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1.
Methods Mol Biol ; 2375: 77-90, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-34591300

RESUMEN

Human tissue-engineered blood vessels (TEBVs) that exhibit vasoactivity can be used to test drug toxicity, modulate pro-inflammatory cytokines, and model disease states in vitro. We developed a novel device to fabricate arteriole-scale human endothelialized TEBVs in situ with smaller volumes and higher throughput than previously reported. Both primary and induced pluripotent stem cell (iPSC)-derived cells can be used. Four collagen TEBVs with 600µm inner diameter and 2.9 mm outer diameter are fabricated by pipetting a solution of collagen and medial cells into a three-layer acrylic mold. After gelation, the TEBVs are released from the mold and dehydrated. After suturing the TEBVs in place and changing the mold parts to form a perfusion chamber, the TEBVs are endothelialized in situ, and then media is perfused through the lumen. By removing 90% of the water after gelation, the TEBVs become mechanically strong enough for perfusion at the physiological shear stress of 0.4 Pa within 24 h of fabrication and maintain function for at least 5 weeks.

2.
Zhongguo Zhen Jiu ; 41(10): 1171-4, 2021 Oct 12.
Artículo en Chino | MEDLINE | ID: mdl-34628753

RESUMEN

Through analyzing the indication distribution of the different acupoints located at the upper limbs recorded in Science of Acupoints and Science of Meridians and Acupoints, the industry planning teaching materials of traditional Chinese medicine, it is discovered that the acupoints located at the upper arms are commonly selected for the treatment of scrofula and goiter, while the acupoints below the elbow at the hand meridians and those at the lower limbs of the foot meridians which running through the neck, do not have the similar indications. Based on a further analysis on the literature at ancient and modern times, it is believed that the acupoints located on the lateral side of the upper arms, especially those at the large intestine meridian of hand-yangming perhaps have the specific effect in treatment of scrofula and goiter.


Asunto(s)
Bocio , Meridianos , Tuberculosis Ganglionar , Puntos de Acupuntura , Brazo , Humanos
3.
Trials ; 22(1): 691, 2021 Oct 10.
Artículo en Inglés | MEDLINE | ID: mdl-34629085

RESUMEN

BACKGROUND: Anemia is one of the main complications of chronic kidney disease especially kidney failure, which includes treatment with erythropoiesis-stimulating agents and iron supplementation, including intravenous and oral iron. However, intravenous iron may pose limitations, such as potential infusion reactions. Oral iron is mainly composed of divalent iron, which can excessively stimulate the gastrointestinal tract. Iron polysaccharide complex capsules are a novel oral iron trivalent supplement with higher iron content and lower gastrointestinal irritation. However, since high-quality evidence-based medicinal support is lacking, it is necessary to conduct clinical studies to further evaluate the effectiveness and safety of oral iron polysaccharide complex in chronic kidney disease patients. METHODS: This randomized controlled trial uses an open-label, parallel group design, where the efficacy and safety of maintenance hemodialysis (MHD) participants is evaluated. The experimental group is assigned erythropoietins and iron polysaccharide complex (two capsules each time, bid), and the control group is assigned erythropoietin and sucrose iron (100mg, 2w) injection. Participants (aged 18-75 years) undergoing maintenance hemodialysis were considered for screening. Inclusion criteria included hemoglobin (Hb) ≥110g/L and < 130g/L, transferrin saturation (TSAT) > 20% and < 50%, and serum ferritin (SF) > 200µg/L and < 500µg/L. Exclusion criteria included acute or chronic bleeding, serum albumin < 35g/L, hypersensitive C-reactive protein (HsCRP) > 10 mg/L, and severe secondary hyperparathyroidism (iPTH ≥ 800 pg/mL). Full inclusion and exclusion criteria are described in the "Methods" section. The primary endpoint is TSAT of the participants at week 12. Secondary endpoints include Hb, SF, hematocrit (Hct), HsCRP, pharmacoeconomic evaluation, drug costs, quality of life, and indicators of oxidative stress. The treatment will last for 24 weeks with a follow-up visit at baseline (within 7 days prior to initial treatment) and weeks 4, 8, 12, 16, 20, and 24 after initial treatment. This clinical research includes 9 hemodialysis centers in mainland China and plans to enroll 186 participants. DISCUSSION: It is expected that it will provide strong evidence to reveal the clinical efficacy and safety of oral iron in the treatment of chronic CKD-related anemia in MHD patients through this clinical trial. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2000031166 . Registered on March 23, 2020.


