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1.
Artigo em Inglês | MEDLINE | ID: mdl-35577318

RESUMO

The objective of the present research was to assess the influence of inositol supplementation on growth performance, histological morphology of liver, immunity and expression of immune-related genes in juvenile hybrid grouper (♀ Epinephelus fuscoguttatus × ♂ E. lanceolatu). Hybrid grouper (initial weight 6.76 ±â€¯0.34 g) were fed isonitrogenous and isolipidic diets (16%) with various inositol levels of 0.17 g/kg (J1, the control group), 0.62 g/kg (J2), 1.03 g/kg (J3), 1.78 g/kg (J4), 3.43 g/kg (J5), 6.59 g/kg (J6), respectively. The growth experiment lasted for 8 weeks. The results indicated that dietary inositol had a significant promoting effect on final mean body weight of the J5 and J6 groups and specific growth rate (SGR) of the J3, J4, J5 and J6 groups (P < 0.05). In the serum, superoxide dismutase (SOD) of the J4 group became significantly active compared with that of the control group (P < 0.05), while aspartate transaminase (AST), alanine transaminase (ALT) and alkaline phosphatase (AKP) activities in the inositol-treated groups showed distinctly decreased compared with those of the control group (P < 0.05). In the liver, dietary inositol could significantly increase the activities of SOD, catalase (CAT), lysozyme (LYZ) and the contents of total antioxidative capacity (T-AOC) and immunoglobulin M (IgM) (P < 0.05), and distinctly reduce the content of malondialdehyde (MDA) as well as reactive oxygen species (ROS) (P < 0.05). Compared with the control group, the damaged histological morphology of the liver was relieved and even returned to normal after an inositol increase (0.4-3.2 g/kg). In the liver, the remarkable up-regulation of SOD, CAT, glutathione peroxidase (GPX), heat shock protein70 (HSP70) and heat shock protein90 (HSP90) expression levels were stimulated by supply of inositol, while interleukin 6 (IL6), interleukin 8 (IL8) and transforming growth factor ß (TGF-ß) expression levels were down-regulated by supply of inositol. In head kidney, the mRNA of toll-like receptor 22 (TLR22), myeloid differentiation factor 88 (MyD88) and interleukin 1ß (IL1ß) expression levels were significantly down-regulated (P < 0.05), which could further lead to remarkable down-regulation of IL6 and tumor necrosis factor α (TNF-α) expression (P < 0.05). These results indicated that high-lipid diets with supply of inositol promoted growth, increased the antioxidant capacity, and suppressed the inflammation of the liver and head kidney by inhibiting the expression of pro-inflammation factors (IL6, IL8, TGF-ß and TNF-α). In conclusion, these results indicated that dietary inositol promoted growth, improved antioxidant capacity and immunity of hybrid grouper fed high-lipid diets. Based on SGR, broken-line regression analysis showed that 1.66 g/kg inositol supply was recommended in high-lipid diets of juvenile grouper.

2.
Clin Drug Investig ; 42(5): 459-464, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35511414

RESUMO

BACKGROUND: Osimertinib may improve the prognosis of patients with epidermal growth factor receptor (EGFR) T790M-mutated non-small cell lung cancer (NSCLC); however, to date, the efficacy and safety of osimertinib plus bevacizumab have not been elucidated. OBJECTIVE: We aimed to investigate the additional effect of bevacizumab plus osimertinib compared with osimertinib alone in NSCLC patients with EGFR T790M mutation. METHODS: In this study, 32 patients received osimertinib alone, while 20 patients received osimertinib plus bevacizumab. The median follow-up was 12 months. Overall survival (OS) and progression-free survival (PFS) were estimated and adverse events (AEs) were compared. RESULTS: The overall response rate (ORR) was higher in the combination group than in the osimertinib-alone group (70.0% vs. 43.8%), and the OS (12.8% ± 7.7% vs. 45.4% ± 12.0%; p = 0.038) and PFS (37.3% ± 11.9% vs. 55.3% ± 14.3%; p = 0.045) were also significantly improved in patients who underwent osimertinib plus bevacizumab. Furthermore, the incidence of hypertension was significantly higher in the combination arm when compared with osimertinib alone (p = 0.003), and the number of other AEs were not significantly increased by adding bevacizumab (all p > 0.05). CONCLUSION: Concomitant use of bevacizumab and osimertinib in NSCLC patients with EGFR T790M mutation may have potential therapeutic effect than osimertinib alone. Further studies with a larger number of patients are warranted to confirm results of this study.

