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1.
Front Endocrinol (Lausanne) ; 15: 1336402, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38742197

RESUMEN

Diabetic kidney disease (DKD), a significant complication associated with diabetes mellitus, presents limited treatment options. The progression of DKD is marked by substantial lipid disturbances, including alterations in triglycerides, cholesterol, sphingolipids, phospholipids, lipid droplets, and bile acids (BAs). Altered lipid metabolism serves as a crucial pathogenic mechanism in DKD, potentially intertwined with cellular ferroptosis, lipophagy, lipid metabolism reprogramming, and immune modulation of gut microbiota (thus impacting the liver-kidney axis). The elucidation of these mechanisms opens new potential therapeutic pathways for DKD management. This research explores the link between lipid metabolism disruptions and DKD onset.


Asunto(s)
Nefropatías Diabéticas , Metabolismo de los Lípidos , Humanos , Nefropatías Diabéticas/metabolismo , Animales , Trastornos del Metabolismo de los Lípidos/metabolismo , Trastornos del Metabolismo de los Lípidos/complicaciones , Microbioma Gastrointestinal
2.
J Ethnopharmacol ; 331: 118303, 2024 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-38734390

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Realgar, a traditional mineral Chinese medicine, has been used in China for more than 2000 years. It has been recorded in many ancient and modern works that it has anti-cancer and anti-tumor effects. Of course, colon cancer is also within the scope of its treatment. Realgar needs to be processed into realgar decoction pieces by water grinding before being used for medicine. To ensure the consistency of efficacy and quality of realgar decoction pieces, modern methods need to be used for further quality control. AIM OF THE STUDY: The research of traditional mineral Chinese medicine is relatively difficult, and the related research is less. The purpose of this study is to control the quality of realgar decoction pieces by modern analytical technology and analyze its components. On this basis, its anti-colon cancer activity was discussed. MATERIALS AND METHODS: Several batches of realgar decoction pieces were analyzed by XRD, and the components of realgar decoction pieces were obtained. The quality control fingerprints of realgar decoction pieces were established by processing XRD spectra and similarity evaluation. Then, the effects of realgar decoction pieces on apoptosis of CT26 and HTC-116 cells were observed in vitro by Hoechst 33258 staining, flow cytometry, measurement of mitochondrial membrane potential and Western blot; In vivo, the mouse model of tumor-in-situ transplantation of colon cancer was established, and the related indexes were observed. RESULT: The explorations showed that the XRD Fourier fingerprints of realgar decoction pieces samples that had the same phase revealed 10 common peaks, respectively. The similarity evaluation of the established XRD Fourier fingerprint was greater than 0.900. We also demonstrated that realgar decoction pieces can promote apoptosis and inhibit tumor growth in colon cancer cells, its activating effect on p53 protein, and its safety when used within reasonable limits. CONCLUSION: The quality control of realgar decoction pieces by XRD is scientific and has the inhibitory effect on colon cancer, which has the development potential.

3.
Heliyon ; 10(7): e28619, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38590862

RESUMEN

Introduction: Malnutrition is strongly associated with heart failure (HF); however, the causal link remains unclear. We used Mendelian randomization (MR) to infer causal associations between different nutritional assessment phenotypes and HF and to analyze whether these associations were mediated by common HF risk factors. Methods: Two-sample bidirectional MR was used to infer causal associations between nutritional assessment phenotypes and HF. Mutual influences between different nutritional assessment phenotypes and potential correlations were estimated using multivariate MR methods. Two-step MR was used to quantify the mediating effects of common HF risk factors on the causal associations. Results: Three phenotypes were positively associated with the development of HF: waist circumference (WC) (odds ratio [OR] = 1.74; 95% confidence interval [CI], 1.60-1.90; P = 3.95 × 10-39), body mass index (BMI) (OR = 1.70; 95%CI, 1.60-1.80; P = 1.35 × 10-73), and whole body fat mass (WBFM) (OR = 1.54; 95%CI, 1.44-1.65; P = 4.82 × 10-37). Multivariate MR indicated that WBFM remained positively associated with HF after conditioning on BMI and WC (OR = 2.05; 95%CI, 1.27-3.31; P = 0.003). Three phenotypes were negatively correlated with the development of HF: usual walking pace (UWP) (OR = 0.40; 95%CI, 0.27-0.60; P = 8.41 × 10-6), educational attainment (EA) (OR = 0.73; 95%CI, 0.67-0.79; P = 2.27 × 10-13), and total cholesterol (TC) (OR = 0.90; 95%CI, 0.84-0.96; P = 4.22 × 10-3). There was a bidirectional causality between HF and UWP (Effect estimate = -0.03; 95%CI, -0.05 to -0.01; P = 1.95 × 10-3). Mediation analysis showed that common risk factors for HF (hypertension, coronary artery disease, cardiomyopathy, and valvular heart disease) mediated these causal associations (all P < 0.05). Conclusions: BMI, WC, and WBFM are potential risk factors for HF, and the correlation between WBFM and HF was significantly stronger than that between BMI and WC, and HF. EA, UWP, and TC are potential protective factors against HF. Common risk factors for HF mediate these causal pathways. Early identification of potential risk or protective factors for HF patients from the dimension of nutritional status is expected to further improve patient outcomes.

