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1.
Food Chem ; 462: 140909, 2025 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-39208727

RESUMEN

Probiotics serve a very important role in human health. However, probiotics have poor stability during processing, storage, and gastrointestinal digestion. The gellan gum (GG) is less susceptible to enzymatic degradation and resistant to thermal and acidic environments. This study investigated the effect of casein (CS)-GG emulsions to encapsulate Lactiplantibacillus plantarum CICC 6002 (L. plantarum CICC 6002) on its storage stability, thermal stability, and gastrointestinal digestion. L. plantarum CICC 6002 was suspended in palm oil and emulsions were prepared using CS or CS-GG complexes. We found the CS-GG emulsions improved the viability of L. plantarum CICC 6002 after storage, pasteurization, and digestion compared to the CS emulsions. In addition, we investigated the influence of the gellan gum concentration on emulsion stability, and the optimal stability was observed in the emulsion prepared by CS-0.8% GG complex. This study provided a new strategy for the protection of probiotics based on CS-GG delivery system.


Asunto(s)
Caseínas , Emulsiones , Lactobacillus plantarum , Polisacáridos Bacterianos , Probióticos , Emulsiones/química , Probióticos/química , Polisacáridos Bacterianos/química , Caseínas/química , Humanos , Lactobacillus plantarum/química , Lactobacillus plantarum/metabolismo , Pasteurización , Tracto Gastrointestinal/microbiología , Tracto Gastrointestinal/metabolismo , Viabilidad Microbiana/efectos de los fármacos , Composición de Medicamentos , Digestión , Almacenamiento de Alimentos
2.
Artículo en Inglés | MEDLINE | ID: mdl-39283417

RESUMEN

BACKGROUND: Psoriasis, a chronic, immune-mediated, inflammatory disease, affects 2‒3% of the population. Tyrosine kinase 2 (TYK2) mediates cytokine signaling involved in adaptive [interleukin (IL)-12, IL-23] and innate (type-I interferons) immune responses; IL-23-driven T-helper (Th)17 pathways play a key role in chronic inflammation in psoriasis. In a phase 2 trial, deucravacitinib, an oral, selective, allosteric TYK2 inhibitor, reduced IL-23/Th17 and type-I interferon pathway expression in the skin of patients with moderate to severe plaque psoriasis, reductions that were accompanied by clinical improvement of psoriatic lesions. OBJECTIVES: The aim of this study was to identify biomarkers of psoriatic disease in serum from patients enrolled in the phase 2 trial and to assess the effects of deucravacitinib on those biomarkers. METHODS: Serum biomarkers from Olink proteomics and other quantitative assays were evaluated for a pharmacodynamic response to deucravacitinib treatment and correlation with psoriasis disease activity measures. RESULTS: Serum biomarkers associated with the IL-23/Th17 pathway [IL-17A, IL-17C, IL-19, IL-20, beta-defensin, and peptidase inhibitor 3 (PI3)] were upregulated in patients with psoriasis versus healthy controls. Deucravacitinib treatment reduced IL-17A (adjusted mean change from baseline at Day 85; 12 mg once daily versus placebo; -0.240 versus -0.067), IL-17C (-14.850 versus -1.664), IL-19 (-96.445 versus -8.119), IL-20 (-0.265 versus -0.064), beta-defensin (-65,025.443 versus -7553.961), and PI3 (-14.005 versus -1.360) expression. Reductions in serum biomarker expression occurred in a dose- and time-dependent manner, with significant reductions from baseline seen with deucravacitinib doses ≥ 3 mg twice daily (P ≤ 0.05). Biomarker expression correlated with disease activity measures such as Psoriasis Area and Severity Index (PASI) at baseline. Biomarker expression also correlated with PASI scores at Week 12. CONCLUSION: IL-23/Th17 pathway expression in the serum of patients with psoriasis is an indicator of disease activity and response to deucravacitinib treatment. TRIAL REGISTRATION NUMBER: NCT02931838.