3.
Int J Biol Sci ; 18(7): 2684-2702, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35541921

RESUMO

Macroautophagy/autophagy is the process of self-digestion through the lysosomes; it disassembles unnecessary or dysfunctional long-lived proteins and damaged organelles for the recycling of biomacromolecules. Unfortunately, cancer cells can hijack this mechanism to survive under metabolic stress or develop drug resistance during chemotherapy. Increasing evidence indicates that the combination of autophagy inhibition and chemotherapy is a promising cancer treatment strategy. However, effective autophagy inhibitors with satisfied potency, bioavailability, and clearly-defined drug targets are still rare. Here, we report the identification of a potent autophagy inhibitor toosendanin which can effectively block autophagosome maturation, causing the accumulation of autophagy substrates in multiple cancer cells. Toosendanin did not inhibit the fusion process between autophagosome and lysosome but elevated lysosomal pH and impaired lysosomal enzymes activity. Using rat liver lysosome fraction and purified yeast V-ATPase, we found that toosendanin directly inhibited V-ATPase activity. By applying cellular thermal shift assay (CETSA), immunoprecipitation-coupled LC-MS/MS analysis, and biotin-toosendanin pull-down assay, we confirmed the direct binding between toosendanin and V-ATPase. Furthermore, toosendanin blocked chemotherapy-induced protective autophagy in cultured cancer cells and xenograft tumor tissues to significantly enhance anti-cancer activity. These results suggest that toosendanin has the potential to be developed into an anti-cancer drug by blocking chemotherapy-induced protective autophagy.


Assuntos
Antineoplásicos , Neoplasias , ATPases Vacuolares Próton-Translocadoras , Adenosina Trifosfatases/metabolismo , Animais , Antineoplásicos/farmacologia , Autofagia , Cromatografia Líquida , Humanos , Neoplasias/tratamento farmacológico , Ratos , Espectrometria de Massas em Tandem , Triterpenos , ATPases Vacuolares Próton-Translocadoras/metabolismo , ATPases Vacuolares Próton-Translocadoras/farmacologia
4.
Transl Cancer Res ; 11(4): 813-822, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35571660

RESUMO

Background: Lovastatin is an inhibitor of 3-hydroxy-3-methylglutaryl-CoA reductase, effectively inhibiting cholesterol synthesis. Previous research findings showed that lovastatin markedly suppressed tumor cell proliferation and metastasis and induced apoptosis. The present study aimed to determine the underlying mechanism of the suppressive effect of lovastatin on the growth of human lung cancer cells. Methods: The A549 cell line was treated with different concentrations of lovastatin. Subsequently, cell proliferation and colony formation were analyzed, along with the expression of apoptosis-related proteins (ERK1/2, c-JUN, COX-2, BCL-2, and BAX) by western blotting and immunofluorescence staining. Experimental data were analyzed with SPSS 25.0 and expressed as the mean ± SEM. One-way ANOVA or two-way independent samples t-test were used. Results: The results confirmed that lovastatin suppressed cell viability and reduced the numbers of cell colonies, and a concentration-dependent response was observed with increasing lovastatin concentrations (P<0.05). Accordingly, these suppressive effects were related to decreased protein expression levels of p-ERK1/2/ERK1/2, p-c-JUN/c-JUN, COX-2, and BCL-2 and increased BAX protein expression (P<0.05). Furthermore, we conducted an experimental intervention with low-dose LPS+ATP to stimulate A549 cell growth, and then examined the proliferation and apoptosis of A549 cells after LPS+ATP+50 µM lovastatin intervention. The principal finding of this research was that lovastatin still suppressed A549 cell growth after LPS+ATP stimulation via modulation of ERK1/2, c-JUN, COX-2, BCL-2, and BAX protein levels (P<0.05). Conclusions: Collectively, the findings presented in this study confirmed that lovastatin can inhibit A549 cell proliferation by regulating the ERK1/2 and COX-2 pathways.