4.
Biomater Adv ; 160: 213848, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38581745

RESUMEN

Tissue engineering shows promise in repairing extensive bone defects. The promotion of proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) by biological scaffolds has a significant impact on bone regeneration outcomes. In this study we used an injectable hydrogel, known as aminated mesoporous silica gel composite hydrogel (MSNs-NH2@GelMA), loaded with a natural drug, processed pyritum (PP), to promote healing of bone defects. The mechanical properties of the composite hydrogel were significantly superior to those of the blank hydrogel. In vitro experiments revealed that the composite hydrogel stimulated the osteogenic differentiation of BMSCs, and significantly increased the expression of type I collagen (Col 1), runt-related transcription factor 2 (Runx 2), alkaline phosphatase (ALP), osteocalcin (OCN). In vivo experiments showed that the composite hydrogel promoted the generation of new bones. These findings provide evidence that the composite hydrogel pyritum-loaded holds promise as a biomaterial for bone repair.


Asunto(s)
Regeneración Ósea , Diferenciación Celular , Hidrogeles , Células Madre Mesenquimatosas , Osteogénesis , Osteogénesis/efectos de los fármacos , Células Madre Mesenquimatosas/efectos de los fármacos , Células Madre Mesenquimatosas/metabolismo , Hidrogeles/química , Hidrogeles/farmacología , Diferenciación Celular/efectos de los fármacos , Animales , Regeneración Ósea/efectos de los fármacos , Ingeniería de Tejidos/métodos , Materiales Biocompatibles/farmacología , Materiales Biocompatibles/química , Andamios del Tejido/química , Dióxido de Silicio/química , Dióxido de Silicio/farmacología
5.
Adv Mater ; : e2400622, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38489844

RESUMEN

Existing tear sensors are difficult to perform multiplexed assays due to the minute amounts of biomolecules in tears and the tiny volume of tears. Herein, the authors leverage DNA tetrahedral frameworks (DTFs) modified on the wireless portable electrodes to effectively capture 3D hybridization chain reaction (HCR) amplifiers for automatic and sensitive monitoring of multiple cytokines in human tears. The developed sensors allow the sensitive determination of various dry eye syndrome (DES)-associated cytokines in human tears with the limit of detection down to 0.1 pg mL-1, consuming as little as 3 mL of tear fluid. Double-blind testing of clinical DES samples using the developed sensor and commercial ELISA shows no significant difference between them. Compared with single-biomarker diagnosis, the diagnostic accuracy of this sensor based on multiple biomarkers has improved by ≈16%. The developed system offers the potential for tear sensors to enable personalized and accurate diagnosis of various ocular diseases.

