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1.
Acta Trop ; : 106844, 2023 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-36706827

RESUMO

Blastocystis is an enteric protozoan able to infect humans and a large variety of animal hosts worldwide. It exhibits significant genetic diversity, with at least 17 subtypes (STs) identified to date, most of which have low host specificity. In the present study, a cross-sectional survey was conducted on Blastocystis infection among humans and domestic animals sharing habitats in northeastern China's Heilongjiang Province, in order to investigate the frequency and subtype distribution and to evaluate the risk of the zoonotic transmission of Blastocystis sp..Results show that the frequency was 10.5% (6/57), and three subtypes (ST1, ST2, and ST3) were found in humans; in animals, the frequency was 17.9% (46/257), and six subtypes (ST1, ST3, ST5, ST7, ST10, and ST26) were detected. A significant association between Blastocystis sp. infection and eating unwashed vegetables and fruits was found (P = 0.007). We found no effect on gender, age and season on Blastocystis sp. colonization. Phylogenetic analysis showed that Blastocystis ST7 sequences from chicken in two geographical locations formed two distinct clades. Alleles were identified using the Blastocystis 18S database, and a total of 10 different alleles were found in seven STs. Overlap of STs in humans and domestic animals (pig or cattle) was observed in Dongfanghong village. The findings of potentially zoonotic subtypes in domestic animals suggest that these animals may serve as reservoirs of human Blastocystis sp. infections. Multisectoral cooperation is needed to slow down the transmission of Blastocystis in domestic animals, minimize environmental contamination by Blastocystis cysts, and increase molecular epidemiological surveillance of Blastocystis sp. in humans and animals.

2.
Food Sci Nutr ; 11(1): 443-457, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36655068

RESUMO

Acrylamide has been well known for its neurotoxicity, genotoxicity, carcinogenicity, etc. Recently, the immunotoxicity of acrylamide has been reported by different research groups, although the underlying mechanisms of acrylamide endangering immune systems have not been fully elucidated. In this study, mouse monocyte-macrophage cells model was used to clarify the toxic mechanism of acrylamide and the inhibitory effect of Yam polysaccharides (YPS) on acrylamide-induced damage. We found that acrylamide induced RAW 264.7 cell death in a time- and concentration-dependent manner. After acrylamide (2.0, 3.0, 4.0 mmol/L) treatment for 24 h, cell apoptosis, autophagy, and pyroptosis were observed. However, the levels of autophagy and pyroptosis decreased at a high concentration of acrylamide (4.0 mmol/L). Acrylamide upregulated P2X7 expression, but the P2X7 level was not showing a monotone increasing trend. When the P2X7 antagonist was applied, the effect of acrylamide on autophagy and pyroptosis was weakened. Additionally, acrylamide triggered the occurrence of oxidative stress and a decreased nitric oxide (NO) level. However, reactive oxygen species (ROS) generation, the decrease of heme oxygenase-1 (HO-1) expression, and the increase of inducible nitric oxide synthase (iNOS) expression were reversed by the inhibition of P2X7. Yam polysaccharides (50.0 µg/ml) significantly inhibited acrylamide-induced oxidative stress and cell death (including apoptosis, autophagy, and pyroptosis). Yam polysaccharides also effectively reversed the increase of iNOS expression induced by acrylamide. However, Yam polysaccharides promoted the expression of P2X7 rather than prohibit it. These results indicated that acrylamide caused RAW 264.7 cell death due to pro-apoptosis as well as excessive autophagy and pyroptosis. Apoptosis might be more predominant than autophagy and pyroptosis under a higher concentration of acrylamide (4.0 mmol/L). P2X7-stimulated oxidative stress was responsible for acrylamide-induced programmed cell death (PCD), but P2X7 showed limited regulatory effect on apoptosis. Yam polysaccharides with antioxidant activity inhibited acrylamide-induced cell death (apoptosis, autophagy, and pyroptosis), but exerted limited effect on the acrylamide-induced P2X7 expression. These findings would offer an insight into elucidating the immunotoxic mechanism of acrylamide and the potential approaches to control its toxicity.

