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1.
Ann Intern Med ; 177(1): 12-17, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-38109739

RESUMEN

BACKGROUND: Transgender persons are disproportionately affected by HIV, but preexposure prophylaxis (PrEP) use has been low in this population. Clinical encounters for gender-affirming hormone therapy (GAHT) provide opportunities for HIV prevention. OBJECTIVE: To estimate the number of commercially insured transgender women (TGW) and transgender men (TGM) in the United States and their use of HIV prevention services. DESIGN: Retrospective analysis of secondary data. SETTING: Merative MarketScan commercial databases from 2014 to 2021. PARTICIPANTS: TGW and TGM, defined as those with transgender-related diagnoses and prescriptions for feminizing or masculinizing GAHT. MEASUREMENTS: HIV testing and PrEP use. RESULTS: A substantially increasing trend was observed in the prevalence of transgender-related diagnosis codes from 2014 to 2021 and in the proportion of persons who used GAHT. The increases were driven by persons aged 18 to 34 years. In 2021, among 10 613 TGW with a test for or a diagnosis of a sexually transmitted infection (STI) in the previous 12 months, 61.1% had an HIV test; among those, 20.2% were prescribed PrEP. Among 4184 TGM with STI risk, 48.3% had an HIV test; among those, 10.2% were prescribed PrEP. The prevalence of TGW and TGM who had a test for or a diagnosis of an STI, had an HIV test, and were prescribed PrEP increased substantially from 2014 to 2021. LIMITATION: The findings represent only persons with commercial health insurance who sought health care services for GAHT. CONCLUSION: It is important to identify transgender persons to monitor their receipt of HIV prevention services. Encounters for GAHT provide opportunities to offer HIV prevention and other prevention services. Many HIV prevention opportunities were likely missed at clinical encounters for GAHT. PRIMARY FUNDING SOURCE: None.


Asunto(s)
Infecciones por VIH , Profilaxis Pre-Exposición , Enfermedades de Transmisión Sexual , Personas Transgénero , Masculino , Humanos , Femenino , Estados Unidos/epidemiología , Infecciones por VIH/diagnóstico , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Homosexualidad Masculina , Estudios Retrospectivos , Prescripciones , Prueba de VIH
2.
Nano Lett ; 24(1): 104-113, 2024 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-37943097

RESUMEN

Optical meron is a type of nonplanar topological texture mainly observed in surface plasmon polaritons and highly symmetric points of photonic crystals in the reciprocal space. Here, we report Poynting-vector merons formed at the real space of a photonic crystal for a Γ-point illumination. Optical merons can be utilized for subwavelength-resolution manipulation of nanoparticles, resembling a topological Hall effect on electrons via magnetic merons. In particular, staggered merons and antimerons impose strong radiation pressure on large gold nanoparticles (AuNPs), while focused hot spots in antimerons generate dominant optical gradient forces on small AuNPs. Synergistically, differently sized AuNPs in a still environment can be trapped or orbit in opposite directions, mimicking a coupled galaxy system. They can also be separated with a 10 nm precision when applying a flow velocity of >1 mm/s. Our study unravels a novel way to exploit topological textures for optical manipulation with deep-subwavelength precision and switchable topology in a lossless environment.

3.
J Org Chem ; 89(17): 12062-12070, 2024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-39146516

RESUMEN

A TMSCN-promoted difunctionalization of styrenes with CHCl3 and TBHP is reported via the radical addition/cross coupling process. A wide range of dichloromethyl-substituted alcohol derivatives were synthesized under transition-metal-free conditions. Besides, this method is also applicable to unactive alkenes. The key to this success lies in the role of TMSCN, which prevents the reaction toward dichloromethylperoxylation of olefins. This represents an alternative approach for synthesizing diverse alcohol derivatives using readily available substrates, holding significant promise in the fields of pharmaceutical chemistry and natural product synthesis.

4.
J Org Chem ; 89(3): 1524-1533, 2024 Feb 02.
Artículo en Inglés | MEDLINE | ID: mdl-38207216

RESUMEN

An efficient and convenient method for the synthesis of oxalamides by the reaction of ß-ketoamides with tertiary amines and TBHP was developed. A variety of ß-ketoamides and tertiary amines substrates were well-tolerated in this transformation. Based on the control experiments, a plausible mechanism for this reaction was proposed that involved the tandem oxidation/amination process. In addition, α,ß-epoxy amides could be obtained by adjusting the reaction conditions.