6.
Phytomedicine ; 127: 155483, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38432036

RESUMEN

BACKGROUND: Genus Paeonia, which is the main source of Traditional Chinese Medicine (TCM) Paeoniae Radix Rubra (Chishao in Chinese), Paeoniae Radix Alba (Baishao in Chinese) and Moutan Cortex (Mudanpi in Chinese), is rich in active pharmaceutical ingredient such as monoterpenoid glycosides (MPGs). MPGs from Paeonia have extensive pharmacological effects, but the pharmacological effects and molecular mechanisms of MPGs has not been comprehensively reviewed. PURPOSE: MPGs compounds are one of the main chemical components of the genus Paeonia, with a wide variety of compounds and strong pharmacological activities, and the structure of the mother nucleus-pinane skeleton is similar to that of a cage. The purpose of this review is to summarize the pharmacological activity and mechanism of action of MPGs from 2012 to 2023, providing reference direction for the development and utilization of Paeonia resources and preclinical research. METHODS: Keywords and phrases are widely used in database searches, such as PubMed, Web of Science, Google Scholar and X-Mol to search for citations related to the new compounds, extensive pharmacological research and molecular mechanisms of MPGs compounds of genus Paeonia. RESULTS: Modern research confirms that MPGs are the main compounds in Paeonia that exert pharmacological effects. MPGs with extensive pharmacological characteristics are mainly concentrated in two categories: paeoniflorin derivatives and albiflflorin derivatives among MPGs, which contains 32 compounds. Among them, 5 components including paeoniflorin, albiflorin, oxypaeoniflorin, 6'-O-galloylpaeoniflorin and paeoniflorigenone have been extensively studied, while the other 28 components have only been confirmed to have a certain degree of anti-inflammatory and anticomplementary effects. Studies of pharmacological effects are widely involved in nervous system, endocrine system, digestive system, immune system, etc., and some studies have identified clear mechanisms. MPGs exert pharmacological activity through multilateral mechanisms, including anti-inflammatory, antioxidant, inhibition of cell apoptosis, regulation of brain gut axis, regulation of gut microbiota and downregulation of mitochondrial apoptosis, etc. CONCLUSION: This systematic review delved into the pharmacological effects and related molecular mechanisms of MPGs. However, there are still some compounds in MPGs whose pharmacological effects and pharmacological mechanisms have not been clarified. In addition, extensive clinical randomized trials are needed to verify the efficacy and dosage of MPGs.


Asunto(s)
Medicamentos Herbarios Chinos , Glucósidos , Paeonia , Glicósidos/farmacología , Paeonia/química , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/química , Monoterpenos/farmacología , Monoterpenos/química , Antiinflamatorios
7.
ACS Appl Mater Interfaces ; 16(13): 16474-16481, 2024 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-38502742

RESUMEN

The development of lead halide perovskite X-ray detectors has promising applications in medical imaging and security inspection but is hindered by poor long-term stability and drift of the dark current and photocurrent. Herein, we design a (Cs0.05MA0.65FA0.3)PbI3-(Cs0.1MA1.3FA0.6)AgBiI6 double-layer perovskite film to assemble a self-powered flat-panel X-ray detector. The demonstrated X-ray detector achieves an outstanding self-powered sensitivity of 80 µC Gyair-1 cm-2 under a 0 V bias. More importantly, owing to the inhibition of the phase transition process and ion migration of (Cs0.05MA0.65FA0.3)PbI3 by the (Cs0.1MA1.3FA0.6)AgBiI6 layer, the device exhibits excellent continuous operating stability with a retention rate of 99% dark current and photocurrent over X-ray pulses of up to 4000 s and excellent long-term stability without a loss of the original response current after 150 days in an air environment. The strategy of double-layer perovskites improves the stability and sensitivity of devices, which paves a path for the industrial application of lead halide perovskite X-ray detectors.

8.
Expert Rev Clin Immunol ; : 1-9, 2024 Mar 11.
Artículo en Inglés | MEDLINE | ID: mdl-38445835

RESUMEN

OBJECTIVE: This article aims to evaluate the magnitude of adverse pregnancy outcomes (APOs) risks associated with different antiphospholipid antibody (aPL) profiles in women with systemic lupus erythematosus (SLE). METHODS: Multiple databases were investigated to identify articles that explored the relationship between aPLs and APOs in SLE patients. A random effects model was used for calculating pooled odds ratios (OR). Stata version 15.0 was utilized to conduct the meta-analysis. RESULTS: There were 5234 patients involved in 30 studies. Overall aPL was linked to an increased incidence of any kind of APOs, fetal loss, and preterm birth. Any kind of APOs and preterm delivery were more common in patients with lupus anticoagulant (LA) positive. Anticardiolipin antibody (aCL) was associated with an increased risk of any kind of APOs and fetal loss. The association between aCL-IgM and fetal loss was also significant. Patients with anti-beta2-glycoprotein1 antibody (antiß2GP1) positivity had an increased risk of fetal loss. CONCLUSIONS: Both LA and aCL were risk factors of APOs in patients with SLE. Not only ACL, particularly aCL-IgM, but antiß2GP1 were associated with an increased risk of fetal loss, while LA appeared to indicate the risk of preterm birth.PROSPERO (CRD42023388122).