Asunto(s)
Anemia Ferropénica , Calidad de Vida , Anemia Ferropénica/diagnóstico , Anemia Ferropénica/tratamiento farmacológico , Anemia Ferropénica/etiología , Cápsulas , Sacarato de Óxido Férrico , Humanos , Hierro , Estudios Multicéntricos como Asunto , Polisacáridos/efectos adversos , Ensayos Clínicos Controlados Aleatorios como Asunto , Diálisis Renal
5.
J Am Chem Soc ; 2021 Oct 04.
Artículo en Inglés | MEDLINE | ID: mdl-34607434

RESUMEN

Solid-state Li-metal batteries offer a great opportunity for high-security and high-energy-density energy storage systems. However, redundant interfacial modification layers, intended to lead to an overall satisfactory interfacial stability, dramatically debase the actual energy density. Herein, a dual-interface amorphous cathode electrolyte interphase/solid electrolyte interphase CEI/SEI protection (DACP) strategy is proposed to conquer the main challenges of electrochemical side reactions and Li dendrites in hybrid solid-liquid batteries without sacrificing energy density via LiDFOB and LiBF4 in situ synergistic conversion. The amorphous CEI/SEI products have an ultralow mass proportion and act as a dynamic shield to cooperatively enforce dual electrodes with a well-preserved structure. Thus, this in situ DACP layer subtly reconciles multiple interfacial compatibilities and a high energy density, endowing the hybrid solid-liquid Li-metal battery with a sustainably brilliant cycling stability even at practical conditions, including high cathode loading, high voltage (4.5 V), and high temperature (45 °C) conditions, and enables a high-energy-density (456 Wh kg-1) pouch cell (11.2 Ah, 5 mA h cm-2) with a lean electrolyte (0.92 g Ah-1, containing solid and liquid phases). The compatible modification strategy points out a promising approach for the design of practical interfaces in future solid-state battery systems.

6.
J Mol Cell Biol ; 2021 Oct 05.
Artículo en Inglés | MEDLINE | ID: mdl-34609491

RESUMEN

Microtubules consisting of α/ß-tubulin dimers play critical roles in cells. More than seven genes encode α-tubulin in vertebrates. However, the property of microtubules composed of different α-tubulin isotypes is largely unknown. Here, we purified recombinant tubulin heterodimers of mouse α-tubulin isotypes including α1A and α1C with ß-tubulin isotype ß2A. In vitro microtubule reconstitution assay detected that α1C/ß2A microtubules grew faster and underwent catastrophe less frequently than α1A/ß2A microtubules. Generation of chimeric tail-swapped and point-mutation tubulins revealed that the carboxyl-terminal (C-terminal) tails of α-tubulin isotypes largely accounted for the differences in polymerization dynamics of α1A/ß2A and α1C/ß2A microtubules. Kinetics analysis showed that in comparison to α1A/ß2A microtubules, α1C/ß2A microtubules displayed higher on-rate, lower off-rate, and similar GTP hydrolysis rate at the plus-end, suggesting a contribution of higher plus-end affinity to faster growth and less frequent catastrophe of α1C/ß2A microtubules. Furthermore, EB1 had a higher binding ability to α1C/ß2A microtubules than to α1A/ß2A ones, which could also be attributed to the difference in the C-terminal tails of these two α-tubulin isotypes. Thus, α-tubulin isotypes diversify microtubule properties, which, to a great extent, could be accounted by their C-terminal tails.

