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1.
Ann Surg Treat Res ; 107(1): 8-15, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38978689

RESUMO

Purpose: Tumescent in nipple-sparing mastectomy (NSM) has been reported to increase the risk of necrosis by impairing blood flow to the skin flap and nipple-areolar complex. At our institution, we introduced a tumescent-free robotic NSM using the da Vinci single-port system (Intuitive Surgical, Inc.). Methods: We conducted a retrospective analysis of patients who underwent tumescent-free robotic NSM between October 2020 and March 2023 at Asan Medical Center (Seoul, Korea). Clinicopathological characteristics, adverse events, and operative time were evaluated. Results: During the study period, 118 patients underwent tumescent-free robotic NSM. Thirty-one patients (26.3%) experienced an adverse event. Five patients (4.2%) were classified as grade III based on the Clavien-Dindo classification and required surgery. The mean total operative time was 467 minutes for autologous tissue reconstruction (n = 49) and 252 minutes for implants (n = 69). No correlation was found between the cumulative number of surgical cases and the breast operative time (P = 0.30, 0.52, 0.59 for surgeons A, B, C) for the 3 surgeons. However, a significant linear relationship (P < 0.001) was observed, with the operative time increasing by 13 minutes for every 100-g increase in specimen weight. Conclusion: Tumescent-free robotic NSM is a safe procedure with a feasible operative time and few adverse events.

2.
Int J Numer Method Biomed Eng ; : e3845, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38979678

RESUMO

Virtual compression tests based on finite element analysis are representative noninvasive methods to evaluate bone strength. However, owing to the characteristic porous structure of bones, the material obtained from micro-computed tomography images in the finite-element model is not uniformly distributed. These characteristics cause differences in the apparent elastic moduli depending on the boundary conditions and affect the accuracy of bone-strength evaluation. Therefore, this study aimed to evaluate and compare the apparent elastic moduli under various, virtual-compression and shear-test boundary conditions. Four, nonuniform models were constructed with increasing model complexity. For representative boundary conditions, two, different, testing directions, and constrained surfaces were applied. As a result, the apparent elastic moduli of the nonuniform model varied up to 55.2% based on where the constrained surface was located in the single-end-cemented condition. Additionally, when connectivity in the test direction was lost, the accuracy of the apparent elastic moduli was low. A graphical comparison showed that the equivalent-stress distribution was more advantageous for analyzing load transferability and physical behavior than the strain-energy distribution. These results clearly show that the prediction accuracy of the apparent elastic moduli can be guaranteed if the boundary condition on the constraint and loading surfaces of the nonuniform model are applied symmetrically and the connectivity of the elements in the testing direction is well maintained. This study will aid in precision improvement of bone-strength-indicator determination for osteoporosis prevention.

3.
Front Oncol ; 14: 1392592, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39007102

RESUMO

Introduction: Male breast cancer (MBC) is a rare condition, and recent research has underscored notable distinctions between MBC and breast cancer in women. This study aimed to assess and contrast the long-term survival outcomes and disease patterns of MBC patients with those of their female counterparts. Methods: We analyzed data from 113,845 patients diagnosed with breast cancer who had undergone curative surgery from the Korean Breast Cancer Registry (KBCR) between January 1990 and August 2014 in Seoul, Korea. The five-year overall survival was analyzed according to clinicopathological characteristics. Results: Among 113,845 patients with breast cancer, 473 MBC cases were included. The median duration of follow-up was 72 months. The median age at diagnosis was 60 and 48 years for MBC and female breast cancer, respectively. Most male patients (92.6%) underwent total mastectomy, while 50.4% of female patients underwent breast-conserving surgery. Among MBC, 63.2% received chemotherapy, and 83.9% of hormone receptor-positive male patients received endocrine therapy. In survival analysis, MBC demonstrated distinct 5-year overall survival patterns compared with female breast cancer, according to age at diagnosis. In women with breast cancer, the younger age group (≤40 years) demonstrated worse 5-year overall survival than did the older age group (>40 years) (91.3% vs 92.7%, p <0.05). While in MBC, the younger age group (≤40 years) demonstrated better 5-year overall survival than did the older age group (>40 years) (97.4% vs 86.4%, p <0.05). Discussion: In conclusion within this extensive cohort, we have revealed unique survival patterns in MBC that diverge from those observed in women with breast cancer. This study enhances our comprehension of MBC prognosis and can potentially shed light on unresolved questions, paving the way for future research in the realm of MBC.