Plaque psoriasis is a long-term disease that causes inflammation, scaling, and itching of the skin. Compared with healthy volunteers without psoriasis, patients with psoriasis have higher amounts of certain biomarkers (molecules that indicate what is happening in the body) in their blood that are associated with inflammation. Higher amounts of these biomarkers are also associated with more severe psoriasis. In a study of patients with psoriasis, those who received the oral drug deucravacitinib had lower amounts of biomarkers after 12 weeks of treatment compared with patients who received a placebo (a lookalike pill that contains no medicine). Patients who were treated with deucravacitinib also saw an improvement in their psoriasis after 12 weeks compared with patients who received placebo.

3.
Heliyon ; 10(17): e37319, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-39296065

RESUMEN

The organism's normal physiological function is greatly impacted in a febrile environment, leading to the manifestation of pathological conditions including elevated body temperature, dehydration, gastric bleeding, and spermatogenic dysfunction. Numerous lines of evidence indicate that heat stress significantly impacts the brain's structure and function. Previous studies have demonstrated that both animals and humans experience cognitive impairment as a result of exposure to high temperatures. However, there is a lack of research on the effects of prolonged exposure to high-temperature environments on learning and memory function, as well as the underlying molecular regulatory mechanisms. In this study, we examined the impact of long-term heat stress exposure on spatial memory function in rats and conducted transcriptome sequencing analysis of rat hippocampal tissues to identify the crucial molecular targets affected by prolonged heat stress exposure. It was found that the long-term heat stress impaired rats' spatial memory function due to the pathological damages and apoptosis of hippocampal neurons at the CA3 region, which is accompanied with the decrease of growth hormone level in peripheral blood. RNA sequencing analysis revealed the signaling pathways related to positive regulation of external stimulation response and innate immune response were dramatically affected by heat stress. Among the verified differentially expressed genes, the knockdown of Arhgap36 in neuronal cell line HT22 significantly enhances the cell apoptosis, suggesting the impaired spatial memory induced by long-term heat stress may at least partially be mediated by the dysregulation of Arhgap36 in hippocampal neurons. The uncovered relationship between molecular changes in the hippocampus and behavioral alterations induced by long-term heat stress may offer valuable insights for the development of therapeutic targets and protective drugs to enhance memory function in heat-exposed individuals.

4.
Clin Breast Cancer ; 2024 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-39289111

RESUMEN

BACKGROUND: Nipple-sparing mastectomy (NSM) and skin-sparing mastectomy (SSM) are challenging for surgical training among fellow trainees. We developed a surgical training course with novel concept of breast modular resection (BMR) for NSM/SSM procedure, and performed this study to investigate whether BMR could improve surgical outcomes compared to classical procedure resection (CPR). METHODS: The records of 105 breast cancer patients undergoing NSM/SSM with immediate reconstruction performed by fellow trainees were reviewed. Clinicopathological characteristics and surgical outcomes were compared between 2 groups. Laser speckle contrast imaging (LSCI) was performed to intraoperatively evaluate the blood supply of the NAC, and the absolute perfusion unit (PU) values and relative perfusion unit (rPU) values were further compared. RESULTS: Surgical training outcomes of BMR group (N = 52) were insignificantly improved compared to CPR group (N = 53). The rates of NAC necrosis, flap necrosis and implant removal all reduced respectively. Among the 60 NSM patients, the blood loss (P = .011) and surgery time (P < .001) was significantly reduced in BMR group (N = 30) and all the other outcomes were insignificantly improved. Both the absolute PU values and rPU values were significantly higher among patients without NAC necrosis (P < .001). The absolute PU values were significantly higher in BMR group (P = .002). CONCLUSION: Compared to CPR, the BMR-based surgical training course for NSM demonstrated the reduction in complications and operating time, offering a potential streamlined, efficient, and safe method for NSM procedure. LSCI was effective for intraoperative visualized evaluation of NAC blood supply and could provide effective real-time feedback for fellow trainees.

