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1.
Am J Cancer Res ; 14(4): 1561-1576, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38726259

RESUMO

Lung squamous cell carcinoma (LUSC) remains a difficult-to-treat disease with a poor prognosis. While prominin-1 (PROM1/CD-133) is largely investigated in a variety of malignancies, the role of prominin-2 (PROM2), the other member of the prominin family, has not been studied in LUSC. Transcriptomic data derived from matched tumor and adjacent non-tumorous lung tissues of LUSC patients were employed to conduct an in-depth analysis of the genetic and epigenetic regulation of prominin genes within LUSC, utilizing bioinformatic approaches. Furthermore, cellular behavior experiments were executed to discern the biological functions of PROM2. It was observed that PROM2, in contrast to PROM1, exhibited significant upregulation and overexpression at both the mRNA and protein levels in LUSC, and this upregulation was correlated with shortened patient survival. Transcriptomic analysis unveiled DNA methylation as an epigenetic regulatory mechanism associated with PROM2 expression. Notably, two transcription factors, CBFB and NRIP1, were identified as potential regulators of PROM2 expression. Subsequent in vitro investigations demonstrated that knocking down PROM2 led to the inhibition of cancer cell migration and the epithelial-to-mesenchymal transition (EMT). In summary, the pronounced upregulation of PROM2 in LUSC patients was linked to an unfavorable prognosis, possibly attributable to its influence on cancer cell migration and EMT. These findings suggest that PROM2 could serve as a promising diagnostic biomarker and therapeutic target in the management of LUSC. Consequently, further research into the mechanistic aspects and potential therapeutic interventions targeting PROM2 is warranted in the clinical context.

3.
Int Neurourol J ; 28(1): 59-66, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38569621

RESUMO

PURPOSE: This study was conducted to evaluate the efficacy of bladder outlet surgery in patients with detrusor underactivity (DU) and to identify factors associated with successful outcomes. METHODS: We conducted a retrospective review of men diagnosed with DU in urodynamic studies who underwent bladder outlet surgery for lower urinary tract symptoms between May 2018 and April 2023. The International Prostate Symptom Score (IPSS) questionnaire, uroflowmetry (UFM), and multichannel urodynamic studies were administered. Successful treatment outcomes were defined as either an IPSS improvement of at least 50% or the regaining of spontaneous voiding in patients urethral catheterization prior to surgery. RESULTS: The study included 93 male patients. Men diagnosed with significant or equivocal bladder outlet obstruction (BOO) experienced significant postoperative improvements in IPSS (from 20.6 to 6.0 and from 17.4 to 6.5, respectively), maximum urine flow rate (from 5.0 mL/sec to 14.4 mL/sec and from 8.8 mL/sec to 12.2 mL/sec, respectively) and voiding efficiency (from 48.8% to 86.0% and from 61.2% to 85.1%, respectively). However, in the group without obstruction, the improvements in IPSS and UFM results were not significant. The presence of detrusor overactivity (odds ratio [OR], 3.152; P=0.025) and preoperative urinary catheterization (OR, 2.756; P=0.040) were associated with favorable treatment outcomes. Conversely, an unobstructed bladder outlet was identified as a negative prognostic factor. CONCLUSION: In men with DU accompanied by equivocal or significant BOO, surgical intervention to alleviate the obstruction may enhance the IPSS, quality of life, and UFM results. However, those with DU and an unobstructed bladder outlet face a comparatively high risk of treatment failure. Preoperative detrusor overactivity and urinary catheterization are associated with more favorable surgical outcomes. Consequently, active deobstructive surgery should be considered for patients with DU who are experiencing urinary retention.