7.
Mol Imaging Biol ; 2021 Oct 07.
Artículo en Inglés | MEDLINE | ID: mdl-34622423

RESUMEN

PURPOSE: Positron emission tomography (PET) imaging was not efficiently used in the early diagnosis of hepatocellular carcinoma (HCC) due to the lack of appropriate tracers. Sodium pump Na + /K + ATPase subunit α1 (NKAα1) emerges to be a potential diagnostic biomarker of HCC. Here, we investigated the feasibility of 18F-ALF-NOTA-S3, a PET tracer based on an NKAα1 peptide, to detect small HCC. PROCEDURES: GEPIA database was searched to obtain the expression characteristics of NKAα1 in HCC and its relationship with the prognosis. PET/CT was performed in orthotopic, diethylnitrosamine (DEN)-induced and genetically engineered HCC mouse models to evaluate the use of 18F-ALF-NOTA-S3 to detect HCC lesions. RESULTS: NKAα1 is overexpressed in early HCC with a high positive rate and may correlate with poor survival. In orthotopic, DEN-induced and genetically engineered HCC mouse models, PET/CT imaging showed a high accumulation of 18F-ALF-NOTA-S3 in the tumor. The tumor-to-liver ratios are 2.56 ± 1.02, 4.41 ± 1.09, and 4.59 ± 0.65, respectively. Upregulated NKAα1 expression in tumors were verified by immunohistochemistry. Furthermore, 18F-ALF-NOTA-S3 has the ability to detect small HCC lesions with diameters of 2-5 mm. CONCLUSIONS: NKAα1 may serve as a suitable diagnostic biomarker for HCC. 18F-ALF-NOTA-S3 shows great potential for PET imaging of HCC.

8.
Artículo en Inglés | MEDLINE | ID: mdl-34622650

RESUMEN

The metal-organic framework (MOF)-based polyamide (PA) membranes applied for desalination with high permeability and selectivity are attracting more and more attention. However, the design and fabrication of high-quality and stable MOF-based PA nanocomposite reverse osmosis (RO) membrane still remain a big challenge. Herein, Fe3+-polyphenolic complex coating via interfacial coordination was first explored as an interlayer of an in situ assembled stable and high-quality Fe(BTC)-based PA nanocomposite RO membranes for desalination. Although depositing the Fe3+-polyphenolic complex on the polymer support, sufficient heterogeneous nucleation sites for the in situ synthesizing Fe(BTC) are provided. Using this strategy, we can not only facilely prepare continuous MOF-based PA nanocomposite RO membranes, ignoring the complicated and time-consuming co-blending process and the MOF-particle aggregation, but also restrict the formation of PA matrix inside the pores of the support membrane and increase the rigidity of the polyamide chain. The method also gives a proper level of generality for the fabrication of versatile stable MOF-based PA RO membranes on various supports. The prepared PA/Fe(BTC) composite membrane exhibited excellent separation performance with a large permeate flux of 2.93 L m-2 h-1 bar-1 and a high NaCl rejection of 96.8%.

9.
J Hazard Mater ; 424(Pt A): 127333, 2021 Sep 24.
Artículo en Inglés | MEDLINE | ID: mdl-34600380

RESUMEN

Sulfamethoxazole (SMX) is frequently detected in the environment and causes a huge threaten to human health. Biochar (BC) is a metal-free adsorbent and generally exhibits a good adsorption capacity for SMX. However, the current activated methods usually result in the high energy consumption and low yield of the biochar. In this study, biochar was activated by boric acid under limited oxygen condition. The yield of biochar was increased by 103% after the activated by boric acid. The specific surface area of BC was significantly increased from 766.6 m2·g-1 to 1190.6 m2·g-1. The intensity of the (111) diamond peak of B-BC was higher than that of BC, suggesting that boric acid affected the surface pyrolysis temperature of biochar. The proposed roles of boric acid in the activation process were to: 1) enhance the generation of micropores during the pyrolysis process; 2) improve the yield of biochar via the transformation pathways of C-corresponding bonds and physical blocking. The boric acid activated biochar (B-BC) had a higher adsorption capacity for SMX than BC under the various aqueous conditions. Hence, boric acid activated biochar is a promising porous adsorbent to enhance the removal of SMX and achieve practical application.