5.
Small Methods ; : e2400525, 2024 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-39268793

RESUMEN

Mitochondria are essential organelles that not only undergo dynamic morphological changes but also exhibit functional activities such as mitochondrial membrane potential (MMP). While super-resolution techniques such as stimulated emission depletion (STED) nanoscopy can visualize the ultrastructure of mitochondria and the MMP probe can monitor mitochondria function, few dyes meet both demands. Here, a small molecule (MitoPDI-90) based on perylene diimide with cationic groups is reported and used for mitochondrial STED imaging and MMP indication. Characterized by excellent photostability, biocompatibility, and high quantum yield, MitoPDI-90 exhibits STED imaging compatibility, facilitating visualization of mitochondrial cristae and time-lapse imaging of highly dynamic mitochondria in living cells. Besides, MitoPDI-90 targets the mitochondria through electrical potential, also enabling live-cell MMP monitoring. MitoPDI-90 allows for super-resolution visualization and time-lapse imaging of mitochondria, and more importantly, indication of changes in MMP, providing insight into the functional activity of live-cell mitochondria.

7.
J Am Chem Soc ; 146(33): 23092-23102, 2024 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-39108025

RESUMEN

Enantiopure Si-stereogenic organosilanes are highly valued in the fields of organic synthesis, development of advanced materials, and drug discovery. However, they are not naturally occurring, and their synthesis has been largely confined to resolution of racemic silanes or desymmetrization of symmetric silanes. In contrast, the dynamic kinetic asymmetric transformation (DYKAT) of racemic organosilanes offers a mechanistically distinct approach and would broaden the accessibility of Si-stereogenic silanes in an enantioconvergent manner. In this study, we report a Lewis base-catalyzed DYKAT of racemic chlorosilanes. The chiral isothiourea catalyst, (S)-benzotetramisole, facilitates silyletherification with phenols, yielding (R)-silylethers in good yields with high enantioselectivity (27 examples, up to 86% yield, up to 98:2 er). Kinetic analysis, control experiments, and DFT calculations suggest that a two-catalyst-bound pentacoordinate silicate is responsible for the Si-configurational epimerization of the ion-paired tetracoordinated silicon intermediates.

8.
Mol Divers ; 2024 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-39207663

RESUMEN

Idiopathic Pulmonary Fibrosis (IPF) is a disease characterized by pulmonary interstitial fibrosis and collagen proliferation, currently lacking effective therapeutic options. The combined use of Celastrol and Ligustrazine has been proved to synergistically improve the pathological processes of inflammation and fibrosis. In earlier studies, we designed and synthesized a Celastrol-Ligustrazine compound CL-001, though its role in IPF remains unclear. Here, the effects and mechanisms of CL-001 in bleomycin (BLM)-induced IPF were investigated. In vivo, CL-001 significantly improved lung function, reduced pulmonary inflammation, and decreased collagen deposition, thereby preventing the progression of IPF. In vitro, CL-001 concurrently inhibited both Smad-dependent and Smad-independent pathways, thereby suppressing TGF-ß1-induced epithelial-mesenchymal transition (EMT) and epithelial cell migration. This inhibitory effect was superior to that of Celastrol or Ligustrazine administered alone. Additionally, CL-001 significantly increased the level of apoptosis and promoted the expression of apoptosis-related proteins (Caspase-8 and PARP), ultimately leading to widespread apoptosis in activated lung epithelial cells. In summary, CL-001 exhibits excellent anti-IPF effects both in vitro and in vivo, suggesting its potential as a novel candidate drug for IPF, warranting further development.

9.
Artículo en Inglés, Chino | MEDLINE | ID: mdl-39183065

RESUMEN

Orthodontic treatment is a commonly utilized method for improving both facial aesthetics and occlusal function. During orthodontic treatment irregular, nodular labial protuberances on the labial side of the anterior teeth may occasionally occur, varying in number and size, which is closely connected to the differential bone remodeling patterns on the internal and external surfaces of the labial alveolar bone. Labial protuberances can not only affect the aesthetic results of orthodontic treatment, but also pose potential risks to periodontal health. Currently, it is believed that the influencing factors of the formation of the labial protuberances may be related to the patient's gender and age, tooth movement speed, and extent of anterior teeth retraction. Labial protuberances typically resolve spontaneously, however, if it is persistent, alveoloplasty may be necessary for treatment. This review provides a summary on the occurrence hypothesis, influencing factors of formation, potential biological mechanisms, and corresponding treatment methods of labial protuberances during orthodontic treatment.