9.
Sci Rep ; 14(1): 3144, 2024 02 07.
Artículo en Inglés | MEDLINE | ID: mdl-38326538

RESUMEN

The objective of this study was to evaluate the predictive value of the Geriatric Nutritional Risk Index (GNRI) combined with the Systemic Immunoinflammatory Index (SII) for the risk of major adverse cardiovascular events (MACE) following percutaneous coronary intervention in elderly patients with acute coronary syndrome (ACS). We retrospectively reviewed the medical records of 1202 elderly patients with acute coronary syndromes divided into MACE and non-MACE groups according to whether they had a MACE. The sensitivity analysis utilized advanced machine learning algorithms to preliminarily identify the critical role of GNRI versus SII in predicting MACE risk. We conducted a detailed analysis using a restricted cubic spline approach to investigate the nonlinear relationship between GNRI, SII, and MACE risk further. We constructed a clinical prediction model based on three key factors: GNRI, SII, and Age. To validate the accuracy and usefulness of this model, we compared it to the widely used GRACE score using subject work and recall curves. Additionally, we compared the predictive value of models and GRACE scores in assessing the risk of MACE using the Integrated Discriminant Improvement Index (IDI) and the Net Reclassification Index (NRI). This study included 827 patients. The GNRI scores were lower in the MACE group than in the non-MACE group, while the SII scores were higher in the MACE group (P < 0.001). The multifactorial analysis revealed a low GNRI (OR = 2.863, 95% CI: 2.026-4.047, P = 0.001), High SII (OR = 3.102, 95% CI: 2.213-4.348, P = 0.001). The area under the curve (AUC) for the predictive model was 0.778 (95% CI: 0.744-0.813, P = 0.001), while the AUC for the GRACE score was 0.744 (95% CI: 0.708-0.779, P = 0.001). NRI was calculated to be 0.5569, with NRI + at 0.1860 and NRI- at 0.3708. The IDI was found to be 0.0571, with a P-value of less than 0.001. These results suggest that the newly developed prediction model is more suitable for use with the population in this study than the GRACE score. The model constructed using GNRI and SII demonstrated good standardization and clinical impact, as evidenced by the standard, DCA, and clinical impact curves. The study shows that combining GNRI and SII can be a simple, cost-effective, and valuable way to predict the risk of MACE within one year in elderly acute coronary syndromes.


Asunto(s)
Síndrome Coronario Agudo , Intervención Coronaria Percutánea , Humanos , Anciano , Síndrome Coronario Agudo/diagnóstico , Síndrome Coronario Agudo/etiología , Pronóstico , Estudios Retrospectivos , Modelos Estadísticos , Intervención Coronaria Percutánea/efectos adversos , Medición de Riesgo
10.
MedComm (2020) ; 5(2): e472, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38292328

RESUMEN

Phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) has recently emerged as a novel tumor suppressor. Researchers have observed that LHPP plays a crucial role in inhibiting proliferation, growth, migration, invasion, and cell metabolism across various cancers. Nevertheless, the specific functions and underlying mechanisms of LHPP as a tumor suppressor in gastric cancer (GC) require further exploration. The expression of LHPP was assessed in human GC specimens and cell lines. Various assays were employed to evaluate the impact of LHPP on GC cells. RNA sequencing and Gene Set Enrichment Analysis were conducted to unravel the mechanism through which LHPP regulates GC cell behavior. Additionally, xenograft nude mouse models were utilized to investigate the in vivo effects of LHPP. The findings indicate that LHPP, functioning as a tumor suppressor, is downregulated in both GC tissues and cells. LHPP emerges as an independent risk factor for GC patients, and its expression level exhibits a positive correlation with patient prognosis. LHPP exerts inhibitory effects on the adhesion and proliferation of GC cells by suppressing the expression of insulin-like growth factor 1 receptor (IGF1R) and modulating downstream signaling pathways. Consequently, LHPP holds potential as a biomarker for targeted therapy involving IGF1R inhibition in GC patients.

11.
Sensors (Basel) ; 24(2)2024 Jan 16.
Artículo en Inglés | MEDLINE | ID: mdl-38257645

RESUMEN

With the rapid development of unmanned aerial vehicle technology and its increasing application across various fields, current airspace resources are insufficient for unmanned aerial vehicles' needs. This paper, taking Zigong General Aviation Airport in Sichuan as a case study, explores the lateral safety spacing in a mixed operation mode of unmanned aerial vehicles and manned aircraft. Currently, there are no standardized regulations for the safe spacing of the fusion operation of unmanned and manned aircraft. Theoretical research is essential to provide a reference for actual operations. It introduces the UM-Event (unmanned and manned aircraft-event) collision risk model, an adaptation of the Event collision risk model, considering factors like communication, navigation, surveillance performance, human factors, collision avoidance equipment performance, and meteorology. Safety spacing was determined via simulation experiments and actual data analysis, adhering to the target safety level (TSL). Findings indicate that surveillance performance has a minor impact on safety spacing, while communication and navigation significantly influence it. The safety spacing, influenced solely by CNS (communication performance, navigation performance, surveillance performance) and combined factors, increased from 4.42 to 4.47 nautical miles. These results offer theoretical guidance for unmanned aerial vehicle safety in non-segregated airspace.