5.
Br J Nutr ; 132(3): 382-391, 2024 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-38832664

RESUMEN

Achieving optimal nutritional status in patients with penetrating Crohn's disease is crucial in preparing for surgical resection. However, there is a dearth of literature comparing the efficacy of total parenteral nutrition (TPN) v. exclusive enteral nutrition (EEN) in optimising postoperative outcomes. Hence, we conducted a case-matched study to assess the impact of preoperative EEN v. TPN on the incidence of postoperative adverse outcomes, encompassing overall postoperative morbidity and stoma formation, among penetrating Crohn's disease patients undergoing bowel surgery. From 1 December 2012 to 1 December 2021, a retrospective study was conducted at a tertiary centre to enrol consecutive patients with penetrating Crohn's disease who underwent surgical resection. Propensity score matching was utilised to compare the incidence of postoperative adverse outcomes. Furthermore, univariate and multivariate logistic regression analyses were conducted to identify the risk factors associated with adverse outcomes. The study included 510 patients meeting the criteria. Among them, 101 patients in the TPN group showed significant improvements in laboratory indicators at the time of surgery compared with pre-optimisation levels. After matching, TPN increased the occurrence of postoperative adverse outcomes (92·2 % v. 64·1 %, P = 0·001) when compared with the EEN group. In the multivariate analysis, TPN showed a significantly higher OR for adverse outcomes than EEN (OR = 4·241; 95 % CI 1·567-11·478; P = 0·004). The study revealed that penetrating Crohn's disease patients who were able to fulfil their nutritional requirements through EEN exhibited superior nutritional and surgical outcomes in comparison with those who received TPN.


Asunto(s)
Enfermedad de Crohn , Nutrición Enteral , Nutrición Parenteral Total , Complicaciones Posoperatorias , Humanos , Enfermedad de Crohn/cirugía , Estudios Retrospectivos , Masculino , Femenino , Nutrición Enteral/métodos , Nutrición Parenteral Total/métodos , Complicaciones Posoperatorias/etiología , Adulto , Persona de Mediana Edad , Estado Nutricional , Factores de Riesgo
6.
Scand J Gastroenterol ; 59(1): 39-45, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-37622924

RESUMEN

BACKGROUND: Few studies have compared endoscopic balloon dilation (EBD) and surgery in the treatment of duodenal stricture in patients with Crohn's disease (CD). METHODS: We performed a retrospective study to compare the efficacy and safety among patients with CD-associated duodenal stricture treated with EBD or surgery from October 2013 to December 2021. Univariate and multivariate analyses were performed to evaluate factors associated with recurrence-free or surgery-free survival. RESULTS: A total of 48 eligible patients were included, including 30 patients treated with EBD only and 18 patients treated with surgery. Patients treated with surgery experienced more symptomatic improvement (100% vs. 63.33%, p = 0.003) and significantly longer recurrence-free survival (6.31 [IQR: 3.00-8.39] years vs. 2.96 [IQR: 1.06-5.42] years, p = 0.01) but suffered more postprocedural adverse events (16.67% vs. 0.74% per procedure, p = 0.001). In patients initially treated with EBD (n = 41), a total of 11 (26.83%) required subsequent surgical intervention. Younger age at CD diagnosis (HR = 0.90, 95% CI: 0.81-1.00, p = 0.04) was associated with a higher risk for subsequent surgery. CONCLUSIONS: Surgery for CD-associated duodenal strictures was associated with a longer recurrence-free survival. EBD was safe and effective with minimal postprocedural adverse events but led to a high frequency of recurrence.


