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1.
Eye (Lond) ; 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39261653

RESUMEN

OBJECTIVES: To compare the 2-year efficacy and safety of various anti-vascular endothelial growth factor (VEGF) regimens for neovascular age-related macular degeneration (nAMD). METHODS: A comprehensive search was performed on multiple electronic databases up to April 2023 and updated in June 2024, to identify relevant randomized controlled trials (RCTs). Key outcomes included the proportion of patients achieving a vision gain of ≥15 letters and maintaining stable vision (loss of <15 letters) in best-corrected visual acuity (BCVA), changes in mean BCVA from baseline, serious ocular adverse events (SAEs), adverse events leading to treatment discontinuation and any cause of death at 2 years. RESULTS: Nineteen trials with 12,654 patients and 25 treatment regimens were analyzed in the study. All anti-VEGF regimens showed superior efficacy compared to sham therapy. Specifically, faricimab 6 mg (4+up to Q16W) and ranibizumab 0.5 mg (2-week T&E) displayed top-level effect in vision gain. Bevacizumab 1.25 mg (2-week T&E) and aflibercept 2 mg (2-week T&E) demonstrated the most stable vision outcomes. Bevacizumab 1.25 mg (2-week T&E) and ranibizumab 0.5 mg (2-week T&E) exhibited the most pronounced mean BCVA improvement. Compared to sham therapy, the risk of SAEs was significantly higher for brolucizumab 6 mg (3 + Q12W/ Q8W) (RR = 6.04, 95% CI: 1.30-28.02) and PDS 100 mg/ml (Q24W) (RR = 10.95, 95% CI: 2.14-56.02), but not for other anti-VEGF regimens. CONCLUSIONS: Ranibizumab 0.5 mg (2-week T&E) emerges as a potentially optimal regimen for nAMD over a 2-year period. Future studies need to consider the impact of baseline characteristics on treatment outcomes.

2.
JCI Insight ; 9(16)2024 08 22.
Artículo en Inglés | MEDLINE | ID: mdl-39171524

RESUMEN

Decidual regulatory T cells (Tregs) are essential for successful pregnancy outcome. A subset of Tregs, T cell immunoglobulin and mucin domain-containing protein 3-positive regulatory T cells (TregsTim-3+), plays a central role in the acceptance of the fetus during early stages of normal pregnancy. The molecular mechanism regulating the differentiation and function of TregsTim-3+ is unknown. Here, we investigated the role of the transcription factor B lymphocyte-induced maturation protein 1 (Blimp-1) on decidual TregTim-3+ differentiation. We demonstrated that Blimp-1 enhanced the coexpression of negative costimulatory molecules (Tim-3, T cell immunoreceptor with Ig and ITIM domains, and programmed cell death protein 1) on Tregs and improved their immunosuppressive functions, including increased IL-10 secretion, suppression of effector T cell proliferation, and promotion of macrophage polarization toward the M2 phenotype. Furthermore, we showed that IL-27 regulated the expression of Tim-3 and Blimp-1 through the STAT1 signaling pathway and that transfer of TregsBlimp-1+ into an abortion-prone mouse model effectively reduced embryo absorption rate. We postulated that abnormalities in the IL-27/Blimp-1 axis might be associated with recurrent pregnancy loss (RPL). These findings provided insights for developing more efficient immunotherapies for women with RPL.


Asunto(s)
Diferenciación Celular , Receptor 2 Celular del Virus de la Hepatitis A , Factor 1 de Unión al Dominio 1 de Regulación Positiva , Linfocitos T Reguladores , Femenino , Animales , Embarazo , Factor 1 de Unión al Dominio 1 de Regulación Positiva/metabolismo , Factor 1 de Unión al Dominio 1 de Regulación Positiva/genética , Receptor 2 Celular del Virus de la Hepatitis A/metabolismo , Ratones , Diferenciación Celular/inmunología , Linfocitos T Reguladores/inmunología , Linfocitos T Reguladores/metabolismo , Factor de Transcripción STAT1/metabolismo , Transducción de Señal , Humanos , Decidua/inmunología , Decidua/metabolismo , Decidua/citología , Interleucina-10/metabolismo , Interleucinas/metabolismo , Interleucinas/inmunología , Interleucina-27/metabolismo
3.
Sci Rep ; 14(1): 17522, 2024 07 30.
Artículo en Inglés | MEDLINE | ID: mdl-39080370

