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1.
J Asian Nat Prod Res ; : 1-8, 2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38904480

RESUMEN

Dendroochreatene (1), a new phenanthrene derivative with a spirolactone ring, was isolated from the whole Dendrobium ochreatum plant together with 11 known compounds (2-12). The structure of the new compound was elucidated spectroscopically and phenolic compounds were firstly reported from D. ochreatum. Moscatilin (4), major compound isolated from D. ochreatum, was found to be cytotoxic toward H460 lung-cancer cells, with an IC50 value of 147.3 ± 0.9 µM, while loddigesiinol C (7), C-α-methoxy derivative was inactive.

2.
Front Pharmacol ; 15: 1361085, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38666017

RESUMEN

Background: The upgrade of natural products for cancer treatment is essential since current anticancer drugs still pose severe side effects. Cymensifin A (Cym A) isolated from an orchid Cymbidium ensifolium has shown its potential to induce the death of several cancer cells; however, its underlying molecular mechanisms are hitherto unknown. Methods: Here, we conducted a set of in vitro preliminary tests to assess the cytotoxic effects of Cym A on non-small-cell lung cancer (NSCLC) cells (A549, H23, H292, and H460). A flow cytometry system and Western blot analyses were employed to unveil molecular mechanisms underlying cancer cell apoptosis caused by Cym A. Results: Cym A at 25-50 µM caused the death of all NSCLC cells tested, and its cytotoxicity was comparable to cisplatin, a currently used anticancer drug. The compound induced apoptosis of all NSCLC cells in a dose-dependent manner (5-50 µM), proven by flow cytometry, but H460 cells showed more resistance compared to other cells tested. Cym A-treated H460 cells demonstrated increased reactive oxygen species (ROS) and downregulated antioxidants (catalase, superoxide dismutase, and thioredoxin). The compound also upregulated the tumor suppressor P53 and the pro-apoptotic protein BAX but downregulated pro-survival proteins (BCL-2 and MCL-1) and deactivated survival signals (AKT and ERK) in H460 cells. Cym A was proven to trigger cellular ROS formation, but P53 and BAX were 2-fold more activated by Cym A compared to those treated with hydrogen peroxide. Our findings also supported that Cym A exerted its roles in the downregulation of nuclear factor erythroid 2-related factor 2 (a regulator of cellular antioxidant activity) and the increased levels of cleaved poly (ADP-ribose) polymerase (PARP) and cleaved caspase 3/7 during apoptosis. Conclusion: We propose that Cym A induces lung cancer cell death via ROS-mediated apoptosis, while the modulation of cellular ROS/antioxidant activity, the upregulation of P53 and BAX, the downregulation or deactivation of BCL-2, MCL-1, AKT, and ERK, and the increased cleavage of PARP and caspase 3/7, were the elucidated underlying molecular mechanisms of this phytochemical. The compound can be a promising candidate for future anticancer drug development.

3.
Sci Rep ; 14(1): 9018, 2024 04 19.
Artículo en Inglés | MEDLINE | ID: mdl-38641685

RESUMEN

Cyperus rotundus rhizomes have been used in longevity remedies in Thailand for nourishing good health, which led us to investigate the effect on energy homeostasis, especially glucose utilization in myotubes and adipocytes, and on inhibition of lipogenesis in adipocytes. The results showed that an ethyl acetate extract of C. rotundus rhizomes (ECR) containing 1.61%w/w piceatannol, with a half-maximal concentration of 17.76 ± 0.03 µg/mL in 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay, caused upregulation and cell-membrane translocation of glucose transporters GLUT4 and 1 in L6 myotubes but downregulation and cytoplasmic localization of GLUT4 expression in 3T3-L1 adipocytes and was related to the p-Akt/Akt ratio in both cells, especially at 100 µg/mL. Moreover, ECR (25-100 µg/mL) significantly inhibited lipid accumulation via Adenosine Monophosphate-Activated Protein Kinase (AMPK), Acetyl CoA Carboxylase (ACC), and Glycogen Synthase Kinase (GSK) pathways. Its immunoblot showed increased expression of p-AMPKα/AMPKα and p-ACC/ACC but decreased expression of p-Akt/Akt and p-GSK3ß/GSK3ß in 3T3-L1 adipocytes. Moreover, the decreased expression of the adipogenic effectors, perilipin1 and lipoprotein lipase, in ECR-incubated adipocytes (50 and 100 µg/mL) indicated reduced de novo lipogenesis. Our study elucidated mechanisms of C. rotundus that help attenuate glucose tolerance in skeletal muscle and inhibit lipid droplet accumulation in adipose tissue.


