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1.
Paediatr Anaesth ; 2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39291464

RESUMEN

BACKGROUND: Pediatric surgery is associated with high levels of anxiety for both children and parents/caregivers. To mitigate anxiety, auricular acupuncture has shown its potential in the perioperative setting. Accordingly, our team developed a wearable prototype auricular laser acupuncture system, AcuHealth V1.0, as a portable acupuncture device and conducted a proof-of-concept evaluation with parents of children undergoing surgery. AIMS: The primary aim of this study was to conduct feasibility testing of the AcuHealth V1.0 system in delivering auricular laser acupuncture. METHODS: Parents of children who were scheduled to undergo outpatient surgery were randomly assigned to one of three groups: authentic acupuncture (laser beams at known anxiolytic acupoints, n = 13), sham acupuncture (non-anxiolytic acupoints, n = 14), or a placebo control group (inactive laser, n = 14). Parent self-reported anxiety (0-10 numerical rating scale) was assessed at baseline, pre-intervention (once child was taken to the OR), post-intervention, and at 30 min after the intervention. Usability and acceptability data regarding the device were assessed after the intervention. RESULTS: Baseline data revealed no significant difference in anxiety between the three groups. Parent-reported anxiety level at 30-min post-intervention as compared to baseline in the authentic group was significantly decreased (delta mean ± std = -3.58 ± 2.07) compared to both the sham acupuncture (-1.35 ± 2.65) and placebo control group (0.54 ± 1.13). Evaluation of changes in parent-reported anxiety between groups over time using two-way repeated-measures analysis of variance (ANOVA) revealed a significant difference between the three groups (p = 0.001). Post hoc analysis with Scheffe test pairwise comparisons showed that at 30-min post-intervention compared to baseline, the authentic intervention group was significantly less anxious compared with both the sham group (p = 0.033) and the placebo control group (p = 0.001). Additionally, feedback regarding the usage of the device supported the acceptability and usability of the device with no adverse events. CONCLUSIONS: This pilot study administering laser auricular acupuncture via the AcuHealth V1.0 system decreased parental anxiety after 30 min in parents who received treatment immediately after their children were taken to the operating room with no adverse effect.

2.
Front Pharmacol ; 15: 1448319, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39268473

RESUMEN

Objective: Addressing the rising prevalence of pain disorders and limitations of current analgesics, our study explores repurposing antihypertensive drugs for pain management, inspired by the link between hypertension and pain. We leverage a drug-target Mendelian Randomization (MR) approach to explore their dual benefits and establish causal connections. Methods: A comprehensive compilation of antihypertensive drug classes was undertaken through British National Formulary, with their target genes identified using the DrugBank database. Relevant single nucleotide polymorphisms (SNPs) associated with these targets were selected from published genomic studies on systolic blood pressure (SBP) as genetic instruments. These SNPs were validated through MR against acute coronary artery disease (CAD) to ensure genes not linked to CAD were excluded from acting as proxies for antihypertensive drugs. An MR analysis of 29 pain-related outcomes was conducted using the FinnGen R10 database employing the selected and validated genetic instruments. We utilized the Inverse Variance Weighted (IVW) method for primary analysis, applying Bonferroni correction to control type I error. IVW's multiplicative random effects (MRE) addressed heterogeneity, and MR-PRESSO managed pleiotropy, ensuring accurate causal inference. Results: Our analysis differentiates strong and suggestive evidence in linking antihypertensive drugs to pain disorder risks. Strong evidence was found for adrenergic neuron blockers increasing migraine without aura risk, loop diuretics reducing panniculitis, and vasodilator antihypertensives lowering limb pain risk. Suggestive evidence suggests alpha-adrenoceptor blockers might increase migraine risk, while beta-adrenoceptor blockers could lower radiculopathy risk. Adrenergic neuron blockers also show a potential protective effect against coxarthrosis (hip osteoarthritis) and increased femgenpain risk (pain and other conditions related to female genital organs and menstrual cycle). Additionally, suggestive links were found between vasodilator antihypertensives and reduced radiculopathy risk, and both alpha-adrenoceptor blockers and renin inhibitors possibly decreasing dorsalgianas risk (unspecified dorsalgia). These findings highlight the intricate effects of antihypertensive drugs on pain disorders, underlining the need for further research. Conclusion: The findings indicate that antihypertensive medications may exert varied effects on pain management, suggesting a repurposing potential for treating specific pain disorders. The results advocate for further research to confirm these associations and to explore underlying mechanisms, to optimize pain management practices.