RESUMEN

Peritoneal metastasis (PM), the regional progression of intra-abdominal malignancies, is a common sequelae of colorectal cancer (CRC). Immunotherapy is slated to be effective in generating long-lasting anti-tumour response as it utilizes the specificity and memory of the immune system. In the tumour microenvironment, tumour associated macrophages (TAMs) are posited to create an anti-inflammatory pro-tumorigenic environment. In this paper, we aimed to identify immunomodulatory factors associated with colorectal PM (CPM). A publicly available colorectal single cell database (GSE183916) was analysed to identify possible immunological markers that are associated with the activation of macrophages in cancers. Immunohistochemical analysis for V-set and immunoglobin containing domain 4 (VSIG4) expression was performed on tumour microarrays (TMAs) of tumours of colorectal origin (n = 211). Expression of VSIG4 in cell-free ascites obtained from CPM patients (n = 39) was determined using enzyme-linked immunosorbent assay (ELISA). CD163-positive TAMs cluster expression was extracted from a publicly available single cell database and evaluated for the top 100 genes. From these macrophage-expressed genes, VSIG4, a membrane protein produced by the M2 macrophages, mediates the up-regulation of anti-inflammatory and down-regulation of pro-inflammatory macrophages, contributing to an overall anti-inflammatory state. CRC TMA IHC staining showed that low expression of VSIG4 in stromal tissues of primary CRC are associated with poor prognosis (p = 0.0226). CPM ascites also contained varying concentrations of VSIG4, which points to a possible role of VSIG4 in the ascites. The contribution of VSIG4 to CPM development can be further evaluated for its potential as an immunotherapeutic agent.


Asunto(s)
Neoplasias Colorrectales , Neoplasias Peritoneales , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/inmunología , Regulación Neoplásica de la Expresión Génica , Inmunomodulación , Comunicación Paracrina , Neoplasias Peritoneales/secundario , Neoplasias Peritoneales/metabolismo , Microambiente Tumoral/inmunología , Macrófagos Asociados a Tumores/metabolismo , Macrófagos Asociados a Tumores/inmunología
4.
J Affect Disord ; 360: 214-220, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-38824963

RESUMEN

BACKGROUND: Post-marketing surveillance found montelukast use was associated with an increased risk of depression. However, results of observational studies are inconsistent. OBJECTIVE: This study aimed to assess whether montelukast exposure is associated with depression and elucidate the possible molecular mechanism. METHOD: We conducted a cross-sectional study of 9508 adults from the National Health and Nutrition Examination Survey (NHANES) 2007-2016. Multivariable regression was used to evaluate the association between montelukast exposure and depression. Network pharmacology was conducted to identify the mechanisms of montelukast on depression. RESULTS: Montelukast exposure had a higher prevalence of depression (37.4 %). In a multivariable logistic regression model adjusted for sociodemographic, behavioural, and health characteristics, montelukast exposure was associated with depression (odds ratio [OR]: 1.61; confidence interval [CI]: 1.18-2.19). Network pharmacology was identified 69 key targets of montelukast on depression. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis suggested montelukast mainly works through multiple pathways in endocrine resistance, chemical carcinogenesis-receptor activation, estrogen signaling pathway, etc. LIMITATIONS: Cross-sectional data. CONCLUSIONS: The study implies a potential positive association between long-term montelukast exposure and depression through multi-faceted mechanisms. It is suggested that attention be given to the possibility of depression in patients undergoing prolonged montelukast therapy.