12.
Int J Phytoremediation ; 26(4): 448-458, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-37565667

RESUMEN

Pyrite exhibits considerable potential as an adsorbent in wastewater treatment. However, few pyrite adsorbents are directly obtained from natural pyrite, as most are composite materials that require a complex preparation process. To develop a pyrite-based adsorbent with a simple preparation process, pyrite was processed by calcination at 400, 600, and 800 °C for 4 h and ball-milled into a fine powder. The adsorption properties of the pyrite powder were systematically explored. The calcined pyrite powder was characterized by SEM-EDS and XRD. The results revealed that the pyrite calcined at 600 °C exhibited excellent adsorption properties and was primarily composed of Fe7S8. The optimum conditions for Cr(VI) removal were a temperature of 45 °C, an adsorbent dosage of 1 g, an equilibration time of 60 min, and an initial pH of 3. Moreover, the calcined pyrite powder exhibited excellent reusability, and the Cr(VI) removal rate exceeded 65% after three cycles. The Cr(VI) adsorption on pyrite can be well described by the Freundlich model and pseudo-second-order kinetic equation. The calcination temperature is the main factor affecting the adsorption performance of pyrite. Therefore, the calcined pyrite powder is expected to be an excellent adsorbent for Cr(VI) in the wastewater treatment industry.


Pyrite has shown promising development prospects in the field of wastewater purification. However, the preparation of most pyrite-based adsorbents is complicated. Upon high-temperature calcination, pyrite is used in traditional Chinese medicine clinics to promote the healing of fractures. The efficiency and underlying mechanism of Cr(VI) adsorption from water using calcined pyrite was investigated. The adsorbent was prepared using a simple method and exhibited excellent adsorption performance, thus allowing its application in preparing ore-based adsorbents for water pollution treatment.


Asunto(s)
Cromo , Hierro , Sulfuros , Contaminantes Químicos del Agua , Polvos , Biodegradación Ambiental , Cromo/química , Adsorción , Cinética , Contaminantes Químicos del Agua/química , Concentración de Iones de Hidrógeno
13.
Exp Dermatol ; 33(1): e14862, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37350230

RESUMEN

Tapinarof is an aryl hydrocarbon receptor (AHR) ligand which is used to treat plaque psoriasis in adults. However, the underlying mechanism is not yet fully understood. In this study, we applied two of the most studied psoriasis mouse models: topical application of imiquimod (IMQ) and subcutaneous injection of IL-23. Although both models successfully induced psoriasis-like lesions in mice, tapinarof had a completely opposite effect on the two models. Tapinarof decreased the expression of multiple essential cytokines involved in the pathological IL-23/IL-17/IL-22 axis and ameliorated IMQ-induced psoriatic dermatitis, inhibiting keratinocyte proliferation and abnormal differentiation. However, in the IL-23-injection-model, tapinarof instead aggravated the disease. Here, tapinarof increased epidermal thickness and differentiated epidermal dysplasia in mice. Our data suggest that tapinarof may have different effects on varied types of psoriasis.


Asunto(s)
Psoriasis , Estilbenos , Animales , Ratones , Imiquimod , Psoriasis/metabolismo , Resorcinoles/efectos adversos , Interleucina-23 , Modelos Animales de Enfermedad , Ratones Endogámicos BALB C
14.
ACS Pharmacol Transl Sci ; 6(12): 1909-1923, 2023 Dec 08.
Artículo en Inglés | MEDLINE | ID: mdl-38093834

