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1.
ESC Heart Fail ; 2022 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-35032103

RESUMO

AIMS: Heart failure (HF) is a systemic inflammatory disorder with infections being an important cause of morbidity and mortality. We asked if HF patients have a higher susceptibility to infections compared with the general population and if a subtle secondary immunodeficiency facilitates infectious complications. METHODS AND RESULTS: In a cohort of 92 patients with HF with reduced ejection fraction, we analysed recirculating lymphocyte subpopulations, serum immunoglobulin levels, and specific antibody titres against pneumococcal antigens. We quantified susceptibility to infections of the respiratory tract with a validated questionnaire and compared it to the general population. Susceptibility to infections of the respiratory tract was comparable in HF patients and the general population. Hypogammaglobulinaemia was present in 16% of HF patients, but anti-pneumococcal titres showed no evidence of specific secondary antibody deficiency. Relative lymphopaenia in our HF cohort was due to B lymphocytopenia with a relative reduction in naive B-cells and expansion of memory B-cells while CD4+ and CD8+ T-lymphocytes as well as NK-cell counts were comparable between HF and healthy donors. The intake of the angiotensin receptor neprilysin (CD10) inhibitor (ARNI) sacubitril/valsartan was associated with increased B-lymphocyte counts, possibly by an increased output of CD10+ transitional B lymphocytes from the bone marrow. CONCLUSION: Despite a reduction of B lymphocytes in HF and mild hypogammaglobulinaemia, patients showed no evidence of secondary immunodeficiency or increased susceptibility to infections. The relevance of B-cell lymphopenia in HF patients and modulation of B-cell counts under ARNI treatment remains to be investigated.

2.
BMJ Open ; 12(1): e050579, 2022 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-35027416

RESUMO

INTRODUCTION: There have been many meta-analyses of randomised controlled trials on the influence of different diets on obesity-related anthropometric characteristics in adults. However, whether diet interventions can effectively decrease obesity-related anthropometric characteristics remains unclear. The objective of this study is to summarise and synthesise the evidence on the effects of diet on obesity-related anthropometric characteristics in adults by an umbrella review of meta-analyses of randomised controlled trials. METHODS AND ANALYSIS: We will first retrieve English articles only published before 15 December 2021 by searching PubMed, Embase and Web of Science. Only articles that are meta-analyses of randomised controlled trials will be included. Three researchers will independently screen the titles and abstracts of retrieved articles and check the data extracted from each eligible meta-analysis. In each meta-analysis, we will consider calculating the effect size of the mean difference of the effect of each diet on obesity-related anthropometric characteristics in adults using a random-effect model or a fixed-effect model according to heterogeneity. Study heterogeneity (Cochrane's Q and I2 statistics) and small-study effects (Egger's test or Begg's test) will be considered. Evidence of each effect size will be graded according to the NutriGrade scoring system. We will use AMSTAR-2 (A Measurement Tool to Assess Systematic Reviews V.2) to assess the methodological quality of each meta-analysis. ETHICS AND DISSEMINATION: This umbrella review will provide information on the effects of different diets on obesity-related anthropometric characteristics in adults. Ethical approval is not necessary for this study. We will publish the completed umbrella review and related data online. PROSPERO REGISTRATION NUMBER: CRD42021232826.

