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The incidence of Parkinson's disease (PD) rises rapidly with the increase of age. With the advent of global aging, the number of patients with PD is rising along with the elderly population, especially in China. Previously, we found that Yishen chuchan decoction (YCD), prescribed based on clinical experience, has the potential of alleviating symptoms, delaying the progression, and controlling the development of PD. Nonetheless, the underlying mechanistic role is yet to be explored. Aim: This research examined the possible therapeutic effects of YCD in alleviating PD via a systematic approach with network pharmacology and experimental validation, aiming at providing a new understanding of traditional Chinese medicine management regarding PD. Methods: The chemical structure and properties of YCD were adopted from Traditional Chinese Medicine System Pharmacology Database (TCMSP), SwissADME, PubChem, and PubMed. The potential targets for YCD and PD were identified using Swiss Target Prediction, GeneCard, PubChem, and UniProt. The herbal-component-target network was created via the Cytoscape software. Moreover, by using the STRING database, the protein-protein interaction (PPI) network was screened. Gene function GO and KEGG pathway enrichment analyses were performed via the Metascape database. YCD-medicated Rat Serum from Sprague-Dawley (SD) Rats was prepared, and SH-SY5Y cells were preconditioned with rotenone to develop the PD model. To examine the impact of YCD on these cells and explore the mechanistic role of the p38 mitogen-activated protein kinase (MAPK) pathway, the cells were pretreated with either serum or a p38 MAPK pathway inhibitor. This study employed the Cell Counting Kit (CCK)-8 assay and Hoechst 33,342 staining to evaluate the viability and morphological changes induced by the YCD-medicated rat serum on rotenone-treated SH-SY5Y cells. Apoptosis was assessed by Flow cytometry. Immunofluorescence staining assessed the microtubule-associated protein 2 (MAP2) level. Enzyme-linked immunosorbent assay (ELISA) was employed to quantify the concentrations of inflammatory mediators interleukin-1ß (IL-1ß), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α). Also, reactive oxygen species (ROS) and superoxide dismutase (SOD) levels were determined. Western Blotting measured the expression of total and phospho-p38 MAPK (p-p38). Results: This study identified 65 active components in YCD, which were found to target 801 specific genes. By screening, 63 potential core targets were identified from a pool of 172 overlapping targets between PD and YCD. These targets were examined by GO and KEGG analyses revealing their substantial correlation to MAPK, PI3K-Akt signaling pathways, positively controlling protein phosphorylation, and pathways of neurodegenerative diseases. SH-SY5Y cells were treated with 2 µM rotenone for 48 h, which reduced cell viability to 50 %, and reduced MAP2 expression, increased the rate of apoptosis, oxidative stress, inflammation, and p-p38 expressions. YCD-medicated rat serum significantly improved the viability, reduced the apoptosis rate, and increased the MAP2 expression. YCD-medicated serum increased SOD, reduced ROS and suppressed IL-6, IL-1ß and TNF-α levels, thus inhibiting oxidative stress and inflammation in rotenone-treated SH-SY5Y cells. Moreover, YCD-medicated serum substantially lowered the p-p38 expression induced by rotenone. SB203580, a specific inhibitor of p38 MAPK, could also inhibit the p-p38 expression, apoptosis, and restore morphological damage of cells, also improve inflammation and oxidative stress. Conclusion: YCD enhanced cell viability and reduced apoptosis rate, inflammation, and oxidative stress in vitro. These beneficial effects could potentially involve the suppression of p38 pathway and suppressed the phosphorylation of p38 MAPK.
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Auxin regulates plant growth and development through downstream signaling pathways, including the best-known SCFTIR1/AFB-Aux/IAA-ARF pathway and several other less characterized "noncanonical" pathways. Recently, one SCFTIR1/AFB-independent noncanonical pathway, mediated by Transmembrane Kinase 1 (TMK1), was discovered through the analyses of its functions in Arabidopsis apical hook development. Asymmetric accumulation of auxin on the concave side of the apical hook triggers DAR1-catalyzed release of the C-terminal of TMK1, which migrates into the nucleus, where it phosphorylates and stabilizes IAA32/34 to inhibit cell elongation, which is essential for full apical hook formation. However, the molecular factors mediating IAA32/34 degradation have not been identified. Here, we show that proteins in the CYTOKININ INDUCED ROOT WAVING 1 (CKRW1)/WAVY GROWTH 3 (WAV3) subfamily act as E3 ubiquitin ligases to target IAA32/34 for ubiquitination and degradation, which is inhibited by TMK1c-mediated phosphorylation. This antagonistic interaction between TMK1c and CKRW1/WAV3 subfamily E3 ubiquitin ligases regulates IAA32/34 levels to control differential cell elongation along opposite sides of the apical hook.