4.
bioRxiv ; 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-39005296

RESUMO

Staphylococcus aureus has evolved mechanisms to cope with low iron (Fe) availability in host tissues. S. aureus uses the ferric uptake transcriptional regulator (Fur) to sense titers of cytosolic Fe. Upon Fe depletion, apo-Fur relieves transcriptional repression of genes utilized for Fe uptake. We demonstrate that an S. aureus Δ fur mutant has decreased expression of acnA , which codes for the Fe-dependent enzyme aconitase. Decreased acnA expression prevented the Δ fur mutant from growing with amino acids as sole carbon and energy sources. Suppressor analysis determined that a mutation in isrR , which produces a regulatory RNA, permitted growth by decreasing isrR transcription. The decreased AcnA activity of the Δ fur mutant was partially relieved by an Δ isrR mutation. Directed mutation of bases predicted to facilitate the interaction between the acnA transcript and IsrR, decreased the ability of IsrR to control acnA expression in vivo and IsrR bound to the acnA transcript in vitro . IsrR also bound to the transcripts coding the alternate TCA cycle proteins sdhC , mqo , citZ , and citM . Whole cell metal analyses suggest that IsrR promotes Fe uptake and increases intracellular Fe not ligated by macromolecules. Lastly, we determined that Fur and IsrR promote infection using murine skin and acute pneumonia models.

5.
Discov Oncol ; 15(1): 288, 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39017974

RESUMO

PURPOSE: This research aimed to clarify the impact of residual ductal carcinoma in situ(DCIS) in surgical specimens obtained after neoadjuvant chemotherapy(NAC) for breast cancer on the associated prognosis outcomes. METHODS: This retrospective study was performed on a cohort of 1,009 patients who achieved pCR following NAC for breast cancer and underwent subsequent breast surgery at a single institution between January 2008 and December 2019. Overall survival, local recurrence-free survival, distant metastasis-free survival, and disease-free survival of the residual and non-residual DCIS groups were the outcomes compared, with further subgroup analysis performed according to hormone receptor status. RESULTS: 260 individuals (25.8%) presented with residual DCIS. Based on a median follow-up of 54.0 months, no significant differences in outcomes were observed between the two groups. Patients with residual DCIS and hormone receptor-negative (HR-) breast cancer demonstrated a significant decrease in distant metastasis-free survival (p = 0.030) compared to those without residual DCIS. In the HR + cohort, no significant difference was observed between the two groups. Multivariate analysis of the HR- cohort demonstrated a significant association between residual DCIS and an elevated risk for distant recurrence (hazard ratio = 2.3, 95% confidence interval = 1.01-5.20, p = 0.047). CONCLUSIONS: Residual DCIS following NAC may impact breast cancer outcomes, particularly with respect to the occurrence of distant metastasis in HR- patients. Therefore, clinicians must vigilantly monitor patients with residual DCIS after NAC, and further research is needed to expand our understanding of the clinical implications of residual DCIS.

6.
Toxics ; 12(6)2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38922087

RESUMO

Pyroptosis represents a type of cell death mechanism notable for its cell membrane disruption and the subsequent release of proinflammatory cytokines. The Nod-like receptor family pyrin domain containing inflammasome 3 (NLRP3) plays a critical role in the pyroptosis mechanism associated with various diseases resulting from particulate matter (PM) exposure. Tert-butylhydroquinone (tBHQ) is a synthetic antioxidant commonly used in a variety of foods and products. The aim of this study is to examine the potential of tBHQ as a therapeutic agent for managing sinonasal diseases induced by PM exposure. The occurrence of NLRP3 inflammasome-dependent pyroptosis in RPMI 2650 cells treated with PM < 4 µm in size was confirmed using Western blot analysis and enzyme-linked immunosorbent assay results for the pyroptosis metabolites IL-1ß and IL-18. In addition, the inhibitory effect of tBHQ on PM-induced pyroptosis was confirmed using Western blot and immunofluorescence techniques. The inhibition of tBHQ-mediated pyroptosis was abolished upon nuclear factor erythroid 2-related factor 2 (Nrf2) knockdown, indicating its involvement in the antioxidant mechanism. tBHQ showed potential as a therapeutic agent for sinonasal diseases induced by PM because NLRP3 inflammasome activation was effectively suppressed via the Nrf2 pathway.