Asunto(s)
Cyperus , Proteínas Proto-Oncogénicas c-akt , Ratones , Animales , Proteínas Proto-Oncogénicas c-akt/metabolismo , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Adipogénesis , Glucosa/metabolismo , Adipocitos/metabolismo , Fibras Musculares Esqueléticas/metabolismo , Células 3T3-L1
4.
Biol Res ; 56(1): 44, 2023 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-37542350

RESUMEN

BACKGROUND: Malignant cells adopt anoikis resistance to survive anchorage-free stresses and initiate cancer metastasis. It is still unknown how varying periods of anchorage loss contribute to anoikis resistance, cell migration, and metabolic reprogramming of cancerous cells. RESULTS: Our study demonstrated that prolonging the anchorage-free lifetime of non-small-cell lung cancer NCI-H460 cells for 7 days strengthened anoikis resistance, as shown by higher half-life and capability to survive and grow without anchorage, compared to wild-type cells or those losing anchorage for 3 days. While the prolonged anchorage-free lifetime was responsible for the increased aggressive feature of survival cells to perform rapid 3-dimensional migration during the first 3 h of a transwell assay, no significant influence was observed with 2-dimensional surface migration detected at 12 and 24 h by a wound-healing method. Metabolomics analysis revealed significant alteration in the intracellular levels of six (oxalic acid, cholesterol, 1-ethylpyrrolidine, 1-(3-methylbutyl)-2,3,4,6-tetramethylbenzene, ß-alanine, and putrescine) among all 37 identified metabolites during 7 days without anchorage. Based on significance values, enrichment ratios, and impact scores of all metabolites and their associated pathways, three principal metabolic activities (non-standard amino acid metabolism, cell membrane biosynthesis, and oxidative stress response) offered potential links with anoikis resistance. CONCLUSIONS: These findings further our insights into the evolution of anoikis resistance in lung cancer cells and identify promising biomarkers for early lung cancer diagnosis.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Anoicis , Neoplasias Pulmonares/patología , Línea Celular Tumoral , Metabolómica
6.
Foods ; 11(19)2022 Sep 29.
Artículo en Inglés | MEDLINE | ID: mdl-36230099

RESUMEN

Obesity is a critical factor for chronic metabolic syndromes. The culinary plant fingerroot (Boesenbergia rotunda) has been reported for its anti-obesity activity. The anti-adipogenic effects of pandurantin A, a main component of fingerroot cultivated in Indonesia, have been studied. Nevertheless, the suppressive effect and related mechanisms of pinostrobin, a major constituent of Thai fingerroot, on adipogenesis have never been thoroughly investigated. This study aimed to evaluate the potential of pinostrobin to inhibit adipocyte differentiation. Culturing pre-adipocytes from both mouse (3T3-L1) and human (PCS-210-010) with pinostrobin at non-toxic concentrations (5-20 µM) for 48 h obviously hindered their differentiation into mature adipocyte as evidenced by reduced cellular lipid droplets. The lower levels of lipid metabolism-mediating proteins, namely C/EBPα, PPARγ, and SREBP-1c, as well as cellular triglyceride content were demonstrated in pinostrobin-treated 3T3-L1 cells when compared to the untreated control group. Additionally, pinostrobin modulated the signals of MAPK (p38 and JNK) and Akt (Akt/GSK3ß, Akt/AMPKα-ACC). These findings suggest the benefit of fingerroot as a source of phytopharmaceuticals for obesity prevention and management, with pinostrobin as the active principle.