10.
Mikrochim Acta ; 191(9): 566, 2024 08 28.
Artículo en Inglés | MEDLINE | ID: mdl-39196453

RESUMEN

Staphylococcus aureus (S. aureus) is a common foodborne pathogen, posing a serious threat to public health. Consequently, it is crucial to establish a platform for sensitive and specific determination of S. aureus in food. Herein, phage SapYZUH5, isolated by our lab, was covalently immobilized on Co3O4 to synthesize SapYZUH5@Co3O4. Notably, SapYZUH5@Co3O4 exhibited remarkable oxidase-like activity, enabling the catalysis of dissolved oxygen to generate superoxide anion free radicals and accelerate the TMB chromogenic reaction. Upon introduction of S. aureus, specific capture by SapYZUH5@Co3O4 resulted in inhibiting its oxidase-like activity and decelerating the 3,3',5,5'-tetramethylbenzidine (TMB) chromogenic reaction. Moreover, S. aureus can be lysed to release the reductive bacterial contents, which can further inhibit the TMB chromogenic reaction. Based on this principle, SapYZUH5@Co3O4 + TMB reaction system was employed for detection with enhanced sensitivity of S. aureus, yielding an equation: A = - 0.092 Log (CSA) + 0.79 (R2 = 0.987), with an ultralow limit of detection (LOD) of 28 CFU mL-1. This system exhibited remarkable specificity and anti-interfere towards S. aureus, owing to the excellent affinity of SapYZUH5 towards S. aureus. In addition, S. aureus in the actual food samples was detected using this system, yielding recoveries ranging from 96.34 to 109.43%, demonstrating its exceptional accuracy. Hence, our proposed covalent immobilization of phage on the nanozyme can realize sensitive and specific colorimetric determination of S. aureus in food samples.


Asunto(s)
Bencidinas , Cobalto , Colorimetría , Límite de Detección , Óxidos , Staphylococcus aureus , Staphylococcus aureus/aislamiento & purificación , Colorimetría/métodos , Cobalto/química , Óxidos/química , Bencidinas/química , Contaminación de Alimentos/análisis , Técnicas Biosensibles/métodos , Microbiología de Alimentos
11.
Physiol Plant ; 176(4): e14434, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38981863

RESUMEN

Anthocyanin is a type of plant secondary metabolite beneficial to human health. The anthocyanin content of vegetable and fruit crops signifies their nutritional quality. However, the molecular mechanism of anthocyanin accumulation, especially tissue-specific accumulation, in Caitai, as well as in other Brassica rapa varieties, remains elusive. In the present study, taking advantage of three kinds of Caitai cultivars with diverse colour traits between leaves and stems, we conducted a comparative transcriptome analysis and identified the molecular pathway of anthocyanin biosynthesis in Caitai leaves and stems, respectively. Our further investigations demonstrate that bHLH42, which is robustly induced by MeJA, closely correlates with tissue-specific accumulation of anthocyanins in Caitai; bHLH42 upregulates the expression of flavonoid/anthocyanin biosynthetic pathway genes to activate anthocyanin biosynthesis pathway, importantly, overexpression of bHLH42 significantly improves the anthocyanin content of Caitai. Our analysis convincingly suggests that bHLH42 induced by jasmonic acid signalling plays a crucial role in tissue-specific accumulation of anthocyanins in Caitai.


Asunto(s)
Acetatos , Antocianinas , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico , Ciclopentanos , Flavonoides , Regulación de la Expresión Génica de las Plantas , Oxilipinas , Proteínas de Plantas , Antocianinas/metabolismo , Ciclopentanos/metabolismo , Oxilipinas/metabolismo , Flavonoides/metabolismo , Acetatos/metabolismo , Acetatos/farmacología , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Hojas de la Planta/metabolismo , Hojas de la Planta/genética , Reguladores del Crecimiento de las Plantas/metabolismo
12.
Biosens Bioelectron ; 262: 116573, 2024 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-39018976