7.
Am J Med Genet A ; : e63790, 2024 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-38922739

RESUMO

A 7-month-old boy presented to our clinic with developmental delay, Magnetic Resonance Imaging (MRI) features of delayed myelination and diffusion restriction, and a homozygous variant of uncertain significance (c.4T>G, p.Phe2Val) in HIKESHI, a gene associated with autosomal-recessive hypomyelinating leukodystrophy 13. We hypothesized that the variant is disease-causing and aimed to rescue the cellular phenotype with vector-mediated gene replacement. HIKESHI mediates heat-induced nuclear accumulation of heat-shock proteins, including HSP70, to protect cells from stress. We generated skin fibroblasts from the proband and proband's mother (heterozygous) to compare protein expression and subcellular localization of HSP70 under heat stress conditions, and the effect of vector-mediated overexpression of HIKESHI in the proband's cells under the same heat stress conditions. Western blot analysis revealed absent HIKESHI protein from proband fibroblasts, contrasted with ample expression in parental cells. Under heat stress conditions, while the mother's cells displayed appropriate nuclear localization of HSP70, the proband's cells displayed impaired nuclear translocalization. When patient fibroblasts were provided exogenous HIKESHI, the transfected proband's cells showed restored heat-induced nuclear translocalization of HSP70 under conditions of heat stress. These functional data establish that the patient's variant is a pathogenic loss-of-function mutation, thus confirming a diagnosis of hypomyelinating leukodystrophy 13 and that vector-mediated gene replacement may be an effective treatment approach for patients with this disorder.

8.
ACS Cent Sci ; 10(5): 1001-1011, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38799672

RESUMO

Here, we present HelixDiff, a score-based diffusion model for generating all-atom helical structures. We developed a hot spot-specific generation algorithm for the conditional design of α-helices targeting critical hotspot residues in bioactive peptides. HelixDiff generates α-helices with near-native geometries for most test scenarios with root-mean-square deviations (RMSDs) less than 1 Å. Significantly, HelixDiff outperformed our prior GAN-based model with regard to sequence recovery and Rosetta scores for unconditional and conditional generations. As a proof of principle, we employed HelixDiff to design an acetylated GLP-1 D-peptide agonist that activated the glucagon-like peptide-1 receptor (GLP-1R) cAMP accumulation without stimulating the glucagon-like peptide-2 receptor (GLP-2R). We predicted that this D-peptide agonist has a similar orientation to GLP-1 and is substantially more stable in MD simulations than our earlier D-GLP-1 retro-inverse design. This D-peptide analogue is highly resistant to protease degradation and induces similar levels of AKT phosphorylation in HEK293 cells expressing GLP-1R compared to the native GLP-1. We then discovered that matching crucial hotspots for the GLP-1 function is more important than the sequence orientation of the generated D-peptides when constructing D-GLP-1 agonists.