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Proteínas de Arabidopsis , Arabidopsis , Proteínas F-Box , Ubiquitina-Proteína Ligasas/genética , Ubiquitina-Proteína Ligasas/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Ácidos Indolacéticos/metabolismo , Transducción de Señal , Ubiquitinas/metabolismo , Regulación de la Expresión Génica de las Plantas , Proteínas F-Box/genética , Proteínas F-Box/metabolismoRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCY: Zexieyin formula (ZXYF) has been identified to have therapeutic actions of atherosclerosis (AS). It's unknown that whether ZXYF has therapeutic potential of atherosclerosis (AS) with cognitive impairment (CI) and its underlying mechanisms. AIM OF THE STUDY: To elucidate therapeutic effect of ZXYF for AS with CI as well as its underlying mechanisms in AS with CI mice model. METHODS AND MATERIALS: To establish AS with CI model, we fed ApoE-/- mice with high-fat diet (HFD) for 8 weeks. Oil red O staining (ORO) and Hematoxylin-eosin staining (HE) were used to detect aortic plaque area. Morris water maze (MWM) and Y-maze were used to measure cognitive function and cognitive improvement after administration of ZXYF and atorvastatin (ATO). Network pharmacology was used to screen for potential mechanisms for improving cognitive function. Western blot was used to detect expressions of MAPK, Aß and synaptic proteins in hippocampus. RESULTS: HFD caused and accelerated the AS in ApoE-/- mice, while it was easier able to produce CI than normal mice. Administration of ZXYF or ATO for 8 weeks significantly reduced aortic plaque area in ORO and HE tests, and improved cognitive abilities in MWM and Y-maze tests. Network pharmacology results showed that MAPK or synaptic proteins were highly associated with CI. HFD contributed to abnormal expressions of MAPK (pERK, pP38, pJNK), NF-kB, synaptic proteins (PSD95, synapsin1) and ß-amyloid (Aß) in hippocampus, which were all reversed by ZXYF. However, ERK and PSD95 expressions were not reversed by ATO in hippocampus. CONCLUSIONS: ZXYF mitigated AS, further alleviating CI by modulating MAPK signaling, relating to synaptic proteins enhancing and Aß protein decreasing in the hippocampus. This study firstly lit up the new clinical application of ZXYF, which might promote the use of ZXYF in AS and CI patients.
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Aterosclerosis , Trastornos del Conocimiento , Disfunción Cognitiva , Placa Aterosclerótica , Humanos , Ratones , Animales , Disfunción Cognitiva/tratamiento farmacológico , Aterosclerosis/tratamiento farmacológico , Aterosclerosis/metabolismo , Cognición , Placa Aterosclerótica/tratamiento farmacológico , Apolipoproteínas E/genéticaRESUMEN
AIM To evaluate the quality of Beidougen Formula Granules.METHODS Fifteen batches of standard decoctions and three batches of formula granules were prepared,after which paste rate and contents,transfer rates of magnoflorine,daurisoline,dauricine were determined.HPLC specific chromatograms were established,and cluster analysis was adopted in chemical pattern recognition.RESULTS For three batches of formula granules,the paste rates were 15.1%-16.6%,the contents of magnoflorine,daurisoline,dauricine were 18.93-19.39,9.42-9.60,6.79-6.85 mg/g with the transfer rates of 34.42%-35.25%,43.81%-44.65%,27.27%-27.51%from decoction pieces to formula granules,respectively,and there were seven characteristic peaks in the specific chromatograms with the similarities of more than 0.95,which demonstrated good consistence with those of standard decoctions and accorded with related limit requirements.Fifteen batches of standard decoctions were clustered into two types,and the medicinal materials produced from Jilin,Hebei,Shangdong could be used for the preparation of formula granules.CONCLUSION This reasonable and reliable method can provide references for the quality control and clinical application of Beidougen Formula Granules.
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The precise control of free auxin (indole-3-acetic acid, IAA) gradient, which is orchestrated by biosynthesis, conjugation, degradation, hydrolyzation, and transport, is critical for all aspects of plant growth and development. Of these, the GRETCHEN HAGEN 3 (GH3) acyl acid amido synthetase family, pivotal in conjugating IAA with amino acids, has garnered significant interest. Recent advances in understanding GH3-dependent IAA conjugation have positioned GH3 functional elucidation as a hot topic of research. This review aims to consolidate and discuss recent findings on (i) the enzymatic mechanisms driving GH3 activity, (ii) the influence of chemical inhibitor on GH3 function, and (iii) the transcriptional regulation of GH3 and its impact on plant development and stress response. Additionally, we explore the distinct biological functions attributed to IAA-amino acid conjugates.