Asunto(s)
Acetatos , Ciclopropanos , Quinolinas , Sulfuros , Humanos , Acetatos/farmacología , Acetatos/efectos adversos , Quinolinas/farmacología , Quinolinas/efectos adversos , Femenino , Masculino , Estudios Transversales , Adulto , Persona de Mediana Edad , Depresión/tratamiento farmacológico , Encuestas Nutricionales
5.
J Integr Plant Biol ; 66(7): 1263-1265, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38818976

RESUMEN

Reactive oxygen species (ROS) and phosphatidic acid (PA) are important second messengers in plant immunity. PA binding to RBOHD, an NADPH oxidase responsible for ROS production, enhances RBOHD stability and promotes ROS production. Distinct phosphorylation of the lipid kinase DGK5 optimizes the PA burst in regulating ROS production.


Asunto(s)
Homeostasis , Ácidos Fosfatidicos , Inmunidad de la Planta , Especies Reactivas de Oxígeno , Ácidos Fosfatidicos/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Inmunidad de la Planta/fisiología , NADPH Oxidasas/metabolismo , Arabidopsis/metabolismo , Arabidopsis/inmunología , Transducción de Señal , Proteínas de Arabidopsis/metabolismo , Diacilglicerol Quinasa/metabolismo , Fosforilación
6.
J Affect Disord ; 356: 728-736, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38663558

RESUMEN

INTRODUCTION: Post-market monitoring has shown a potential link between the use of leukotriene-modifying agents (LTRAs) and an increased risk of neuropsychiatric events, such as depression. However, observational studies have produced inconsistent findings, offering no definitive conclusions. OBJECTIVE: To assess the potential correlation between LTRAs exposure and depression in US adults. METHOD: This cross-sectional study, based on population data from the National Health and Nutrition Examination Survey (NHANES) 2007-2016 cycle. The Patient Health Questionnaire-9 was used to assess depression. Multivariable regression was used to evaluate the association between LTRAs exposure and depression. Sensitivity and subgroup analyses were conducted, with the calculation of the E-value. Network pharmacology was employed to investigate the influence of LTRAs on mechanisms of depression. RESULTS: Among the 9414 participants, 595 (6.3 %) were classified as having depression. LTRAs exposure was associated with a higher prevalence of depression (16.9 % vs. 6.0 %). The multivariable logistic regression results showed that LTRAs use increased the risk of depression (OR = 1.70; 95 % CI, 1.05-2.75). An association between LTRAs exposure and depression was found in sensitivity analyses conducted regardless of multivariable linear regression with the PHQ-9 score as a continuous variable (ß = 0.97; 95 % CI, 0.44-1.50) or multivariable logistic regression with the PHQ-9 cut-off of 5 (OR = 1.52; 95 % CI, 1.08-2.14). The association between LTRAs and depression was stable in the different subgroups. CONCLUSION: LTRAs exposure is positively associated with depression in US adults. Therefore, the risk for depression in patients receiving long-term LTRAs treatment should be considered.


Asunto(s)
Depresión , Encuestas Nutricionales , Humanos , Estudios Transversales , Masculino , Femenino , Persona de Mediana Edad , Adulto , Depresión/epidemiología , Depresión/inducido químicamente , Estados Unidos/epidemiología , Antagonistas de Leucotrieno/farmacología , Antagonistas de Leucotrieno/efectos adversos , Prevalencia , Factores de Riesgo , Anciano
7.
Vet Res Forum ; 15(2): 65-73, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38465319

RESUMEN

The non-structural protein (nsp) 8 of the porcine epidemic diarrhea virus (PEDV) is highly stable across different PEDV strains and plays an important role in PEDV virulence. In current study, nsp8 prokaryotic expression vectors were constructed based on parental vectors pMAL-c2x-maltose binding protein (MBP) and pET-28a (+). Subsequently, the optimization of expression conditions in Escherichia coli, including induced temperature, time and isopropyl ß-D-thiogalactopyranoside concentration were performed to obtain a stable expression of MBP-nsp8 and nsp8. The nsp8 fused with MBP increased the water solubility of the expressed products. Target proteins were further purified from E. coli culture and their immunogenicities were evaluated in vivo by mice. The antibody titers of serum from nsp8 immunized mice were up to 1:7,750,000 when measured by indirect enzyme-linked immunosorbent assay; meanwhile, the mice immunized with MBP-nsp8 gave an antibody titer reaching 1:1,000,000. In all, the expression and purification system of PEDV nsp8 and MBP-nsp8 were successfully established in this work and a strong immune response was elicited in mice by both purified nsp8 and MBP-nsp8, providing a basis for the study of the structure and function of PEDV nsp8.