5.
Proc Natl Acad Sci U S A ; 119(19): e2115231119, 2022 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-35500118

RESUMO

SignificanceMassive carbon (C) release with abrupt warming has occurred repeatedly during greenhouse states, and these events have driven episodes of ocean deoxygenation and extinction. Records from these paleo events, coupled with biogeochemical modeling, provide clear evidence that with continued warming, the modern oceans will experience substantial deoxygenation. There are, however, few constraints from the geologic record on the effects of rapid warming under icehouse conditions. We document a C-cycle perturbation that occurred under an Earth system state experiencing recurrent glaciation. A suite of proxies suggests increased seafloor anoxia during this event in step with abrupt increase in CO2 partial pressure and a biodiversity nadir. Warming-mediated increases in marine anoxia may be more pronounced in a glaciated versus unglaciated climate state.


Assuntos
Aquecimento Global , Água do Mar , Carbono/análise , Humanos , Hipóxia , Oceanos e Mares
6.
J Sci Food Agric ; 2022 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-35510347

RESUMO

BACKGROUND: Protein-polysaccharide complexes have been widely used to stabilize high-internal-phase emulsion (HIPEs). However, it is still unknown whether soy protein isolate-dextran (SPI-Dex) complexes can stabilize HIPEs or what is the effect of Dex concentration on the HIPEs. Besides, the noncovalent interaction mechanism between SPI and Dex is also unclear. Therefore, we fabricated SPI-Dex complexes and used them to stabilize HIPEs-loaded quercetin to explore the interaction mechanism between SPI and Dex and the effect of Dex concentration on the particle size, ζ-potential, microstructure, rheology, quercetin encapsulation efficiency, and gastrointestinal fate of the HIPEs. RESULTS: Spectral analysis (fourier transform infrared spectroscopy, ultraviolet spectroscopy, and fluorescence spectroscopy) results identified the formation of SPI-Dex complexes, and indicated that the addition of Dex changed the spatial structure of SPI, while thermodynamic analysis (ΔH > 0, ΔS > 0) showed that hydrophobic interactions were the main driving forces in the formation of SPI-Dex complexes. Compared with HIPEs stabilized by SPI, the SPI-Dex complex-stabilized HIPEs had smaller particles (3000.33 ± 201.22 nm) and higher ζ-potential (-21.73 ± 1.10 mV), apparent viscosities, modulus, and quercetin encapsulation efficiency (98.19±0.14%). In addition, in vitro digestion revealed that SPI-Dex complex-stabilized HIPEs significantly reduced the release of free fatty acid and improved quercetin bioaccessibility. CONCLUSION: HIPEs stabilized by SPI-Dex complexes delayed the release of free fat acid and improved the bioaccessibility of quercetin, may be help in designing delivery systems for bioactive substances with specific properties. This article is protected by copyright. All rights reserved.

7.
Sleep Breath ; 2022 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-35579792

RESUMO

OBJECTIVES: The purpose of this study was to systematically analyze the studies of hypertension associated with obstructive sleep apnea to assess the current status and hot spots in this field. METHODS: We searched the Web of Science Core Collection for publications related to hypertension associated with obstructive sleep apnea published before July 3, 2021. Bibliometric analyses and science mappings were carried out using the CiteSpace 5.8.R1 and Microsoft Office Excel 2019. CiteSpace 5.8.R1 was used to visualize the distribution of research fields, analyze co-occurring keywords and burst terms to detect trends and frontiers, and identify leading collaborations among countries, authors, and institutions. Microsoft Office Excel 2019 was used to make bar graphs, histograms and line graphs. RESULTS: According to the search strategy, a total of 7263 published articles and reviews were retrieved. The research on hypertension associated with obstructive sleep apnea has been developing quickly at present. Sleep and Breathing was the most productive journal. The USA was a major producing country and Harvard Medical School was the most productive institution in this field. In the field of hypertension associated with obstructive sleep apnea, the main research hotspots were continuous positive airway pressure, cardiovascular disease, and obesity. CONCLUSIONS: The present study provides a new perspective for the study of hypertension associated with obstructive sleep apnea and valuable information for researchers to find potential partners and cooperative institutions, hot issues and research frontiers.