10.
Opt Lett ; 46(19): 4781-4784, 2021 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-34598198

RESUMEN

We report an omnidirectional light absorption enhancement of a perovskite solar cell (PSC) using antireflection (AR) film with soft imprinted microstructures from master molds via holographic lithography technology, which has high throughput and repeatability. The PSC's omnidirectional power conversion efficiency (PCE) enhancement is achieved by reducing Fresnel surface reflections and enhancing the optical path length. The maximum PCE of PSCs with AR film is up to 20.27%, corresponding to an absolute increase of 0.93% compared to 19.34% of control devices. Significantly, the enhancements of PCE increase with incident angle enlargement, which attributes to more effective Fresnel surface reflection suppression. Moreover, AR films exhibit water and dust repellent properties due to hydrophobicity, which is beneficial for PSC's long-term stability and light harvesting.

11.
Adv Sci (Weinh) ; : e2101176, 2021 Oct 04.
Artículo en Inglés | MEDLINE | ID: mdl-34605222

RESUMEN

Most breast cancers at an advanced stage exhibit an aggressive nature, and there is a lack of effective anticancer options. Herein, the development of patient-derived organoids (PDOs) is described as a real-time platform to explore the feasibility of tailored treatment for refractory breast cancers. PDOs are successfully generated from breast cancer tissues, including heavily treated specimens. The microtubule-targeting drug-sensitive response signatures of PDOs predict improved distant relapse-free survival for invasive breast cancers treated with adjuvant chemotherapy. It is further demonstrated that PDO pharmaco-phenotyping reflects the previous treatment responses of the corresponding patients. Finally, as clinical case studies, all patients who receive at least one drug predicate to be sensitive by PDOs achieve good responses. Altogether, the PDO model is developed as an effective platform for evaluating patient-specific drug sensitivity in vitro, which can guide personal treatment decisions for breast cancer patients at terminal stage.

12.
Cell Death Dis ; 12(10): 907, 2021 Oct 05.
Artículo en Inglés | MEDLINE | ID: mdl-34611127

RESUMEN

Cholesterols are the main components of myelin, and are mainly synthesized in astrocytes and transported to oligodendrocytes and neurons in the adult brain. It has been reported that Hippo/yes-associated protein (YAP) pathways are involved in cholesterol synthesis in the liver, however, it remains unknown whether YAP signaling can prevent the demyelination through promoting cholesterol synthesis in experimental autoimmune encephalomyelitis (EAE), a commonly used animal model of multiple sclerosis characterized by neuroinflammation and demyelination. Here, we found that YAP was upregulated and activated in astrocytes of spinal cords of EAE mice through suppression of the Hippo pathway. YAP deletion in astrocytes aggravated EAE with earlier onset, severer inflammatory infiltration, demyelination, and more loss of neurons. Furthermore, we found that the neuroinflammation was aggravated and the proliferation of astrocytes was decreased in YAPGFAP-CKO EAE mice. Mechanically, RNA-seq revealed that the expression of cholesterol-synthesis pathway genes such as HMGCS1 were decreased in YAP-/- astrocytes. qPCR, western blot, and immunostaining further confirmed the more significant reduction of HMGCS1 in spinal cord astrocytes of YAPGFAP-CKO EAE mice. Interestingly, upregulation of cholesterol-synthesis pathways by diarylpropionitrile (DPN) (an ERß-ligand, to upregulate the expression of HMGCS1) treatment partially rescued the demyelination deficits in YAPGFAP-CKO EAE mice. Finally, activation of YAP by XMU-MP-1 treatment promoted the expression of HMGCS1 in astrocytes and partially rescued the demyelination and inflammatory infiltration deficits in EAE mice. These findings identify unrecognized functions of astrocytic YAP in the prevention of demyelination through promoting cholesterol synthesis in EAE, and reveal a novel pathway of YAP/HMGCS1 for cholesterol synthesis in EAE pathology.