3.
Med Sci Monit ; 29: e939464, 2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36628645

RESUMO

This publication has been retracted by the Editor due to the identification of non-original figure images and manuscript content that raise concerns regarding the credibility and originality of the study and the manuscript. Reference: Jiang, He Li, Heping Xiang, Ming Gao, Chunlin Yin, Haiping Wang, Yuansong Sun, Maoming Xiong. Long Chain Non-Coding RNA (lncRNA) HOTAIR Knockdown Increases miR-454-3p to Suppress Gastric Cancer Growth by Targeting STAT3/Cyclin D1. Med Sci Monit, 2019; 25: 1537-1548. DOI: 10.12659/MSM.913087.

4.
Artigo em Inglês | MEDLINE | ID: mdl-36674288

RESUMO

Heatwaves occur frequently in summer, severely harming the natural environment and human society. While a few long-term spatiotemporal heatwave studies have been conducted in China at the grid scale, their shortcomings involve their discrete distribution and poor spatiotemporal continuity. We used daily data from 691 meteorological stations to obtain torridity index (TI) and heatwave index (HWI) datasets (0.01°) in order to evaluate the spatiotemporal distribution of heatwaves in the Chinese mainland for the period of 1990-2019. The results were as follows: (1) The TI values rose but with fluctuations, with the largest increase occurring in North China in July. The areas with hazard levels of medium and above accounted for 22.16% of the total, mainly in the eastern and southern provinces of China, South Tibet, East and South Xinjiang, and Chongqing. (2) The study areas were divided into four categories according to the spatiotemporal distribution of hazards. The "high hazard and rapidly increasing" and "low hazard and continually increasing" areas accounted for 8.71% and 41.33% of the total, respectively. (3) The "ten furnaces" at the top of the provincial capitals were Zhengzhou, Nanchang, Wuhan, Changsha, Shijiazhuang, Nanjing, Hangzhou, Haikou, Chongqing, and Hefei. While the urbanization level and population aging in the developed areas were further increased, the continuously increasing heatwave hazard should be fully considered.


Assuntos
Humanos , Estações do Ano , China/epidemiologia , Cidades , Tibet
5.
Biomater Sci ; 2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36601967

RESUMO

Multimodal image-guided photothermal therapy (PTT) has great application potential in cancer treatment due to its advantages of low side effects and good efficacy. There is an urgent need for PTT nanocarriers with high loading efficiency and modified surfaces. Goat milk-derived extracellular vesicles (GMVs) an ideal PTT nanoplatforms due to their anti-inflammatory ability, tumor retention ability, high yield, and high biosafety. This study used GMVs to design a theranostic nanoprobe for positron emission tomography/computer tomography/near-infrared fluorescence (PET/CT/NIRF) imaging and image-guided PTT for colon cancer. The key genes, important biological processes, and important signaling pathways of indocyanine green (ICG)-mediated PTT and N3-GMV@ICG-mediated PTT were analyzed. The nanoprobe triggered anti-tumor immune and inflammation responses to enhance PTT. In addition, the nanoprobe could attenuate PTT-induced inflammation benefiting from the anti-inflammatory efficacy of GMVs. Therefore, our findings conceptually advanced the diagnosis and treatment of colon cancer. We believed that the nanoprobe had broad clinical transformation prospects, and GMVs might be ideal nanocarriers for constructing integrated diagnostic and PTT probes.