8.
Chin Med ; 17(1): 55, 2022 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-35524271

RESUMO

BACKGROUND: Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer that develops resistance to chemotherapy frequently. Autophagy has been reported as a pro-survival response to chemotherapeutic drugs in TNBC, and suppression of autophagy can be a strategy to overcome drug resistance. METHODS: The efficacy of toosendanin (TSN) in blocking autophagy flux was measured by western blot analysis of autophagy markers, and the fluorescent imaging of RFP-GFP-LC3 probe. The co-localization of autophagosomes and lysosomes was analyzed by fluorescent imaging. Then, lysosome function was determined by measuring the lysosomal pH value and the activity of lysosomal hydrolytic proteases. For in vitro study, human triple-negative breast cancer MDA-MB-231 and MDA-MB-436 cell lines were used for evaluating the anti-proliferative effect. For in vivo study, the RFP-GFP-LC3 MDA-MB-231 xenograft nude mice received intraperitoneal injection of irinotecan (10 mg/kg), TSN (0.5 mg/kg) or a combination, and the autophagy activity and cell apoptosis were determined in tumor tissue. The degree of pathological injury of tissue was evaluated by liver index. RESULTS: The natural autophagy inhibitor TSN, a triterpenoid extracted from Melia toosenda Sieb. et Zucc, potently inhibited late-stage autophagy in TNBC cells. This effect was achieved via elevating lysosome pH rather than blocking the fusion of autophagosomes and lysosomes. We further investigated the effects of TSN on the in vitro and in vivo TNBC models, in combination with chemotherapeutic drug irinotecan (or its active metabolite 7-ethyl-10-hydroxycamptothecin), a topoisomerase I inhibitor showing therapeutic potential for TNBC. The data showed that TSN blocked 7-ethyl-10-hydroxycamptothecin (SN-38)/irinotecan-induced protective autophagy, and significantly induced apoptosis in TNBC cells and tumor xenograft models when compared to SN-38/irinotecan alone group.

9.
Mol Hum Reprod ; 2022 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-35536241

RESUMO

Human cytotrophoblast differentiation into syncytiotrophoblast is essential for placental formation and function. Understanding the molecular mechanisms involved in trophoblast differentiation is necessary as it would help in the development of novel therapeutic agents to treat placentation-mediated pregnancy complications. In this study, we found a common up-regulated gene, ADAMDEC1, from five published microarray and RNA-sequencing datasets. Interference to ADAMDEC1 impaired forskolin-induced BeWo cells differentiation, while ADAMDEC1 overexpression promoted BeWo cells and 3D JEG-3 spheroids differentiation. Interestingly, ADAMDEC1 may inhibit THBS1 rather than E-cadherin to trigger the activation of the cAMP signal pathway during cytotrophoblast differentiation into syncytiotrophoblast. More importantly, a decreasing in ADAMDEC1 might be involved in the development of preeclampsia. Therefore, ADAMDEC1 is expected to become a new target for prediction of and intervention in placenta-derived pregnancy diseases.

10.
Fitoterapia ; : 105207, 2022 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-35569637

RESUMO

Oxidative stress has been considered as the main factor of neurodegenerative diseases. Activation of the Nrf2/HO-1 pathway, as one of the most crucial endogenous protection systems, was regarded as an effective strategy to against oxidative injury. Here, a series of phosphate esters or phosphonates of scutellarein derivatives were designed, synthesized and evaluated on SH-SY5Y cell lines to examine neuroprotective effects against H2O2 induced damage. Among them, compound 16d exhibited more potent cytoprotective effect than the lead compound scutellarin. Preliminary mechanism studies showed that compound 16d could prevent H2O2 induced neuronal apoptosis, significantly decrease ROS generation, elevate SOD and reduce MDA levels in a dose-dependent manner in SH-SY5Y cell lines. Furthermore, western blot assay disclosed that compound 16d could activate Nrf2, and increase the expression of its downstream genes HO-1 in a concentration-dependent manner, thus displaying potent neuroprotective activity. Overall, these findings demonstrated that compound 16d, as a promising neuroprotective agent, deserved further development.