3.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 32(4): 1207-1211, 2024 Aug.
Artículo en Chino | MEDLINE | ID: mdl-39192421

RESUMEN

OBJECTIVE: To explore the causes of platelet aggregation in version 6.4 Trima Accel automated blood collection system and the effect of 2 intervention measures. METHODS: The data on platelet aggregation (n=61) and non-aggregation (n=323) of 61 donors in 2020 were collected and the causes of aggregation were analyzed. Then the 72 donors with platelet aggregation in 2021 were randomized into intervention group A (increasing the anticoagulant-to-blood ratio) and intervention group B (wrapping the donor's arm with an electric blanket to keep warm and improve the blood flow speed). The collection time, average blood flow speed, number of machine alarms, anticoagulant usage, deaggregation and citrate reaction of the two groups were compared. RESULTS: Platelet aggregation was negatively correlated with the average blood flow speed (r =-0.394) and positively correlated with the collection time (r =0.458). The equations for predicting aggregation and non-aggregation were constructed based on Bayesian and Fisher discriminant analysis, and the predicted accuracy was 77.1%. The comparison of the effects of two intervention measures showed that the average blood flow speed in group B was higher than that in group A; the collection time, number of machine alarms, anticoagulant usage and proportion of citrate reaction in blood donors in group B were all lower than those in Group A, all these differences were significant (P < 0.05). In the entire cohort in 2021, 90.28% of the products were immediately deaggregated after collection, and 9.72% of the products were deaggregated within 4 hours. There was no statistically significant difference in deaggregation between the two intervention groups (P >0.05). CONCLUSION: During apheresis platelet collection, the predictive equations for aggregation and non-aggregation can be used to predict the occurrence probability of aggregation, and the intervention can be made in advance. Both intervention measures are effective in reducing platelet aggregation, however, measure B has the advantages of improving the speed of blood collection, shortening the collection time, reducing the alarm frequency and the anticoagulant usage, and reducing the incidence of citrate reaction in blood donors.


Asunto(s)
Anticoagulantes , Agregación Plaquetaria , Humanos , Donantes de Sangre , Plaquetoferesis
4.
Nurs Health Sci ; 26(3): e13150, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39103223

RESUMEN

This study investigated sex differences perceived relocation stress and glycemic control among older adults with type 2 diabetes in long-term care facilities. A cross-sectional correlation design was used to recruit 120 residents during their first year after moving into the facilities in southern Taiwan. The results showed that almost two-thirds of the participants (64.2%) were women. The mean age was 79.62 (SD = 1.71). Older women with diabetes were reported to have significantly lower levels of education and poor glycemic control but higher levels of perceived relocation stress than men; however, functional independence was significantly higher in men. Although perceived relocation stress significantly predicted HbA1c levels in both women and men, length of stay was also significant in predicting HbA1c levels in women. These findings indicate the need for effective physical and psychological measures to improve glycemic control during the first year of stay in long-term care facilities.


Asunto(s)
Diabetes Mellitus Tipo 2 , Control Glucémico , Estrés Psicológico , Humanos , Femenino , Masculino , Anciano , Estudios Transversales , Control Glucémico/métodos , Control Glucémico/psicología , Taiwán , Diabetes Mellitus Tipo 2/psicología , Diabetes Mellitus Tipo 2/terapia , Estrés Psicológico/psicología , Anciano de 80 o más Años , Factores Sexuales , Cuidados a Largo Plazo/métodos , Cuidados a Largo Plazo/psicología , Cuidados a Largo Plazo/normas , Cuidados a Largo Plazo/estadística & datos numéricos , Hemoglobina Glucada/análisis , Glucemia/análisis
5.
J Cancer ; 15(15): 4902-4921, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39132155