7.
Psychiatry Res ; 320: 115052, 2023 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-36645990

RESUMO

Thyroid dysfunction is common in major depressive disorder (MDD) patients; however, its relationship with psychotic depression (PD) remains unclear. We aimed to assess thyroid hormones in 1718 first episode drug naïve (FEND) MDD patients and to determine their association with PD. The positive subscale of the Positive and Negative Symptom Scale (PANSS-P), Hamilton Anxiety Rating Scale (HAMA), and Hamilton Depression Rating Scale (HAMD) were used to detect clinical symptoms. The serum levels of free triiodothyronine (FT3), free thyroxine (FT4), thyroid stimulating hormone (TSH), anti-thyroglobulin (TgAb), and thyroid peroxidases antibody (TPOAb) were assessed. The logistic regression model was conducted to determine risk factors for PD, and the Area Under the Curve (AUC) was used to test the performance of this model. 171 (10%) patients were identified as having PD. Serum levels of TSH, TgAb, and TPOAb displayed small-to-moderate associations with PANSS-P. HAMA score, HAMD score, and TSH levels were independently associated with PD. The regression model had excellent power to distinguish PD patients from non-PD patients with an AUC value of 0.93. Our study suggests TSH levels and severity of depression and anxiety symptoms were independent risk factors for PD. Regular thyroid function tests may help early detect PD.

8.
Sci Total Environ ; 866: 161250, 2023 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-36610627

RESUMO

Large scale Ecosystem restoration projects (ERPs) have been implemented to restore vegetation and increase carbon stocks across China. However, whether restored vegetation is strongly resistant to Extreme drought events (EDEs) remains unclear, especially when compared to natural vegetation. Therefore, we used the standardized anomaly of 3-month Standard Precipitation-Evapotranspiration Index (SPEI) to characterize the spatial-temporal trends of EDEs, and figured out the capacity of restored vegetation to withstand the strongest EDE in Southwest China by analyzing their changes of Gross Primary Productivity (GPP) and Water Use Efficiency (WUE). The results showed that Southwest China had experienced six typical EDEs with increasing frequency and severity from 1982 to 2017, particularly the EDE during 2009-2010 (EDE 2009/2010) which had the longest duration and strongest severity. Overall, the EDE 2009/2010 substantially suppressed the vegetation GPP and ecosystem WUE in both restored and natural vegetation area. Compared with natural vegetation, the GPP and WUE of restored vegetation was relative higher and moreover, their GPP decreased more slowly during the EDE 2009/2010 and increased more quickly during the recovery period. This indicates that restored vegetation had a higher drought resistance to the EDE than natural vegetation. Additionally, karst landforms have a stronger negative impact on vegetation GPP and WUE during the EDE. Furthermore, the reduction in the afforestation areas was more obviously observed than that in natural forest areas. Therefore, we suggest that vegetation suitable for regional characteristics should be selected during vegetation restoration, such as afforestation in the non-karst areas.

9.
Nat Commun ; 14(1): 221, 2023 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-36639386

RESUMO

Imitating the natural photosynthesis to synthesize hydrocarbon fuels represents a viable strategy for solar-to-chemical energy conversion, where utilizing low-energy photons, especially near-infrared photons, has been the ultimate yet challenging aim to further improving conversion efficiency. Plasmonic metals have proven their ability in absorbing low-energy photons, however, it remains an obstacle in effectively coupling this energy into reactant molecules. Here we report the broadband plasmon-induced CO2 reduction reaction with water, which achieves a CH4 production rate of 0.55 mmol g-1 h-1 with 100% selectivity to hydrocarbon products under 400 mW cm-2 full-spectrum light illumination and an apparent quantum efficiency of 0.38% at 800 nm illumination. We find that the enhanced local electric field plays an irreplaceable role in efficient multiphoton absorption and selective energy transfer for such an excellent light-driven catalytic performance. This work paves the way to the technique for low-energy photon utilization.