11.
Pharm Dev Technol ; : 1-26, 2022 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-35575444

RESUMO

Oxybutynin (OXY) is the most common drug to treat overactive bladder (OAB) syndrome. Transdermal administration is a more ideal route replacing oral administration to resolve problems of low bioavailability and severe side effects. However, commercial transdermal products of OXY frequently cause skin irritation and low permeation efficiency arising discontinued medication. Here, oxybutynin nanosuspension (OXY-NS) and its gel preparation (OXY-NG) were constructed to resolve these issues. In vitro permeation test and in vivo pharmacokinetics study confirmed that OXY-NG significantly enhanced the transdermal permeation of OXY, about 4-fold and 3-fold higher than oxybutynin coarse suspension (OXY-CG) respectively and in vitro retention test certified that OXY-NG increased OXY concentration especially in viable epidermis (VE) and Dermis (about 3 times that of OXY-CG), consequently improving the bioavailability. Skin irritation assay demonstrated that OXY-NG would not trigger skin adverse effects. In addition, selectively blocking hair follicles test evidenced that hair follicles pathway played an important role in OXY-NS transdermal delivery. In general, by virtue of excellent drug loading, low toxicity and ease of scale-up, OXY-NG is a promising strategy to ameliorate skin permeation of insoluble OXY for better transdermal treatment for OAB, hence increasing its bioavailability, reducing adverse effects and achieving good patient compliance.

12.
Comput Math Methods Med ; 2022: 9222541, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35437448

RESUMO

Background: Allergic contact dermatitis (ACD) is a form of chronic cutaneous inflammatory disease of immunological origin that has adverse impacts on patient quality of life, underscoring the need for the development of safe and effective therapeutic agents to treat affected individuals. Fisetin is a Chinese herbal preparation that reportedly exhibits antitumor, antioxidant, antimicrobial, anticoagulatory, and antimalarial activity. In the current report, the immunomodulatory activity of fisetin was appraised by assessing its impact on balance between regulatory T (Treg) and Th17 cells in an ACD model. Methods: BALB/c mice (n = 60) were randomized into control, ACD model, CTX positive control (20 mg/kg), and fisetin treatment groups (three dose levels: 2, 4, or 8 mg/kg). ACD induction was achieved by sensitizing mice on the shaved ventral abdomen via the application of 5% DNFB (50 µL) on days 1 and 2, followed by rechallenge in the right ear with 5% DNFB (20 µL) on day 5. Beginning on day 1, immunized mice were intraperitoneally injected with the appropriate fisetin dose (in saline) once per day for 7 days. On day 7, ear swelling, transcription factor expression, Th17/Treg cell populations, and cytokine production were assessed in vivo. Results: Fisetin treatment significantly suppressed ear swelling and associated inflammatory cell infiltration, besides reducing the production of Th17 cytokines (IL-17, TNF-α, and IL-6) and the expression of the Th17 lineage transcription factor RORγt while simultaneously enhancing Treg-specific cytokine production (TGF-ß and IL-10) and the expression of the Treg lineage transcription factor Foxp3, thereby restoring the Th17/Treg cell in ACD mice. Conclusions: These data indicate that fisetin exhibits immunomodulatory activity and can alter the Th17/Treg cell balance, highlighting its potential value as a treatment drug for ACD.


Assuntos
Dermatite Alérgica de Contato , Linfócitos T Reguladores , Animais , Citocinas , Dinitrofluorbenzeno/farmacologia , Flavonóis , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Qualidade de Vida , Células Th17 , Fatores de Transcrição
13.
Nutr Diabetes ; 12(1): 25, 2022 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-35468888