8.
Pediatr Emerg Care ; 38(10): e1646-e1649, 2022 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-36173437

RESUMEN

OBJECTIVE: This study aims to validate the DIVA (Difficult Intravenous Access) score in our population and to identify any additional patient characteristics that may be associated with difficult access in children. METHODS: This was a cross-sectional study in an urban quaternary pediatric emergency department with patients younger than 21 years and Emergency Severity Index ≥2 who require intravenous (IV) access for their management. In addition to patient characteristics comprising the DIVA score, data were collected on patient "history of difficult access," hydration status, skin shade, history of sickle cell disease or diabetes, technology dependence, and body mass index. The number of IV cannulation attempts and total time taken were recorded for each patient. "Difficult access" was defined as ≥2 or more attempts or time >30 minutes to achieve successful IV cannulation. RESULTS: A convenience sample of 300 pediatric patients was enrolled. The DIVA score had a sensitivity of 51% (95% confidence interval [CI], 40.8%-61.14%) and a specificity of 82.99% (95% CI, 76.95%-87.99%) for predicting "difficult access" in our population. Among all patient characteristics examined in this study, only "history of difficult access" improved the identification of "difficult access" patients. The "history of difficult access" variable had a sensitivity of 61% (95% CI, 50.7%-70.6%) and a specificity of 75.7% (95% 95% CI, 69.12%-81.62%) in predicting "difficult access." With the addition of "history of difficult access" to the original DIVA score, we developed a "modified DIVA score (m-DIVA)." The m-DIVA score had a sensitivity of 78% (95% CI, 68.6%-85.6%) and specificity of 67% (95% CI, 59.9%-73.58%), representing a 52.9% improvement in correctly identifying "difficult access" patients over the original DIVA score. CONCLUSIONS: The m-DIVA score, which incorporates prior history, increases the screening test's sensitivity in identifying "difficult access" patients and should be further investigated as clinical tool.


Asunto(s)
Cateterismo Periférico , Administración Intravenosa , Niño , Estudios Transversales , Servicio de Urgencia en Hospital , Humanos , Estudios Prospectivos
9.
J Emerg Med ; 63(1): 72-82, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35934650

RESUMEN

BACKGROUND: Although procedural pain is effectively treated with analgesics, managing anxiety during laceration repair is more challenging. OBJECTIVES: We examined the feasibility of using immersive virtual reality (VR) as anxiolysis during laceration repair in the pediatric emergency department (ED). METHODS: We conducted a non-blinded, observational, pilot study in an urban pediatric ED that enrolled a convenience sample of children aged 5-13 years undergoing sutured repair of non-facial lacerations. Subjects played an immersive VR game while undergoing laceration repair. Parents assessed their child's anxiety on a 100-mm visual analogue scale at enrollment and during laceration repair. The primary outcome measure was the percentage of children whose anxiety score did not increase by ≥ 20 mm from enrollment to the first stitch. RESULTS: Forty patients completed the study. Mean initial anxiety score was 54 mm (standard deviation 33 mm). Thirty-seven of forty patients (93%; 95% confidence interval [CI] 83-99%) had anxiety scores that did not increase by 20 mm or more from enrollment to the first stitch. Eighty percent (95% CI 64-91%) of patients' anxiety scores decreased between enrollment and first stitch. The mean change in anxiety score at first stitch was -39 mm (95% CI -51 mm to -27 mm; p < 0.001). Similar downward trends in anxiety scores were noted throughout the procedure. All laceration repairs were successfully completed without sedation or restraints. There were no adverse events noted, and the main barriers identified with VR use involved easily correctable technical difficulties with the equipment. CONCLUSION: Immersive VR is a safe and effective distractive technique to reduce procedural anxiety during laceration repair in the pediatric ED.


Asunto(s)
Laceraciones , Dolor Asociado a Procedimientos Médicos , Realidad Virtual , Ansiedad/etiología , Niño , Servicio de Urgencia en Hospital , Humanos , Laceraciones/cirugía , Dolor Asociado a Procedimientos Médicos/etiología , Dolor Asociado a Procedimientos Médicos/prevención & control , Proyectos Piloto
10.
Nutrients ; 14(14)2022 Jul 14.
Artículo en Inglés | MEDLINE | ID: mdl-35889842

