanism of specific biological processes against diseases. Here, we have performed RNAseq and bioinformatic analysis to explain proof of concept that walnut intake can rescue from H. pylori infection and explore unidentified mode of actions of walnut polyphenol extract (WPE). As results, BIRC3, SLC25A4, f3 transcription, VEGFA, AZU1, HMOX1, RAB3A, RELBTNIP1, ETFB, INPP5J, PPME1, RHOB, TPI1, FOSL1, JUND.RELB, KLF2, MUC1, NDRG1, ALDOA, ENO1, PFKP, GPI, GDF15, and NRTN genes were newly discovered to be enriched with WPE, whereas CCR4, BLNK, CCR7, CXCR4, CDO1, KLSG1, SELE, RASGRP2, PIK3R3, TSPAN32, HOXC-AS3, HCG8, BTNL8, and CXCL3 genes as inhibitory targets by WPE in H. pylori infection. We identified additional genes what WPE afforded actions of avoiding H. pylori-driven onco-inflammation and rejuvenating precancerous atrophic gastritis. Conclusively, after applying RNAseq analysis in order to document walnut intake for precision medicine against H. pylori infection, significant transcriptomic profiling applicable for validation were drawn.
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The fact that Fat-1 transgenic mice producing n-3 polyunsaturated fatty acids via overexpressed 3-desaturase significantly mitigated Helicobacter pylori (H. pylori)-associated gastric tumorigenesis through rejuvenation of chronic atrophic gastritis (CAG) led us to study whether dietary intake of walnut plentiful of n-3 PUFAs can be nutritional intervention to prevent H. pylori-associated gastric cancer. In our model that H. pylori-initiated, high salt diet-promoted gastric carcinogenesis, pellet diet containing 100 mg/kg and 200 mg/kg walnut was administered up to 36 weeks. As results, control mice (24 weeks) developed significant chronic CAG, in which dietary walnuts significantly ameliorated chronic atrophic gastritis. Expressions of COX-2/PGE2/NF-κB/c-Jun, elevated in 24 weeks control group, were all significantly decreased with walnut (p<0.01). Tumor suppressive enzyme, 15-PGDH, was significantly preserved with walnut. Control mice (36 weeks) all developed significant tumors accompanied with severe CAG. However, significantly decreased tumorigenesis was noted in group treated with walnuts, in which expressions of COX-2/PGE2/NF-κB/IL-6/STAT3, all elevated in 36 weeks control group, were significantly decreased with walnut. Defensive proteins including HO-1, Nrf2, and SOCS-1 were significantly increased in walnut group. Proliferative index as marked with Ki-67 and PCNA was significantly regulated with walnut relevant to 15-PGDH preservation. Conclusively, walnut can be an anticipating nutritional intervention against H. pylori.
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Purpose: To evaluate the usefulness and effectiveness of bronchial occluders in the treatment of postoperative bronchopleural fistula (BPF). Materials and Methods: The subjects of the study were six out of seven postoperative BPF patients who underwent surgery due to tuberculosis or lung cancer between 2009 and 2019. Each patient had a bronchial occluder inserted to treat BPF that occurred after surgery. Of the six patients, five had lung cancers and one had tuberculosis. Five were male and one was female; their ages ranged from 59 to 74 years, with an average of 69 years. The diagnosis of BPF was based on findings from bronchoscopy and CT, and treatment was initiated approximately 1 to 2 weeks after diagnosis. The technical and clinical success of the bronchial occluders in the treatment of BPF was evaluated. The study assessed the postoperative clinical effects of the occluders, survival duration, and additional treatments. Results: All six patients were successfully treated. Clinical success was achieved in five patients, while partial clinical success was achieved in one; there was no clinical failure. No complications during the migration of the device or device perforations were observed. Two patients were diagnosed with BPF by CT, while four were diagnosed by bronchoscopy. Lobectomy, bilobectomy, and pneumonectomy were performed on two patients each. The periods between surgery and diagnosis ranged from 1 to 34 months; the average was 10 months. Four patients (59-103 days; an average of 80.5 days) died and two (313 days, 3331 days) survived. The causes of death were aggravation of the underlying disease (n = 2), pulmonary edema and pleural effusion (n = 1), and pneumonia (n = 1). Additional catheter drainage was performed in one patient, and a chest tube was maintained in two patients. Conclusion: Bronchial occluders are useful and effective in the treatment of BPF after pulmonary resection.