RESUMO

BACKGROUND: Inappropriate weight gain may increase the risk of gestational diabetes mellitus (GDM). However, the relationship between pre-pregnancy body mass index (BMI), weight gain, and GDM has not been precisely quantified. This study aimed to explore whether gestational weight gain played a mediating role between pre-pregnancy BMI and GDM and whether the mediating effect was sex specific. METHODS: This study established a population-based observational cohort to assess weight gain in pregnant women. Mediation analyses were performed to quantify whether weight gain mediated the association between pre-pregnancy BMI and GDM. RESULTS: A total of 67,777 pregnant women were included in the final analysis, among whom 6751 (10.0%) were diagnosed with GDM. We verified that both pre-pregnancy BMI and weight gain were associated with GDM, and that BMI negatively contributed to weight gain. We also found that weight gain had a significant mediating effect on the relationship between pre-pregnancy BMI and GDM (Za × Zb confidence intervals [CIs] 0.00234-0.00618). Furthermore, the effect was sex-specific, in that it was only significant in overweight women carrying female fetuses (Za × Zb CIs 0.00422-0.01977), but not male fetuses (Za × Zb CIs -0.00085 to 0.01236). CONCLUSIONS: Weight gain during pregnancy had a fetal sex-specific mediating effect between pre-pregnancy BMI and GDM.


Assuntos
Diabetes Gestacional , Ganho de Peso na Gestação , Índice de Massa Corporal , Feminino , Humanos , Masculino , Sobrepeso/complicações , Gravidez , Ganho de Peso
14.
Front Immunol ; 13: 847200, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35479085

RESUMO

Objectives: The purpose of this study was to investigate the association of neutrophil percentage-to-albumin ratio (NPAR) with the severity at admission and discharge (short-term prognosis) in patients with anti-N-methyl-D-aspartic acid receptor (NMDAR) encephalitis. Methods: Multivariable logistic regression models such as NPAR were constructed based on univariable regression results. Receiver operating characteristic (ROC) curves, nomograms, and concordance index (c-index) were used to evaluate the efficacy of the models in assessing disease severity at admission and predicting short-term prognosis, validated by bootstrap, Hosmer-Lemeshow goodness-of-fit test, calibration curves, and decision curve analysis. Results: A total of 181 patients with anti-NMDAR encephalitis diagnosed at the First Affiliated Hospital of Zhengzhou University were included. The results showed that NPAR had good sensitivity and specificity in assessing disease severity at admission and predicting short-term prognosis. The multivariable logistic regression models based on NPAR and other influencing factors had good discrimination, consistency, accuracy, calibration ability, applicability, and validity in assessing the severity at admission and predicting short-term prognosis. Conclusion: NPAR has good clinical value in assessing disease severity at admission and predicting short-term prognosis of patients with anti-NMDAR encephalitis.


Assuntos
Encefalite Antirreceptor de N-Metil-D-Aspartato , Neutrófilos , Albuminas , Encefalite Antirreceptor de N-Metil-D-Aspartato/diagnóstico , Humanos , Prognóstico , Curva ROC
15.
Proc Natl Acad Sci U S A ; 119(15): e2110018119, 2022 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-35377805

RESUMO

SignificanceThermal diffusion is dissipative and strongly related to non-Hermitian physics. At the same time, non-Hermitian Weyl systems have spurred tremendous interest across photonics and acoustics. This correlation has been long ignored and hence shed little light upon the question of whether the Weyl exceptional ring (WER) in thermal diffusion could exist. Intuitively, thermal diffusion provides no real parameter dimensions, thus prohibiting a topological nature and WER. This work breaks this perception by imitating synthetic dimensions via two spatiotemporal advection pairs. The WER is achieved in thermal diffusive systems. Both surface-like and bulk states are demonstrated by coupling two WERs with opposite topological charges. These findings extend topological notions to diffusions and motivate investigation of non-Hermitian diffusive and dissipative control.