8.
Pathology ; 56(3): 325-333, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38195375

RESUMEN

The frequency of MET and HER2 amplification being detected by next generation sequencing (NGS) is increasing due to NGS being increasingly adopted for molecular profiling of cancers. However, the accuracy of NGS in detecting these gene amplifications remains uncertain due to conflicting reports in the scientific literature. We studied the accuracy of an amplicon-based large panel NGS assay in detecting MET and HER2 amplification in lung and breast cancers, respectively, by comparing it against conventional testing methods. Amongst 48 lung cancers, four of five cancers that were MET amplified on fluorescence in situ hybridisation (FISH) were classified as amplified on NGS while 42 of the remaining 43 non-amplified cancers were classified as non-amplified on NGS, giving a sensitivity of 80%, specificity of 97.7% and overall concordance of 95.8%. Of the 46 breast cancers tested, only six of the nine cancers that were HER2-positive on immunohistochemistry (IHC)/FISH were HER2-positive on NGS, while all the remaining HER2-negative cases were negative on NGS, giving a sensitivity of 66.7%, specificity of 100% and overall concordance of 93.5%. All the false-negative cases had low level gene amplification (MET:CEP7 or HER2:CEP17 FISH ratio of <3). The low sensitivity for HER2 amplification may be confounded by the small sample size and disproportionate number of cases with low level amplification. In summary, the NGS assay has good concordance with conventional testing methods but may be less sensitive in detecting low level gene amplification.


Asunto(s)
Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/genética , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Secuenciación de Nucleótidos de Alto Rendimiento , Amplificación de Genes , Pulmón/metabolismo
9.
Ann Pharmacother ; 58(4): 349-359, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37488978

RESUMEN

BACKGROUND: Different clinical trials for recurrent or metastatic nasopharyngeal carcinoma have studied different combinations of immuno-oncology in first-line treatment, but the optimal choice has not been determined. OBJECTIVE: To systematically examine and compare the efficacy and safety of different immune checkpoint inhibitors (ICIs) combined with chemotherapy as first-line treatment for recurrent or metastatic nasopharyngeal carcinoma. METHODS: Several electronic databases were systematically searched up to February 2023. Articles meeting the inclusion criteria were included. RESULTS: Three RCTs were eligible in the study. Compared with placebo plus gemcitabine-cisplatin (GP), toripalimab plus GP (HR = 0.59, 95% CI: 0.37-0.95) was significantly associated with a better OS. Tislelizumab plus GP generated best progression-free survival (PFS) benefit (HR = 0.50, 95% CI: 0.37-0.67), greatest improvement in 1-year PFS rate (RR = 3.00, 95% CI: 1.84-5.22), and objective response rate (ORR) (RR = 1.26, 95% CI: 1.04-1.53) over the placebo plus GP. Furthermore, tislelizumab plus GP appeared to be safer than toripalimab plus GP and camrelizumab plus GP in terms of adverse events (AEs)-grade ≥3, treatment-related AEs (TRAEs)-grade ≥3, serious AEs (SAEs), treatment-related SAEs (TRSAEs), and AEs leading to discontinuation of treatment. CONCLUSION AND RELEVANCE: In recurrent or metastatic nasopharyngeal carcinoma, programmed death 1 (PD-1) inhibitors plus GP as first-line treatment have better survival outcomes than placebo plus GP with comparable toxicity. Toripalimab plus GP shows the best OS benefit over placebo plus GP, while tislelizumab plus GP generates the best PFS, 1-year PFS rate, ORR, and safety. Tislelizumab plus GP could be the best choice among the ICIs combined with chemotherapy regimens as first-line treatment in recurrent or metastatic nasopharyngeal carcinoma.