RESUMEN

Although many natural products have proven their potential to regulate obesity through the modulation of adipocyte biology, none of them has yet been approved for clinical use in obesity therapy. This work aims to isolate valuable secondary metabolites from an orchid species (Dendrobium heterocarpum) and evaluate their possible roles in the growth and differentiation of 3T3-L1 pre-adipocytes. Six compounds were isolated from the orchid's methanolic extracts and identified as amoenylin (1), methyl 3-(4-hydroxyphenyl) propionate (2), 3,4-dihydroxy-5,4'-dimethoxybibenzyl (3), dendrocandin B (4), dendrofalconerol A (5), and syringaresinol (6). Among these phytochemicals, compounds 2, 3, and 6 exhibited lower effects on the viability of 3T3-L1 cells, offering non-cytotoxic concentrations of ≲10 µM. Compared to others tested, compound 3 was responsible for the maximum reduction of lipid storage in 3T3-L1 adipocytes (IC50 = 6.30 ± 0.10 µM). A set of protein expression studies unveiled that compound 3 at non-cytotoxic doses could suppress the expression of some key transcription factors in adipocyte differentiation (i.e., PPARγ and C/EBPα). Furthermore, this compound could deactivate some proteins involved in the MAPK pathways (i.e., JNK, ERK, and p38). Our findings prove that D. heterocarpum is a promising source to explore bioactive molecules capable of modulating adipocytic growth and development, which can potentially be assessed and innovated further as pharmaceutical products to defeat obesity.


Asunto(s)
Dendrobium , Células 3T3-L1 , Adipocitos , Adipogénesis , Animales , Diferenciación Celular , Dendrobium/metabolismo , Lípidos/farmacología , Metanol/farmacología , Ratones , Obesidad/metabolismo , PPAR gamma/metabolismo , Extractos Vegetales/química
11.
Eur J Pharm Sci ; 176: 106263, 2022 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-35853596

RESUMEN

The purpose of this study was to develop astaxanthin (AST)-loaded self-microemulsifying drug delivery system (SMEDDS) tablets and evaluate their physicochemical and biological properties. The optimized liquid (L)-AST SMEDDS formulation was composed of rice bran oil (33.67%), Kolliphor® RH 40 (34.70%), and Span® 20 (31.63%). Two types of hydrophilic polymers (hydroxypropyl methylcellulose, HPMC, and polyvinyl alcohol, PVA) solutions were selected as a precipitation inhibitor for AST and incorporated into L-AST SMEDDS to obtain supersaturation and enhance dissolution of AST. The formulation was then mixed with microcrystalline cellulose and subsequently transformed to solid S-AST SMEDDS particles using a spray dryer prior to direct compression into tablets. The HPMC AST SMEDDS tablet and PVA AST SMEDDS tablet were characterized for their physicochemical properties, dissolution, AST release, and stabilities. Moreover, the cellular uptake and antioxidant effect of AST SMEDDS tablets were evaluated in Caco-2 cells. With good tablet characters, both HPMC AST SMEDDS tablet and PVA AST SMEDDS tablet dissolution profiles were improved compared to that of raw AST. While initially less than 50% of AST released from HPMC AST SMEDDS tablet and PVA AST SMEDDS tablet in pH 1.2 medium, after 6 h more than 98% of AST releases in pH 6.8 were achieved which was similar to L-AST SMEDDS profile. Cellular antioxidant activities of L-AST SMEDDS and HPMC AST SMEDDS tablet & PVA AST SMEDDS tablet were significantly greater than pure AST powder. HPMC AST SMEDDS tablet showed better uptake and deeper penetration through Caco-2 cells than that in PVA AST SMEDDS tablet and pure powder. Our successfully developed AST SMEDDS tablets were demonstrated to be a potential platform to deliver highly lipophilic AST and improve permeation and bioavailability.


Asunto(s)
Antioxidantes , Sistemas de Liberación de Medicamentos , Administración Oral , Antioxidantes/química , Disponibilidad Biológica , Células CACO-2 , Emulsiones/química , Humanos , Polvos , Solubilidad , Comprimidos , Xantófilas
12.
Artículo en Inglés | MEDLINE | ID: mdl-35831070

RESUMEN

The Bronx was an early epicenter of the COVID-19 pandemic in the USA. We conducted temporal genomic surveillance of 104 SARS-CoV-2 genomes across the Bronx from March October 2020. Although the local structure of SARS-CoV-2 lineages mirrored those of New York City and New York State, temporal sampling revealed a dynamic and changing landscape of SARS-CoV-2 genomic diversity. Mapping the trajectories of mutations, we found that while some became 'endemic' to the Bronx, other, novel mutations rose in prevalence in the late summer/early fall. Geographically resolved genomes enabled us to distinguish between cases of reinfection and persistent infection in two pediatric patients. We propose that limited, targeted, temporal genomic surveillance has clinical and epidemiological utility in managing the ongoing COVID pandemic.