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OBJECTIVE: To investigate the effect of Bushen Chushi decoction combined with platelet-rich plasma(PRP) to treat knee osteoarthritis(KOA) in early and middle stage and its regulation on TGF-ß1 and Smad-1 expression in serum. METHODS: Total of 45 patients with KOA in early and middle stage from May 2020 to April 2022 were treated and divided into control group and observation group. In control group, there were 30 patients including 12 males and 18 females, aged from 43 to 69 years old with an average of(57.3±6.5) years old and disease duration ranged from 1.5 to 5.0 years with an average of(3.8±1.7) years, and there were 8 cases in gradeâ , 13 cases in gradeâ ¡, and 9 cases in grade â ¢ according to Kellgren-Lawrence Grade, PRP 5 ml was injected into knee joint on the first day of No1, 3 week together for 2 times. In the observation group, there were 15 cases including 7 males and 8 females, aged from 45 to 70 years old with an average of (56.7±6.2) years old and disease duration ranged from 1.8 to 5.7 years with an average of (4.0±1.8) years, there were 4 cases in gradeâ , 9 cases in gradeâ ¡and 4 cases in grade â ¢ according to the Kellgren-Lawrence Grade, PRP 5 ml were injected into knee joints that the time and frequency were the same as those in the control group, and at the same time Bushen Chushi decoction orally were taken 1 dose per day with a total of 28 doses. All patients were treated for four weeks. Visual analogue scale(VAS) and Lequesne MG score before and after treatment were used to evaluate improvement of knee pain and joint function. The TGF-ß1 and Smad-1 levels in serum were measured before and after treatment in two groups. The incidence of complications in two groups was observed. RESULTS: All patients were followed up for 26 to 30 days with an average of (28.0±0.6) days. There was no significant difference in VAS and knee Lequesne MG scores between two groups before treatment(P>0.05). The scores of VAS and knee Lequesne MG on the first day after treatment in both groups were lower than those before treatment(P<0.05). The VAS and knee Lequesne MG scores in observation group were lower than those in control group(P<0.05) on the first day after treatment. The TGF-ß1 level in serum after treatment were higher significantly than that before treatment in two groups(P<0.05). After treatment, TGF-ß1 level in serum in observation group were lower than those in control group with statistically significant differences(P<0.05). The Smad-1 levels in serum after treatment in observation group were higher significantly than that in control group(P<0.05). The levels of Smad-1 were not statistically significant between before and after treatment(P>0.05). There was no significant difference in postopertaive complications between two groups (P>0.05). CONCLUSION: The efficacy of Bushen Chushi decoction combined with PRP in treatment of early and middle KOA is better than that of PRP injection alone. The combined treatment could reduce TGF-ß1 level and increase Smad-1 level in serum, which may be a mechanism to inhibit inflammation and alleviate cartilage degeneration to some extent.
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Osteoartritis de la Rodilla , Plasma Rico en Plaquetas , Masculino , Femenino , Humanos , Adulto , Persona de Mediana Edad , Anciano , Osteoartritis de la Rodilla/tratamiento farmacológico , Factor de Crecimiento Transformador beta1/genética , Resultado del Tratamiento , Inyecciones IntraarticularesRESUMEN
The indole-3-pyruvic acid (IPA) pathway is the main auxin biosynthesis pathway in the plant kingdom. Local control of auxin biosynthesis through this pathway regulates plant growth and development and the responses to biotic and abiotic stresses. During the past decades, genetic, physiological, biochemical, and molecular studies have greatly advanced our understanding of tryptophan-dependent auxin biosynthesis. The IPA pathway includes two steps: Trp is converted to IPA by TRYPTOPHAN AMINOTRANSFERASE OF ARABIDOPSIS/TRYPTOPHAN AMINOTRANSFERASE RELATED PROTEINs (TAA1/TARs), and then IPA is converted to IAA by the flavin monooxygenases (YUCCAs). The IPA pathway is regulated at multiple levels, including transcriptional and post-transcriptional regulation, protein modification, and feedback regulation, resulting in changes in gene transcription, enzyme activity and protein localization. Ongoing research indicates that tissue-specific DNA methylation and miRNA-directed regulation of transcription factors may also play key roles in the precise regulation of IPA-dependent auxin biosynthesis in plants. This review will mainly summarize the regulatory mechanisms of the IPA pathway and address the many unresolved questions regarding this auxin biosynthesis pathway in plants.