Asunto(s)
Neoplasias Pulmonares , Neoplasias Nasofaríngeas , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Neoplasias Pulmonares/tratamiento farmacológico , Carcinoma Nasofaríngeo/tratamiento farmacológico , Carcinoma Nasofaríngeo/etiología , Neoplasias Nasofaríngeas/tratamiento farmacológico , Neoplasias Nasofaríngeas/etiología , Neoplasias Nasofaríngeas/patología , Metaanálisis en Red , Ensayos Clínicos Controlados Aleatorios como Asunto
10.
Technol Health Care ; 32(1): 467-479, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-37840510

RESUMEN

BACKGROUND: Vascular tortuosity is a prevalent morphological change that frequently occurs in arteries across different parts of the body. OBJECTIVE: To analyze the relationship between the tortuosities of the extracranial internal carotid artery (EICA) and extracranial vertebral artery (EVA) with mild cognitive impairment. METHODS: The tortuosity index (TI), vascular deviation degree, tortuosity degree, and angle number of the EICA and EVA were retrospectively analyzed and calculated in 160 patients who underwent computed tomography angiography (CTA) in this study's department, and the Montreal cognitive assessment was adopted to evaluate the cognitive function of the patients. RESULTS: The differences in age, gender, arterial hypertension (AH), and diabetes mellitus (DM) between the normal group and the mild cognitive impairment group were statistically significant (p< 0.01). The TI was negatively correlated with the score of cognitive function. The tortuosities of the EICA and EVA were correlated with mild cognitive impairment (p< 0.05). The reduction in visual-spatial ability was correlated with the right EICA tortuosity, and the reduction in memory was correlated with the EVA tortuosity. Age, gender, HP, DM, and coronary heart disease (CHD) were potential risk factors for carotid tortuosity (p< 0.05). CONCLUSION: There was a significant correlation observed between the TIs of both the EICA and EVA and the presence of mild cognitive impairment. Advanced age, female, HP, DM, and CHD were independent risk factors for EICA and EVA tortuosities.


Asunto(s)
Arteria Carótida Interna , Disfunción Cognitiva , Humanos , Femenino , Arteria Carótida Interna/diagnóstico por imagen , Estudios Retrospectivos , Arteria Vertebral/diagnóstico por imagen
11.
Plant J ; 117(3): 653-668, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37997486

RESUMEN

Air humidity significantly impacts plant physiology. However, the upstream elements that mediate humidity sensing and adaptive responses in plants remain largely unexplored. In this study, we define high humidity-induced cellular features of Arabidopsis plants and take a quantitative phosphoproteomics approach to obtain a high humidity-responsive landscape of membrane proteins, which we reason are likely the early checkpoints of humidity signaling. We found that a brief high humidity exposure (i.e., 0.5 h) is sufficient to trigger extensive changes in membrane protein abundance and phosphorylation. Enrichment analysis of differentially regulated proteins reveals high humidity-sensitive processes such as 'transmembrane transport', 'response to abscisic acid', and 'stomatal movement'. We further performed a targeted screen of mutants, in which high humidity-responsive pathways/proteins are disabled, to uncover genes mediating high humidity sensitivity. Interestingly, ethylene pathway mutants (i.e., ein2 and ein3eil1) display a range of altered responses, including hyponasty, reactive oxygen species level, and responsive gene expression, to high humidity. Furthermore, we observed a rapid induction of ethylene biosynthesis genes and ethylene evolution after high humidity treatment. Our study sheds light on the potential early signaling events in humidity perception, a fundamental but understudied question in plant biology, and reveals ethylene as a key modulator of high humidity responses in plants.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Humedad , Etilenos/metabolismo , Arabidopsis/metabolismo , Proteínas de la Membrana/metabolismo , Regulación de la Expresión Génica de las Plantas
12.
Biotechnol Biofuels Bioprod ; 16(1): 151, 2023 Oct 05.
Artículo en Inglés | MEDLINE | ID: mdl-37798770