RESUMEN

Colorectal cancer (CRC) is a common malignant tumor and is one of the three most common cancers worldwide. Traditional surgical treatment, supplemented by chemotherapy and radiotherapy, has obvious side effects on patients. Immunotherapy may lead to some unpredictable complications. Low introduction rate and high cost are some of the problems of gene therapy, so finding a safe, reliable and least toxic treatment method became the main research direction for this study. Lactic acid bacteria and their metabolites are widely used in functional foods or as adjuvant therapies for various diseases because they are safe to eat and have no adverse reactions. Research has shown that lactic acid bacteria and their metabolites play an auxiliary therapeutic role in colorectal cancer mainly by improving the intestinal flora composition, inhibiting the growth of pathogenic bacteria and inhibiting the proliferation of cancer cells. It is now widely believed that the substances that probiotics such as lactic acid bacteria exert anti-cancer effects are mainly secondary metabolites such as butyric acid. Lb. plantarum AY01 isolated from fermented food has good anti-cancer ability, and its main anti-cancer substance is 2'-deoxyinosine. Through flow cytometry detection, it was found that Lb. plantarum AY01 can block cell proliferation in the S phase. In addition, Lb. plantarum AY01 culture reduces the sensitivity of mice to colitis-associated CRC induced by azoxymethane (AOM)/dextran sulfate sodium salt (DSS) and exhibits the occurrence and promotion of tumors. According to transcriptome analysis, Lb. plantarum AY01 may induce apoptosis of colorectal cancer cells by activating the p38 MAPK pathway. This experiment provided possibilities for the treatment of CRC.

6.
Nano Lett ; 24(33): 10055-10061, 2024 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-39047260

RESUMEN

Nonlocal metasurfaces, exemplified by resonant waveguide gratings (RWGs), spatially and angularly configure optical wavefronts through narrow-band resonant modes, unlike the broad-band and broad-angle responses of local metasurfaces. However, forward design techniques for RWGs remain constrained at lower efficiency. Here, we present a topology-optimized metasurface resonant waveguide grating (MRWG) composed of titanium dioxide on a glass substrate capable of operating simultaneously at red, yellow, green, and blue wavelengths. Through adjoint-based topology optimization, while considering nonlocal effects, we significantly enhance its diffraction efficiency, achieving numerical efficiencies up to 78% and Q-factors as high as 1362. Experimentally, we demonstrated efficiencies of up to 59% with a Q-factor of 93. Additionally, we applied our topology-optimized metasurface to color selectivity, producing vivid colors at 4 narrow-band wavelengths. Our investigation represents a significant advancement in metasurface technology, with potential applications in see-through optical combiners and augmented reality platforms.

7.
Appl Microbiol Biotechnol ; 108(1): 427, 2024 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-39046587

RESUMEN

Filamentous fungi are prolific producers of bioactive natural products and play a vital role in drug discovery. Yet, their potential cannot be fully exploited since many biosynthetic genes are silent or cryptic under laboratory culture conditions. Several strategies have been applied to activate these genes, with heterologous expression as one of the most promising approaches. However, successful expression and identification of new products are often hindered by host-dependent factors, such as low gene targeting efficiencies, a high metabolite background, or a lack of selection markers. To overcome these challenges, we have constructed a Penicillium crustosum expression host in a pyrG deficient strain by combining the split-marker strategy and CRISPR-Cas9 technology. Deletion of ligD and pcribo improved gene targeting efficiencies and enabled the use of an additional selection marker in P. crustosum. Furthermore, we reduced the secondary metabolite background by inactivation of two highly expressed gene clusters and abolished the formation of the reactive ortho-quinone methide. Finally, we replaced the P. crustosum pigment gene pcr4401 with the commonly used Aspergillus nidulans wA expression site for convenient use of constructs originally designed for A. nidulans in our P. crustosum host strain. As proof of concept, we successfully expressed a single polyketide synthase gene and an entire gene cluster at the P. crustosum wA locus. Resulting transformants were easily detected by their albino phenotype. With this study, we provide a highly efficient platform for heterologous expression of fungal genes. KEY POINTS: Construction of a highly efficient Penicillium crustosum heterologous expression host Reduction of secondary metabolite background by genetic dereplication strategy Integration of wA site to provide an alternative host besides Aspergillus nidulans.


Asunto(s)
Sistemas CRISPR-Cas , Penicillium , Metabolismo Secundario , Penicillium/genética , Penicillium/metabolismo , Metabolismo Secundario/genética , Aspergillus nidulans/genética , Aspergillus nidulans/metabolismo , Sintasas Poliquetidas/genética , Sintasas Poliquetidas/metabolismo , Familia de Multigenes , Marcación de Gen/métodos , Regulación Fúngica de la Expresión Génica , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Vías Biosintéticas/genética , Ingeniería Metabólica/métodos , Expresión Génica
8.
Biomed Pharmacother ; 177: 117099, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38981240