4.
Kaohsiung J Med Sci ; 40(5): 467-476, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38523603

RESUMO

Combining epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) with an anti- vascular endothelial growth factor (VEGF) agent, bevacizumab or ramucirumab, is indicated for advanced lung adenocarcinoma harboring EGFR mutation. This study aimed to show the real-world data of combination therapy and compare the effectiveness between bevacizumab and ramucirumab in combination with an EGFR-TKI. This retrospective study enrolled 47 patients diagnosed of stage IV lung adenocarcinoma with exon 19 deletion or L858R point mutation, receiving a first-line EGFR-TKI with anti-VEGF agent, including 34 (72%) and 13 (28%) patients receiving bevacizumab and ramucirumab, respectively. The response rate was similar in both groups (p = 0.38). Patients receiving bevacizumab had similar progression free survival (PFS) as those receiving ramucirumab (median PFS: 21.9 vs. 24.2 months, p = 0.4871); similar finding was noted in overall survival (OS) (median OS: 33.5 months vs. not reached, p = 0.4618). Patients receiving ramucirumab experienced a significantly high-grade hypertension compared to those receiving bevacizumab (p = 0.0351). Multivariable Cox regression analysis found independent risk factors for worse PFS included poorer ECOG performance status, multiple (≥3) metastatic sites, brain metastasis, and pleural metastasis/effusion, while the type of anti-VEGF agent was not a risk factor. Pericardial metastasis/effusion was the only one independent risk factor for worse OS. In summary, ramucirumab may have similar effectiveness as bevacizumab in combination with an EGFR-TKI as first line therapy for advanced lung adenocarcinoma harboring susceptible EGFR mutation. Further large-scale registry-based cohort studies may be needed to validate our findings.


Assuntos
Anticorpos Monoclonais Humanizados , Bevacizumab , Carcinoma Pulmonar de Células não Pequenas , Receptores ErbB , Neoplasias Pulmonares , Mutação , Inibidores de Proteínas Quinases , Ramucirumab , Humanos , Masculino , Feminino , Receptores ErbB/genética , Receptores ErbB/antagonistas & inibidores , Bevacizumab/uso terapêutico , Bevacizumab/administração & dosagem , Anticorpos Monoclonais Humanizados/uso terapêutico , Pessoa de Meia-Idade , Idoso , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Inibidores de Proteínas Quinases/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Resultado do Tratamento , Adulto , Estudos Retrospectivos , Idoso de 80 Anos ou mais , Estadiamento de Neoplasias , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia
5.
Front Nutr ; 11: 1354486, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38524850

RESUMO

Introduction: With the increasing demand for protein utilization, exploring new protein resources has become a research hotspot. Sacha Inchi Protein (SIP) is a high-quality plant protein extracted from Sacha Inchi meal. This study aimed to investigate the impact of SIP on mouse metabolomics and gut microbiota diversity and explore the underlying pathways responsible for its health benefits. Methods: In this study, the structural composition of SIP was investigated, and the effects of SIP on fecal metabolomics and intestinal microorganisms in mice were explored by LC-MS metabolomics technology analysis and 16S rRNA gene sequencing. Results: The results showed that SIP was rich in amino acids, with the highest Manuscript Click here to view linked References content of arginine, which accounted for 22.98% of the total amino acid content; the potential fecal metabolites of mice in the SIP group involved lipid metabolism, sphingolipid metabolism, arginine biosynthesis, and amino acid metabolism; SIP altered the microbial composition of the cecum in mice, decreased the Firmicutes/Bacteroidetes value, and It decreased the abundance of the harmful intestinal bacteria Actinobacteriota and Desulfobacterota, and increased the abundance of the beneficial intestinal bacteria Faecalibaculum, Dubosiella. Discussion: In conclusion, SIP is a high-quality plant protein with great potential for development in lipid-lowering, intestinal health, and mental illness, providing valuable clues for further research on its health-promoting mechanisms.

6.
Biomed Opt Express ; 15(3): 1355-1369, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38495722

RESUMO

Carotid endarterectomy (CEA) involves removal of plaque in the carotid artery to reduce the risk of stroke and improve cerebral perfusion. This study aimed to investigate the utility of assessing pulsatile blood volume and flow during CEA. Using a combined near-infrared spectroscopy/diffuse correlation spectroscopy instrument, pulsatile hemodynamics were assessed in 12 patients undergoing CEA. Alterations to pulsatile amplitude, pulse transit time, and beat morphology were observed in measurements ipsilateral to the surgical side. The additional information provided through analysis of pulsatile hemodynamic signals has the potential to enable the discovery of non-invasive biomarkers related to cortical perfusion.