14.
Urol J ; 2021 10 04.
Artículo en Inglés | MEDLINE | ID: mdl-34606083

RESUMEN

PURPOSE: To compare the treatment outcomes of robotic retroperitoneal lymph node dissection (R-RPLND) versus laparoscopic RPLND (L-RPLND) for clinical stage I non-seminomatous germ cell testicular tumors (NSGCTs). MATERIALS AND METHODS: We retrospectively reviewed the data of patients with stage I NSGCTs who underwent robotic or laparoscopic RPLND between 2008 and 2017.  Perioperative data and oncologic outcomes were reviewed and compared between the two groups. Progression-free survival was analyzed using Kaplan-Meier survival curves and compared between two groups. RESULTS: A total of 31 and 28 patients underwent R-RPLND and L-RPLND respectively. The preoperative characteristics of the patients were comparable in the two groups. Patients in R-RPLND group had significantly shorter median operative time (140 vs. 175 minutes, P < .001), a shorter median duration to surgical drain removal (2 vs. 4 days, P = .002) and a shorter median postoperative hospital stay (5 vs. 6 days, P = .001). There were no statistical differences in intra- and post-operative complication rate between the groups and the oncologic outcomes were similar in the two groups. CONCLUSION: In expert hands, R-RPLND and L-RPLND were comparable in oncological parameter and morbidity rate; R-RPLND showed superiority in operation duration, median days to surgical drain removal and postoperative hospital stay for stage I NSGCTs. Multicenter and randomized studies with good power of study and sufficient follow-up duration are required to validate our result.

15.
Clin Lung Cancer ; 2021 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-34645582

RESUMEN

BACKGROUND: Pleural effusion (PE) has been one of the promising sources of liquid biopsy in advanced lung cancer patients. However, its clinical utility is not widely accepted due to the lack of full estimation of its potential versus routine clinical samples. METHOD: A total of 164 advanced lung cancer patients were enrolled with 164 matched tumor tissue and PE-cfDNA, 153 accompanied plasma and 63 1PE-sDNA. RESULT: PE-cfDNA displayed significantly higher median mutant allele frequency and an overall mutation concordance rate of 65% to tissue, which was higher than PE-sDNA (43%) and plasma-cfDNA (43%). The discrepancies between PE-cfDNA and tumor tissue were high in several genes, including SMARCA4, PIK3CA, ERBB2, KM T2A, ALK and NF1. For clinically actionable mutations, the concordance rate between PE-cfDNA and tumor tissue is 87%. Eleven patients were identified with actionable mutations in PE-cfDNA and four patients benefited from PE-cfDNA-guided targeted. Meanwhile, PE-cfDNA recapitulated mutations of diverse tissue origins and provided more mutational information under the circumstance that tumor tissue or tumor tissue of different origins were unavailable. The combination of tumor tissue and PE-cfDNA profiling increased positive detection rates of patients compared to tumor tissue alone. Our finding highlighted the importance of PE-cfDNA in the optimal selection of patients for targeted therapy. CONCLUSION: The PE-cfDNA-based liquid biopsy displays better performance in the characterization of gene alterations than PE-sDNA and plasma-cfDNA. PE-cfDNA together with tumor tissue profiling optimizes comprehensively genomic profiling of lung cancer patients, which might be important for selecting patients for better treatment management.

16.
Theranostics ; 11(19): 9605-9622, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34646389

RESUMEN

Rationale: Recurrent and metastatic cancers often undergo a period of dormancy, which is closely associated with cellular quiescence, a state whereby cells exit the cell cycle and are reversibly arrested in G0 phase. Curative cancer treatment thus requires therapies that either sustain the dormant state of quiescent cancer cells, or preferentially, eliminate them. However, the mechanisms responsible for the survival of quiescent cancer cells remain obscure. Methods: Dual genome-editing was carried out using a CRISPR/Cas9-based system to label endogenous p27 and Ki67 with the green and red fluorescent proteins EGFP and mCherry, respectively, in melanoma cells. Analysis of transcriptomes of isolated EGFP-p27highmCherry-Ki67low quiescent cells was conducted at bulk and single cell levels using RNA-sequencing. The extracellular acidification rate and oxygen consumption rate were measured to define metabolic phenotypes. SiRNA and inducible shRNA knockdown, chromatin immunoprecipitation and luciferase reporter assays were employed to elucidate mechanisms of the metabolic switch in quiescent cells. Results: Dual labelling of endogenous p27 and Ki67 with differentiable fluorescent probes allowed for visualization, isolation, and analysis of viable p27highKi67low quiescent cells. Paradoxically, the proto-oncoprotein c-Myc, which commonly drives malignant cell cycle progression, was expressed at relatively high levels in p27highKi67low quiescent cells and supported their survival through promoting mitochondrial oxidative phosphorylation (OXPHOS). In this context, c-Myc selectively transactivated genes encoding OXPHOS enzymes, including subunits of isocitric dehydrogenase 3 (IDH3), whereas its binding to cell cycle progression gene promoters was decreased in quiescent cells. Silencing of c-Myc or the catalytic subunit of IDH3, IDH3α, preferentially killed quiescent cells, recapitulating the effect of treatment with OXPHOS inhibitors. Conclusion: These results establish a rigorous experimental system for investigating cellular quiescence, uncover the high selectivity of c-Myc in activating OXPHOS genes in quiescent cells, and propose OXPHOS targeting as a potential therapeutic avenue to counter cancer cells in quiescence.