RESUMEN

Immunogenic cell death (ICD) can activate adaptive immune response in the host with normal immune system. Some synthetic chemotherapeutic drugs and natural compounds have shown promising results in cancer treatment by triggering the release of damage-associated molecules (DAMPs) to trigger ICD. However, most chemotherapeutic drugs exhibit non-selective cytotoxicity and may also induce and promote metastasis, thereby significantly reducing their clinical efficacy. Among the natural compounds that can induce ICD, plant-derived compounds account for the largest proportion, which are of increasing value in the treatment of cancer. Understanding which plant-derived natural compounds can induce ICD and how they induce ICD is crucial for developing strategies to improve chemotherapy outcomes. In this review, we focus on the recent findings regarding plant-derived natural compounds that induce ICD according to the classification of flavonoids, alkaloids, glycosides, terpenoids and discuss the potential mechanisms including endoplasmic reticulum (ER) stress, DNA damage, apoptosis, necroptosis autophagy, ferroptosis. In addition, plant-derived natural compounds that can enhance the ICD induction ability of conventional therapies for cancer treatment is also elaborated. The rational use of plant-derived natural compounds to induce ICD is helpful for the development of new cancer treatment methods.


Asunto(s)
Muerte Celular Inmunogénica , Neoplasias , Humanos , Neoplasias/tratamiento farmacológico , Neoplasias/inmunología , Neoplasias/patología , Muerte Celular Inmunogénica/efectos de los fármacos , Animales , Estrés del Retículo Endoplásmico/efectos de los fármacos , Productos Biológicos/farmacología , Productos Biológicos/uso terapéutico , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/uso terapéutico , Apoptosis/efectos de los fármacos , Daño del ADN/efectos de los fármacos
9.
Org Lett ; 26(31): 6670-6674, 2024 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-39073982

RESUMEN

The great variety and fascinating complexity of terpenoid skeletons are achieved through different cyclizations catalyzed by terpene cyclases. Here, we report a sesquiterpene cyclase (MfdS) from Aspergillus ustus for the formation of malfilanol D, a member of the group of biochemically less investigated sesquiterpenes with a bicyclo[5.4.0]undecane skeleton. Feeding 13C-labeled acetates in Aspergillus nidulans with the mfdS sequence provides evidence for a C-1 to C-10 cyclization with subsequent 1,2-alkyl and 1,2-hydride shifts in the formation of the 6/7-fused rings.


Asunto(s)
Aspergillus , Sesquiterpenos , Aspergillus/química , Aspergillus/metabolismo , Sesquiterpenos/química , Sesquiterpenos/metabolismo , Estructura Molecular , Ciclización , Alcanos/química , Alcanos/metabolismo , Aspergillus nidulans/metabolismo , Aspergillus nidulans/química , Compuestos Bicíclicos con Puentes/química , Compuestos Bicíclicos con Puentes/metabolismo
10.
Plant Cell Environ ; 2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-39016637

RESUMEN

Wheat yellow mosaic virus (WYMV) causes severe viral wheat disease in Asia. The WYMV P1 protein encoded by RNA2 has viral suppressor of RNA silencing (VSR) activity to facilitate virus infection, however, VSR activity has not been identified for P2 protein encoded by RNA2. In this study, P2 protein exhibited strong VSR activity in Nicotiana benthamiana at the four-leaf stage, and point mutants P70A and G230A lost VSR activity. Protein P2 interacted with calmodulin (CaM) protein, a gene-silencing associated protein, while point mutants P70A and G230A did not interact with it. Competitive bimolecular fluorescence complementation and competitive co-immunoprecipitation experiments showed that P2 interfered with the interaction between CaM and calmodulin-binding transcription activator 3 (CAMTA3), but the point mutants P70A and G230A could not. Mechanical inoculation of wheat with in vitro transcripts of WYMV infectious cDNA clone further confirmed that VSR-deficient mutants P70A and G230A decreased WYMV infection in wheat plants compared with the wild type. In addition, RNA silencing, temperature, ubiquitination and autophagy had significant effects on accumulation of P2 protein in N. benthamiana leaves. In conclusion, WYMV P2 plays a VSR role in N. benthamiana and promotes virus infection by interfering with calmodulin-related antiviral RNAi defense.