10.
Am J Med Genet A ; 2023 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-36598158

RESUMO

Protein phosphatase 1 regulatory subunit 35 (PPP1R35) encodes a centrosomal protein required for recruiting microtubule-binding elongation machinery. Several proteins in this centriole biogenesis pathway correspond to established primary microcephaly (MCPH) genes, and multiple model organism studies hypothesize PPP1R35 as a candidate MCPH gene. Here, using exome sequencing (ES) and family-based rare variant analyses, we report a homozygous, frameshifting indel deleting the canonical stop codon in the last exon of PPP1R35 [Chr7: c.753_*3delGGAAGCGTAGACCinsCG (p.Trp251Cysfs*22)]; the variant allele maps in a 3.7 Mb block of absence of heterozygosity (AOH) in a proband with severe MCPH (-4.3 SD at birth, -6.1 SD by 42 months), pachygyria, and global developmental delay from a consanguineous Turkish kindred. Droplet digital PCR (ddPCR) confirmed mutant mRNA expression in fibroblasts. In silico prediction of the translation of mutant PPP1R35 is expected to be elongated by 18 amino acids before encountering a downstream stop codon. This complex indel allele is absent in public databases (ClinVar, gnomAD, ARIC, 1000 genomes) and our in-house database of 14,000+ exomes including 1800+ Turkish exomes supporting predicted pathogenicity. Comprehensive literature searches for PPP1R35 variants yielded two probands affected with severe microcephaly (-15 SD and -12 SD) with the same homozygous indel from a single, consanguineous, Iranian family from a cohort of 404 predominantly Iranian families. The lack of heterozygous cases in two large cohorts representative of the genetic background of these two families decreased our suspicion of a founder allele and supports the contention of a recurrent mutation. We propose two potential secondary structure mutagenesis models for the origin of this variant allele mediated by hairpin formation between complementary GC rich segments flanking the stop codon via secondary structure mutagenesis.

11.
Food Chem ; 409: 135321, 2023 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-36586250

RESUMO

The contamination of mycotoxin in edible oil has always been a major threat to human health. In this study, magnetic soybean dreg-based biochar SDB-6-K-9@Fe3O4 was prepared via co-precipitation and used to remove aflatoxin B1 (AFB1) from contaminated oil. The adsorbent characterization results revealed that the Fe3O4 was successfully loaded to the SDB-6-K-9. The 0.45SDB-6-K-9@Fe3O4 had paramagnetic properties with a saturation magnetization of 45.15 emu/g, which could be quickly separated from the peanut oil using an external magnet. The maximum adsorption capacity of peanut oil contaminated with 200 ng/mL AFB1 by 50 mg 0.45SDB-6-K-9@Fe3O4 for 2 h reached 0.1354 mg/g, while the removal process minimally affected the quality of the oil. The adsorption behavior results followed a pseudo-second-order kinetic and fitted well with the Freundlich model. The excellent adsorption removal efficiency and facile magnetic separation of the adsorbents provide a simple and efficient method for removing contaminants from the oil.


Assuntos
Aflatoxina B1 , Poluentes Químicos da Água , Humanos , Adsorção , Óleo de Amendoim , Aflatoxina B1/análise , Soja , Porosidade , Fenômenos Magnéticos , Poluentes Químicos da Água/análise , Cinética
12.
Chemosphere ; 314: 137641, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36584828

RESUMO

Much attention has been paid on polybrominated diphenyl ethers (PBDEs) in household dust due to their ubiquitous occurrences in the environment. Based on the data from 59 articles sampled from 2005 to 2020, we investigated the spatio-temporal distribution, sources, and health risk of 8 PBDE homologues in household dusts worldwide. BDE-209 is the predominant PBDE in household dusts, followed by BDE-99 and BDE-47. The total concentrations of PBDEs (∑8PBDEs) are found to be high in household dusts sampled from 2005 to 2008 and show a significant decline trend from 2009 to 2016 (p < 0.05) and a little upward tendency from 2017 to 2020. The concentrations of PBDEs in household dusts vary greatly in different countries of the world. The use of penta-BDE is the main source of three to five bromo-biphenyl ether monomers contributing 17.4% of ∑8PBDEs, while BDE-209 and BDE-183 are derived from the use of household appliances contributing 82.6% of ∑8PBDEs. Ingestion is the main exposure route for adults and toddlers, followed by dermal contact. The values of hazard index (HI) exposed to PBDEs in household dusts are all less than 1 for both adults and toddlers, indicating a low non-cancer risk. The incremental lifetime cancer risks (ILCRs) of BDE-209 are less than 10-6 for both adults and toddlers, suggesting a negligible risk. However, the total carcinogenic risk of toddlers is higher than that of adults, indicating that much attention should be paid to toddlers exposed to BDE-209 in household dust.