16.
Crit Rev Food Sci Nutr ; : 1-13, 2022 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-35380474

RESUMO

Individual omega-6 polyunsaturated fatty acids (PUFAs), principally linoleic acid (LA) and arachidonic acid (AA), may have differential impacts on cardiovascular risk. We aimed to summarize the up-to-date epidemiology evidence on the relationship between blood levels of omega-6 PUFAs and the risk of coronary heart disease (CHD). Population-based studies determining PUFA levels in blood were identified until May 2021 in PubMed, Embase, Web of Science, and Cochrane Library. Random-effects meta-analyses of cohorts comparing the highest versus lowest category were conducted to combine study-specific risk ratios (RRs) with 95% confidence intervals (CIs). Blood levels of omega-6 PUFAs were compared between the CHD case and non-case, presented as a weight mean difference (WMD). Twenty-one cohorts and eleven case-control studies were included. The WMD was -0.71 (95% CI: -1.20, -0.21) for LA and 0.08 (95% CI: -0.28, 0.43) for AA. LA levels were inversely associated with total CHD risk (RR: 0.85, 95% CI: 0.71, 1.00), but not AA. Each one-SD increase in LA levels resulted in 10% reductions in the risk of fatal CHD (RR: 0.90, 95% CI: 0.86, 0.95), but not in non-fatal CHD. Such findings highlight that the current recommendation for optimal intakes of omega-6 PUFAs (most LA) may offer a coronary benefit in primary prevention.

17.
Pharmaceuticals (Basel) ; 15(4)2022 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-35455393

RESUMO

Osteoporosis is a systemic skeletal disorder affecting over 200 million people worldwide and contributes dramatically to global healthcare costs. Available anti-osteoporotic drug treatments including hormone replacement therapy, anabolic agents, and bisphosphonates often cause adverse events which limit their long-term use. Therefore, the application of natural products has been proposed as an alternative therapy strategy. Icaritin (ICT) is not only an enzyme-hydrolyzed product of icariin but also an intestinal metabolite of eight major flavonoids of the traditional Chinese medicinal plant Epimedium with extensive pharmacological activities, such as strengthening the kidney and reinforcing the bone. ICT displays several therapeutic effects, including osteoporosis prevention, neuroprotection, antitumor, cardiovascular protection, anti-inflammation, and immune-protective effect. ICT inhibits bone resorption activity of osteoclasts and stimulates osteogenic differentiation and maturation of bone marrow stromal progenitor cells and osteoblasts. As for the mechanisms of effect, ICT regulates relative activities of two transcription factors Runx2 and PPARγ, determines the differentiation of MSCs into osteoblasts, increases mRNA expression of OPG, and inhibits mRNA expression of RANKL. Poor water solubility, high lipophilicity, and unfavorable pharmacokinetic properties of ICT restrict its anti-osteoporotic effects, and novel drug delivery systems are explored to overcome intrinsic limitations of ICT. The paper focuses on osteogenic effects and mechanisms, pharmacokinetics and delivery systems of ICT, and highlights bone-targeting strategies to concentrate ICT on the ideal specific site of bone. ICT is a promising potential novel therapeutic agent for osteoporosis.

18.
BMC Pregnancy Childbirth ; 22(1): 336, 2022 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-35440068

RESUMO

BACKGROUND: Gestational diabetes mellitus (GDM) is associated with adverse health consequences for women and their offspring. It is associated with maternal body mass index (BMI) and may be associated with gestational weight gain (GWG). But due to the heterogeneity of diagnosis and treatment and the potential effect of GDM treatment on GWG, the association between the two has not been thoroughly clarified. Compared to body weight, BMI has the advantage that it considers height during the whole course of pregnancy. Understanding BMI changes during pregnancy may provide new evidence for the prevention of GDM. METHODS: This study investigated the BMI change of pregnant women based on a retrospective study covering all communities in Tianjin, China. According to the results of GDM screening at 24-28 weeks of gestation, pregnancies were divided into the GDM group and the non-GDM group. We compared gestational BMI change and GWG in the two groups from early pregnancy to GDM screening. GWG was evaluated according to the IOM guidelines. Logistic regression was applied to determine the significance of variables with GDM. RESULTS: A total of 41,845 pregnant women were included in the final analysis (GDM group, n = 4257 vs. non-GDM group, n = 37,588). BMI gain has no significant differences between the GDM and non-GDM groups at any early pregnancy BMI categories (each of 2 kg/m2), as well as weight gain (P > 0.05). Early pregnancy BMI was a risk factor for GDM (OR 1.131, 95% CI 1.122-1.139). And BMI gain was associated with a decreased risk of GDM in unadjusted univariate analysis (OR 0.895, 95% CI 0.869-0.922). After adjusting on early pregnancy BMI and other confounding factors, the effect of BMI gain was no longer significant (AOR 1.029, 95% CI 0.999-1.061), as well as weight gain (AOR 1.006, 95% CI 0.995-1.018) and GWG categories (insufficient: AOR 1.016, 95% CI 0.911-1.133; excessive: AOR 1.044, 95% CI 0.957-1.138). CONCLUSIONS: BMI in early pregnancy was a risk factor for GDM, while BMI gain before GDM screening was not associated with the risk of GDM. Therefore, the optimal BMI in early pregnancy is the key to preventing GDM.