9.
Sleep Breath ; 2024 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-38795279

RESUMO

OBJECTIVE: The epiglottis plays an integral role in the swallowing mechanism and is also implicated as an obstruction site in obstructive sleep apnea (OSA). The underlying causes of epiglottic collapse during sleep remain unclear. This study aimed to investigate the cognitive functions using the Loewenstein Occupational Therapy Cognitive Assessment (LOTCA) and the neurophysiological and anatomical factors using videofluoroscopic swallowing studies (VFSS). We compared patients with OSA exhibiting epiglottic collapse to those without, assessing differences in anatomical or neurophysiological characteristics. METHODS: The study included 12 patients with epiglottic collapse (Epi-group) and 68 without (non-Epi group), all undergoing overnight polysomnography (PSG), drug-induced sleep endoscopy (DISE), LOTCA, and VFSS. Oral transit time (OTT), pharyngeal delay time (PDT), and pharyngeal transit time (PTT) were considered as neurophysiological traits, and laryngeal elevation length (LE) as anatomical trait, and were measured across various test diets (10 ml of liquid, soft, or solid). RESULTS: The study comprised 80 individuals, 57 men and 23 women, with no significant age, sex, body mass index or PSG parameters between groups, or DISE findings, with the exception of epiglottic collapse. Swallowing metrics from VFSS were normal, with no differences in OTT, PDT, PTT, or LOTCA scores. Notably, patients with epiglottic collapse showed a greater laryngeal elevation when swallowing soft and solid foods (p = 0.025 and p = 0.048, respectively). CONCLUSIONS: Patients with epiglottic collapse do not exhibit neurophysiological or cognitive impairments when compared to non-Epi group. However, the Epi-group displayed a significantly increased laryngeal elevation length. This suggests that anatomical factors may have a more substantial role in the development of epiglottic collapse than neurophysiological factors.

10.
Antonie Van Leeuwenhoek ; 117(1): 80, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38772982

RESUMO

A novel strictly anaerobic bacterium, strain JBNU-10 T, was isolated from BALB/c mouse feces. Cells of the strain JBNU-10 T were Gram-stain positive, non-motile and rod-shaped. Optimum growth occurred at 37℃, with 1% (w/v) NaCl and at pH 7. Phylogenetic analysis based on 16S rRNA gene sequence showed that strain JBNU-10 T belonged to the genus Adlercreutzia and were closely related to Adlercreutzia muris WCA-131-CoC-2 T (95.90%). The genome sequencing of strain JBNU-10 T revealed a genome size of 2,790,983 bp, a DNA G + C content of 69.4 mol%. It contains a total of 2,266 CDSs, 5 rRNA genes and 49 tRNA genes. According to the data obtained strain JBNU-10 T shared ANI value below 77.6- 67.7%, dDDH value below 23.8% with the closely type species. Strain JBNU-10 T possessed iso-C16:0 DMA, C18:1 CIS 9 FAME, and C18:0 DMA as the major fatty acids and had DMMK-6. The major end products of fermentation is propionate and acetate. Based on phylogenetic, physiological and chemotaxonomic characteristics, strain JBNU-10 T represent a novel species of the genus Adlercreutzia. The type strain is JBNU-10 T (= KCTC 25028 T = CCUG 75610 T).


Assuntos
Acetatos , Composição de Bases , Fezes , Camundongos Endogâmicos BALB C , Filogenia , Propionatos , RNA Ribossômico 16S , Animais , Fezes/microbiologia , Camundongos , RNA Ribossômico 16S/genética , Acetatos/metabolismo , Propionatos/metabolismo , DNA Bacteriano/genética , Ácidos Graxos/metabolismo , Ácidos Graxos/análise , Técnicas de Tipagem Bacteriana , Análise de Sequência de DNA , Genoma Bacteriano
11.
Cell Death Dis ; 15(5): 374, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38811543

RESUMO

High workload-induced cellular stress can cause pancreatic islet ß cell death and dysfunction, or ß cell failure, a hallmark of type 2 diabetes mellitus. Thus, activation of molecular chaperones and other stress-response genes prevents ß cell failure. To this end, we have shown that deletion of the glucose-regulated protein 94 (GRP94) in Pdx1+ pancreatic progenitor cells led to pancreas hypoplasia and reduced ß cell mass during pancreas development in mice. Here, we show that GRP94 was involved in ß cell adaption and compensation (or failure) in islets from leptin receptor-deficient (db/db) mice in an age-dependent manner. GRP94-deficient cells were more susceptible to cell death induced by various diabetogenic stress conditions. We also identified a new client of GRP94, insulin-like growth factor-1 receptor (IGF-1R), a critical factor for ß cell survival and function that may mediate the effect of GRP94 in the pathogenesis of diabetes. This study has identified essential functions of GRP94 in ß cell failure related to diabetes.