11.
J Chin Med Assoc ; 87(9): 828-835, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-39017650

RESUMEN

BACKGROUND: Acute kidney injury (AKI) is a severe complication of coronavirus disease 2019 (COVID-19) and is associated with a higher risk of mortality. Understanding the risk factors contributing to COVID-19-related AKI and mortality before vaccination is important for the initiation of preventative measures and early treatment strategies. METHODS: This study included patients aged ≥18 years diagnosed with COVID-19 through polymerase chain reaction from May 2020 to July 2021, admitted in three local hospitals in Taiwan, with an extended follow-up until June 30, 2022. A median follow-up period of 250 days was used to assess AKI development and mortality. AKI was defined according to the Kidney Disease Improving Global Outcomes criteria. Multivarible Cox regression analysis of AKI and mortality-related risk factors were performed. RESULTS: Of the 720 hospitalized patients with COVID-19, 90 (22%) developed AKI. Moreover, 80%, 10.1%, and 8.9% of the patients had stage 1, 2, and 3 AKI, respectively. Patients with stage 1 to 3 AKI had significantly lower survival rates than those without AKI ( p = 0.001). The mean duration of post-admission AKI occurrence was 9.50 ± 11.32 days. Older age, hypoalbuminemia, and higher D-dimer and ferritin levels were associated with COVID-19 mortality. In COVID-19 AKI, in addition to older age and high D-dimer and ferritin levels, chronic kidney disease emerged as an independent risk factor. CONCLUSION: COVID-19-related AKI develops early, exhibits a temporal association with respiratory failure, and is linked to an unfavorable prognosis. The mortality rate increased according to the AKI stage ( p = 0.001). Age, albumin, D-dimer, and ferritin levels, and the underlying chronic kidney disease status upon admission are crucial factors for predicting AKI development, which increases the mortality risk. Monitoring the renal function not only within 10 days of COVID-19 onset, but also within 1 month after the disease onset.


Asunto(s)
Lesión Renal Aguda , COVID-19 , SARS-CoV-2 , Humanos , COVID-19/complicaciones , COVID-19/mortalidad , Lesión Renal Aguda/mortalidad , Lesión Renal Aguda/etiología , Masculino , Persona de Mediana Edad , Femenino , Factores de Riesgo , Anciano , Estudios de Seguimiento , Adulto , Vacunación
12.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 32(3): 883-889, 2024 Jun.
Artículo en Chino | MEDLINE | ID: mdl-38926984

RESUMEN

OBJECTIVE: To investigate the effects of mild SARS-CoV-2 infection on hematological parameters of adult blood donors and the suitability of apheresis platelet donation, the changes of the hematological parameters in blood donors with mild infection of the SARS-CoV-2 Omicron variant strain were evaluated. METHODS: Seventy-two blood donors with mild COVID-19 symptoms who donated consecutive apheresis platelets for 3 times from December 2022 to January 2023, 42 cases among which were included in the infection-positive group, and 30 cases in the suspected infection group. Forty-two donors un-vaccinated against SARS-CoV-2, un-infected, and donated three consecutive apheresis platelets from October to November 2022 were included in the control group. The changes of blood routine testing in the positive group and the suspected infection group were retrospectively compared before (Time1) and after (Time2 and Time3) the onset of symptoms, three consecutive times (Time1, Time2, Time3) in the control group by repeated measures analysis of variance. The Bayesian discriminant method was used to establish a discriminant equation to determine whether the recent infection of SARS-CoV-2 occurred or not. RESULTS: Simple effect of the number times of tests in the positive and suspected infection groups was significant( Finfection-positive group=6.98, P < 0.001, partial η2=0.79, Fsuspected infection group=4.31, P < 0.001, partial η2=0.70). The positive group and the suspected infection group had lower RBC, HCT, and HGB, and higher PLT and PCT at Time2 compared to Time1 and Time3(P < 0.05). The positive group and the suspected infection group showes RDW-CV and RDW-SD at Time3 higher than Time1 and Time2 (P < 0.001). The simple effect of the number times of tests in the control group was not significant ( F=0.96, P =0.55, partial η2=0.34). The difference of the whole blood count parameters in the control group for three times was not statistically significant (P >0.05). We established a discriminant equation to determine whether the recent infection of SARS-CoV-2 occurred or not. The equation had an eigenvalue of 0.22, a canonical correlation of 0.43 (χ2=27.81, P < 0.001), and an analysis accuracy of 72.9%. CONCLUSION: The hematological indicators of RBC, HCT, HGB, PLT, PCT, RDW-CV and RDW-SD in blood donors who had infected with mild COVID-19 showed dynamic changes. The discriminant equation for whether they are infected recently with COVID-19 has a high accuracy rate.