Assuntos
Diabetes Gestacional , Índice de Massa Corporal , Diabetes Gestacional/diagnóstico , Diabetes Gestacional/epidemiologia , Feminino , Humanos , Gravidez , Resultado da Gravidez , Gestantes , Estudos Retrospectivos , Ganho de Peso
19.
Front Pharmacol ; 13: 745074, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35450051

RESUMO

Shenerjiangzhi formulation (SEJZ) is a new traditional Chinese medicine formulation (patent number: CN110680850A). SEJZ contains Eleutherococcus senticosus (Rupr. and Maxim.), Maxim (Araliaceae; E. senticosus radix and rhizome), Lonicera japonica Thunb (Caprifoliaceae; Lonicera japonica branch, stem), Crataegus pinnatifida Bunge (Rosaceae; Crataegus pinnatifida fruit), and Auricularia auricula. SEJZ has been designed to treat hyperlipidemia. Despite the therapeutic benefits of SEJZ, its underlying mechanism of action is not known. We explored the efficacy of SEJZ against hyperlipidemia by integrating network pharmacology and 16S rRNA gene sequencing and elucidated its mechanism of action. First, SEJZ targets were found through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and from the literature. Hyperlipidemia-related therapeutic targets were obtained from GeneCards, Online Mendelian Inheritance in Man, and DrugBank databases. Then, Search Tool for the Retrieval of Interacting Genes/Proteins and Cytoscape were applied for the analyses and construction of a protein-protein interaction (PPI) network. The Kyoto Encyclopedia of Genes and Genomes database was employed to identify signaling pathways that were enriched. Second, the therapeutic effects of SEJZ against hyperlipidemia induced by consumption of a high-fat diet in rats were evaluated by measuring body weight changes and biochemical tests. SEJZ treatment was found to alleviate obesity and hyperlipidemia in rats. Finally, 16S rRNA gene sequencing showed that SEJZ could significantly increase the abundance of short-chain fatty acid-producing bacteria, restore the intestinal barrier, and maintain intestinal-flora homeostasis. Using PICRUSt2, six metabolic pathways were found to be consistent with the results of network pharmacology: "African trypanosomiasis", "amoebiasis", "arginine and proline metabolism", "calcium signaling pathway", "NOD-like receptor signaling pathway", and "tryptophan metabolism". These pathways might represent how SEJZ works against hyperlipidemia. Moreover, the "African trypanosomiasis pathway" had the highest association with core genes. These results aid understanding of how SEJZ works against dyslipidemia and provide a reference for further studies.

20.
Zhongguo Zhen Jiu ; 42(4): 447-50, 2022 Apr 12.
Artigo em Chinês | MEDLINE | ID: mdl-35403408

RESUMO

HUANG Xue-long is a direct disciple of CHENG Dan-an. He is the second-generation representative heir of Chengjiang school. Through research on his practice and achievements of acupuncture and moxibustion scientization, we found that his main contributions were as follows. He has carried out beneficial explorations along with the scientific thinking of Chengjiang school, elucidated the theory of acupoints, clarified acupuncture and moxibustion manipulations, and explained the mechanism of acupuncture and moxibustion. His explorations promote the scientific process of acupuncture and moxibustion and enrich the academic system of acupuncture and moxibustion.


Assuntos
Terapia por Acupuntura , Acupuntura , Moxibustão , Pontos de Acupuntura , China , Humanos , Masculino , Instituições Acadêmicas
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