Asunto(s)
Enfermedad de Crohn , Obstrucción Intestinal , Humanos , Enfermedad de Crohn/cirugía , Constricción Patológica/etiología , Constricción Patológica/cirugía , Estudios Retrospectivos , Dilatación/efectos adversos , Obstrucción Intestinal/etiología , Resultado del Tratamiento , Endoscopía Gastrointestinal/métodos
7.
J Nat Prod ; 2024 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-39109656

RESUMEN

Metabolites with high chemical reactivity serve important roles in chemical defenses of organisms. Formaldehyde, as a simple and highly reactive small molecule, can be produced by microorganisms, plants, and animals. Its toxicity is well known, but information about its other biological functions remains scarce. Here, we report that the natural product SEK34b produced by Streptomyces species can react nonenzymatically with formaldehyde in water to yield the methylene-bridged dimer phaeochromycin F. This process can eliminate the toxic substance formaldehyde produced by Staphylococcus aureus. Furthermore, there is a substantial inhibitory impact of phaeochromycin F on S. aureus. We hypothesize that these constitute an integrated system of defense and attack of Streptomyces species against competitors. Our study indicates that formaldehyde can react with vancomycin and tigecycline under mild conditions to generate the derivatives bearing an imidazolidin-4-one moiety, thereby reducing the antibacterial activity of these antibiotics. These data provide a possible chemical interaction mechanism of bacteria involving the nonenzymatic reactions of formaldehyde with highly reactive natural products.

8.
J Nat Prod ; 87(7): 1778-1785, 2024 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-38949068

RESUMEN

Ten undocumented carbazole derivatives (2-11) along with the reported analogue (1) were isolated from the mangrove-derived Streptomyces sp. OUCMDZ-5511, cultured with NaBr-supplemented liquid medium. Compounds 1-7 are brominated carbazoles, and 8, 10, and 11 feature an additional thiazole or 2,3-dihydro-1,4-oxathiine rings, respectively. Their structures were identified through spectroscopic techniques, computational chemistry, and X-ray crystallography. Notably, compounds 6 and 8 effectively inhibited immune cell migration, indicating anti-inflammatory activity in vivo, potentially via Myd88/Nf-κB pathways, as suggested for compound 6.


Asunto(s)
Carbazoles , Streptomyces , Streptomyces/química , Carbazoles/química , Carbazoles/farmacología , Carbazoles/aislamiento & purificación , Estructura Molecular , Cristalografía por Rayos X , Bromo/química , Azufre/química , Antiinflamatorios/farmacología , Antiinflamatorios/química , Antiinflamatorios/aislamiento & purificación , Biología Marina , FN-kappa B/antagonistas & inhibidores , FN-kappa B/metabolismo , Animales
9.
J Nat Prod ; 87(2): 404-414, 2024 02 23.
Artículo en Inglés | MEDLINE | ID: mdl-38288586

RESUMEN

Twelve new polyenic macrolactams, cyclamenols G-R (1 and 3-13), together with the known analogue cyclamenol A (2), were isolated from Streptomyces sp. OUCMDZ-4348. Their structures were elucidated by spectroscopic analysis, quantum chemical calculations, chemical derivatizations, and Mosher's methods. The sequenced genome of OUCMDZ-4348 revealed the putative biosynthetic gene cluster of cyclamenols. It was proposed that the polycyclic natural products, cyclamenols H-R, might be formed from cyclamenols A and G through nonenzymatic intramolecular cycloadditions and oxidative cyclizations.


Asunto(s)
Streptomyces , Lactamas Macrocíclicas/química , Streptomyces/genética , Streptomyces/química , Regiones Antárticas , Estructura Molecular
10.
Chem Biodivers ; 21(6): e202400578, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38634186

RESUMEN

Psychrophilic fungus Pseudogymnoascus sp. OUCMDZ-4032 derived from Antarctica was cultivated under 16 °C to produce a new glucolipid compound (1). Its structure was elucidated by analysis of detailed spectroscopic data, acid hydrolysis and 1-phenyl-3-methyl-5-pyrazolone precolumn derivatization, and 13C NMR quantum chemical calculations. Though compound 1 did not show inhibitory activity against bacteria, it can reduce the minimum inhibitory concentration (MIC) of ciprofloxacin against Gram-negative bacteria Pseudomonas aeruginosa, Escherichia coli, and Salmonella paratyphi by 1024, 256 and 256-fold. Compound 1 showed potential as a synergistically inhibiting adjuvant in co-administration with antibiotic to enhance antibacterial activities.