Asunto(s)
Donantes de Sangre , COVID-19 , Plaquetoferesis , SARS-CoV-2 , Humanos , COVID-19/sangre , Plaquetas , Estudios Retrospectivos , Recuento de Plaquetas , Adulto , Masculino
13.
Ann Rehabil Med ; 48(3): 220-227, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38830633

RESUMEN

OBJECTIVE: To construct a prognostic model for unsuccessful removal of nasogastric tube (NGT) was the aim of our study. METHODS: This study examined patients with swallowing disorders receiving NGT feeding due to stroke or traumatic brain injury in a regional hospital. Clinical data was collected, such as age, sex, body mass index (BMI), level of activities of daily living (ADLs) dependence. Additionally, gather information regarding the enhancement in Functional Oral Intake Scale (FOIS) levels and the increase in food types according to the International Dysphagia Diet Standardization Initiative (IDDSI) after one month of swallowing training. A stepwise logistic regression analysis model was employed to predict NGT removal failure using these parameters. RESULTS: Out of 203 patients, 53 patients (26.1%) had experienced a failed removal of NGT after six months of follow-up. The strongest predictors for failed removal were age over 60 years, underweight BMI, total dependence in ADLs, and ischemic stroke. The admission prediction model categorized patients into high, moderate, and low-risk groups for removal failure. The failure rate of NGT removal was high not only in the high-risk group but also in the moderate-risk groups when there was no improvement in FOIS levels and IDDSI food types. CONCLUSION: Our predictive model categorizes patients with brain insults into risk groups for swallowing disorders, enabling advanced interventions such as percutaneous endoscopic gastrostomy for high-risk patients struggling with NGT removal, while follow-up assessments using FOIS and IDDSI aid in guiding rehabilitation decisions for those at moderate risk.

14.
Phytochemistry ; 224: 114149, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38763314

RESUMEN

Farnesylated chalcones were favored by researchers due to their different biological activities. However, only five naturally occurring farnesylated chalcones were described in the literature until now. Here, the farnesylation of six chalcones by the Aspergillus terreus aromatic prenyltransferase AtaPT was reported. Fourteen monofarnesylated chalcones (1F1-1F5, 2F1-2F3, 3F1, 3F2, 4F1, 4F2, 5F1, 6F1, and 6F2) and a difarnesylated product (2F3) were obtained, enriching the diversity of natural farnesylated chalcones significantly. Ten of them are C-farnesylated products, which complement O-farnesylated chalcones by chemical synthesis. Fourteen products have not been reported prior to this study. Nine of the produced compounds (1F2-1F5, 2F1-2F3, 5F1, and 6F1) exhibited inhibitory effect on α-glucosidase with IC50 values ranging from 24.08 ± 1.44 to 190.0 ± 0.28 µM. Among them, compounds 2F3 with IC50 value at 24.08 ± 1.44 µM and 1F4 with IC50 value at 30.09 ± 0.59 µM showed about 20 times stronger than the positive control acarbose with an IC50 at 536.87 ± 24.25 µM in α-glucosidase inhibitory assays.


Asunto(s)
Aspergillus , Chalconas , Dimetilaliltranstransferasa , Dimetilaliltranstransferasa/metabolismo , Dimetilaliltranstransferasa/química , Dimetilaliltranstransferasa/antagonistas & inhibidores , Chalconas/química , Chalconas/farmacología , Chalconas/metabolismo , Aspergillus/enzimología , Aspergillus/química , Estructura Molecular , Prenilación , Relación Estructura-Actividad , Inhibidores de Glicósido Hidrolasas/química , Inhibidores de Glicósido Hidrolasas/farmacología , alfa-Glucosidasas/metabolismo , alfa-Glucosidasas/química , Relación Dosis-Respuesta a Droga
15.
J Am Chem Soc ; 146(20): 14357-14367, 2024 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-38726589

RESUMEN

Introducing dynamic behavior into periodic frameworks has borne fruit in the form of flexible porous crystals. The detailed molecular design of frameworks in order to control their collective dynamics is of particular interest, for example, to achieve stimulus-induced behavior. Herein, by varying the degree of rigidity of ditopic pillar linkers, two isostructural flexible metal-organic frameworks (MOFs) with common rigid supermolecular building bilayers were constructed. The subtle substitution of single (in bibenzyl-4,4'-dicarboxylic acid; H2BBDC) with double (in 4,4'-stilbenedicarboxylic acid; H2SDC) C-C bonds in pillared linkers led to markedly different flexible behavior of these two MOFs. Upon the removal of guest molecules, both frameworks clearly show reversible single-crystal-to-single-crystal transformations involving the cis-trans conformation change and a resulting swing of the corresponding pillar linkers, which gives rise to Flex-Cd-MOF-1a and Flex-Cd-MOF-2a, respectively. Strikingly, a more favorable gas-induced dynamic behavior in Flex-Cd-MOF-2a was verified in detail by stepwise C3H6/C3H8 sorption isotherms and the corresponding in situ powder X-ray diffraction experiments. These insights are strongly supported by molecular modeling studies on the sorption mechanism that explores the sorption landscape. Furthermore, a consistency between the macroscopic elasticity and microscopic flexibility of Flex-Cd-MOF-2 was observed. This work fuels a growing interest in developing MOFs with desired chemomechanical functions and presents detailed insights into the origins of flexible MOFs.