RESUMEN

With the invasion of green tides and the increase of urban green areas worldwide, multimillion tons of Enteromorpha need to be reutilized. In this study, Enteromorpha prolifera powder is considered a promising biomass resource for the production of commercial chemical products production. Ilamycins, novel cyclic heptapeptides with significant anti-TB activities, are isolated from Streptomyces atratus SCSIO ZH16, a deep-sea-derived strain. Using EP powder as a nitrogen source, the production of ilamycins reached 709.97 mg/L through optimization of the nitrogen source using the engineered strain S. atratus SCSIO ZH16 ΔR. After mutant strain constructions and tests, strain S. atratus SCSIO ZH16 ΔR::bldD EP powder achieved a higher production titer of ilamycins. Furthermore, the production titer of ilamycins and ilamycin E reached 1561.77 mg/L and 745.44 mg/L, respectively, in a 5 L bioreactor. This study suggests that E. prolifera is a promising and eco-friendly nitrogen source for the production of ilamycins.

13.
Trends Microbiol ; 31(11): 1093-1095, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37770374

RESUMEN

Phytopathogenic microbes obtain nutrients from host plants to support their growth and metabolism. A recent study by Zhu et al. revealed that the oomycete pathogen Phytophthora sojae upregulates the activity of soybean trehalose 6-phosphate synthase 6 (GmTPS6) and increases trehalose accumulation (through an effector PsAvh413) to promote nutritional gain.

14.
EMBO J ; 42(21): e113499, 2023 11 02.
Artículo en Inglés | MEDLINE | ID: mdl-37728254

RESUMEN

The occurrence of plant disease is determined by interactions among host, pathogen, and environment. Air humidity shapes various aspects of plant physiology and high humidity has long been known to promote numerous phyllosphere diseases. However, the molecular basis of how high humidity interferes with plant immunity to favor disease has remained elusive. Here we show that high humidity is associated with an "immuno-compromised" status in Arabidopsis plants. Furthermore, accumulation and signaling of salicylic acid (SA), an important defense hormone, are significantly inhibited under high humidity. NPR1, an SA receptor and central transcriptional co-activator of SA-responsive genes, is less ubiquitinated and displays a lower promoter binding affinity under high humidity. The cellular ubiquitination machinery, particularly the Cullin 3-based E3 ubiquitin ligase mediating NPR1 protein ubiquitination, is downregulated under high humidity. Importantly, under low humidity the Cullin 3a/b mutant plants phenocopy the low SA gene expression and disease susceptibility that is normally observed under high humidity. Our study uncovers a mechanism by which high humidity dampens a major plant defense pathway and provides new insights into the long-observed air humidity influence on diseases.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Ácido Salicílico/metabolismo , Humedad , Proteínas Cullin/genética , Proteínas Cullin/metabolismo , Arabidopsis/metabolismo , Plantas/metabolismo , Factores de Transcripción/metabolismo , Enfermedades de las Plantas/genética , Regulación de la Expresión Génica de las Plantas
15.
Phytochemistry ; 214: 113816, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37536654

RESUMEN

Four previously undescribed diketopiperazine-type alkaloids including one oxepin-containing diketopiperazine-type alkaloid, oxepinamide L (1), three 4-quinazolinone alkaloids, puniceloids E-G (10-12), together with 12 known analogues, protuboxepin D (2), oxepinamides D-G, J-K and I (3-9), puniceloids B-D (13-15) and protubonine B (16), were isolated from the culture of the marine-derived fungus Aspergillus puniceus FAHY0085. The structures of the previously undescribed compounds were comprehensively elucidated by detailed interpretation of their NMR and HRESIMS data. Their absolute configurations were unambiguously determined by ROESY experiments, Marfey's method, calculated ECD experiments and single-crystal X-ray diffraction analysis. Compounds (3-4, 6-8, 14-15) were evaluated for their cytotoxic activity against HepG2, MCF-7, SW1116 and HeLa cells and compound 6 and 14 showed moderate cytotoxic activity against HeLa cells with IC50 49.61 ± 2.91 and 28.38 ± 1.57 µM, respectively. Compounds (1-8, 11-15) were screened for their transcriptional activation of liver X receptor α and compound 11 with known compounds 13-15 showed significant transcriptional activation of liver X receptor α with EC50 values in the range 2-50 µM.