13.
J Nat Prod ; 85(6): 1591-1602, 2022 06 24.
Artículo en Inglés | MEDLINE | ID: mdl-35679136

RESUMEN

Obesity and its global prevalence has become a threat to human health, while its pharmacotherapy via the application of natural products is still underdeveloped. Here, we probed how 4,5,4'-trihydroxy-3,3'-dimethoxybibenzyl (TDB) derived from an orchid (Dendrobium ellipsophyllum) could exert its roles on the differentiation and function of murine (3T3-L1) and human (PCS-210-010) pre-adipocytes and offer some implications to modulate obesity. Cytotoxic effects of TDB on adipocytes were 2-fold lower than those detected with pre-adipocytes, and no significant difference was detected in cytotoxic profiles between both cell lineages. TDB in a dose-dependent manner decreased cellular lipid accumulation and enhanced lipolysis of both cell lines assessed at early differentiation and during maturation. Underlining molecular mechanisms proved that TBD paused the cell cycle progression by regulating inducers and inhibitors in mitotic clonal expansion, leading to growth arrest of pre-adipocytes at the G0/G1 phase. The compound also governed adipocyte differentiation by repressing expressions of crucial adipogenic regulators and effectors through deactivating the AKT/GSK-3ß signaling pathway and activating the AMPK-ACC pathway. To this end, TDB has shown its pharmaceutical potential for modulating adipocyte development and function, and it would be a promising candidate for further assessments as a therapeutic agent to defeat obesity.


Asunto(s)
Adipogénesis , Bibencilos , Obesidad , Células 3T3-L1 , Animales , Bibencilos/farmacología , Diferenciación Celular , Dendrobium/química , Glucógeno Sintasa Quinasa 3 beta , Humanos , Ratones , Obesidad/tratamiento farmacológico
14.
J Sch Health ; 92(8): 735-738, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35467021

RESUMEN

BACKGROUND: Pediatric mental health issues are increasing while access to care is decreasing. This is reflected in a growing number of patients seeking emergency psychiatric evaluations (EPEs) in the emergency department (ED). METHODS: This was a retrospective review of patients seeking EPE in the ED of a children's hospital between September and December 2018, which compares patients referred from the community versus those from schools as well as patients from schools with and without school-based mental health services (SMH). RESULTS: A total of 546 EPEs were analyzed, with 187 (34%) referred from schools. School referrals were younger, had a shorter length of stay and lower admission rates. When comparing those from schools with SMH, those referred from schools without SMH were younger and less acutely ill. CONCLUSIONS: Higher acuity children from schools with SMH suggest that SMH staff managed less severe situations on site. The role of SMH as a triaging tool and provider of mental health services should be studied as they may reduce the burden on EDs for EPEs.


Asunto(s)
Servicios de Salud Mental , Servicios de Salud Mental Escolar , Niño , Servicio de Urgencia en Hospital , Humanos , Ciudad de Nueva York , Derivación y Consulta
15.
Molecules ; 27(4)2022 Feb 09.
Artículo en Inglés | MEDLINE | ID: mdl-35208957

RESUMEN

Chemical investigation of Dendrobium delacourii revealed 11 phenolic compounds, and the structures of these compounds were determined by analysis of their NMR and HR-ESI-MS data. All compounds were investigated for their α-glucosidase inhibitory activity and anti-adipogenic properties. Phoyunnanin E (10) and phoyunnanin C (11) showed the most potent α-glucosidase inhibition by comparing with acarbose, which was used as a positive control. Kinetic study revealed the non-competitive inhibitors against the enzyme. For anti-adipogenic activity, densifloral B (3) showed the strongest inhibition when compared with oxyresveratrol (positive control). In addition, densifloral B might be responsible for the inhibition of adipocyte differentiation via downregulating the expression of peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT enhancer-binding protein alpha (C/EBPα), which are major transcription factors in adipogenesis.