17.
Nurse Educ Pract ; 57: 103221, 2021 Sep 29.
Artículo en Inglés | MEDLINE | ID: mdl-34649129

RESUMEN

AIM: The aim of this systematic review was to synthesize evidence on the application of the Omaha System in the education of nursing students and to provide advice for educators to apply the Omaha System to practice and research effectively and meaningfully. BACKGROUND: It is a necessary part of nursing education to provide students with informatics experience. The Omaha System is a standardized nursing terminology designed to enhance practice, documentation, and information management. DESIGN: A systematic review and narrative synthesis. METHODS: Studies from eight databases (PubMed, Web of Science, Embase, CINAHL, PsycINFO, China Biology Medicine disc, CNKI, Wanfang Data) were systematically retrieved. Twenty-three articles were found and synthesized. RESULTS: Existing studies showed that the Omaha System was mainly applied in student community practice as a tool for guiding practice and collecting information, and the practice data were used by educators to analyse the outcomes of nursing education. Recently, the Omaha System was introduced into the classroom environment and achieved positive results in terms of teaching. Students' feedback on the use of the Omaha System was generally positive. CONCLUSIONS: The Omaha System can be an active teaching and learning tool for nursing education, and further research is needed to explore and realize its potential in the field of education.

18.
Artículo en Inglés | MEDLINE | ID: mdl-34651231

RESUMEN

PURPOSE: The aim of this study was to determine a better criterion for end-of-treatment PET (EoT-PET) assessment and prognostic evaluation of patients with diffuse large B cell lymphoma (DLBCL). METHOD: EoT-PET scans were assessed using the visual Deauville 5-point scale (5PS) and LLR, the maximum standard uptake value ratio between the lesion and the liver. The cutoff value of LLR was obtained by receiver operator characteristic curve analysis. Patient outcomes were compared using Kaplan-Meier survival analysis. Prognostic indexes of different criteria were compared. Multivariate Cox regression analysis was performed to evaluate the prognostic factors. RESULTS: Four hundred forty-nine newly diagnosed DLBCL patients who received rituximab-based immunochemotherapy were included, and the median follow-up duration was 41.4 months. Patients with Deauville score (DS) 4 displayed significantly longer PFS and OS compared with patients with DS 5 (both p < 0.001), and they had significantly shorter PFS (p < 0.01) but similar OS (p = 0.057) compared with patients with DS 1-3. The differences in PFS and OS between groups were all significant whether positive EoT-PET was defined as DS 4-5 or DS 5 (all p < 0.001). The optimal cutoff of LLR was 1.83, and both PFS and OS were significantly different between EoT-PET-positive and EoT-PET-negative patients as defined by the cutoff (both p < 0.001). LLR-based criterion displayed higher specificity, positive predictive value, and accuracy than 5PS-based criterion in the prediction of disease progression and death events. In the multivariate analysis, positive EoT-PET (as defined by LLR) was related to unfavorable PFS and OS (both p < 0.001). Additional treatment was not correlated with outcomes of EoT-PET-negative patients either defined by LLR or 5PS or EoT-PET-positive patients classified by 5PS, but it was the only beneficial factor for OS (p < 0.05) in EoT-PET-positive patients with LLR ≥ 1.83. CONCLUSION: The optimal cutoff of LLR may be superior to Deauville criteria in identifying low-risk DLBCL patients with negative EoT-PET after the first-line immunochemotherapy and sparing them the cost and toxicity of additional treatment.