7.
Am J Cancer Res ; 14(2): 854-868, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38455397

RESUMO

The poor outcome of patients with lung adenocarcinoma (LUAD) highlights the importance to identify novel effective prognostic markers and therapeutic targets. Long noncoding RNAs (lncRNAs) have generally been considered to serve important roles in tumorigenesis and the development of various types of cancer, including LUAD. Here, we aimed to investigate the role of ENTPD3-AS1 (ENTPD3 Antisense RNA 1) in LUAD and to explore its potential mechanisms by performing comprehensive bioinformatic analyses. The regulatory effect of ENTPD3-AS1 on the expression of NR3C1 was validated by siRNA-based silencing. The effect of miR-421 on the modulation of NR3C1 was determined by miRNA mimics and inhibitors transfection. ENTPD3-AS1 was expressed at lower levels in tumor parts and negatively correlated with unfavorable prognosis in LUAD patients. It exerted functions as a tumor suppressor gene by competitively binding to oncomir, miR-421, thereby attenuating NR3C1 expression. Transfection of lung cancer A549 cells with miR-421 mimics decreased the expression of NR3C1. Transfection of lung cancer A549 cells with miR-421 inhibitors increased the expression of NR3C1 with lower cellular functions as proliferation and migration via epithelial-mesenchymal transition. In addition, inhibition of ENTPD3-AS1 by siRNA transfection decreased the levels of NR3C1, supporting the ENTPD3-AS1/miR-421/NR3C1 cascade. Moreover, the bioinformatic analysis also showed that ENTPD3-AS1 could interact with the RNA-binding proteins (RBPs), CELF2 and QKI, consequently regulating RNA expression and processing. Taken together, we identified that ENTPD3-AS1 and its indirect target NR3C1 can act as novel biomarkers for determining the prognosis of patients with LUAD, and further study is required.

8.
Neurourol Urodyn ; 43(3): 646-654, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38314960

RESUMO

PURPOSE: Benign prostatic obstruction (BPO) is the most common cause of lower urinary tract symptoms among men. GreenLight photoselective vaporization of the prostate (GL-PVP) using a 180-W Xcelerated performance system (XPS) laser is a well-established method for treating BPO-induced voiding symptoms. However, its therapeutic effects on storage symptoms remain unclear. This study aimed to analyze the storage outcomes in patients who underwent 180-W XPS GL-PVP for BPO and to identify outcome predictors. MATERIALS AND METHODS: Patients who underwent 180-W XPS GL-PVP for BPO between May 2018 and May 2021 were retrospectively reviewed. Data on clinical characteristics, prostate volume, preoperative and postoperative International Prostate Symptom Scores (IPSS), and preoperative urodynamic parameters were collected. A favorable storage outcome was defined as ≥50% reduction in the IPSS storage subscore. RESULTS: Ninety-nine male patients were included, with a mean age of 69.4 ± 9.6 years and a baseline prostatic volume of 75.9 ± 33.1 mL. The IPSS total, storage, and voiding subscores significantly decreased after GL-PVP (all p < 0.001). Seventy-two patients achieved favorable storage outcome at 6 months. Multivariate analysis revealed that detrusor underactivity was predictive of unfavorable storage outcomes (p = 0.022), while IPSS voiding-to-storage subscore ratio >1.25 and the presence of detrusor overactivity were predictive of favorable storage outcomes (p = 0.008 and 0.033, respectively). CONCLUSION: 180-W XPS GL-PVP provided excellent outcomes in both voiding and storage lower urinary tract symptoms concomitant with BPO. Preoperative IPSS and multichannel urodynamic parameters including detrusor overactivity and underactivity are valuable predictors of postoperative storage outcomes.


Assuntos
Terapia a Laser , Sintomas do Trato Urinário Inferior , Hiperplasia Prostática , Ressecção Transuretral da Próstata , Obstrução Uretral , Humanos , Masculino , Pessoa de Meia-Idade , Idoso , Próstata/cirurgia , Hiperplasia Prostática/complicações , Hiperplasia Prostática/cirurgia , Estudos Retrospectivos , Volatilização , Ressecção Transuretral da Próstata/efeitos adversos , Ressecção Transuretral da Próstata/métodos , Sintomas do Trato Urinário Inferior/cirurgia , Sintomas do Trato Urinário Inferior/complicações , Obstrução Uretral/complicações , Terapia a Laser/efeitos adversos , Terapia a Laser/métodos , Resultado do Tratamento
9.
Clin Nutr ; 43(3): 603-619, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38301284