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Ácidos Indolacéticos , Plantas , Regulación de la Expresión Génica de las Plantas , Ácidos Indolacéticos/metabolismo , Plantas/metabolismo , Triptófano-Transaminasa/genética , Triptófano-Transaminasa/metabolismoRESUMEN
CONTEXT: Previously, we found Alisma orientalis beverage (AOB), a classic traditional Chinese medicine (TCM) formulation, had the potential effect of treating atherosclerosis (AS). The underlying mechanism was still unclear. OBJECTIVE: As an extention of our previous work, to investigate the underlying mechanism of action of AOB in the treatment for AS. MATERIALS AND METHODS: Network pharmacology was conducted using SwissTargetPrediction, GeneCards, DrugBank, Metascape, etc., to construct component-target-pathway networks. In vivo, AS models were induced by a high-fat diet (HFD) for 8 consecutive weeks in APOE-/- mice. After the administration of AOB (3.8 g/kg, i.g.) for 8 weeks, we assessed the aortic plaque, four indicators of blood lipids, and expression of the PI3K/AKT/SREBP-1 pathway in liver. RESULTS: Network pharmacology showed that PI3K/AKT/SREBP-1 played a role in AOB's treatment for AS (PI3K: degree = 18; AKT: degree = 17). Moreover, we found that the arterial plaque area and four indicators of blood lipids were all significantly reversed by AOB treatment in APOE-/- mice fed with HFD (plaque area reduced by about 37.75%). In addition, phosphorylated expression of PI3K/AKT and expression of SREBP-1 were obviously increased in APOE-/- mice fed with HFD, which were all improved by AOB (PI3K: 51.6%; AKT: 23.6%; SREBP-1: 40.0%). CONCLUSIONS: AOB had therapeutic effects for AS by improving blood lipids and inhibition of the PI3K/AKT/SERBP-1 pathway in the liver. This study provides new ideas for the treatment of AS, as well as new evidence for the clinical application of AOB.
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Alisma , Aterosclerosis , Placa Aterosclerótica , Animales , Ratones , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Alisma/metabolismo , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/metabolismo , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/farmacología , Transducción de Señal , Dieta Alta en Grasa/efectos adversos , Aterosclerosis/tratamiento farmacológico , Placa Aterosclerótica/tratamiento farmacológico , Lípidos , Apolipoproteínas E/genética , Apolipoproteínas E/farmacología , Apolipoproteínas E/uso terapéutico , Ratones Endogámicos C57BLRESUMEN
The auxin IAA (Indole-3-acetic acid) plays key roles in regulating plant growth and development, which depends on an intricate homeostasis that is determined by the balance between its biosynthesis, metabolism and transport. YUC flavin monooxygenases catalyze the rate-limiting step of auxin biosynthesis via IPyA (indole pyruvic acid) and are critical targets in regulating auxin homeostasis. Despite of numerous reports on the transcriptional regulation of YUC genes, little is known about those at the post-translational protein level. Here, we show that loss of function of CKRC3/TCU2, the auxiliary subunit (Naa25) of Arabidopsis NatB, and/or of its catalytic subunit (Naa20), NBC, led to auxin-deficiency in plants. Experimental evidences show that CKRC3/TCU2 can interact with NBC to form a NatB complex, catalyzing the N-terminal acetylation (NTA) of YUC proteins for their intracellular stability to maintain normal auxin homeostasis in plants. Hence, our findings provide significantly new insight into the link between protein NTA and auxin biosynthesis in plants.