Assuntos
Células Secretoras de Insulina , Receptor IGF Tipo 1 , Animais , Camundongos , Morte Celular , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Diabetes Mellitus Tipo 2/genética , Células Secretoras de Insulina/metabolismo , Células Secretoras de Insulina/patologia , Glicoproteínas de Membrana/metabolismo , Glicoproteínas de Membrana/genética , Camundongos Endogâmicos C57BL , Camundongos Knockout , Receptor IGF Tipo 1/metabolismo , Receptor IGF Tipo 1/genética , Receptores para Leptina/metabolismo , Receptores para Leptina/genética
13.
Elife ; 122024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38687677

RESUMO

The agr quorum-sensing system links Staphylococcus aureus metabolism to virulence, in part by increasing bacterial survival during exposure to lethal concentrations of H2O2, a crucial host defense against S. aureus. We now report that protection by agr surprisingly extends beyond post-exponential growth to the exit from stationary phase when the agr system is no longer turned on. Thus, agr can be considered a constitutive protective factor. Deletion of agr resulted in decreased ATP levels and growth, despite increased rates of respiration or fermentation at appropriate oxygen tensions, suggesting that Δagr cells undergo a shift towards a hyperactive metabolic state in response to diminished metabolic efficiency. As expected from increased respiratory gene expression, reactive oxygen species (ROS) accumulated more in the agr mutant than in wild-type cells, thereby explaining elevated susceptibility of Δagr strains to lethal H2O2 doses. Increased survival of wild-type agr cells during H2O2 exposure required sodA, which detoxifies superoxide. Additionally, pretreatment of S. aureus with respiration-reducing menadione protected Δagr cells from killing by H2O2. Thus, genetic deletion and pharmacologic experiments indicate that agr helps control endogenous ROS, thereby providing resilience against exogenous ROS. The long-lived 'memory' of agr-mediated protection, which is uncoupled from agr activation kinetics, increased hematogenous dissemination to certain tissues during sepsis in ROS-producing, wild-type mice but not ROS-deficient (Cybb-/-) mice. These results demonstrate the importance of protection that anticipates impending ROS-mediated immune attack. The ubiquity of quorum sensing suggests that it protects many bacterial species from oxidative damage.


Assuntos
Proteínas de Bactérias , Regulação Bacteriana da Expressão Gênica , Peróxido de Hidrogênio , Estresse Oxidativo , Percepção de Quorum , Staphylococcus aureus , Transativadores , Staphylococcus aureus/genética , Staphylococcus aureus/fisiologia , Staphylococcus aureus/metabolismo , Percepção de Quorum/genética , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Animais , Transativadores/metabolismo , Transativadores/genética , Peróxido de Hidrogênio/metabolismo , Peróxido de Hidrogênio/farmacologia , Camundongos , Infecções Estafilocócicas/microbiologia , Viabilidade Microbiana , Espécies Reativas de Oxigênio/metabolismo , Deleção de Genes
14.
Fam Cancer ; 23(2): 121-132, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38662264

RESUMO

Despite increased awareness and availability of genetic testing for hereditary breast and ovarian cancer (HBOC) syndrome for over 20 years, there is still significant underuse of cascade genetic testing among at-risk relatives. This scoping review synthesized evidence regarding psychosocial barriers and facilitators of family communication and/or uptake of cascade genetic testing in relatives from HBOC families. Search terms included 'hereditary breast and ovarian cancer' and 'cascade genetic testing' for studies published from 2012-2022. Through searching common databases, and manual search of references, 480 studies were identified after excluding duplications. Each article was reviewed by two researchers independently and 20 studies were included in the final analysis. CASP, RoBANS 2.0, RoB 2.0, and MMAT were used to assess the quality of included studies. A convergent data synthesis method was used to integrate evidence from quantitative and narrative data into categories and subcategories. Evidence points to 3 categories and 12 subcategories of psychosocial barriers and facilitators for cascade testing: (1) facilitators (belief in health protection and prevention; family closeness; decisional empowerment; family support, sense of responsibility; self-efficacy; supportive health professionals); (2) bidirectional concepts (information; perception of genetic/cancer consequences; negative emotions and attitude); and (3) barriers (negative reactions from family and negative family dynamics). Healthcare providers need to systematically evaluate these psychosocial factors, strengthen facilitators and alleviate barriers to promote informed decision-making for communication of genetic test results and uptake of genetic testing. Bidirectional factors merit special consideration and tailored approaches, as they can potentially have a positive or negative influence on family communication and uptake of genetic testing.