RESUMO

BACKGROUND: The hypothalamus is a crucial brain region that mediates the effects of insulin and leptin signals on peripheral metabolic functions. Previous research has shown that insulin signals in the hypothalamus act via multiple neuronal circuits and anabolic/catabolic pathways that converge on the vagus nerve and sympathetic fibers to coordinate energy metabolism in peripheral organs. Additionally, neuropeptide FF (NPFF) has been identified as a regulator of feeding behaviors and energy homeostasis in the hypothalamus, but the mechanisms underlying its involvement in metabolic control remain unclear. This study aims to explore the underlying mechanisms of NPFF in modulating metabolic disorders. METHODS: In this study, we investigated the physiological role of NPFF in insulin-related energy homeostasis and metabolic health. First, we evaluated the effects of NPFF and its receptors on central insulin signaling using mouse hypothalamic cell lines and Npffr2-overexpressing mice. To further explore the effects of NPFFR2 on insulin-related metabolic disorders, such as diabetes mellitus, we used Npffr2-deleted mice in combination with the streptozotocin (STZ)-induced type 1 diabetes and high-fat diet/STZ-induced type 2 diabetic mouse models. The impacts of central NPFFR2 were demonstrated specifically through Npffr2 overexpression in the hypothalamic arcuate nucleus, which subsequently induced type 2 diabetes. RESULTS: We found that stimulating NPFFR2 in the hypothalamus blocked hypothalamic insulin activity. Npffr2 deletion improved central and peripheral metabolic symptoms in both mouse models of diabetes mellitus, exerting effects on central and systemic insulin resistance, feeding behaviors, glucose and insulin intolerance, lipid metabolism, liver steatosis, and inflammation of white adipose tissues. The overexpression of ARC Npffr2 augmented the metabolic dysregulation in the mouse model of type 2 diabetes. CONCLUSIONS: Our findings demonstrate that hypothalamic NPFFR2 negatively regulates insulin signaling in the central nervous system and plays an important role in maintaining systemic metabolic health, thereby providing valuable insights for potential clinical interventions targeting these health challenges.


Assuntos
Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Animais , Camundongos , Insulina , Diabetes Mellitus Tipo 2/genética , Hipotálamo , Homeostase , Modelos Animais de Doenças
10.
Foods ; 13(3)2024 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-38338535

RESUMO

In recent years, green and healthy foods have attracted much attention. Plant-based foods have become an alternative to animal-derived foods. In this study, we used walnut and purple rice as the primary raw materials to produce a fermented plant drink. The process included boiling, mixing, grinding, inoculation, fermentation, and sterilization. We then analyzed the similarities and differences between the resulting walnut and purple rice fermented plant drink and an unfermented walnut and purple rice plant drink, as well as dairy-based yoghurt, in terms of physical chemistry, flavor, and sensory characteristics. We also examined the similarities and differences between the walnut and purple rice fermented plant drink and room-temperature yoghurt. The study results revealed that the walnut and purple rice fermented plant drink exhibited greater viscosity than the walnut and purple rice unfermented plant drink and room-temperature yoghurt. Additionally, the former displayed enhanced stability and recovery ability. Notably, distinguishable differences were observed between the three samples in terms of the presence of unknown volatiles and the umami signal, as indicated by electronic nose/tongue and GC-IMS analyses. The umami flavor of the walnut and purple rice fermented plant drink surpasses that of room-temperature yoghurt, while its taste is less salty than that of the walnut and purple rice plant drink. Despite possessing a weaker aroma than dairy-based yogurt, it is more potent than the walnut and purple rice plant drink. Additionally, its relative abundance of olefins, ketones, and alcohols enhances its unique flavor profile, surpassing both other options. Based on sensory analysis, it can be deduced that walnut and purple rice fermented plant drink has the highest overall acceptance rate.

11.
Urol Case Rep ; 53: 102657, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38304065

RESUMO

Sclerosing epithelioid fibrosarcoma (SEF) represents a rare variant of fibrosarcoma primarily arising in the deep soft tissue of the extremities and trunk. The author reported a rare case of SEF emerged primarily in the kidney. Clinically, the patient complained of hematuria. The diagnosis was confirmed by histological examination and immunohistochemical staining of MUC4. Subsequent fluorescence in situ hybridization (FISH) analysis detected the presence of EWSR1 gene rearrangement, further confirming the histological diagnosis. The patient has been alive with 12 months follow-ups after nephrectomy. The disease should be considered in the differential diagnosis for primary renal tumors.