RESUMEN

Drug-induced liver injury (DILI) poses a severe threat to public health. Endoplasmic reticulum (ER) stress contributes significantly to DILI pathogenesis, with peroxynitrite (ONOO-) identified as a pivotal indicator. However, the temporal and spatial fluctuations of ONOO- associated with ER stress in the pathogenesis of DILI remain unclear. Herein, a novel ER-specific near-infrared (NIR) probe (QM-ONOO) with aggregation-induced emission (AIE) features for monitoring ONOO- fluctuations in DILI was elaborately constructed. QM-ONOO exhibited excellent ER-targeting specificity, a large Stoke's shift, and a low detection limit (26.9 nM) toward ONOO-. QM-ONOO performed well in imaging both exogenous and endogenous ONOO- in HepG2 cells. Furthermore, molecular docking calculations validated the ER-targeting mechanism of QM-ONOO. Most importantly, using this probe allowed us to intuitively observe the dynamic fluctuations of ONOO- during the formation and remediation processes of DILI in the acetaminophen (APAP)-induced mouse model. Consequently, this work provides a promising tool for in-depth research of ONOO- associated pathological processes in DILI.


Asunto(s)
Acetaminofén , Enfermedad Hepática Inducida por Sustancias y Drogas , Retículo Endoplásmico , Colorantes Fluorescentes , Ácido Peroxinitroso , Ácido Peroxinitroso/metabolismo , Ácido Peroxinitroso/química , Humanos , Animales , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Colorantes Fluorescentes/química , Retículo Endoplásmico/metabolismo , Ratones , Células Hep G2 , Acetaminofén/toxicidad , Acetaminofén/efectos adversos , Técnicas Biosensibles/métodos , Estrés del Retículo Endoplásmico/efectos de los fármacos , Simulación del Acoplamiento Molecular , Imagen Óptica/métodos
13.
BMC Geriatr ; 24(1): 569, 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38956519

RESUMEN

BACKGROUND: Obstructive sleep apnea (OSA) was associated with the increased cardiovascular events and all-cause mortality. And anti-inflammatory dietary has potential to improve the prognosis of OSA. This study aimed to investigate the association of anti-inflammatory dietary patterns with all-cause mortality among individuals with OSA. METHODS: This retrospective cohort study involved 1522 older adults with OSA from 2005 to 2008 in the National Health and Nutrition Examinations Survey (NHANES). Mortality status was determined by routine follow-up through December 31, 2019, using the National Death Index. Anti-inflammatory dietary patterns included Alternate Mediterranean Diet Score (aMED), Healthy Eating Index-2015 (HEI-2015), and Alternate Healthy Eating Index-2010 (AHEI-2010). Weighted Cox proportional hazard regression models were performed to investigate the association between anti-inflammatory dietary pattern and all-cause mortality. RESULTS: After a median follow-up of 131 months, 604 participants were recorded all-cause mortality. The mean age of OSA patients was 68.99 years old, of whom 859 were male (52.34%). Higher adherence of aMED (HR = 0.61, 95%CI: 0.48 to 0.78) and HEI-2015 (HR = 0.75, 95%CI: 0.60 to 0.95) were associated with lower all-cause mortality risk in the elderly with OSA. Conversely, no association was found between AHEI-2010 dietary pattern and all-cause mortality in individuals with OSA. In the component analysis of aMED, it was found that a higher intake of vegetables and olive oil potentially contributes to the reduction all-cause mortality risk in the elderly with OSA (HR = 0.60, 95%CI: 0.48 to 0.76; HR = 0.67, 95%CI: 0.63 to 0.71). CONCLUSION: Higher adherence to the aMED and the HEI-2015 was associated with a lower risk of all-cause mortality in OSA. Future interventions in the elderly with OSA should considering adopting anti-inflammatory dietary patterns.