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The health beneficial effects of walnut plentiful of n-3 polyunsaturated fatty acid had been attributed to its anti-inflammatory and anti-oxidative properties against various clinical diseases. Since we have published Fat-1 transgenic mice overexpressing 3-desaturase significantly mitigated Helicobacter pylori (H. pylori)-associated gastric pathologies including rejuvenation of chronic atrophic gastritis and prevention of gastric cancer, in this study, we have explored the underlying molecular mechanisms of walnut against H. pylori infection. Fresh walnut polyphenol extracts (WPE) were found to suppress the phosphorylation and nuclear translocation of signal transducer and activator of transcription 3 (STAT3) induced by H. pylori infection in RGM-1 gastric mucosal cells. Notably, H. pylori infection significantly decreased suppressor of cytokine signaling 1 (SOCS1), but WPE induced expression of SOCS1, by which the suppressive effect of walnut extracts on STAT3Tyr705 phosphorylation was not seen in SOCS1 KO cells. WPE induced significantly increased nuclear translocation nuclear translocation of PPAR-γ in RGM1 cells, by which PPAR-γ KO inhibited transcription of SOCS1 and suppressive effect of WPE on p-STAT3Tyr705 was not seen. WPE inhibited the expression of c-Myc and IL-6/IL-6R signaling, which was attenuated in the RGM1 cells harboring SOCS1 specific siRNA. Conclusively, WPE inhibits H. pylori-induced STAT3 phosphorylation in a PPAR-γ and SOCS1-dependent manner.
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Kimchi is composed of various chemopreventive phytochemicals and profuse probiotics, defining kimchi as probiotic foods. Concerns had increased on the modulation of intestinal microbiota on various kinds of systemic diseases. Under the hypothesis that dietary intake of kimchi can be ideal intervention for either ameliorating colitis or preventing colitic cancer, we performed the study to validate the efficolitic cancery of fermented kimchi on preventing colitic cancer. Using azoxymethane-initiated and dextran sulfate sodium-promoted colitic cancer models, we have administrated fermented or non-fermented kimchi to modulate colitic cancer preemptively. Detailed molecular mechanisms were explored. Preemptive administration of fermented kimchi significantly afforded colitic cancer prevention through attenuating inflammasomes (IL-18, IL-1ß, caspase-1), enhancing antioxidative (NQO1, GST-π), imposing anti-proliferative (Bax, caspase-3, ß-catenin), and affording cytoprotective actions (HSP70, 15-PGDH), while non-fermented kimchi did not prevent colitic cancer. Special recipe cancer preventive kimchi (cpkimchi) was more effective compared to standard recipe fermented kimchi (p<0.01), while non-fermented kimchi (kimuchi) worsened colitic cancer development, telling the importance of fermentation in cancer prevention. Repression of NF-kB p65, induction of tumor suppressive 15-PGDH, and inactivation of ERK1/2 by cpkimchi contributed to colitic cancer prevention. Dietary intake of cpkimchi ameliorated colitis and prevented colitic cancer via concerted anti-inflammatory, antioxidative, and anti-mutagenic actions.
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Aging is a universal process that renders individuals vulnerable to many diseases. Although this process is irreversible, dietary modulation and caloric restriction are often considered to have antiaging effects. Dietary modulation can increase and maintain circulating ketone bodies, especially ß-hydroxybutyrate (ß-HB), which is one of the most abundant ketone bodies in human circulation. Increased ß-HB has been reported to prevent or improve the symptoms of various age-associated diseases. Indeed, numerous studies have reported that a ketogenic diet or ketone ester administration alleviates symptoms of neurodegenerative diseases, cardiovascular diseases, and cancers. Considering the potential of ß-HB and the intriguing data emerging from in vivo and in vitro experiments as well as clinical trials, this therapeutic area is worthy of attention. In this review, we highlight studies that focus on the identified targets of ß-HB and the cellular signals regulated by ß-HB with respect to alleviation of age-associated ailments.
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Ácido 3-Hidroxibutírico/metabolismo , Envelhecimento/metabolismo , Suscetibilidade a Doenças , Metabolismo dos Lipídeos , Animais , Humanos , Envelhecimento da PeleRESUMO
The term "single enzyme nanoparticle" (SEN) refers to a chemically or biologically engineered single enzyme molecule. SENs are distinguished from conventional protein nanoparticles in that they can maintain their individual structure and enzymatic activity following modification. Furthermore, SENs exhibit enhanced properties as biopharmaceuticals, such as reduced antigenicity, and increased stability and targetability, which are attributed to the introduction of specific moieties, such as poly(ethylene glycol), carbohydrates, and antibodies. Enzyme replacement therapy (ERT) is a crucial therapeutic option for controlling enzyme-deficiency-related disorders. However, the unfavorable properties of enzymes, including immunogenicity, lack of targetability, and instability, can undermine the clinical significance of ERT. As shown in the cases of Adagen®, Revcovi®, Palynziq®, and Strensiq®, SEN can be an effective technology for overcoming these obstacles. Based on these four licensed products, we expect that additional SENs will be introduced for ERT in the near future. In this article, we review the concepts and features of SENs, as well as their preparation methods. Additionally, we summarize different types of enzyme deficiency disorders and the corresponding therapeutic enzymes. Finally, we focus on the current status of SENs in ERT by reviewing FDA-approved products.