RESUMEN

Nonalcoholic fatty liver disease (NAFLD) is a clinicopathological entity that is typically characterized by intrahepatic ectopic steatosis. Nowadays, NAFLD has surpassed viral hepatitis and become the most common chronic liver disease worldwide, which poses a great threat to human health. Silibinin (Sil), a well-known natural product, has been widely used in clinical treatment for liver disorders and exhibited therapeutic potential for NAFLD. However, the suitability of Sil for NAFLD treatment still requires further investigation due to its limited absorption and low bioavailability. This study aimed to construct a Sil-loaded liposome (Sil-Lip) to overcome the limitations of Sil, thereby enhancing its beneficial effects on NAFLD and then investigate the underlying mechanisms of action of Sil-Lip. Herein, Sil-Lip was fabricated by a well-established thin-film dispersion method and carefully characterized, followed by evaluating their therapeutic efficacy using high-fat diet-induced NAFLD mice and free fatty acid -stimulated HepG2 cells. Then, liver transcriptome analysis and 16S ribosomal RNA (16S rRNA) sequencing were utilized to elucidate the potential mechanisms of action of Sil-Lip. Our data indicated that Sil-Lip harbored good gastrointestinal tract stability, mucus layer permeation, and excellent oral absorption and bioavailability. In vivo and in vitro NAFLD models demonstrated that Sil-Lip had better effects in alleviating lipid metabolism disorders, insulin resistance, and inflammation than did Sil alone. Further investigations revealed that the beneficial effects of Sil-Lip were mediated by modulating intrahepatic insulin resistance-related and nuclear factor-kappa B (NF-κB) signaling pathways and extrahepatic gut microbiota. Our study confirmed that Sil-Lip can effectively improve the absorption and bioavailability of Sil, resultantly potentiating its ameliorative effects on NAFLD through modulating intrahepatic insulin resistance-related and NF-κB signaling pathways and extrahepatic gut microbiota.

15.
Int J Mol Sci ; 24(22)2023 Nov 17.
Artículo en Inglés | MEDLINE | ID: mdl-38003616

RESUMEN

Engineering the yeast Yarrowia lipolytica as an efficient host to produce recombinant proteins remains a longstanding goal for applied biocatalysis. During the protein overproduction, the accumulation of unfolded and misfolded proteins causes ER stress and cell dysfunction in Y. lipolytica. In this study, we evaluated the effects of several potential ER chaperones and translocation components on relieving ER stress by debottlenecking the protein synthetic machinery during the production of the endogenous lipase 2 and the E. coli ß-galactosidase. Our results showed that improving the activities of the non-dominant translocation pathway (SRP-independent) boosted the production of the two proteins. While the impact of ER chaperones is protein dependent, the nucleotide exchange factor Sls1p for protein folding catalyst Kar2p is recognized as a common contributor enhancing the secretion of the two enzymes. With the identified protein translocation components and ER chaperones, we then exemplified how these components can act synergistically with Hac1p to enhance recombinant protein production and relieve the ER stress on cell growth. Specifically, the yeast overexpressing Sls1p and cytosolic heat shock protein Ssa8p and Ssb1p yielded a two-fold increase in Lip2p secretion compared with the control, while co-overexpressing Ssa6p, Ssb1p, Sls1p and Hac1p resulted in a 90% increase in extracellular ß-galp activity. More importantly, the cells sustained a maximum specific growth rate (µmax) of 0.38 h-1 and a biomass yield of 0.95 g-DCW/g-glucose, only slightly lower than that was obtained by the wild type strain. This work demonstrated engineering ER chaperones and translocation as useful strategies to facilitate the development of Y. lipolytica as an efficient protein-manufacturing platform.


Asunto(s)
Yarrowia , Vías Secretoras , Escherichia coli/genética , Escherichia coli/metabolismo , Chaperonas Moleculares/genética , Chaperonas Moleculares/metabolismo , Proteínas de Choque Térmico/metabolismo , Proteínas Recombinantes/genética , Proteínas Recombinantes/farmacología , Proteínas Recombinantes/metabolismo , Ingeniería Metabólica/métodos
16.
Sci Rep ; 13(1): 20333, 2023 11 21.
Artículo en Inglés | MEDLINE | ID: mdl-37989757