Asunto(s)
Alcaloides , Antineoplásicos , Humanos , Células HeLa , Receptores X del Hígado , Estructura Molecular , Hongos/química , Dicetopiperazinas/química , Alcaloides/química , Antineoplásicos/farmacología
16.
Virology ; 587: 109861, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37572518

RESUMEN

Porcine epidemic diarrhea virus (PEDV) causes acute diarrhea, vomiting, dehydration, and high mortality in newborn piglets, which leads to significant economic losses. Coronavirus nonstructural protein 9 (Nsp9) is an essential RNA binding protein for coronavirus replication, which renders it a promising candidate for developing antiviral drugs and diagnosis targeting PEDV. In this study, PEDV Nsp9 protein fused with MBP protein and His-tag were expressed and purified in Escherichia coli. Furthermore, immunization of MBP-Nsp9 enhances both humoral and cellular immunity responses as compared with that of His-Nsp9 protein. Finally, the swine immunization showed that Nsp9 protein could stimulate the swine immunity system to carry out humoral immunity, and the generated antibody could inhibit the proliferation of PEDV in Vero cells. Altogether, our data provide direct evidence for the immunogenicity of PEDV Nsp9, which sheds light on the future developments of anti-PEDV drugs and vaccines for PED prevention.


Asunto(s)
Infecciones por Coronavirus , Coronavirus , Virus de la Diarrea Epidémica Porcina , Enfermedades de los Porcinos , Chlorocebus aethiops , Animales , Porcinos , Virus de la Diarrea Epidémica Porcina/fisiología , Células Vero , Inmunización , Vacunación , Infecciones por Coronavirus/prevención & control , Infecciones por Coronavirus/veterinaria , Diarrea
17.
Medicine (Baltimore) ; 102(33): e34902, 2023 Aug 18.
Artículo en Inglés | MEDLINE | ID: mdl-37603507

RESUMEN

BACKGROUND: Novel-fosfamides (NFOs) belong to active metabolites of ifosfamide that bypass the generation of toxic byproducts. In this analysis, we aimed to comprehensively assess the benefits and risks of NFO monotherapy or in combination with doxorubicin (DOX) versus single-drug DOX in previously untreated patients with advanced soft-tissue sarcoma (ASTS). METHODS: Online PubMed, Web of Science, Embase, and Cochrane CENTRAL databases were systematically searched on April 26, 2022. Objective response rate and disease control rate were primary outcomes. Overall survival (OS), progression-free survival (PFS), and grade ≥ 3 treatment-related adverse events were secondary outcomes. RESULTS: In all, 3 randomized clinical trials with a total of 1207 ASTS patients were eligible. DOX plus NFO combination therapy showed higher risk ratios of objective response rate (1.50, 95% CI 1.20-1.68, P = .0003) and disease control rate (1.15, 95% CI 1.05-1.27, P = .0030) compared with DOX monotherapy. Nevertheless, NFO-based monotherapy and combination therapy were found no improvements on OS (hazard ratio 0.93, 95% CI 0.52-1.65, P = .8050) and PFS (hazard ratio 0.88, 95% CI 0.54-1.43, P = .6088) against DOX. More incidences of grade 3 or worse anemia, thrombocytopenia, stomatitis, diarrhea, constipation, and febrile neutropenia were observed in NFO-based treatments. CONCLUSION: Adding NFO to DOX as first-line therapy improved the responses in ASTS patients but did not prolong OS and PFS. Grade 3 or worse treatment-related adverse events should be treated with caution during the NFO-based therapies.


Asunto(s)
Sarcoma , Neoplasias de los Tejidos Blandos , Trombocitopenia , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto , Doxorrubicina/efectos adversos , Sarcoma/tratamiento farmacológico
18.
J Clin Pharmacol ; 63(12): 1377-1386, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37492894