Asunto(s)
Apnea Obstructiva del Sueño , Humanos , Apnea Obstructiva del Sueño/mortalidad , Apnea Obstructiva del Sueño/epidemiología , Masculino , Femenino , Estudios Retrospectivos , Anciano , Encuestas Nutricionales/métodos , Dieta Mediterránea , Causas de Muerte/tendencias , Dieta Saludable/tendencias , Persona de Mediana Edad , Factores de Riesgo , Mortalidad/tendencias , Patrones Dietéticos
14.
Phytochemistry ; 226: 114206, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38972440

RESUMEN

Eighteen compounds including eleven previously undescribed diterpenes were isolated from the leaves of Croton mangelong. The structures were determined by HRESIMS, IR, NMR, X-ray diffraction and ECD spectroscopic analysis. All isolates were assayed for their anti-hyperglycemic activities in insulin resistance (IR) 3T3-L1 adipocytes, and compound 4 was tested for its anti-diabetic activity in vivo. Results suggested compound 4 could effectively reduce blood glucose level in diabetic SD rats in a dose of 30 mg/kg.


Asunto(s)
Células 3T3-L1 , Croton , Diterpenos , Hipoglucemiantes , Hojas de la Planta , Ratas Sprague-Dawley , Hojas de la Planta/química , Diterpenos/farmacología , Diterpenos/química , Diterpenos/aislamiento & purificación , Croton/química , Animales , Ratones , Hipoglucemiantes/farmacología , Hipoglucemiantes/química , Hipoglucemiantes/aislamiento & purificación , Ratas , Estructura Molecular , Diabetes Mellitus Experimental/tratamiento farmacológico , Masculino , Resistencia a la Insulina , Glucemia/efectos de los fármacos , Adipocitos/efectos de los fármacos
15.
Int J Ophthalmol ; 17(7): 1273-1282, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39026905

RESUMEN

AIM: To evaluate the trending visual performance of different intraocular lenses (IOLs) over time after implantation. METHODS: Ninety-one patients received cataract surgery with implantations of monofocal (Mon) IOLs, segmental refractive (SegRef) IOLs, diffractive (Dif) IOLs, and extended-depth-of-focus (EDoF) IOLs were included. The aberrations and optical quality collected with iTrace and OQAS within postoperative 6mo were followed and compared. RESULTS: Most of the visual parameters improved over the postoperative 6mo. The postoperative visual acuity (POVA) of the Mon IOL, SegRef IOL, and EDoF IOL groups achieved relative stability in earlier states compared with the Dif IOL group. Nevertheless, the overall visual performance of the 3 IOLs continued to upturn in small extents within the postoperative 6mo. The optical quality initially improved in the EDoF IOL group, then in the Mon IOL, SegRef IOL, and Dif IOL groups. POVA and objective visual performance of the Mon IOL and EDoF IOL groups, as well as POVA and visual quality of the Dif IOL group, improved in the postoperative 1mo and stabilized. Within the postoperative 6mo, gradual improvements were observed in the visual acuity and objective visual performance of the SegRef IOL group, as well as in the postoperative optical quality of the Dif IOL group. CONCLUSION: The visual performance is different among eyes implanted with different IOLs. The findings of the current study provide a potential reference for ophthalmologists to choose suitable IOLs for cataract patients in a personalized solution.

16.
ACS Infect Dis ; 10(8): 2705-2716, 2024 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-38989983

RESUMEN

The development of new effective antifungal agents is essential to combat fungal infections. Tetrahydrocarbazole has been exploited as a promising skeleton against various pathogenic microorganisms and is used to search for novel active antifungal compounds. In this study, a library composed of small tetrahydrocarbazole compounds was screened, and a potent antifungal agent, CAR-8, was identified with a minimum inhibitory concentration of 2-4 µg/mL against Candida albicans. CAR-8 showed strong fungicidal activities and killed almost all C. albicans within 3 h at a concentration of 16 µg/mL. At concentrations of 2 and 8 µg/mL, CAR-8 significantly inhibited the formation of hyphae and biofilms. Moreover, CAR-8 at 10 and 20 mg/kg reduced the fungal load and improved the survival in the C. albicans infection model in the invertebrate Galleria mellonella. Transcriptome analysis revealed significant changes in the expression of genes associated with protein processing in the endoplasmic reticulum (ER), ER-associated degradation, and unfolded protein response (UPR), which suggested that CAR-8 treatment induced ER stress. Moreover, CAR-8 treatment resulted in various phenotypes similar to tunicamycin, a classical ER stress inducer. These included nonconventional splicing of HAC1 mRNA, the fragmented morphology of ER, the distribution changes of GFP-Snc1 in Saccharomyces cerevisiae, and cell apoptosis probably caused by ER stress. More importantly, the disruption of IRE1 or HAC1 increased the sensitivity of C. albicans to CAR-8, confirming that the UPR signaling pathway was critical for CAR-8 resistance. Overall, our study identifies a potent ER stress-induced antifungal compound that will help the discovery of new antifungal drugs.