RESUMEN

To determine the most appropriate nutritional assessment tool for predicting the occurrence of major adverse cardiovascular events (MACE) within 1 year in elderly ACS patients undergoing PCI from four nutritional assessment tools including PNI, GNRI, CONUT, and BMI. Consecutive cases diagnosed with acute coronary syndrome (ACS) and underwent percutaneous coronary intervention (PCI) in the Department of Cardiovascular Medicine of the Air force characteristic medical center from 1 January 2020 to 1 April 2022 were retrospectively collected. The basic clinical characteristics and relevant test and examination indexes were collected uniformly, and the cases were divided into the MACE group (174 cases) and the non-MACE group (372 cases) according to whether a major adverse cardiovascular event (MACE) had occurred within 1 year. Predictive models were constructed to assess the nutritional status of patients with the Prognostic Nutritional Index (PNI), Geriatric Nutritional Risk Index (GNRI), Controlling nutritional status (CONUT) scores, and Body Mass Index (BMI), respectively, and to analyze their relationship with prognosis. The incremental value of the four nutritional assessment tools in predicting risk was compared using the Integrated Discriminant Improvement (IDI) and the net reclassification improvement (NRI). The predictive effect of each model on the occurrence of major adverse cardiovascular events (MACE) within 1 year in elderly ACS patients undergoing PCI was assessed using area under the ROC curve (AUC), calibration curves, decision analysis curves, and clinical impact curves; comparative analyses were performed. Among the four nutritional assessment tools, the area under the curve (AUC) was significantly higher for the PNI (AUC: 0.798, 95%CI 0.755-0.840 P < 0.001) and GNRI (AUC: 0.760, 95%CI 0.715-0.804 P < 0.001) than for the CONUT (AUC: 0.719,95%CI 0.673-0.765 P < 0.001) and BMI (AUC: 0.576, 95%CI 0.522-0.630 P < 0.001). The positive predictive value (PPV) of PNI: 67.67% was better than GNRI, CONUT, and BMI, and the negative predictive value (NPV): of 83.90% was better than CONUT and BMI and similar to the NPV of GNRI. The PNI, GNRI, and CONUT were compared with BMI, respectively. The PNI had the most significant improvement in the Integrated Discriminant Improvement Index (IDI) (IDI: 0.1732, P < 0.001); the PNI also had the most significant improvement in the Net Reclassification Index (NRI) (NRI: 0.8185, P < 0.001). In addition, of the four nutritional assessment tools used in this study, the PNI was more appropriate for predicting the occurrence of major adverse cardiovascular events (MACE) within 1 year in elderly ACS patients undergoing PCI.


Asunto(s)
Síndrome Coronario Agudo , Intervención Coronaria Percutánea , Humanos , Anciano , Intervención Coronaria Percutánea/efectos adversos , Síndrome Coronario Agudo/epidemiología , Síndrome Coronario Agudo/cirugía , Estudios Retrospectivos , Incidencia , Estado Nutricional
17.
Health Res Policy Syst ; 21(1): 118, 2023 Nov 06.
Artículo en Inglés | MEDLINE | ID: mdl-37932791

RESUMEN

BACKGROUND: Health impact assessment (HIA) is a procedure, method and tool for evaluating the potential health impacts of policies, plans and construction projects, as well as the distribution of these impacts on population. Majority of international studies on health impact assessment have focussed on conceptual papers or case evaluations, neglecting participants' views on policies. METHODS: A semi-structured interview with 30 health impact assessment experts was employed in this study, and the Nvivo software was utilized to analyse factors that influence policy identification. Subsequently, a multi-stage stratified random sampling method was adopted to survey 655 pilot staff members involved in health impact assessment in Zhejiang Province. Descriptive statistics were used to describe the current status and identify the factors influencing policy identification. In addition, hierarchical linear regression analysis and structural equation modelling were employed to determine the relationship between policy identification and influencing factors. RESULTS: Statistically significant differences were found among participants in the level of identification of policies across three dimensions. The policy sentiment dimension had the highest score (4.137 ± 0.664), followed by policy cognition (4.075 ± 0.632) and policy evaluation (3.631 ± 0.797) dimensions. Subject trust had a positive impact on policy cognition (ß = 0.503, P < 0.001), policy sentiment (ß = 0.504, P < 0.001) and policy evaluation (ß = 0.465, P < 0.001). Procedural justice had a positive impact on policy sentiment (ß = 0.085, P < 0.01) and policy evaluation (ß = 0.084, P < 0.05), but not policy cognition (ß = 0.056, P > 0.05). Policy identification is influenced by age and average monthly salary among other factors. CONCLUSION: These results highlight the importance of subjective trust and procedural justice in policy identification of health impact assessment. They provide valuable insights to developing interventions to overcome barriers to the implementation and enhancement of global identification of policies. Going forward, cross-sectoral synergies, enhanced international communication and training to increase participants' trust in the policy should be optimized to improve health impact assessment. Additional measures should be taken, such as ensuring seamless communication channels, embedding health impact assessment in administrative mechanisms, and establishing strong oversight and grievance mechanisms to improve fairness and transparency in the implementation and results of health impact assessment.