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Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Acetilación , Ácidos Indolacéticos/metabolismo , Plantas/metabolismo , HomeostasisRESUMEN
Objective: This study aimed to explore the associations of genetic variants in the semaphorin 3A (SEMA3A) signaling pathway genes, including SEMA3A, NRP1, PLXNA1, PLXNA2 and PLXNA3 with osteoporosis (OP) risk and bone mineral density (BMD) in a Chinese Han older adult population. Study design and method: A two-stage design was adopted. Total of 47.8kb regions in the 5 genes were sequenced using targeted next-generation sequencing (NGS) technology in the discovery stage, and the discovered OP-related single nucleotide polymorphisms (SNPs) were further genotyped using improved multiple linkage detection reaction technique in the validation stage. Methods of ALP/TRAP staining, real-time fluorescent quantitative PCR, and cell proliferation and apoptosis assays were performed with MC3T3-E1 and RAW 264.7 cell lines to clarify biological effects of observed functional variants in cell lines responsible for bone mass remodeling. Results: Total of 400 postmenopausal women (211 OP cases) were involved in the discovery stage, where 6 common and 4 rare genetic variants were found to be associated with OP risk. In the validation stage among another 859 participants (417 women, 270 OP cases), the PLXNA2 rs2274446 T allele was associated with reduced OP risk and increased femoral neck (FN) BMD compared to the C allele. Moreover, significant associations of NRP1 rs2070296 with FN BMD/OP risk and of NRP1 rs180868035 with lumbar spine and FN BMDs were also observed in the combination dataset analysis. Compared to the osteoblasts/osteoclasts transfected with the wild-type NRP1 rs180868035, those transfected with the mutant-type had reduced mRNA expression of osteoblastic genes (i.e., ALP, RUNX2, SP7 and OCN), while elevated mRNA expression of osteoclastic genes (i.e., TRAP, NFATc1 and CTSK). Furthermore, mutant NRP1 rs180868035 transfection inhibited osteoblast proliferation and osteoclast apoptosis, while promoted osteoclast proliferation and osteoblast apoptosis in corresponding cell lines. Conclusion: Genetic variants located in NRP1 and PLXNA2 genes were associated with OP risk and BMD. The NRP1 rs180868035 affects bone metabolism by influencing osteoblasts and osteoclasts differentiation, proliferation and apoptosis.
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Densidad Ósea , Semaforina-3A , Transducción de Señal , Anciano , Femenino , Humanos , Apoptosis , Densidad Ósea/genética , Osteoclastos , Semaforina-3A/genética , Transducción de Señal/genética , Animales , Ratones , Células RAW 264.7 , PosmenopausiaRESUMEN
Since March 2020, the Kingdom of Saudi Arabia (KSA) has launched several digital applications to support the intervention response to reduce the spread of SARS-CoV-2. At the beginning of 2021, the KSA Government introduced a mandatory immunity passport to regulate access to public venues. The passport was part of the strategy of resuming public activities before reaching high vaccination coverage. The passport was implemented as a new service in the Tawakkalna mobile phone application (App). The immunity passport allowed access to public locations only for the users who recovered from COVID-19 or those who were double vaccinated. Our study aimed to evaluate the effectiveness of the immunity passport, implemented through the Tawakkalna App, on SARS-CoV-2 spread. We built a spatial-explicit individual-based model to represent the whole KSA population (IBM-KSA) and its dynamic on a national scale. The IBM-KSA was parameterized using country demographic, remote sensing, and epidemiological data. The model included non-pharmaceutical interventions and vaccination coverage. A social network was created to represent contact heterogeneity and interaction among age groups of the population. The IBM-KSA also simulated the movement of people across the country based on a gravity model. We used the IBM-KSA to evaluate the effect of the immunity passport on the COVID-19 epidemics outcomes. The IBM-KSA results showed that implementing the immunity passport through the Tawakkalna App mitigated the SARS-CoV2 spread. In a scenario without the immunity passport, the KSA could have reported 1,515,468 (95% confidence interval [CI]: 965,725-1,986,966) cases, and 30,309 (95% CI: 19,314-39,739) deaths from March 2021 to November 2021. The comparison of IBM-KSA results with COVID-19 official reporting estimated that the passport effectively reduced the number of cases, hospitalizations, and deaths by 8.7 times, 13.5 times, and 11.9 times, respectively. These results showed that the introduction of the immunity passport through the Tawakkalna App was able to control the spread of the SARS-COV-2 until vaccination reached high coverage. By introducing the immunity passport, The KSA was able to allow to resume most of public activities safely.
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Auxin is one of the most important plant growth regulators of plant morphogenesis and response to environmental stimuli. Although the biosynthesis pathway of auxin has been elucidated, the mechanisms regulating auxin biosynthesis remain poorly understood. The transcription of auxin biosynthetic genes is precisely regulated by complex signaling pathways. When the genes are expressed, epigenetic modifications guide mRNA synthesis and therefore determine protein production. Recent studies have shown that different epigenetic factors affect the transcription of auxin biosynthetic genes. In this review, we focus our attention on the molecular mechanisms through which epigenetic modifications regulate auxin biosynthesis.