Asunto(s)
Antifúngicos , Candida albicans , Carbazoles , Estrés del Retículo Endoplásmico , Pruebas de Sensibilidad Microbiana , Antifúngicos/farmacología , Candida albicans/efectos de los fármacos , Estrés del Retículo Endoplásmico/efectos de los fármacos , Carbazoles/farmacología , Animales , Biopelículas/efectos de los fármacos , Candidiasis/microbiología , Candidiasis/tratamiento farmacológico , Respuesta de Proteína Desplegada/efectos de los fármacos , Hifa/efectos de los fármacos
17.
Funct Integr Genomics ; 24(4): 118, 2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-38935217

RESUMEN

Lung adenocarcinoma (LUAD) has a malignant characteristic that is highly aggressive and prone to metastasis. There is still a lack of suitable biomarkers to facilitate the refinement of precision-based therapeutic regimens. We used a combination of 10 known clustering algorithms and the omics data from 4 dimensions to identify high-resolution molecular subtypes of LUAD. Subsequently, consensus machine learning-related prognostic signature (CMRS) was developed based on subtypes related genes and an integrated program framework containing 10 machine learning algorithms. The efficiency of CMRS was analyzed from the perspectives of tumor microenvironment, genomic landscape, immunotherapy, drug sensitivity, and single-cell analysis. In terms of results, through multi-omics clustering, we identified 2 comprehensive omics subtypes (CSs) in which CS1 patients had worse survival outcomes, higher aggressiveness, mRNAsi and mutation frequency. Subsequently, we developed CMRS based on 13 key genes up-regulated in CS1. The prognostic predictive efficiency of CMRS was superior to most established LUAD prognostic signatures. CMRS demonstrated a strong correlation with tumor microenvironmental feature variants and genomic instability generation. Regarding clinical performance, patients in the high CMRS group were more likely to benefit from immunotherapy, whereas low CMRS were more likely to benefit from chemotherapy and targeted drug therapy. In addition, we evaluated that drugs such as neratinib, oligomycin A, and others may be candidates for patients in the high CMRS group. Single-cell analysis revealed that CMRS-related genes were mainly expressed in epithelial cells. The novel molecular subtypes identified in this study based on multi-omics data could provide new insights into the stratified treatment of LUAD, while the development of CMRS could serve as a candidate indicator of the degree of benefit of precision therapy and immunotherapy for LUAD.


Asunto(s)
Adenocarcinoma del Pulmón , Inmunoterapia , Neoplasias Pulmonares , Aprendizaje Automático , Microambiente Tumoral , Humanos , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/tratamiento farmacológico , Adenocarcinoma del Pulmón/inmunología , Adenocarcinoma del Pulmón/terapia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/patología , Pronóstico , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Regulación Neoplásica de la Expresión Génica , Genómica , Multiómica
18.
Seizure ; 120: 104-109, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38941800

RESUMEN

PURPOSE: To investigate glymphatic function by Virchow-Robin space (VRS) counts and volume in patients with newly diagnosed self-limited epilepsy with centrotemporal spikes (SeLECTS) and evaluate its relationship with structural connectivity and cognitive impairment. METHODS: Thirty-two children with SeLECTS and thirty-two age- and sex-matched typically developing (TD) children were enrolled in this study. VRS counts and volume were quantified. Structural networks were constructed and the topological metrics were analyzed. Wechsler Intelligence Scale (WISC) was used to assess cognitive function in all participants. Correlation analysis assessed the association between VRS counts and volume, network connectivity, and cognitive impairment. Mediation effects of topological metrics of the structural networks on the relationship between glymphatic function and cognitive impairment were explored. RESULTS: Patients with SeLECTS showed a higher VRS counts, VRS volume, and global shortest path length (Lp); they also showed a lower global efficiency (Eg). VRS counts and volume were significantly correlated with full-scale intelligence quotient (FIQ) (r_VRS counts = -0.520, r_VRS volume = -0.639), performance intelligence quotient (PIQ) (r_VRS counts = -0.693, r_VRS volume = -0.597), verbal intelligence quotient (VIQ) (r_VRS counts = -0.713, r_VRS volume = -0.699), Eg (r_VRS counts = -0.499, r_VRS volume = -0.490), and Lp (r_VRS volume = 0.671) in patients with SeLECTS. Eg mediated 24.59% of the effects for the relationship between VRS volume and FIQ. CONCLUSION: Glymphatic function may be impaired in SeLECTS reflected by VRS counts and volume. Glymphatic dysfunction may result in cognitive impairment by disrupting structural connectivity in SeLECTS.