19.
Mol Med Rep ; 24(6)2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34651661

RESUMEN

Cytochrome P450 family 2 subfamily E member 1 (CYP2E1) is a member of the cytochrome P450 enzyme family and catalyzes the metabolism of various substrates. CYP2E1 is upregulated in multiple heart diseases and causes damage mainly via the production of reactive oxygen species (ROS). In mice, increased CYP2E1 expression induces cardiac myocyte apoptosis, and knockdown of endogenous CYP2E1 can attenuate the pathological development of dilated cardiomyopathy (DCM). Nevertheless, targeted inhibition of CYP2E1 via the administration of drugs for the treatment of DCM remains elusive. Therefore, the present study aimed to investigate whether diallyl sulfide (DAS), a competitive inhibitor of CYP2E1, can be used to inhibit the development of the pathological process of DCM and identify its possible mechanism. Here, cTnTR141W transgenic mice, which developed typical DCM phenotypes, were used. Following treatment with DAS for 6 weeks, echocardiography, histological analysis and molecular marker detection were conducted to investigate the DAS­induced improvement on myocardial function and morphology. Biochemical analysis, western blotting and TUNEL assays were used to detected ROS production and myocyte apoptosis. It was found that DAS improved the typical DCM phenotypes, including chamber dilation, wall thinning, fibrosis, poor myofibril organization and decreased ventricular blood ejection, as determined using echocardiographic and histopathological analyses. Furthermore, the regulatory mechanisms, including inhibition both of the oxidative stress levels and the mitochondria­dependent apoptosis pathways, were involved in the effects of DAS. In particular, DAS showed advantages in terms of improved chamber dilation and dysfunction in model mice, and the improvement occurred in the early stage of the treatment compared with enalaprilat, an angiotensin­converting enzyme inhibitor that has been widely used in the clinical treatment of DCM and HF. The current results demonstrated that DAS could protect against DCM via inhibition of oxidative stress and apoptosis. These findings also suggest that inhibition of CYP2E1 may be a valuable therapeutic strategy to control the development of heart diseases, especially those associated with CYP2E1 upregulation. Moreover, the development of DAS analogues with lower cytotoxicity and metabolic rate for CYP2E1 may be beneficial.

20.
Sci Total Environ ; 807(Pt 1): 150791, 2021 Oct 05.
Artículo en Inglés | MEDLINE | ID: mdl-34619203

RESUMEN

The inhalation is one of important exposure ways to arsenic. Traditionally, the health risk of arsenic exposure from particulate matter (PM) was assessed by using total arsenic, which may erroneously estimate the health risk of arsenic since the toxicity of arsenic depends on its chemical species and not all arsenic in PM is bio-accessible. Herein, total suspended particles (TSP) were collected from Taiyuan in China during whole year of 2018, and the species and concentrations of arsenic in TSP were investigated in order to more accurately assess the health risk of arsenic exposure from TSP and evaluate the possible sources of arsenic in TSP. Total arsenic varied within 1.16-28.4 ng/m3 with a mean value of 7.40 ng/m3, which exceeded the standard limit of China (6 ng/m3). Two arsenic species, As5+ and As3+, were detected out in soluble fractions of TSP, with As5+ as dominant species. Total arsenic, soluble arsenic and soluble As5+ in TSP revealed closed correlation each other, indicating that they may originate from similar anthropogenic and crust sources. Soluble As3+ showed no obvious correlations with total arsenic, implying that soluble As3+ has different dominant sources. The ratio of As5+/As3+ significantly varied within 1.08-32.5 and the percentages of soluble arsenic in total arsenic varied within 50%-93%, implying that arsenic in TSP of Taiyuan has multiple sources and none of them stably dominated during 2018. Non-carcinogenic risk and carcinogenic risk indicators calculated with soluble arsenic species showed significant difference to that calculated with total arsenic or soluble arsenic when TSP contained equivalent As5+ and As3+, verifying that it is necessary and more accurate to assess the health risk of arsenic exposure from TSP by using soluble arsenic species, rather than total arsenic or soluble arsenic.

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