Asunto(s)
Antibacterianos , Ciprofloxacina , Bacterias Gramnegativas , Pruebas de Sensibilidad Microbiana , Ciprofloxacina/farmacología , Ciprofloxacina/química , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/síntesis química , Bacterias Gramnegativas/efectos de los fármacos , Sinergismo Farmacológico , Estructura Molecular
11.
Surg Innov ; 31(2): 157-166, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38339842

RESUMEN

BACKGROUND: Prophylactic intraoperative drains have been shown not superior for patients underwent intestinal surgery. However, for patients with Crohn's disease (CD), this needs further exploration. METHODS: In this pilot study, CD patients were randomly assigned to drain (n = 50) and no-drain (n = 50) groups. The primary endpoint was the rate of postoperative prolonged ileus (PPOI). The secondary endpoints were postoperative abdominal ascites, postoperative systemic inflammatory response syndrome (SIRS) and C-reactive protein (CRP) levels. RESULTS: The incidences of PPOI and postoperative abdominal ascites were significantly lower in the drain group (12% vs 44%; 0% vs 24%, both P < .05). Postoperative SIRS incidence and CRP levels were significantly increased in the no-drain group [36% vs 10%; 54.9 vs 34.3 mg/L, both P < .05]. In multivariate analysis, prophylactic drainage was the independent protective factor for PPOI and postoperative LOS. CONCLUSIONS: Prophylactic drainage may be associated with improved clinical outcomes in CD patients.


Asunto(s)
Ascitis , Enfermedad de Crohn , Humanos , Ascitis/complicaciones , Enfermedad de Crohn/cirugía , Enfermedad de Crohn/complicaciones , Proyectos Piloto , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/etiología , Drenaje , Síndrome de Respuesta Inflamatoria Sistémica/complicaciones
12.
Clin Infect Dis ; 76(2): 307-314, 2023 01 13.
Artículo en Inglés | MEDLINE | ID: mdl-36124683

RESUMEN

BACKGROUND: Black and Hispanic/Latino men who have sex with men (MSM) are disproportionately affected by human immunodeficiency virus (HIV). In the Targeted Highly Effective Interventions to Reverse the HIV Epidemic (THRIVE) demonstration project, 7 community collaboratives were developed to provide comprehensive HIV prevention services for these populations. METHODS: We analyzed National HIV Surveillance System data to determine the number of HIV diagnoses for each year from 2014 to 2019 among Black, Hispanic/Latino, and White MSM in 7 THRIVE-eligible Metropolitan Statistical Areas (MSAs) that were awarded funding and 12 THRIVE-eligible MSAs that were not awarded funding. We used generalized linear Poisson regression models to estimate adjusted estimated annual percentage changes (EAPCs) with 95% confidence intervals for HIV diagnosis rates controlling for HIV prevalence, viral suppression, HIV testing rates, preexposure prophylaxis (PrEP) prescription rates, poverty, education, and insurance status. RESULTS: We found larger estimated decreases in HIV diagnosis rates in THRIVE jurisdictions compared with non-THRIVE jurisdictions. The adjusted EAPC among Black MSM was -8.2 (-11.7 to -4.6) in THRIVE MSAs compared with -4.2 (-7.8 to -0.4) in non-THRIVE MSAs. The adjusted EAPC among Hispanic/Latino MSM was -8.6 (-12.2 to -4.8) in THRIVE MSAs compared with -2.6 (-5.1 to -0.1)in non-THRIVE MSAs. The adjusted EAPC among White MSM was -7.6 (-12.0 to -3.1) in THRIVE MSAs compared with 5.9 (1.8-10.1) in non-THRIVE MSAs. CONCLUSIONS: The THRIVE community collaborative model was associated with a decrease in HIV diagnoses among Black and Hispanic/Latino MSM. To achieve the goals of the US Ending the HIV Epidemic initiative, effective interventions aimed to increase PrEP use need to be focused on Black and Hispanic/Latino MSM.


Asunto(s)
Infecciones por VIH , Profilaxis Pre-Exposición , Humanos , Masculino , Hispánicos o Latinos , VIH , Infecciones por VIH/diagnóstico , Infecciones por VIH/epidemiología , Infecciones por VIH/prevención & control , Homosexualidad Masculina , Prevalencia , Negro o Afroamericano
13.
J Am Chem Soc ; 145(48): 26308-26317, 2023 12 06.
Artículo en Inglés | MEDLINE | ID: mdl-37983668