RESUMEN

A large number of studies have evaluated the efficacy of low-dose atropine in preventing or slowing myopic progression. However, it is challenging to evaluate the ocular safety from these studies. We aimed to evaluate the incidence of adverse events induced by atropine in children with myopia. We performed a systematic literature search in several databases for studies published until November 2022. The incidence of adverse events induced by atropine was pooled by a common-effect (fixed-effect) or random-effects model. Subgroup analyses were conducted according to drug doses, types of adverse events, and ethnicity. A total of 31 articles were ultimately included in the study. The overall incidence of adverse events for atropine was 5.9%, and the incidence of severe adverse events was 0.0%. The most commonly reported adverse events were photophobia (9.1%) and blurred near vision (2.9%). Other adverse events including eye irritation/discomfort, allergic reactions, headache, stye/chalazion, glare, and dizziness occurred in less than 1% of the patients. The incidence of atropine-induced adverse events varied depending on the drug doses. A lower dose of atropine was associated with a lower incidence of adverse events. There was no significant difference in the incidence of adverse events for low-dose atropine between Asian and White children. Our study suggests photophobia and blurred near vision are the most frequently reported adverse events induced by atropine. Low-dose atropine is safer than moderate- and high-dose atropine. Our study could provide a safe reference for ophthalmologists to prescribe atropine for myopic children.


Asunto(s)
Atropina , Miopía , Humanos , Niño , Atropina/efectos adversos , Midriáticos/efectos adversos , Fotofobia/inducido químicamente , Incidencia , Progresión de la Enfermedad , Miopía/tratamiento farmacológico , Miopía/inducido químicamente , Miopía/prevención & control , Soluciones Oftálmicas/efectos adversos
19.
Biol Reprod ; 109(3): 244-255, 2023 09 12.
Artículo en Inglés | MEDLINE | ID: mdl-37402700

RESUMEN

During pregnancy, cell senescence at the maternal-fetal interface is required for maternal well-being, placental development, and fetal growth. However, recent reports have shown that aberrant cell senescence is associated with multiple pregnancy-associated abnormalities, such as preeclampsia, fetal growth restrictions, recurrent pregnancy loss, and preterm birth. Therefore, the role and impact of cell senescence during pregnancy requires further comprehension. In this review, we discuss the principal role of cell senescence at the maternal-fetal interface, emphasizing its "bright side" during decidualization, placentation, and parturition. In addition, we highlight the impact of its deregulation and how this "dark side" promotes pregnancy-associated abnormalities. Furthermore, we discuss novel and less invasive therapeutic practices associated with the modulation of cell senescence during pregnancy.


Asunto(s)
Placenta , Nacimiento Prematuro , Embarazo , Femenino , Recién Nacido , Humanos , Parto , Placentación , Senescencia Celular/fisiología
20.
World J Diabetes ; 14(6): 808-819, 2023 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-37383595

RESUMEN

The incidence rate of diabetes in pregnancy is about 20%, and diabetes in pregnancy will have a long-term impact on the metabolic health of mothers and their offspring. Mothers may have elevated blood glucose, which may lead to blood pressure disease, kidney disease, decreased resistance and secondary infection during pregnancy. The offspring may suffer from abnormal embryonic development, intrauterine growth restriction, obesity, autism, and other adverse consequences. Resveratrol (RSV) is a natural polyphenol compound, which is found in more than 70 plant species and their products, such as Polygonum cuspidatum, seeds of grapes, peanuts, blueberries, bilberries, and cranberries. Previous studies have shown that RSV has a potential beneficial effect on complex pregnancy, including improving the indicators of diabetes and pregnancy diabetes syndrome. This article has reviewed the molecular targets and signaling pathways of RSV, including AMP-activated protein kinase, mitogen-activated protein kinases, silent information regulator sirtuin 1, miR-23a-3p, reactive oxygen species, potassium channels and CX3C chemokine ligand 1, and the effect of RSV on gestational diabetes mellitus (GDM) and its complications. RSV improves the indicators of GDM by improving glucose metabolism and insulin tolerance, regulating blood lipids and plasma adipokines, and modulating embryonic oxidative stress and apoptosis. Furthermore, RSV can ameliorate the GDM complications by reducing oxidative stress, reducing the effects on placentation, reducing the adverse effects on embryonic development, reducing offspring's healthy risk, and so on. Thus, this review is of great significance for providing more options and possibilities for further research on medication of gestational diabetes.

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