12.
Cancer Epidemiol ; 89: 102536, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38281454

RESUMO

BACKGROUND: To investigate the cancer types and risk factors of secondary primary malignancy (SPM) in patients with upper tract urothelial carcinoma (UTUC) in Taiwan. METHODS: Using National Health Insurance Research Dataset and catastrophic illness registry, we enrolled newly diagnosed UTUC patients from 2000 to 2013. Those without catastrophic illness registration were excluded from the study. The cancer types and hazard ratios (HRs) of subsequent SPMs were calculated according to the antecedent malignancy. We analyzed the risk factors for developing SPMs using multivariate Cox proportional hazard models. RESULTS: A total of 9050 UTUC patients were registered and 2187 (24.2%) patients developed SPMs during the study period. As compared with primary UTUC, the relative risk ratios of SPM was 2.5 folds and 18% higher in those with antecedent non-UC malignancy and with bladder cancer history, respectively. Totally, 387 (37.8%) of 1022 UTUC patients with antecedent non-UC malignancy developed subsequent SPM after UTUC diagnosis. The antecedent and subsequent cancer types are similar and kidney cancer is most common, followed by hepatoma. Multivariate analysis showed that a history of antecedent non-UC malignancy is the most unfavorable factor for SPM development (HR, 2.50; 95% CI, 2.23-2.81), followed by liver disease, male gender, antecedent bladder cancer history, age ≥ 75 years, and chronic kidney disease. CONCLUSIONS: Our study, conducted in Taiwan and involving 9050 UTUC patients, meticulously examined the types of SPM and the associated risk factors. Our research unearthed several pivotal discoveries: a preceding history of non-UC malignancies emerged as the single most influential factor contributing to the occurrence of subsequent cancers, followed by liver disease, male gender, antecedent bladder cancer history, age ≥75 years, and chronic kidney disease. Futhermore, kidney cancer emerged as the predominant subsequent malignancy, closely trailed by hepatoma..


Assuntos
Carcinoma Hepatocelular , Carcinoma de Células de Transição , Neoplasias Renais , Neoplasias Hepáticas , Segunda Neoplasia Primária , Insuficiência Renal Crônica , Neoplasias da Bexiga Urinária , Humanos , Masculino , Idoso , Neoplasias da Bexiga Urinária/epidemiologia , Neoplasias da Bexiga Urinária/patologia , Carcinoma de Células de Transição/epidemiologia , Carcinoma de Células de Transição/patologia , Doença Catastrófica , Neoplasias Renais/epidemiologia , Segunda Neoplasia Primária/epidemiologia , Sobreviventes
13.
Proc Natl Acad Sci U S A ; 121(5): e2312929121, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38252825

RESUMO

Immunotherapy is a promising approach for treating metastatic breast cancer (MBC), offering new possibilities for therapy. While checkpoint inhibitors have shown great progress in the treatment of metastatic breast cancer, their effectiveness in patients with bone metastases has been disappointing. This lack of efficacy seems to be specific to the bone environment, which exhibits immunosuppressive features. In this study, we elucidate the multiple roles of the sialic acid-binding Ig-like lectin (Siglec)-15/sialic acid glyco-immune checkpoint axis in the bone metastatic niche and explore potential therapeutic strategies targeting this glyco-immune checkpoint. Our research reveals that elevated levels of Siglec-15 in the bone metastatic niche can promote tumor-induced osteoclastogenesis as well as suppress antigen-specific T cell responses. Next, we demonstrate that antibody blockade of the Siglec-15/sialic acid glyco-immune checkpoint axis can act as a potential treatment for breast cancer bone metastasis. By targeting this pathway, we not only aim to treat bone metastasis but also inhibit the spread of metastatic cancer cells from bone lesions to other organs.


Assuntos
Neoplasias Ósseas , Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Ácido N-Acetilneuramínico , Neoplasias Ósseas/tratamento farmacológico , Imunoterapia , Anticorpos Bloqueadores
14.
J Formos Med Assoc ; 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38296698

RESUMO

Blood-based biomarkers (BBM) are potentially powerful tools that assist in the biological diagnosis of Alzheimer's disease (AD) in vivo with minimal invasiveness, relatively low cost, and good accessibility. This review summarizes current evidence for using BBMs in AD, focusing on amyloid, tau, and biomarkers for neurodegeneration. Blood-based phosphorylated tau and the Aß42/Aß40 ratio showed consistent concordance with brain pathology measured by CSF or PET in the research setting. In addition, glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) are neurodegenerative biomarkers that show the potential to assist in the differential diagnosis of AD. Other pathology-specific biomarkers, such as α-synuclein and TAR DNA-binding protein 43 (TDP-43), can potentially detect AD concurrent pathology. Based on current evidence, the working group from the Taiwan Dementia Society (TDS) achieved consensus recommendations on the appropriate use of BBMs for AD in clinical practice. BBMs may assist clinical diagnosis and prognosis in AD subjects with cognitive symptoms; however, the results should be interpreted by dementia specialists and combining biochemical, neuropsychological, and neuroimaging information. Further studies are needed to evaluate BBMs' real-world performance and potential impact on clinical decision-making.