RESUMEN

Friedel-Crafts acylation (FCA) is a highly beneficial approach in organic chemistry for creating the important C-C bonds that are necessary for building intricate frameworks between aromatic substrates and an acyl group. However, there are few reports about enzyme catalyzed FCA reactions. In this study, 4-acyl-5-aminoimidazole alkaloids (AAIAs), streptimidazoles A-C (1-3), and the enantiopure (+)-nocarimidazole C (4) as well as their ribosides, streptimidazolesides A-D (5-8), were identified from the fermentation broth of Streptomyces sp. OUCMDZ-944 or heterologous S. coelicolor M1154 mutant. The biosynthetic gene cluster (smz) was identified, and the biosynthetic pathway of AAIAs was elucidated for the first time. In vivo and in vitro studies proved the catalytic activity of the four essential genes smzB, -C, -E, and -F for AAIAs biosynthesis and clarified the biosynthetic process of the alkaloids. The ligase SmzE activates fatty acyl groups and connects them to the acyl carrier protein (ACP) holo-SmzF. Then, the acyl group is transferred onto the key residue Cys49 of SmzB, a new Friedel-Crafts acyltransferase (FCase). Subsequently, the FCA reaction between the acyl groups and 5-aminoimidazole ribonucleotide (AIR) occurs to generate the key intermediate AAIA-nucleotides catalyzed by SmzB. Finally, the hydrolase SmzC catalyzes the N-glycosidic bond cleavage of the intermediates to form AAIAs. Structural simulation, molecular modeling, and mutational analysis of SmzB showed that Tyr26, Cys49, and Tyr93 are the key catalytic residues in the C-C bond formation of the acyl chain of AAIAs, providing mechanistic insights into the enzymatic FCA reaction.


Asunto(s)
Aciltransferasas , Imidazoles , Aciltransferasas/química , Proteína Transportadora de Acilo/química , Catálisis
14.
Am J Public Health ; 113(9): 1019-1027, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37410983

RESUMEN

Objectives. To describe HIV testing among clients in the Targeted Highly Effective Interventions to Reverse the HIV Epidemic (THRIVE) demonstration project and evaluate testing frequency. Methods. We identified factors associated with an average testing frequency of 180 days or less compared with more than 180 days using adjusted Poisson regression models. We performed the Kaplan-Meier survival analysis to compare time to diagnosis by testing frequency. Results. Among 5710 clients with 2 or more tests and no preexposure prophylaxis (PrEP) prescription, 42.4% were tested frequently. Black/African American clients were 21% less likely and Hispanic/Latino clients were 18% less likely to be tested frequently than were White clients. Among 71 Black/African American and Hispanic/Latino cisgender men who have sex with men and transgender women with HIV diagnoses, those with frequent testing had a median time to diagnosis of 137 days, with a diagnostic testing yield of 1.5% compared with those tested less frequently, with 559 days and 0.8% yield. Conclusions. HIV testing at least every 6 months resulted in earlier HIV diagnosis and was efficient. Persons in communities with high rates of HIV who are not on PrEP can benefit from frequent testing, and collaborative community approaches may help reduce disparities. (Am J Public Health. 2023;113(9):1019-1027. https://doi.org/10.2105/AJPH.2023.307341).


Asunto(s)
Infecciones por VIH , Profilaxis Pre-Exposición , Minorías Sexuales y de Género , Personas Transgénero , Masculino , Humanos , Estados Unidos/epidemiología , Femenino , Homosexualidad Masculina , Infecciones por VIH/diagnóstico , Infecciones por VIH/epidemiología , Infecciones por VIH/prevención & control , Profilaxis Pre-Exposición/métodos , Prueba de VIH
15.
Dis Colon Rectum ; 66(1): e4-e9, 2023 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-36515520