Assuntos
Poluição do Ar em Ambientes Fechados , Neoplasias , Adulto , Humanos , Éteres Difenil Halogenados/análise , Poeira/análise , Poluição do Ar em Ambientes Fechados/análise , Medição de Risco , Monitoramento Ambiental , Exposição Ambiental/análise
13.
Eur J Pharmacol ; 938: 175410, 2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36511324

RESUMO

Hepatocellular carcinoma (HCC) is often diagnosed at advanced stages with no effective treatment options. Mechanistically, it is a complex biological process. Recently, the main cause of its incidence is changing from viral to non-viral. It has been shown that high cholesterol levels can cause the further transformation of non-alcoholic fatty liver disease (NAFLD) to HCC, but some investigations have found that serum cholesterol levels are negatively correlated with morbidity and mortality. Conflicting experimental results and epidemiological investigations illustrate the complex mechanisms of HCC. Cholesterol is essential for the survival of the body and tumors, although research on the function of cholesterol in tumors is evolving, the use of lowering cholesterol drugs in treating HCC remains limited. In this review, the cholesterol-involved mechanisms that cause the development of HCC or reduce the mortality and the latest progress in the use of cholesterol in the treatment of HCC and prospects for prevention and diagnosis have been summarized.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Hepatopatia Gordurosa não Alcoólica , Humanos , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/diagnóstico , Hepatopatia Gordurosa não Alcoólica/patologia , Incidência , Colesterol
14.
Cell Signal ; : 110550, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36464104

RESUMO

Common liver tissue damage is mainly due to the accumulation of toxic aldehydes in lipid peroxidation under oxidative stress. Cumulative toxic aldehydes in the liver can be effectively metabolized by acetaldehyde dehydrogenase 2 (ALDH2), thereby alleviating various liver diseases. Notably, gene mutation of ALDH2 leads to impaired ALDH2 enzyme activity, thus aggravating the progress of liver diseases. However, the relationship and specific mechanism between ALDH2 and liver diseases are not clear. Consequently, the review explains the relationship between ALDH2 and liver diseases such as alcoholic liver disease (ALD), non-alcoholic fatty liver disease (NAFLD), liver fibrosis and hepatocellular carcinoma (HCC). In addition, this review also discusses ALDH2 as a potential therapeutic target for various liver diseases,and focuses on summarizing the regulatory mechanism of ALDH2 in these liver diseases.

15.
Front Med (Lausanne) ; 9: 1001584, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36465896

RESUMO

Background: Stress ulcer (SU) is one of the main causes of prolonged hospital stay, poor prognosis, and increased mortality in critically ill patients. This study aimed to investigate the effect of electroacupuncture (EA) on SU in patients with severe neurological diseases and explore its possible mechanisms. Methods: Taking patients with SU in adult neurocritical care as the research object, they were randomly divided into the EA group and the control group. Through the perioperative EA intervention, the following indicators were documented: main observation indicator (the effective rate of SU treatment), secondary observation indicators (gastric juice pH, gastric juice occult blood test, and stool occult blood test), related mechanisms [repair factors trefoil factor family 2 (TFF2), vascular endothelial growth factor (VEGF), and heat shock protein 70 (HSP70)], complications during hospitalization, and intensive care unit (ICU) stay time. Results: Compared with the control treatment, EA increased the effective rate of SU treatment (85.4% for the EA group, 57.5% for the control group, risk difference: 27.9% (95% CI: 8.3%-45.1%); P < 0.01). EA increased the success rate of gastric juice pH treatment on days 1, 2, and 3 (P < 0.01 for day 1, P < 0.05 for days 2 and 3). EA lowered the positive rate of gastric occult blood test on days 1 and 3 (all P-values < 0.05) and the positive rate of fecal occult blood test on day 3 (P < 0.05). EA also reduced the ICU stay time (P < 0.01) and total hospitalization time (P < 0.05). Compared with day 0, all serum repair factors (VEGF, HSP70, and TFF2) of both groups significantly increased on days 1, 3, and 5 (all P-values < 0.01). Compared with the control group, VEGF in the EA group was increased on days 3 and 5 (all P-values < 0.01); HSP70 was increased on days 1, 3, and 5 (P < 0.05 for day 1, P < 0.01 for days 3 and 5); and TFF2 was increased on days 1, 3, and 5 (all P-values < 0.01). Conclusion: Electroacupuncture promoted the repair of SU damage in severe neurological disease, and its effect was related to enhancing the expression of gastric mucosal repair factors. Clinical trial registration: [https://www.chictr.org.cn/showprojen.aspx?proj=127012], identifier [ChiCTR2100046701].