16.
Heliyon ; 10(9): e30012, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38707419

RESUMEN

Background: In this clinical trial, we evaluated the effects of transcutaneous electroacupoint stimulation (TEAS) on postoperative fatigue (POF) in Parkinson disease (PD) patients undergoing deep brain stimulation (DBS) surgery. Methods: A total 60 PD patients undergoing DBS surgery were enrolled. They were randomized to receive either electrical stimulation [alternative frequency 2/10 Hz, dense and disperse, intensity adjusted to the maximum tolerated by the participants (6-15 mAmp)] via surface electrodes (TEAS group) or surface electrodes only without electrical stimulation (Con group) at bilateral Zusanli and Sanyinjiao acupuncture points. All participants received their assigned intervention (TEAS or Con) during the 1st stage of surgery [(except during microelectrode recording (MER)] and the entire 2nd stage of surgery. Intraoperative anesthetic requirements were adjusted based on bispectral index (BIS) monitor. POF was assessed by Christensen fatigue scales (ChrFS), along with Quality of Recovery-15 (QoR-15) and mini-mental state examination (MMSE) postoperatively over a 7-day-period. We recorded the usage of rescue analgesics and anti-emetics. Results: Fifty-nine patients' datasets were included for final analyses. Fewer patients in TEAS experienced severe POF (defined as ChrFS ≥6) at T3 than those in the Con group (TEAS vs. Con: 7 vs. 22, p < 0.001). During the 1st stage of surgery, more patients in Con group required dexmedetomidine infusion (TEAS vs. Con: 2 vs. 6; P < 0.01). Total dosages of propofol and remifanil during the 2nd stage of surgery were TEAS vs. Con: 374.7 ± 61.2 vs 421.5 ± 81.9; p < 0.001 and 572.3 ± 82.0 vs. 662 ± 148.2; P < 0.001, respectively. Postoperative rescue analgesics (TEAS vs. Con: 2 vs. 6; P < 0.001) were used less in the TEAS group. TEAS patients reported better POF, MMSE and QoR15 scores than those in the Con group during most of the assessment period. Conclusions: Intraoperative TEAS decreased the severity of POF, reduced intraoperative anesthetic requirements and facilitated post-DBS recovery in this group of PD patients.

17.
Int Wound J ; 21(4): e14867, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38597295

RESUMEN

Non-healing wounds are one of the chronic complications of diabetes and have remained a worldwide challenge as one of the major health problems. Hyperbaric oxygen (HBO) therapy is proven to be very successful for diabetic wound treatment, for which the molecular basis is not understood. Adipocytes regulate multiple aspects of repair and may be therapeutic for inflammatory diseases and defective wound healing associated with aging and diabetes. Endothelial cell-derived extracellular vesicles could promote wound healing in diabetes. To study the mechanism by which HBO promotes wound healing in diabetes, we investigated the effect of HBO on fat cells in diabetic mice. A diabetic wound mouse model was established and treated with HBO. Haematoxylin and eosin (H&E) staining and immunofluorescence were used for the analysis of wound healing. To further explore the mechanism, we performed whole-genome sequencing on extracellular vesicles (EVs). Furthermore, we conducted in vitro experiments. Specifically, exosomes were collected from human umbilical vein endothelial cell (HUVEC) cells after HBO treatment, and then these exosomes were co-incubated with adipose tissue. The wound healing rate in diabetic mice treated with HBO was significantly higher. HBO therapy promotes the proliferation of adipose precursor cells. HUVEC-derived exosomes treated with HBO significantly promoted fat cell browning. These data clarify that HBO therapy may promote vascular endothelial cell proliferation and migration, and promote browning of fat cells through vascular endothelial cells derived exosomes, thereby promoting diabetic wound healing. This provides new ideas for the application of HBO therapy in the treatment of diabetic trauma.