Asunto(s)
Adipocitos/metabolismo , Adipogénesis/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Dendrobium/química , Inhibidores de Glicósido Hidrolasas , Células 3T3-L1 , Animales , Inhibidores de Glicósido Hidrolasas/química , Inhibidores de Glicósido Hidrolasas/farmacología , Ratones
16.
medRxiv ; 2022 Mar 17.
Artículo en Inglés | MEDLINE | ID: mdl-33594384

RESUMEN

The Bronx was an early epicenter of the COVID-19 pandemic in the USA. We conducted temporal genomic surveillance of SARS-CoV-2 genomes across the Bronx from March-October 2020. Although the local structure of SARS-CoV-2 lineages mirrored those of New York City and New York State, temporal sampling revealed a dynamic and changing landscape of SARS-CoV-2 genomic diversity. Mapping the trajectories of variants, we found that while some became 'endemic' to the Bronx, other, novel variants rose in prevalence in the late summer/early fall. Geographically resolved genomes enabled us to distinguish between cases of reinfection and persistent infection in two pediatric patients. We propose that limited, targeted, temporal genomic surveillance has clinical and epidemiological utility in managing the ongoing COVID pandemic. One sentence summary: Temporally and geographically resolved sequencing of SARS-CoV-2 genotypes enabled surveillance of novel genotypes, identification of endemic viral variants, and clinical inferences, in the first wave of the COVID-19 pandemic in the Bronx.

17.
Clin Pediatr (Phila) ; 61(2): 159-167, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34789028

RESUMEN

In this retrospective study of 319 children with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, we assessed whether age, asthma, obesity, diabetes, and socioeconomic status were associated with hospitalization for coronavirus disease 2019 (COVID-19). Demographic and clinical characteristics were assessed using univariate statistics, excluding incidental or unrelated positives. There was a bimodal distribution of age among hospitalized children. Obesity (P < .001) and a past medical history of diabetes (P = .001) were significantly more prevalent in hospitalized children, including cases of new-onset diabetes and diabetic ketoacidosis. Neither a past medical history of asthma nor lower socioeconomic status was associated with hospitalization. Although limited to a single center, the findings in this study may have important clinical implications. Targeted, proactive health outreach to children with obesity and diabetes, with prioritization of preventative efforts such as vaccination, may be important in preventing worse SARS-CoV-2 infection in this vulnerable group.


Asunto(s)
COVID-19/complicaciones , Niño Hospitalizado/estadística & datos numéricos , Adolescente , Índice de Masa Corporal , COVID-19/epidemiología , Niño , Niño Hospitalizado/clasificación , Preescolar , Estudios Transversales , Femenino , Humanos , Masculino , Estudios Retrospectivos
18.
Artículo en Inglés | MEDLINE | ID: mdl-34349823

RESUMEN

Cancer stem-like cells (CSCs) are key mediators driving tumor initiation, metastasis, therapeutic failure, and subsequent cancer relapse. Thus, targeting CSCs has recently emerged as a potential strategy to improve chemotherapy. In this study, the anticancer activity and stemness-regulating capacity of 4,5,4'-trihydroxy-3,3'-dimethoxybibenzyl (TDB), a bibenzyl extracted from Dendrobium ellipsophyllum, are revealed in CSCs of various human lung cancer cells. Culture with TDB (5-10 µM) strongly abolished tumor-initiating cells in lung cancer H460, H23, and A549 cells in both anchorage-dependent and anchorage-independent colony formation assays. Through the 3D single-spheroid formation model, attenuation of self-renewal capacity was observed in CSC-enriched populations treated with 1-10 µM TDB for 7 days. Flow cytometry analysis confirmed the attenuation of %cell overexpressing CD133, a CSC biomarker, in TDB-treated lung cancer spheroids. TDB at 5-10 µM remarkably suppressed regulatory signals of p-Akt/Akt, p-GSK3ß/GSK3ß, and ß-catenin corresponding to the downregulated mRNA level of stemness transcription factors including Nanog, Oct4, and Sox2. Moreover, the antiapoptosis Bcl-2 and Mcl-1 proteins, which are downstream molecules of Akt signaling, were evidently decreased in CSC-enriched spheroids after culture with TDB (1-10 µM) for 24 h. Interestingly, the diminution of Akt expression by specific siAkt effectively reversed suppressive activity of TDB targeting on the CSC phenotype in human lung cancer cells. These findings provide promising evidence of the inhibitory effect of TDB against lung CSCs via suppression of Akt/GSK3ß/ß-catenin cascade and related proteins, which would facilitate the development of this bibenzyl natural compound as a novel CSC-targeted therapeutic approach for lung cancer treatment.