Assuntos
Predisposição Genética para Doença , Testes Genéticos , Humanos , Feminino , Predisposição Genética para Doença/psicologia , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/psicologia , Neoplasias Ovarianas/diagnóstico , Síndrome Hereditária de Câncer de Mama e Ovário/genética , Síndrome Hereditária de Câncer de Mama e Ovário/psicologia , Síndrome Hereditária de Câncer de Mama e Ovário/diagnóstico , Neoplasias da Mama/genética , Neoplasias da Mama/psicologia , Neoplasias da Mama/diagnóstico , Família/psicologia
15.
Breast Cancer Res Treat ; 206(3): 495-507, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38658448

RESUMO

PURPOSE: To select patients who would benefit most from sentinel lymph node biopsy (SLNB) by investigating the characteristics and risk factors of axillary lymph node metastasis (ALNM) in microinvasive breast cancer (MIBC). METHODS: This retrospective study included 1688 patients with MIBC who underwent breast surgery with axillary staging at the Asan Medical Center from 1995 to 2020. RESULTS: Most patients underwent SLNB alone (83.5%). Seventy (4.1%) patients were node-positive, and the majority had positive lymph nodes < 10 mm, with micro-metastases occurring frequently (n = 37; 55%). Node-positive patients underwent total mastectomy and axillary lymph node dissection (ALND) more than breast-conserving surgery (BCS) and SLNB compared with node-negative patients (p < 0.001). In the multivariate analysis, independent predictors of ALNM included young age [odds ratio (OR) 0.959; 95% confidence interval (CI) 0.927-0.993; p = 0.019], ALND (OR 11.486; 95% CI 5.767-22.877; p < 0.001), number of lymph nodes harvested (≥ 5) (OR 3.184; 95% CI 1.555-6.522; p < 0.001), lymphovascular invasion (OR 6.831; 95% CI 2.386-19.557; p < 0.001), presence of multiple microinvasion foci (OR 2.771; 95% CI 1.329-5.779; p = 0.007), prominent lymph nodes in preoperative imaging (OR 2.675; 95% CI 1.362-5.253; p = 0.004), and hormone receptor positivity (OR 2.491; 95% CI 1.230-5.046; p = 0.011). CONCLUSION: Low ALNM rate (4.1%) suggests that routine SLNB for patients with MIBC is unnecessary but can be valuable for patients with specific risk factors. Ongoing trials for omitting SLNB in early breast cancer, and further subanalyses focusing on rare populations with MIBC are necessary.


Assuntos
Axila , Neoplasias da Mama , Linfonodos , Metástase Linfática , Biópsia de Linfonodo Sentinela , Humanos , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Feminino , Pessoa de Meia-Idade , Metástase Linfática/patologia , Estudos Retrospectivos , Fatores de Risco , Adulto , Idoso , Linfonodos/patologia , Linfonodos/cirurgia , Excisão de Linfonodo , Invasividade Neoplásica , Mastectomia , Idoso de 80 Anos ou mais
16.
Environ Int ; 185: 108522, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38401434

RESUMO

The rapidly increasing prevalence of obesity and overweight, especially in children and adolescents, has become a serious societal issue. Although various genetic and environmental risk factors for pediatric obesity and overweight have been identified, the problem has not been solved. In this study, we examined whether environmental nanoplastic (NP) pollutants can act as environmental obesogens using mouse models exposed to NPs derived from polystyrene and polypropylene, which are abundant in the environment. We found abnormal weight gain in the progeny until 6 weeks of age following the oral administration of NPs to the mother during gestation and lactation. Through a series of experiments involving multi-omic analyses, we have demonstrated that NP-induced weight gain is caused by alterations in the lipid composition (lysophosphatidylcholine/phosphatidylcholine ratio) of maternal breast milk and he gut microbiota distribution of the progeny. These data indicate that environmental NPs can act as obesogens in childhood.