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Limited evidence was found in the associations of volatile organic compound (VOC) exposure with bone health indicators. This study aimed to explore the associations of individual and combined metabolites of VOCs (mVOCs) in urine, a representative of the internal exposure level of VOCs, with bone mineral density (BMD), osteoporosis (OP) and fracture, and potential mediators. Data of the National Health Examination and Nutrition Survey 2005-2006 and 2013-2014 was used. Multiple linear and logistic regression modeling were performed to analyze the associations of individual mVOC with bone health indicators. The least absolute shrinkage and selection operator (LASSO) regression was adopted to select mVOCs that were more relevant to bone health indicators for further weight quantile sum (WQS) analysis used for analyzing the associations between multiple VOC co-exposure and bone health indicators. Mediation analysis was used to identify potential mediators. Seventeen mVOC members with detection rate of >50% in urine of all 3478 participants aged ≥20 years (1829 females) were involved. Levels of most mVOCs were higher in women than men. Eight mVOCs were negatively associated with BMDs, and two and four mVOCs were positively associated with OP and fracture risks, respectively. WQS regression revealed decreased femoral neck BMD (ß = -0.010 g/cm2, 95% CI: -0.020, -0.0001) and total spine BMD (ß = -0.015 g/cm2, 95% CI: -0.028, -0.002) in response to increasing mVOC mixture levels. And alkaline phosphatase (ALP), body mass index (BMI), fasting insulin (FI) and high-density lipoprotein (HDL), were mediators in the associations with proportions of mediating effect ranging from 4.6% to 10.2%. Individual and combined VOC (co-)exposure were associated with reduced BMDs in American adults. ALP, BMI, FI and HDL were demonstrated to be mediators in the association of multiple VOC co-exposure with BMD.
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Insulinas , Compuestos Orgánicos Volátiles , Absorciometría de Fotón , Adulto , Fosfatasa Alcalina , Densidad Ósea/fisiología , Femenino , Humanos , Lipoproteínas HDL , Masculino , Encuestas Nutricionales , Compuestos Orgánicos Volátiles/análisisRESUMEN
BACKGROUND: Large-scale detection has great potential to bring benefits for containing the COVID-19 epidemic and supporting the government in reopening economic activities. Evaluating the true regional mobile severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus nucleic acid testing capacity is essential to improve the overall fighting performance against this epidemic and maintain economic development. However, such a tool is not available in this issue. We aimed to establish an evaluation index system for assessing the regional mobile SARS-CoV-2 virus nucleic acid testing capacity and provide suggestions for improving the capacity level. METHODS: The initial version of the evaluation index system was identified based on massive literature and expert interviews. The Delphi method questionnaire was designed and 30 experts were consulted in two rounds of questionnaire to select and revise indexes at all three levels. The Analytic Hierarchy Process method was used to calculate the weight of indexes at all three levels. RESULTS: The evaluation index system for assessing the regional mobile SARS-CoV-2 virus nucleic acid testing capacity, including 5 first-level indexes, 17 second-level indexes, and 90 third-level indexes. The response rates of questionnaires delivered in the two rounds of consultation were 100 and 96.7%. Furthermore, the authority coefficient of 30 experts was 0.71. Kendall's coordination coefficient differences were statistically significant (P < 0.001). The weighted values of capacity indexes were established at all levels according to the consistency test, demonstrating that 'Personnel team construction' (0.2046) came first amongst the five first-level indexes, followed by 'Laboratory performance building and maintenance' (0.2023), 'Emergency response guarantee' (0.1989), 'Information management system for nucleic acid testing resources' (0.1982) and 'Regional mobile nucleic acid testing emergency response system construction' (0.1959). CONCLUSION: The evaluation system for assessing the regional mobile SARS-CoV-2 virus nucleic acid testing capacity puts forward a specific, objective, and quantifiable evaluation criterion. The evaluation system can act as a tool for diversified subjects to find the weak links and loopholes. It also provides a measurable basis for authorities to improve nucleic acid testing capabilities.