RESUMEN

BACKGROUND: Anastomotic recurrence after bowel resection is problematic in patients with Crohn's disease. Antimesenteric functional end-to-end handsewn (Kono-S) anastomosis is associated with a low risk of anastomotic recurrence in patients with Crohn's disease. IMPACT OF INNOVATION: Kono-S anastomosis is effective but may be time-consuming. This study aimed to describe stapled antimesenteric functional end-to-end anastomosis for patients with Crohn's disease. TECHNOLOGY MATERIALS AND METHODS: The mesentery of the affected bowel segment was divided. A 5-cm-wide stapled functional end-to-end anastomosis was performed approximately 6 cm from the affected segment. The bowel was divided transversely exactly 90° to the intestinal lumen and the mesentery, and a supporting column was then constructed. PRELIMINARY RESULTS: From January 2018 to June 2021, 17 stapled antimesenteric functional end-to-end anastomoses were performed. The mean operative time was 106 (range, 80-135) minutes, and the time to construct the stapled antimesenteric functional end-to-end anastomosis was 21 (range, 18-28) minutes. The mean follow-up time was 8.9 (range, 1-15) months. In total, 10 patients underwent surveillance endoscopy. The average Rutgeerts score was 0.8 (range, 0-4), and the incidence of endoscopic recurrence was 11.8%. No postoperative mortality or anastomotic leakage was observed. CONCLUSION: Stapled antimesenteric functional end-to-end anastomosis may be a safe and time-saving procedure for patients with Crohn's disease. FUTURE DIRECTIONS: Further prospective studies with a large sample size are warranted.


Asunto(s)
Enfermedad de Crohn , Procedimientos Quirúrgicos del Sistema Digestivo , Humanos , Enfermedad de Crohn/cirugía , Estudios Prospectivos , Anastomosis Quirúrgica/métodos , Procedimientos Quirúrgicos del Sistema Digestivo/métodos , Intestinos/cirugía , Íleon/cirugía
16.
AIDS Behav ; 27(6): 1981-1988, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36417093

RESUMEN

Our objective is to evaluate the effect of navigation on linkage to a PrEP provider among PrEP-eligible men who have sex with men (MSM) in THRIVE, a demonstration project in seven U.S. public health jurisdictions during 2015-2020. We describe PrEP linkage and navigation use among MSM in THRIVE. We performed multivariable probit regression modeling, controlling for demographic covariates, to estimate the association between navigation and linkage to a PrEP provider among MSM and to assess for disparities in linkage to PrEP among MSM who used navigation. Among 9538 PrEP-eligible MSM, 51.3% used navigation and 53.8% were linked to PrEP. From the three sites where navigation was optional and the main form of PrEP support, MSM who used navigation were 16.69 times (95% CI 13.07-21.32) more likely to link to PrEP compared with MSM who did not use navigation. Among 4895 MSM who used navigation from all seven sites, Black MSM were 21% less likely to link to PrEP compared with White MSM (aRR 0.79; 95% CI 0.74-0.83). Navigation is a promising strategy for improving uptake of PrEP among U.S. MSM, but disparities persist. Addressing the underlying causes of inequities will be important to end the HIV epidemic.


Asunto(s)
Infecciones por VIH , Profilaxis Pre-Exposición , Minorías Sexuales y de Género , Humanos , Masculino , Negro o Afroamericano , Infecciones por VIH/epidemiología , Infecciones por VIH/prevención & control , Homosexualidad Masculina , Blanco
17.
J Nat Prod ; 86(4): 882-890, 2023 04 28.
Artículo en Inglés | MEDLINE | ID: mdl-36861650

RESUMEN

Seven new polyketides, diphenyl ketone (1), diphenyl ketone glycosides (2-4), diphenyl ketone-diphenyl ether dimer (6), and anthraquinone-diphenyl ketone dimers (7 and 8), together with compound 5, were isolated from the psychrophilic fungus Pseudogymnoascus sp. OUCMDZ-3578 fermented at 16 °C and identified by spectroscopic analysis. The absolute configurations of 2-4 were determined by acid hydrolysis and 1-phenyl-3-methyl-5-pyrazolone precolumn derivatization. The configuration of 5 was first determined by X-ray diffraction analysis. Compounds 6 and 8 showed the highest activity against amyloid beta (Aß42) aggregation with half-maximal inhibitory concentrations (IC50) of 0.10 and 0.18 µM, respectively. They also showed strong abilities to chelate with metal ions, especially iron, were sensitive to Aß42 aggregation induced by metal ions, and displayed depolymerizing activity. Compounds 6 and 8 show potential as leads for the treatment of Alzheimer's disease to prevent Aß42 aggregation.