15.
J Biomed Sci ; 31(1): 15, 2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38263133

RESUMO

BACKGROUND: CDGSH iron-sulfur domain-containing protein 2 (CISD2), a pro-longevity gene, mediates healthspan in mammals. CISD2 is down-regulated during aging. Furthermore, a persistently high level of CISD2 promotes longevity and ameliorates an age-related skin phenotype in transgenic mice. Here we translate the genetic evidence into a pharmaceutical application using a potent CISD2 activator, hesperetin, which enhances CISD2 expression in HEK001 human keratinocytes from an older person. We also treated naturally aged mice in order to study the activator's anti-aging efficacy. METHODS: We studied the biological effects of hesperetin on aging skin using, firstly, a cell-based platform, namely a HEK001 human keratinocyte cell line established from an older person. Secondly, we used a mouse model, namely old mice at 21-month old. In the latter case, we investigate the anti-aging efficacy of hesperetin on ultraviolet B (UVB)-induced photoaging and naturally aged skin. Furthermore, to identify the underlying mechanisms and potential biological pathways involved in this process we carried out transcriptomic analysis. Finally, CISD2 knockdown HEK001 keratinocytes and Cisd2 knockout mice were used to study the Cisd2-dependent effects of hesperetin on skin aging. RESULTS: Four findings are pinpointed. Firstly, in human skin, CISD2 is mainly expressed in proliferating keratinocytes from the epidermal basal layer and, furthermore, CISD2 is down-regulated in the sun-exposed epidermis. Secondly, in HEK001 human keratinocytes from an older person, hesperetin enhances mitochondrial function and protects against reactive oxygen species-induced oxidative stress via increased CISD2 expression; this enhancement is CISD2-dependent. Additionally, hesperetin alleviates UVB-induced damage and suppresses matrix metalloproteinase-1 expression, the latter being a major indicator of UVB-induced damage in keratinocytes. Thirdly, transcriptomic analysis revealed that hesperetin modulates a panel of differentially expressed genes that are associated with mitochondrial function, redox homeostasis, keratinocyte function, and inflammation in order to attenuate senescence. Intriguingly, hesperetin activates two known longevity-associated regulators, namely FOXO3a and FOXM1, in order to suppress the senescence-associated secretory phenotype. Finally, in mouse skin, hesperetin enhances CISD2 expression to ameliorate UVB-induced photoaging and this occurs via a mechanism involving CISD2. Most strikingly, late-life treatment with hesperetin started at 21-month old and lasting for 5 months, is able to retard skin aging and rejuvenate naturally aged skin in mice. CONCLUSIONS: Our results reveal that a pharmacological elevation of CISD2 expression at a late-life stage using hesperetin treatment is a feasible approach to effectively mitigating both intrinsic and extrinsic skin aging and that hesperetin could act as a functional food or as a skincare product for fighting skin aging.


Assuntos
Hesperidina , Envelhecimento da Pele , Idoso , Animais , Humanos , Camundongos , Queratinócitos , Mamíferos , Camundongos Transgênicos
16.
Hepatol Int ; 18(1): 138-154, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37747618