Asunto(s)
Diabetes Mellitus Experimental , Oxigenoterapia Hiperbárica , Humanos , Animales , Ratones , Cicatrización de Heridas/fisiología , Diabetes Mellitus Experimental/terapia , Células Endoteliales de la Vena Umbilical Humana , Tejido Adiposo Blanco
18.
J Agric Food Chem ; 72(14): 8018-8026, 2024 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-38557039

RESUMEN

Phloretin is widely found in fruit and shows various biological activities. Here, we demonstrate the dimethylallylation, geranylation, and farnesylation, particularly the first dimethylallylation at the nonaromatic carbon of phloretin (1) by the fungal prenyltransferase AnaPT and its mutants. F265 was identified as a key amino acid residue related to dimethylallylation at the nonaromatic carbon of phloretin. Mutants AnaPT_F265D, AnaPT_F265G, AnaPT_F265P, AnaPT_F265C, and AnaPT_F265Y were discovered to generally increase prenylation activity toward 1. AnaPT_F265G catalyzes the O-geranylation selectively at the C-2' hydroxyl group, which involves an intramolecular hydrogen bond with the carbonyl group of 1. Seven products, 1D5, 1D7-1D9, 1G2, 1G4, and 1F2, have not been reported prior to this study. Twelve compounds, 1D3-1D9, 1G1-1G3, and 1F1-1F2, exhibited potential inhibitory effects on α-glucosidase with IC50 values ranging from 11.45 ± 0.87 to 193.80 ± 6.52 µg/mL. Among them, 1G1 with an IC50 value of 11.45 ± 0.87 µg/mL was the most potential α-glucosidase inhibitor, which is about 30 times stronger than the positive control acarbose with an IC50 value of 346.63 ± 15.65 µg/mL.


Asunto(s)
Dimetilaliltranstransferasa , Floretina , Floretina/farmacología , Indoles/química , Carbono , Catálisis , Prenilación
20.
Zhongguo Dang Dai Er Ke Za Zhi ; 26(3): 262-268, 2024 Mar 15.
Artículo en Chino | MEDLINE | ID: mdl-38557378

RESUMEN

OBJECTIVES: To investigate the factors influencing the occurrence of small for gestational age (SGA) at different degrees and provide a basis for early identification of severe SGA cases. METHODS: Neonatal and maternal prenatal information were retrospectively collected from January 2018 to December 2022 at Peking University People's Hospital. The neonates were divided into three groups: severe SGA group (birth weight below the 3rd percentile for gestational age and sex), mild SGA group (birth weight ≥3rd percentile and <10th percentile), and non-SGA group (birth weight ≥10th percentile). An ordered multinomial logistic regression model was used to analyze the factors influencing the occurrence of SGA at different degrees. RESULTS: A total of 14 821 neonates were included, including 258 cases (1.74%) in the severe SGA group, 902 cases (6.09%) in the mild SGA group, and 13 661 cases (92.17%) in the non-SGA group. The proportions of preterm births and stillbirths were higher in the severe SGA group compared to the mild SGA and non-SGA groups (P<0.0125). The proportion of neonatal asphyxia was higher in both the severe SGA and mild SGA groups compared to the non-SGA group (P<0.0125). Ordered multinomial logistic regression analysis showed that maternal pre-pregnancy underweight (OR=1.838), maternal pre-pregnancy obesity (OR=3.024), in vitro fertilization-embryo transfer (OR=2.649), preeclampsia (OR=1.743), connective tissue disease during pregnancy (OR=1.795), nuchal cord (OR=1.213), oligohydramnios (OR=1.848), and intrauterine growth restriction (OR=27.691) were all associated with a higher risk of severe SGA (P<0.05). Maternal parity as a multipara (OR=0.457) was associated with a lower likelihood of severe SGA (P<0.05). CONCLUSIONS: Maternal pre-pregnancy underweight, maternal pre-pregnancy obesity, in vitro fertilization-embryo transfer, preeclampsia, connective tissue disease during pregnancy, oligohydramnios, nuchal cord, and intrauterine growth restriction are closely related to the occurrence of more severe SGA. Maternal parity as a multipara acts as a protective factor against the occurrence of severe SGA.


Asunto(s)
Enfermedades del Tejido Conjuntivo , Cordón Nucal , Oligohidramnios , Preeclampsia , Embarazo , Recién Nacido , Femenino , Humanos , Retardo del Crecimiento Fetal , Peso al Nacer , Edad Gestacional , Estudios Retrospectivos , Delgadez , Recién Nacido Pequeño para la Edad Gestacional , Obesidad
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