19.
Am J Emerg Med ; 50: 183-186, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34375798

RESUMEN

BACKGROUND: The diagnosis of Fitz-Hugh-Curtis syndrome (FHC) is often missed or delayed in patients with right upper quadrant pain (RUQ). OBJECTIVE: To develop a decision rule that predicts FHC in females with RUQ pain based on a constellation of historical features, physical examination findings and laboratory results. METHODS: We conducted a prospective study to test the utility of our FHC decision rule in sexually active females, aged 13-20 years, with RUQ pain who were seen in an urban ED over 57 months. The decision rule was based on 4 features: 1. Presence of pleuritic chest pain, 2. Tenderness over the anterior border of liver, 3. History of worsening pain on R lateral position and 4. An erythrocyte sedimentation rate > 30 mm/h. The rule was considered positive if all 4 features were present. FHC was diagnosed in patients with RUQ pain and a positive GEN-PROBE Aptima Combo Assay for either gonorrhea or chlamydia on urine or endocervical specimens. RESULTS: 130 patients were enrolled. 24 were excluded, leaving 106 (81.5%) for analysis. 34/106 (32%) had STI/FHC. There were no differences in mean age or sexual characteristics between those with and without STI/FHC. A positive FHC decision rule had a positive predictive value of 75% (95%CI: 46.8%-91.1%) based on 96 cases for whom all features were available for analysis. CONCLUSION: Our decision rule shows promise in allowing for the early identification of FHC in adolescent and young adult females. Additional study is needed to corroborate these findings and test its generalizability.


Asunto(s)
Reglas de Decisión Clínica , Hepatitis/diagnóstico , Enfermedad Inflamatoria Pélvica/diagnóstico , Peritonitis/diagnóstico , Adolescente , Diagnóstico Diferencial , Servicio de Urgencia en Hospital , Femenino , Humanos , Dimensión del Dolor , Estudios Prospectivos , Adulto Joven
20.
Am J Emerg Med ; 43: 109-114, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33550101

RESUMEN

BACKGROUND: The Bronx has the highest prevalence of asthma in the United States (US), and was also an early COVID-19 epicenter, making it a unique study location. Worldwide reports describe significant declines in pediatric emergency department (PED) visits during COVID-19. The ongoing impact of COVID-19 on all PED presentations, including asthma, at an early epicenter has not been studied beyond the pandemic peak and into the early phases of state re-opening. OBJECTIVES: To compare PED health-seeking behaviors and clinical characteristics during the 2020 pandemic and subsequent initial New York State (NYS) phased re-opening to the same period in 2019. METHODS: Retrospective chart review of children <21 years utilizing the PED at a high-volume quaternary children's hospital in The Bronx, NY from March 15th 2020 - July 6th 2020 (pandemic cohort) and the same interval in 2019 (comparison cohort). Visits were assigned to pre-determined diagnostic categories. Demographic and clinical data were compared. RESULTS: 19,981 visits were included. Visits declined by 66% during 2020. Proportions of asthma visits (2% vs. 7%, p < 0.0001) and minor medical problems (61% vs. 67%, p < 0.0001) had significant declines in the pandemic cohort, while major medical problems (13% vs. 8%, p < 0.0001), appendicitis (1% vs. 0.4%, p < 0.0001) and other surgical complaints (1% vs. 0.5%, p < 0.0001) had proportional increases in the pandemic cohort. No significant proportional changes were noted among psychosocial and trauma groups between the two cohorts. CONCLUSION: The pandemic cohort experienced a substantial decrease in PED volume, but an increase in acuity and admission rates, which was sustained through the NYS phase-II re-opening. Despite being located in an asthma hub, the incidence of asthma-related PED visits declined appreciably in the pandemic cohort. Future studies examining the effects of indoor allergens in isolation on pediatric asthma are warranted.


Asunto(s)
Asma/epidemiología , COVID-19/epidemiología , Servicio de Urgencia en Hospital/estadística & datos numéricos , Conductas Relacionadas con la Salud , Hospitales Pediátricos/estadística & datos numéricos , Pandemias , Adolescente , Niño , Preescolar , Comorbilidad , Femenino , Humanos , Incidencia , Masculino , Ciudad de Nueva York/epidemiología , Prevalencia , Estudios Retrospectivos , SARS-CoV-2
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