RESUMO

BACKGROUND AND AIMS: Fatty liver disease (FLD) is associated with several metabolic derangements. We conducted a retrospective cross-sectional and longitudinal study to evaluate the role of FL severity in the risk of new-onset and co-existing hypertension (HTN) and diabetes mellitus (DM). METHODS: The cross-sectional cohort consisted of 41,888 adults who received health checkups in a tertiary hospital of Taiwan from 1999 to 2013. Of them, 34,865 without HTN and/or DM at baseline and within 1 year after enrollment were included as a longitudinal cohort (mean, 6.45 years for HTN; 6.75 years for DM). FL severity based on the degree of hepatic steatosis was assessed by ultrasound sonography. RESULTS: In cross-sectional cohort, 22,852 (54.6%) subjects had FL (18,203 [43.46%] mild FL and 4,649 [11.10%] moderate/severe FL); 13.5% (n = 5668) had HTN; and 3.4% (n = 1411) had DM. Moderate/severe FL and mild FL had significantly higher risks of existing HTN (adjusted odds ratio/95% confidence interval [CI] 1.59/1.43-1.77 and 1.22/1.13-1.32, respectively). In longitudinal cohort, 3,209 and 822 subjects developed new-onset HTN and DM, respectively (annual incidence, 14.3 and 3.5 per 1000 person-years; 10-year cumulative incidence, 14.35% and 3.89%, respectively). Moderate/severe and mild FL had significantly higher risks of new-onset HTN (adjusted hazard ratio [aHR]/CI 1.54/1.34-1.77 and 1.26/1.16-1.37, respectively) and DM (aHR/CI 5.88/4.44-7.81 and 3.22/2.56-4.07, respectively). Resolved FL during follow-up decreased the risk of HTN and/or DM. CONCLUSIONS: Patients with FL are at high risk of prevalent and incident HTN and/or DM. The risk increases with the severity of FL.


Assuntos
Diabetes Mellitus , Hipertensão , Hepatopatia Gordurosa não Alcoólica , Adulto , Humanos , Estudos Longitudinais , Estudos Retrospectivos , Estudos Transversais , Fatores de Risco , Diabetes Mellitus/epidemiologia , Hipertensão/epidemiologia , Estudos de Coortes , Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagem , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/complicações
17.
Surgery ; 175(2): 543-551, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38008606

RESUMO

BACKGROUND: Unplanned readmission to the surgical intensive care unit has been demonstrated to worsen patient outcomes. Our objective was to identify risk factors and outcomes associated with unplanned surgical intensive care unit readmission and to develop a predictive scoring model to identify patients at high risk of readmission. METHODS: We retrospectively analyzed patients admitted to the surgical intensive care unit (2020-2021) and categorized them as either with or without unplanned readmission. RESULTS: Of 1,112 patients in the derivation cohort, 76 (6.8%) experienced unplanned surgical intensive care unit readmission, with sepsis being the leading cause of readmission (35.5%). Patients who were readmitted had significantly higher in-hospital mortality rates than those who were not. Multivariate analysis identified congestive heart failure, high Sequential Organ Failure Assessment-Hepatic score, use of carbapenem during surgical intensive care unit stay, as well as factors before surgical intensive care unit discharge such as inadequate glycemic control, positive fluid balance, low partial pressure of oxygen in arterial blood/fraction of inspired oxygen ratio, and receipt of total parenteral nutrition as independent predictors for unplanned readmission. The scoring model developed using these predictors exhibited good discrimination between readmitted and non-readmitted patients, with an area under the curve of 0.74. The observed rates of unplanned readmission for scores of <4 points and ≥4 points were 4% and 20.2% (P < .001), respectively. The model also demonstrated good performance in the validation cohort, with an area under the curve of 0.74 and 19% observed unplanned readmission rate for scores ≥4 points. CONCLUSION: Besides congestive heart failure, clinicians should meticulously re-evaluate critical variables such as the Sequential Organ Failure Assessment-Hepatic score, partial pressure of oxygen in arterial blood/fraction of inspired oxygen ratio, glycemic control, and fluid status before releasing the patient from the surgical intensive care unit. It is crucial to determine the reasons for using carbapenems during surgical intensive care unit stay and the causes for the inability to discontinue total parenteral nutrition before discharging the patient from the surgical intensive care unit.


Assuntos
Insuficiência Cardíaca , Readmissão do Paciente , Humanos , Estudos Retrospectivos , Prognóstico , Estado Terminal/terapia , Unidades de Terapia Intensiva , Fatores de Risco , Oxigênio
18.
Adv Mater ; 36(5): e2307645, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37989269