Asunto(s)
Epilepsia Rolándica , Sistema Glinfático , Humanos , Masculino , Femenino , Niño , Epilepsia Rolándica/fisiopatología , Sistema Glinfático/fisiopatología , Imagen por Resonancia Magnética , Disfunción Cognitiva/fisiopatología , Disfunción Cognitiva/etiología , Encéfalo/fisiopatología , Encéfalo/diagnóstico por imagen , Cognición/fisiología , Escalas de Wechsler , Adolescente
19.
Genome Biol ; 25(1): 157, 2024 06 14.
Artículo en Inglés | MEDLINE | ID: mdl-38877540

RESUMEN

Methylation-based liquid biopsies show promises in detecting cancer using circulating cell-free DNA; however, current limitations impede clinical application. Most assays necessitate substantial DNA inputs, posing challenges. Additionally, underrepresented tumor DNA fragments may go undetected during exponential amplification steps of traditional sequencing methods. Here, we report linear amplification-based bisulfite sequencing (LABS), enabling linear amplification of bisulfite-treated DNA fragments in a genome-wide, unbiased fashion, detecting cancer abnormalities with sub-nanogram inputs. Applying LABS to 100 patient samples revealed cancer-specific patterns, copy number alterations, and enhanced cancer detection accuracy by identifying tissue-of-origin and immune cell composition.


Asunto(s)
Metilación de ADN , Neoplasias , Análisis de Secuencia de ADN , Sulfitos , Humanos , Neoplasias/genética , Análisis de Secuencia de ADN/métodos , Ácidos Nucleicos Libres de Células , Técnicas de Amplificación de Ácido Nucleico/métodos , Variaciones en el Número de Copia de ADN , ADN de Neoplasias/genética , ADN Tumoral Circulante/genética
20.
Microorganisms ; 12(6)2024 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-38930444

RESUMEN

Halo-alkali soil threatens agriculture, reducing growth and crop yield worldwide. In this study, physicochemical and molecular techniques were employed to explore the potential of halo-alkali-tolerant endophytic bacteria strains Sphingomonas sp. pp01, Bacillus sp. pp02, Pantoea sp. pp04, and Enterobacter sp. pp06 to enhance the growth of hybrid Pennisetum under varying saline conditions. The strains exhibited tolerance to high salt concentrations, alkaline pH, and high temperatures. Under controlled conditions, all four strains showed significant growth-promoting effects on hybrid Pennisetum inoculated individually or in combination. However, the effects were significantly reduced in coastal saline soil. The best growth-promoting effect was achieved under greenhouse conditions, increasing shoot fresh and dry weights of hybrid Pennisetum by up to 457.7% and 374.7%, respectively, using irrigating trials. Metagenomic sequencing analysis revealed that the diversity and composition of rhizosphere microbiota underwent significant changes after inoculation with endophytic bacteria. Specifically, pp02 and co-inoculation significantly increased the Dyella and Pseudomonas population. Firmicutes, Mycobacteria, and Proteobacteria phyla were enriched in Bacillus PP02 samples. These may explain the best growth-promoting effects of pp02 and co-inoculation on hybrid Pennisetum under greenhouse conditions. Our findings reveal the performance of endophytic bacterial inoculants in enhancing beneficial microbiota, salt stress tolerance, and hybrid Pennisetum growth.

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