16.
Artigo em Inglês | MEDLINE | ID: mdl-36468174

RESUMO

Superoxide dismutase (SOD) is one of the major antioxidants in vivo and is expected to play critical roles on the defense against reactive oxygen species (ROS)-mediated damages, such as ionizing radiation damages. Herein, inspired by the function and structure of natural SODs and cerium oxide nanozymes, two monovalent cerium-based metal organic frameworks (Ce-MOFs), CeIIIBTC and CeIVBTC, were designed for superoxide radical (O2•-) elimination and ionizing radiation protection. These two Ce-MOFs selectively scavenge O2•- and are excellent SOD mimics. Like natural SODs and cerium oxide nanozymes, the SOD-like catalytic mechanism of Ce-MOFs involves a cycle between Ce(IV) and Ce(III). Furthermore, by constructing monovalent Ce-MOFs, we found that high-valent CeIVBTC are more effective SOD-like nanozymes compared to CeIIIBTC. With smaller size, better monodispersity, and more effective SOD-like activity, CeIVBTC nanozymes were further applied for ionizing radiation protection. Both in vitro and in vivo results demonstrated that CeIVBTC nanozymes could efficiently scavenge ROS, prevent cells from γ-ray radiation-induced cell viability decrease and DNA damages, and improve the survival rate of irradiated mice by recovering the bone marrow DNA damage and alleviating oxidative stress of tissues. The protective effect and good biocompatibility of CeIVBTC nanozymes will enable the development of Ce-MOFs-based radioprotectants and facilitate treatment of other ROS-related diseases.

17.
ACS Nano ; 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36454190

RESUMO

Hepatic fibrosis is a chronic liver disease that lacks effective pharmacotherapeutic treatments. As part of the disease's mechanism, hepatic stellate cells (HSCs) are activated by damage-related stimuli to secrete excessive extracellular matrix, leading to collagen deposition. Currently, the drug delivery system that targets HSCs in the treatment of liver fibrosis remains an urgent challenge due to the poor controllability of drug release. Since the level of reactive oxygen species (ROS) increases sharply in activated HSCs (aHSCs), we designed ROS-responsive micelles for the HSC-specific delivery of a traditional Chinese medicine, resveratrol (RES), for treatment of liver fibrosis. The micelles were prepared by the ROS-responsive amphiphilic block copolymer poly(l-methionine-block-Nε-trifluoro-acetyl-l-lysine) (PMK) and a PEG shell modified with a CRGD peptide insertion. The CRGD-targeted and ROS-responsive micelles (CRGD-PMK-MCs) could target aHSCs and control the release of RES under conditions of high intracellular ROS in aHSCs. The CRGD-PMK-MCs treatment specifically enhanced the targeted delivery of RES to aHSCs both in vitro and in vivo. In vitro experiments show that CRGD-PMK-MCs could significantly promote ROS consumption, reduce collagen accumulation, and avert activation of aHSCs. In vivo results demonstrate that CRGD-PMK-MCs could alleviate inflammatory infiltration, prevent fibrosis, and protect hepatocytes from damage in fibrotic mice. In conclusion, CRGD-PMK-MCs show great potential for targeted and ROS-responsive controlled drug release in the aHSCs of liver fibrosis.