RESUMO

Sodium metal has become one of the most promising anodes for next-generation cheap and high-energy-density metal batteries; however, challenges caused by the uncontrollable sodium dendrite growth and fragile solid electrolyte interphase (SEI) restrict their large-scale practical applications in low-cost and wide-voltage-window carbonate electrolytes. Herein, a novel multifunctional separator with lightweight and high thinness is proposed, assembled by the cobalt-based metal-organic framework nanowires (Co-NWS), to replace the widely applied thick and heavy glass fiber separator. Benefitting from its abundant sodiophilic functional groups and densely stacked nanowires, Co-NWS not only exhibits outstanding electrolyte wettability and effectively induces uniform Na+ ion flux as a strong ion redistributor but also favors constructing the robust N,F-rich SEI layer. Satisfactorily, with 10 µL carbonate electrolyte, a Na|Co-NWS|Cu half-cell delivers stable cycling (over 260 cycles) with a high average Coulombic efficiency of 98%, and the symmetric cell shows a long cycle life of more than 500 h. Remarkably, the full cell shows a long-term life span (over 1500 cycles with 92% capacity retention) at high current density in the carbonate electrolyte. This work opens up a strategy for developing dendrite-free, low-cost, and long-life-span sodium metal batteries in carbonate-based electrolytes.

19.
Diagn Interv Radiol ; 30(1): 65-71, 2024 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-37927038

RESUMO

PURPOSE: The present study aims to assess the short-term clinical outcomes and safety of transarterial embolization (TAE) for symptomatic hand osteoarthritis (OA) refractory to conservative treatment. METHODS: The present retrospective cohort pilot study included nine patients who underwent TAE for symptomatic OA-associated hand pain in a single tertiary center between November 2022 and January 2023. The baseline and post-procedural OA-associated hand pain and function were assessed using the visual analog scale (VAS) and the Australian Canadian Hand Osteoarthritis Index (AUSCAN). The use of conservative treatment and pain medications was also recorded. Post-procedural adverse events were evaluated according to the Society of Interventional Radiology classification. RESULTS: Compared with the baseline, the overall VAS scores were significantly decreased at 1-week, 1-month, 3-months, and 6-months after TAE (76 ± 15 mm versus 34 ± 18 mm, P < 0.001; 32 ± 11 mm, P < 0.001; 21 ± 15 mm, P < 0.001; 18 ± 19 mm, P = 0.002). Similarly, improvement in the mean total AUSCAN scores (22.0 ± 10.0 versus 13.2 ± 6.6, P = 0.007; 14.11 ± 7.3, P = 0.004; 9.8 ± 6.8, P = 0.004; 9.3 ± 7.4, P = 0.011) were documented. The use of other conservative treatment methods also gradually decreased. There were no severe adverse events reported during the follow-up period. CONCLUSION: TAE is a feasible and safe treatment method for symptomatic hand OA refractory to conservative treatment. This minimally invasive procedure effectively relieves debilitating OA-associated joint pain and restores hand function with a durable treatment effect.


Assuntos
Tratamento Conservador , Osteoartrite , Humanos , Estudos Retrospectivos , Projetos Piloto , Austrália , Canadá , Dor/etiologia , Osteoartrite/diagnóstico por imagem , Osteoartrite/terapia , Resultado do Tratamento
20.
Mol Med Rep ; 29(1)2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37997813

RESUMO

Lung adenocarcinoma (LUAD) is one of the deadliest cancers regarding both mortality rate and number of deaths and warrants greater effort in the development of potential therapeutic targets. The enhancer of rudimentary homolog (ERH) has been implicated in the promotion and progression of certain types of cancer. In the present study, ERH was assessed for its expression pattern and survival association with LUAD in public transcriptomic and proteomic databases. Bioinformatic methods and data from websites, including University of Alabama at Birmingham CANcer data analysis Portal and The Cancer Genome Atlas, were utilized to demonstrate the functional behaviors and corresponding pathways of ERH in LUAD. Human A549 and CL1­0 cell lines were used to validate the findings via functional assays. It was demonstrated that the expression of ERH, at both the transcriptomic and proteomic levels, was higher in LUAD compared with in adjacent non­tumor lung tissue and was associated with worse survival prognosis. Moreover, high ERH expression was correlated with more aggressive functional states, such as cell cycle and invasion in LUAD, and the positive ERH­correlated gene set was associated with worse survival and an immunosuppressive tumor microenvironment. Small nuclear ribonucleoprotein polypeptide G was identified as a molecule that potentially interacted with ERH. Lastly, it was demonstrated that ERH promoted epithelial­mesenchymal transition and cell migration in vitro, but not proliferation. In conclusion, higher expression of ERH in LUAD may facilitate cancer progression and confer worse outcomes. Further deep investigation into the role of ERH in LUAD is needed.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Humanos , Adenocarcinoma de Pulmão/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/patologia , Proteômica , Microambiente Tumoral
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