Asunto(s)
Ascomicetos , Policétidos , Péptidos beta-Amiloides , Policétidos/farmacología , Policétidos/química , Ascomicetos/química , Compuestos de Bifenilo , Estructura Molecular
18.
J Nat Prod ; 86(11): 2522-2528, 2023 11 24.
Artículo en Inglés | MEDLINE | ID: mdl-37857311

RESUMEN

A new asteriquinone, ochrindole F (1), and five previously reported analogues (2-6) were isolated from the culture of the fungus Aspergillus sp. GZWMJZ-258, an endophyte of Garcinia multiflora. The structure of compound 1 was determined by a spectroscopic analysis. Furthermore, eight new derivatives (7-14) were synthesized from major metabolites 2 and 3. These compounds showed selective antiproliferative activity against the human acute myeloid leukemia (AML) cell line MV4-11, among which compound 12 showed the strongest activity with an IC50 value of 0.14 µM and the highest selectivity with a selectivity index greater than 710. An initial probe of the mechanism of action showed that compounds 12 and 14 could inhibit the expression of FLT-3 in the MV4-11 cell line.


Asunto(s)
Aspergillus , Leucemia Mieloide Aguda , Humanos , Línea Celular Tumoral , Aspergillus/química , Endófitos/metabolismo , Leucemia Mieloide Aguda/metabolismo , Estructura Molecular
19.
World J Surg ; 47(12): 3365-3372, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37775571

RESUMEN

BACKGROUND: Entero-urinary fistulas (EUF) are a rare complication of Crohn's disease (CD), observed in 1.6 to 7.7%. The management of EUF complicating CD is challenging. We aimed to report the outcome and surgical management of EUF in CD. METHODS: A retrospective chart review was performed in all CD patients with EUF who underwent surgery in our center between January 2012 and December 2021. Patient demographics, preoperative optimization, surgical management, postoperative complications, and follow-up information were collected from a prospectively maintained database. RESULTS: A total of 74 eligible patients were identified. The median interval between CD diagnosis and EUF diagnosis was 2 (0.08-6.29) years. Patients with EUF presented with pneumaturia (75.68%), urinary tract infections (72.97%), fecaluria (66.22%), and hematuria (6.76%). Fistulae originated most commonly from the ileum (63.51%), followed by the colon (14.86%), the rectum (9.46%), the cecum (2.70%), and multiple sites (9.46%). The EUF symptoms, weight, nutritional status, laboratory results were significantly improved after preoperative optimization. The absence of EUF symptoms was observed in 42 patients after the optimization and only 9 of which required bladder repair. However, 19 of 32 patients whose symptoms did not resolve required bladder repair (P = 0.001). Only 1 patient developed a bladder leakage in the early postoperative period and 3 patients experienced recurrent bladder fistula. CONCLUSIONS: Surgical management of EUF complicating CD is effective and safe, with a low rate of postoperative complication and EUF recurrence. Preoperative optimization, which is associated with the resolution of urinary symptoms and improved surgical outcomes, should be recommended.


Asunto(s)
Enfermedad de Crohn , Fístula Intestinal , Fístula de la Vejiga Urinaria , Fístula Urinaria , Humanos , Enfermedad de Crohn/complicaciones , Enfermedad de Crohn/cirugía , Estudios Retrospectivos , Fístula Intestinal/etiología , Fístula Intestinal/cirugía , Fístula Urinaria/cirugía , Fístula Urinaria/complicaciones , Fístula de la Vejiga Urinaria/etiología , Fístula de la Vejiga Urinaria/cirugía , Fístula de la Vejiga Urinaria/diagnóstico , Complicaciones Posoperatorias/etiología
20.
Artículo en Inglés | MEDLINE | ID: mdl-37553541

RESUMEN

With the increasing prevalence of depression among children and adolescents, understanding the role of peer contagion in the spread of emotional distress is a critical area of research. The aim of this study is to examine the effect of classmates' depression on a rural child's own depression in China (aged 9-17, N = 1777). The study controls for possible endogeneity of peer effects through the instrumental variable method (the Wald F statistic is significant at the 1% level) and random class assignment data (all students and teachers are randomly assigned to classes).The results indicate that when the average depression score of a rural child's classmates increases by 1 point, that child's own depression score is likely to increase by 0.345 points (p value < .01).This study further finds that the contagion of depression among classmates is more severe for girls and children who play online games, and less severe for children who are cheerful and good-humored. Online games may be an important mechanism through which peer effects operate. Children's classmates' negative emotions are found to increase the occurrence of the children's internalizing behavior in online games, in turn increasing the occurrence of negative emotions in these children themselves.

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