18.
Foods ; 11(23)2022 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-36496577

RESUMO

Dietary habits have a substantial influence on both planet and individual health. High intake of animal products has significant negative effects on the environment and on human health; hence, a reduction in meat consumption is necessary. The transition towards plant-based meat (PBM) is one of the potential solutions for environmental and health issues. To achieve this goal, it is important to understand the dietary habits and demands of consumers. This review was designed with a focus on PBM alternatives, dietary shifts during the COVID-19 pandemic, the drivers of consumers' perceptions in various countries, and the measures that can promote the shift towards PBM. The PBM market is predicted to grow with rising awareness, familiarity, and knowledge in the coming years. Companies must focus on the categories of anticipated benefits to aid consumers in making the switch to a diet higher in PBM alternatives if they want to win over the target market.

19.
BMC Cardiovasc Disord ; 22(1): 575, 2022 12 30.
Artigo em Inglês | MEDLINE | ID: mdl-36581799

RESUMO

BACKGROUNDS: Remarkable interindividual variability in clopidogrel response is observed, genetic polymorphisms in P2RY12 and its signal pathway is supposed to affect clopidogrel response in CHD patients. METHODS: 539 CHD patients treated with clopidogrel were recruited. The platelet reaction index (PRI) indicated by VASP-P level were detected in 12-24 h after clopidogrel loading dose or within 5-7 days after initiation of maintain dose clopidogrel. A total of 13 SNPs in relevant genes were genotyped in sample A (239 CHD patients). The SNPs which have significant differences in PRI will be validated in another sample (sample B, 300 CHD patients). RESULTS: CYP2C19*2 increased the risk of clopidogrel resistance significantly. When CYP2C19*2 and CYP2C19*3 were considered, CYP2C19 loss of function (LOF) alleles were associated with more obviously increased the risk of clopidogrel resistance; P2RY12 rs6809699C > A polymorphism was also associated with increased risk of clopidogrel resistance (AA vs CC: P = 0.0398). This difference still existed after stratification by CYP2C19 genotypes. It was also validated in sample B. The association was also still significant even in the case of stratification by CYP2C19 genotypes in all patients (sample A + B). CONCLUSION: Our data suggest that P2RY12 rs6809699 is associated with clopidogrel resistance in CHD patients. Meanwhile, the rs6809699 AA genotype can increase on-treatment platelet activity independent of CYP2C19 LOF polymorphisms.


Assuntos
Clopidogrel , Doença das Coronárias , Inibidores da Agregação Plaquetária , Receptores Purinérgicos P2Y12 , Humanos , Clopidogrel/farmacologia , Doença das Coronárias/tratamento farmacológico , Doença das Coronárias/genética , Citocromo P-450 CYP2C19/genética , Genótipo , Inibidores da Agregação Plaquetária/farmacologia , Polimorfismo de Nucleotídeo Único , Antagonistas do Receptor Purinérgico P2Y/farmacologia , Receptores Purinérgicos P2Y12/genética
20.
J Invest Dermatol ; 2022 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-36529262

RESUMO

Although tremendous progress has been made in targeted and immune-based treatments for advanced melanoma, there remains a substantial therapeutic failure rate. For patients with BRAF(V600)-mutant melanomas, resistance to BRAF inhibitors remains a significant survival hurdle. Although multiple compensatory mechanisms to bypass BRAF blockade have been discovered, the epigenetic patterns are still poorly characterized. In this report, we generated eight matched pairs of vemurafenib-sensitive/-resistant melanoma lines and subjected these to concurrent RNA-sequencing and H3K27ac chromatin immunoprecipitation sequencing analysis. Globally, we identified two classes of epigenetic profiles that correlate with resistance. Class 1 resistance involves fewer RNA expression alterations accompanied by fewer enhancer mark changes with H3K27ac. Class 2 resistance shows widespread alterations in transcription and enhancer profiles, which converge on epithelial‒mesenchymal transition and hypoxia-related pathways. We also observed significant and dynamic changes in superenhancers that underpin these transcriptomic patterns. We subsequently verified the two-class structure in pre-BRAF inhibitors and postrelapse human melanoma specimens. Our findings reveal a broad and underappreciated spectrum of epigenetic plasticity during acquired BRAF inhibitor resistance.

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