Assuntos
Microbiota , Obesidade Infantil , Masculino , Criança , Feminino , Animais , Camundongos , Humanos , Adolescente , Sobrepeso/epidemiologia , Microplásticos , Aumento de Peso , Leite Humano , Mães , Lipídeos , Ingestão de Alimentos
17.
Arch Microbiol ; 206(3): 108, 2024 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-38368591

RESUMO

A Gram-stain-positive, anaerobic, motile, and short rod-shaped bacterium, designated KGMB12511T, was isolated from the feces of healthy Koreansubjects. Phylogenetic analysis based on the 16S rRNA gene sequence showed that strain KGMB12511T was closely related to Gordonibacter pamelaeae 7-10-1-bT (95.2%). The draft genome of KGMB12511T comprised 33 contigs and 2,744 protein-coding genes. The DNA G + C content was 59.9% based on whole-genome sequences. The major cellular fatty acids (>10%) of strain KGMB12511T were C18:1 cis9, C18:1 cis9 DMA (dimethylacetal), and C16:0 DMA. The predominant polar lipids included a diphosphatydilglycerol, four glycolipids, and an unidentified phospholipid. The major respiratory quinones were menaquinone 6 (MK-6) and monomethylmenaquinone 6 (MMK-6). Furthermore, HPLC analysis demonstrated the ability of strain KGMB12511T to convert ellagic acid into urolithin. Based on a comprehensive analysis of phenotypic, chemotaxonomic, and phylogenetic data, strain KGMB12511T represents a novel species in the genus Gordonibacter. The type strain is KGMB12511T (= KCTC 25343T = NBRC 116190T).


Assuntos
Ácido Elágico , Taninos Hidrolisáveis , Humanos , Filogenia , RNA Ribossômico 16S/genética , Fezes , República da Coreia
18.
Clin Proteomics ; 21(1): 17, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38424522

RESUMO

BACKGROUND: Immunotherapy is applied to breast cancer to resolve the limitations of survival gain in existing treatment modalities. With immunotherapy, a tumor can be classified into immune-inflamed, excluded and desert based on the distribution of immune cells. We assessed the clinicopathological features, each subtype's prognostic value and differentially expressed proteins between immune subtypes. METHODS: Immune subtyping and proteomic analysis were performed on 56 breast cancer cases with neoadjuvant chemotherapy. The immune subtyping was based on the level of tumor-infiltrating lymphocytes (TILs) and Klintrup criteria. If the level of TILs was ≥ 10%, it was classified as immune-inflamed type without consideration of the Klintrup criteria. In cases of 1-9% TIL, Klintrup criteria 1-3 were classified as the immune-excluded subtype and Klintrup criteria not available (NA) was classified as NA. Cases of 1% TILs and Klintrup 0 were classified as the immune-desert subtype. Mass spectrometry was used to identify differentially expressed proteins in formalin-fixed paraffin-embedded biopsy tissues. RESULTS: Of the 56 cases, 31 (55%) were immune-inflamed, 21 (38%) were immune-excluded, 2 (4%) were immune-desert and 2 (4%) were NA. Welch's t-test revealed two differentially expressed proteins between immune-inflamed and immune-excluded/desert subtypes. Coronin-1A was upregulated in immune-inflamed tumors (adjusted p = 0.008) and α-1-antitrypsin was upregulated in immune-excluded/desert tumors (adjusted p = 0.008). Titin was upregulated in pathologic complete response (pCR) than non-pCR among immune-inflamed tumors (adjusted p = 0.036). CONCLUSIONS: Coronin-1A and α-1-antitrypsin were upregulated in immune-inflamed and immune-excluded/desert subtypes, respectively. Titin's elevated expression in pCR within the immune-inflamed subtype may indicate a favorable prognosis. Further studies involving large representative cohorts are necessary to validate these findings.