Asunto(s)
Evaluación del Impacto en la Salud , Políticas , Humanos , Evaluación del Impacto en la Salud/métodos , Política de Salud
18.
ACS Nano ; 17(22): 22960-22978, 2023 11 28.
Artículo en Inglés | MEDLINE | ID: mdl-37930276

RESUMEN

Infected bone defects (IBDs) exhibit impaired healing due to excessive inflammation triggered by pathogen-associated molecular patterns (PAMPs) from bacteria. As a vital factor in orchestrating immune responses, mitochondrial homeostasis maintenance is central to inflammation blockade. This research developed a chameleon-like nanoplatform by covering hydroxyapatite nanoparticles with a cerium ion coordinated tannic acid supramolecular network (HA@Ce-TA), which adaptively functions to regulate mitochondrial homeostasis based on intra- and extracellular environments. Extracellularly, acidic conditions activate HA@Ce-TA's peroxidase/oxidase-mimicking activity to produce reactive oxygen species (ROS), and external near-infrared (NIR) irradiation excites nanoscale Ce-TA to produce hyperthermia, which is found and explained by chemical computation. ROS production with photothermal therapy can eliminate bacteria effectively and reduce mitochondrial stress. Intracellularly, HA@Ce-TA remodels mitochondrial dynamics by upregulating mitochondrial fusion genes and eliminates excessive ROS by mimicking superoxidase/catalase. Consequently, this comprehensive modulation of mitochondrial homeostasis inhibits inflammasome overactivation. In vitro and in vivo studies showed HA@Ce-TA can modulate the mitochondria-centered inflammatory cascade to enhance IBD treatment, highlighting the potential of engineering nanotherapeutics to recalibrate mitochondrial homeostasis as an infected disease-modifying intervention.


Asunto(s)
Mitocondrias , Nanopartículas , Humanos , Especies Reactivas de Oxígeno/farmacología , Nanopartículas/química , Antioxidantes/farmacología , Inflamación , Homeostasis
19.
Eur J Med Res ; 28(1): 401, 2023 Oct 05.
Artículo en Inglés | MEDLINE | ID: mdl-37798739

RESUMEN

BACKGROUND: Several kinds of physical activities have been applied to improve the prognosis of patients with hemodialysis (HD). However, the comparative efficacy of physical activities on the outcomes in HD patients is still unknown. This study explored the effectiveness and safety of all exercise types in HD patients. METHODS: We searched randomized clinical trials from the PubMed, EMBASE, and Cochrane Library databases. Physical exercises interventions included resistance exercise (RE), aerobic exercise (AE), electrical muscle stimulation (EMS), range of motion (ROM), resistance exercise + aerobic exercise (RE + AE), stretching exercise (STE), respiratory muscle training (RMT), peripheral muscle training (PMT), walking exercise (WE), or usual care/sham exercise (UC/SE). Primary outcomes were six-minute walk test (6-mwt) and quality of life (QOL). Secondary outcomes were Kt/V, VO2max, hemoglobin (Hb), C-reactive protein (CRP), interleukin-6 (IL-6), and systolic and diastolic blood pressure (sbp and dbp). Frequentist network meta-analysis with multivariate random effects models provided mean with 95% confidence intervals (95%CI). RESULTS: A total of 58 eligible studies were included. AE, RMT, and RE + AE significantly improved 6-mwt compared with UC/SE. SE was the worst intervention and reduced QOL much more than the UC/SE and other exercise types. AE and RE + AE were associated with higher VO2max, while ROM and RE + AE induced higher Hb levels. All physical activities did not elevate blood pressure, CRP and IL-6. Only ROM decreased sbp/dbp. CRP is significantly lower in RE. CONCLUSION: Physical activities play a crucial role in the different outcomes of HD patients. They can be applied to specific area for their specific efficacy.


Asunto(s)
Calidad de Vida , Insuficiencia Renal Crónica , Humanos , Metaanálisis en Red , Interleucina-6 , Ejercicio Físico , Pronóstico , Diálisis Renal
20.
Sensors (Basel) ; 23(18)2023 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-37765996

RESUMEN

Monitoring and analyzing radio interference sources play a crucial role in ensuring the safe operation of civil aviation navigation, communication, airport management, and air traffic control. Traditional ground monitoring methods are slow and inadequate for tracking aerial and mobile interference sources effectively. Although flight methods such as helicopters and airships can effectively monitor aerial interference, the flight approval process is time-consuming and expensive. This paper investigates a novel approach to locating civil aviation radio interference sources using four unmanned aerial vehicles (UAVs) to address this issue. It establishes a model for aerial positioning of radio interference sources with the four UAVs and proposes a method for time synchronization and data communication among them. The paper conducts simulations of the four-UAV time-frequency difference positioning method, analyzing the geometric accuracy dilution with different deployment configurations of the UAVs, positioning biases, and root mean square errors (RMSEs) under varying interference source movement speeds. The simulation results provide crucial data to support subsequent experiments.

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