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COVID-19 , Ácidos Nucleicos , COVID-19/diagnóstico , COVID-19/epidemiología , China/epidemiología , Técnica Delphi , Humanos , SARS-CoV-2/genéticaRESUMEN
Background: Few studies have explored the association between water intake and mortality risk, and the findings were inconsistent. Objective: This study aimed to explore the water intake-mortality association, utilizing the data from the National Health and Nutrition Examination Survey (NHANES) and the 2015 public-linked mortality files released by the National Center for Health Statistics. Methods: We used the diet- and mortality-linked data of a total of 35,463 adults (17,234 men) aged ≥20 years in the NHANESs 1999-2014 to perform a prospective study. The multivariate-adjusted Cox proportional hazards model was used to explore the associations of the amount of water intake (expressed by total water, plain water, beverage, and food water) and water intake proportion (expressed by the percentage of each kind of water) with mortality risks due to all causes, malignant neoplasms/cancer, and heart disease. The restricted cubic spline plots were adopted to clarify the dose-response relationships among them. Results: With a median of 88 months (interquartile range: 49-136 months) follow-up, a total of 4,915 all-cause deaths occurred, including 1,073 and 861 deaths from malignant neoplasms/cancer and heart disease, respectively. The amount of water intake in either type was negatively associated with all-cause mortality risk. Additionally, the negative linear dose-response relationships of water intake and all-cause mortality risk were found for all types of water except for food water, which followed a non-linear pattern. Similarly, compared to the lowest quartile (beverage water intake: <676 g/day; food water intake: <532 g/day), beverage and food water intakes in the range of 1,033-1,524 and 1,612-3,802 g/day were associated with decreased malignant neoplasms/cancer mortality risk. A U-shaped dose-response relationship was found for beverage water intake and malignant neoplasms/cancer mortality risk and a negative linear dose-response relationship was found for food water intake and malignant neoplasms/cancer mortality risk. Coffee and/or tea consumption was/were negatively associated with mortality risks due to all causes and malignant neoplasms/cancer. No significant associations of water intake proportion and mortality risks were found. Conclusion: Our findings demonstrated that higher water intake is associated with lower mortality risks among the United States population.
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Background: The prevalence of noncommunicable diseases (NCDs) has been increasing in Saudi Arabia. Aims: Our objective was to estimate the effect of NCDs on direct medical costs and workforce productivity in Saudi Arabia. Methods: To estimate direct medical costs, we estimated the unit cost of treating 10 NCDs, then multiplied the unit cost by disease prevalence and summed across diseases. To estimate workforce productivity losses, we multiplied gross domestic product per person in the labour force by the loss in productivity from each NCD and the prevalence in the labour force of each NCD. Results: We estimated annual direct medical costs of 11.8 billion international dollars (Int$) for the 10 NCDs assessed (13.6% of total annual health expenditure). We estimated workforce productivity losses of Int$ 75.7 billion (4.5% of gross domestic product). Conclusion: The economic burden of NCDs in Saudi Arabia – particularly the effect on worker productivity – is substantial.
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Enfermedades no Transmisibles , Costo de Enfermedad , Estrés Financiero , Gastos en Salud , Recursos Humanos , EmpleoRESUMEN
Interest in functional food, such as non-digestible prebiotic oligosaccharides is increasing day by day and their production is shifting toward sustainable manufacturing. Due to the presence of high carbohydrate content, lignocellulosic biomass (LCB) is the most-potential, cost-effective and sustainable substrate for production of many useful products, including lignocellulose-derived prebiotic oligosaccharides (LDOs). These have the same worthwhile properties as other common oligosaccharides, such as short chain carbohydrates digestible to the gut flora but not to humans mainly due to their resistance to the low pH and high temperature and their demand is constantly increasing mainly due to increased awareness about their potential health benefits. Despite several advantages over the thermo-chemical route of synthesis, comprehensive and updated information on the conversion of lignocellulosic biomass to prebiotic oligomers via controlled enzymatic saccharification is not available in the literature. Thus, the main objective of this review is to highlight recent advancements in enzymatic synthesis of LDOs, current challenges, and future prospects of sustainably producing prebiotic oligomers via enzymatic hydrolysis of LCB substrates. Enzyme reaction engineering practices, custom-made enzyme preparations, controlled enzymatic hydrolysis, and protein engineering approaches have been discussed with regard to their applications in sustainable synthesis of lignocellulose-derived oligosaccharide prebiotics. An overview of scale-up aspects and market potential of LDOs has also been provided.