19.
Antonie Van Leeuwenhoek ; 117(1): 30, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38302626

RESUMO

An obligately anaerobic, non-motile, Gram-stain-negative, and rod-shaped strain KGMB11183T was isolated from the feces of healthy Koreans. The growth of strain KGMB11183T occurred at 30-45 °C (optimum 37 °C), at pH 6-9 (optimum pH 7), and in the presence of 0-0.5% NaCl (optimum 0%). Strain KGMB11183T showed 16S rRNA gene sequence similarities of 95.4% and 94.2% to the closest recognized species, Phocaeicola plebeius M12T, and Phocaeicola faecicola AGMB03916T. Phylogenetic analysis showed that strain KGMB11183T is a member of the genus Phocaeiocla. The major end products of fermentation are acetic acid and isobutyric acid. The major cellular fatty acids (> 10%) of this isolate were C18:1 cis 9, anteiso-C15:0, and summed feature 11 (iso-C17:0 3-OH and/or C18:2 DMA). The assembled draft genome sequences of strain KGMB11183T consisted of 3,215,271 bp with a DNA G + C content of 41.4%. According to genomic analysis, strain KGMB11183T has a number of genes that produce acetic acid. The genome of strain KGMB11183T encoded the starch utilization system (Sus) operon, SusCDEF suggesting that strain uses many complex polysaccharides that cannot be digested by humans. Based on the physiological, chemotaxonomic, phenotypic, and phylogenetic data, strain KGMB11183T is regarded a novel species of the genus Phocaeicola. The type strain is KGMB11183T (= KCTC 25284T = JCM 35696T).


Assuntos
Ácido Acético , Ácidos Graxos , Humanos , Ácido Butírico , Filogenia , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Técnicas de Tipagem Bacteriana , DNA Bacteriano/genética , Ácidos Graxos/química , Bacteroidetes/genética , Fezes
20.
Breast Cancer Res Treat ; 205(1): 117-125, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38332198

RESUMO

PURPOSE: To compare the oncological safety of nipple-sparing breast-conserving surgery (BCS) versus central lumpectomy for centrally located breast cancer (CLBC). METHODS: Patients who underwent BCS for CLBC at Asan Medical Center from 2007 to 2018 were reviewed retrospectively. The oncological outcomes of nipple-sparing BCS (NS-BCS) and central lumpectomy were compared using univariate and multivariate Cox regression analyses and compared again after 1:1 propensity score matching (PSM). RESULTS: The study included 306 patients who underwent NS-BCS and 106 patients who underwent central lumpectomy (median follow-up: 111 months). On multivariate analysis, central lumpectomy had a lower risk of local recurrence compared to NS-BCS, albeit without statistical significance (HR 0.14, 95% CI 0.02-1.24; p = 0.077). There was no significant difference in the risk of death (HR 0.14, 95% CI 0.01-1.68, p = 0.12). After PSM, each group had 106 patients. The 5-year and 10-year local recurrence-free survival rates were 94.2% and 92.9% for NS-BCS, and 99.1% and 99.1% for central lumpectomy, respectively (p = 0.031). There were no significant differences in overall survival, regional recurrence-free survival, or distant recurrence-free survival. Fifteen patients (4.9%) who underwent NS-BCS had ipsilateral breast tumor recurrence (IBTR), of which 40% were in the nipple-areolar complex and previous surgical sites. One patient (0.9%) who underwent central lumpectomy experienced an IBTR in a different quadrant. CONCLUSION: NS-BCS showed more local recurrence than central lumpectomy. When deciding whether to spare the nipple during BCS in CLBC, patients should be sufficiently informed about the risk of IBTR.


Assuntos
Neoplasias da Mama , Mastectomia Segmentar , Recidiva Local de Neoplasia , Mamilos , Pontuação de Propensão , Humanos , Neoplasias da Mama/cirurgia , Neoplasias da Mama/patologia , Neoplasias da Mama/mortalidade , Feminino , Pessoa de Meia-Idade , Mamilos/cirurgia , Mastectomia Segmentar/métodos , Estudos Retrospectivos , Adulto , Idoso , Resultado do Tratamento , Tratamentos com Preservação do Órgão/métodos , Seguimentos
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