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Biomasa , Microbioma Gastrointestinal/efectos de los fármacos , Lignina , Oligosacáridos , Prebióticos , Humanos , Lignina/química , Lignina/uso terapéutico , Oligosacáridos/química , Oligosacáridos/uso terapéuticoRESUMEN
BACKGROUND & AIMS: Existing epidemiological studies explored the associations of circulating vitamins and mortality focusing on individual vitamin effects, and controversial findings were obtained. The joint effects of multiple vitamin co-exposure are worth studying. The study aimed to elucidate the associations of circulating vitamins and the joint effects of these vitamins' co-exposure with all-cause and cause-specific mortality risks. METHODS: We prospectively evaluated the associations of the concentrations of six kinds of vitamins (A, D, E, C, B12 and B9) in serum with risks for all-cause and cause-specific mortalities among U.S. adults. Mortality status and cause of death were determined by NHANES-linked public available files dated up to 31 December 2015. An unsupervised K-means clustering method was used to cluster the participants into several vitamin co-exposure patterns. The Cox proportional hazards model was used for statistical analysis. RESULTS: A total of 1404 deaths occurred during a median of 10.9 years follow-up among 8295 participants. In multivariable adjustment, increasing levels of vitamin D were associated with reduced all-cause and cause-specific mortality risks. A J-shaped nonlinear exposure-response relationship was observed between all studied vitamins (except for vitamin D) and all-cause mortality risk. Four co-exposure patterns were generated based on the studied vitamins, as follows: low-level exposure (cluster 1), vitamin A/D exposure (cluster 2), water-soluble vitamin exposure (cluster 3) and high-level exposure (cluster 4). Compared with those in cluster 1, participants in cluster 2 had lower all-cause and cancer mortality risks, with hazard ratios (95% confidence intervals [CIs]) of 0.67 (0.53, 0.85) and 0.45 (0.29, 0.71), respectively. CONCLUSIONS: The findings in this study indicated that high circulating vitamin D levels were associated with reduced mortality risk among U.S. adults. Vitamin co-exposure at moderate levels appropriately contributed to low all-cause and cancer mortality risks. Our findings provided a novel perspective for exploring the joint health effects of multivitamin co-exposure. Future investigations are needed to further unravel the underlying mechanisms of possible vitamin interactions.
Asunto(s)
Dieta/mortalidad , Exposición Dietética/efectos adversos , Vitaminas/sangre , Adulto , Causas de Muerte , Exposición Dietética/análisis , Femenino , Humanos , Masculino , Persona de Mediana Edad , Encuestas Nutricionales , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Estados Unidos , Adulto JovenRESUMEN
Objective: This study aimed to explore the relationships between the common variants of R-spondin/Wnt signaling genes, gut microbiota composition, and osteoporosis (OP) risk in elderly Chinese Han population. Design: Dual-energy X-ray absorptiometry was used to obtain the OP-associated measurements at multiple skeleton sites among all 1,168 participants. Genotyping data was obtained by using the next-generation sequencing in the discovery stage (n = 400, 228 OP patients) and SNPscan technology in the replication stage (n = 768, 356 OP patients). Bioinformatic analysis was performed to provide more evidence for the genotype-OP associations. The 16S ribosomal RNA gene high-throughput sequencing technology was adopted to explore OP-associated gut microbiota variations. Results: The genetic variants of rs10920362 in the LGR6 gene (P-FDR = 1.19 × 10-6) and rs11178860 in the LGR5 gene (P-FDR = 1.51 × 10-4) were found to associate with OP risk significantly. Several microbial taxa were associated with the BMDs and T-scores at multiple skeleton sites. The associations between rs10920362 and BMD-associated microbiota maintained significance after adjusting confounders. The rs10920362 CT/TT genotype associated with a decreased relative abundance of Actinobacteria (ß = -1.32, P < 0.001), Bifidobacteriaceae (ß = -1.70, P < 0.001), and Bifidobacterium (ß = -1.70, P < 0.001) compared to the CC genotype. Conclusion: Our findings suggested that the variants loci of LGR6 may be associate with OP pathogenesis via gut microbiota modifications. The relationship between host genetics and gut microbiome provides new perspectives about OP prevention and treatment.
RESUMEN
Bacterial cellulose (BC) is higher in demand due to its excellent properties which is attributed to its purity and nano size. Komagataeibacter xylinum is a model organism where BC production has been studied in detail because of its higher cellulose production capacity. BC production mechanism shows involvement of a series of sequential reactions with enzymes for biosynthesis of cellulose. It is necessary to know the mechanism to understand the involvement of regulatory proteins which could be the probable targets for genetic modification to enhance or regulate yield of BC and to alter BC properties as well. For the industrial production of BC, controlled synthesis is desired so as to save energy, hence genetic manipulation opens up avenues for upregulating or controlling the cellulose synthesis in the bacterium by targeting genes involved in cellulose biosynthesis. In this review article genetic modification has been presented as a tool to introduce desired changes at genetic level resulting in improved yield or properties. There has been a lack of studies on genetic modification for BC production due to limited availability of information on whole genome and genetic toolkits; however, in last few years, the number of studies has been increased on this aspect as whole genome sequencing of several Komagataeibacter strains are being done. In this review article, we have presented the mechanisms and the targets for genetic modifications in order to achieve desired changes in the BC production titer as well as its characteristics.