3.
Therap Adv Gastroenterol ; 15: 17562848211067874, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35069802

RESUMO

Background: The quality of randomized crossover studies on digestive diseases is unclear. We aimed to review crossover trials in digestive disease journals and evaluate their reporting quality and risk of bias. Methods: We searched the PubMed, Web of Science, and Scopus databases for all crossover trials in 39 digestive journals between January 2011 and September 2021. Reporting adherence was based on the CONSORT 2010 statement: extension to randomized crossover trials published in July 2019. A newly released Cochrane risk of bias tool 2.0 extension for crossover trials was applied to assess the risk of bias. Results: In total, 173 studies were included in the analysis, and 16.2% were published following the CONSORT statement extension. The crossover design was not only widely used in drug efficacy trials (48.6%) but also in endoscopic ultrasound trials (23.7%) and dietary studies (17.9%) in the field of digestive diseases. The overall reporting adherence was 37.6% for full texts and 43.4% for abstracts. The proportions of trials with low, some concerns, and high risk of bias were 13.9%, 15.6%, and 70.5%, respectively. The difference in reporting adherence and high risk of bias between pre- and post-CONSORT was not significant. Having a sample size plan, defining primary end points, and pre-registration showed higher reporting adherence and lower risk of bias than those who did not. Conclusion: These findings demonstrated the inadequate quality of randomized crossover trials for digestive diseases. Compliance with the CONSORT extension for crossover trials must be strengthened and improved (PROSPERO CRD: 42021248723).

4.
Acta Pharmacol Sin ; 2022 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-35022542

RESUMO

Macrophages play a critical role in the pathogenesis of acetaminophen (APAP)-induced liver injury (AILI), a major cause of acute liver failure or even death. Sapidolide A (SA) is a sesquiterpene lactone extracted from Baccaurea ramiflora Lour., a folk medicine used in China to treat inflammatory diseases. In this study, we investigated whether SA exerted protective effects on macrophages, thus alleviated the secondary hepatocyte damage in an AILI. We showed that SA (5-20 µM) suppressed the phosphorylated activation of NF-κB in a dose-dependent manner, thereby inhibiting the expression and activation of the NOD-like receptor protein 3 (NLRP3) inflammasome and pyroptosis in LPS/ATP-treated mouse bone marrow-derived primary macrophages (BMDMs). In human hepatic cell line L02 co-cultured with BMDMs, SA (10 µM) protected macrophages from the pyroptosis induced by APAP-damaged L02 cells. Moreover, SA treatment reduced the secondary liver cell damage aggravated by the conditioned medium (CM) taken from LPS/ATP-treated macrophages. The in vivo assessments conducted on mice pretreated with SA (25, 50 mg/kg, ip) then with a single dose of APAP (400 mg/kg, ip) showed that SA significantly alleviated inflammatory responses of AILI by inhibiting the expression and activation of the NLRP3 inflammasome. In general, the results reported herein revealed that SA exerts anti-inflammatory effects by regulating NLRP3 inflammasome activation in macrophages, which suggests that SA has great a potential for use in the treatment of AILI patients.

5.
Artigo em Inglês | MEDLINE | ID: mdl-35023627

RESUMO

The globally dominant N2 -fixing cyanobacteria Trichodesmium and Crocosphaera provide vital nitrogen supplies to subtropical and tropical oceans, but little is known about how they will be affected by long-term ocean warming. We tested their thermal responses using experimental evolution methods during 2 years of selection at optimal (28°C), supra-optimal (32°C) and suboptimal (22°C) temperatures. After several hundred generations under thermal selection, changes in growth parameters, as well as N and C fixation rates, suggested that Trichodesmium did not adapt to the three selection temperature regimes during the 2-year evolution experiment, but could instead rapidly and reversibly acclimate to temperature shifts from 20°C to 34°C. In contrast, over the same timeframe apparent thermal adaptation was observed in Crocosphaera, as evidenced by irreversible phenotypic changes as well as whole-genome sequencing and variant analysis. Especially under stressful warming conditions (34°C), 32°C-selected Crocosphaera cells had an advantage in survival and nitrogen fixation over cell lines selected at 22°C and 28°C. The distinct strategies of phenotypic plasticity versus irreversible adaptation in these two sympatric diazotrophs are both viable ways to maintain fitness despite long-term temperature changes, and so could help to stabilize key ocean nitrogen cycle functions under future warming scenarios.

6.
Food Chem ; 379: 132178, 2022 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-35066359

RESUMO

To investigate whether apigenin, a common flavone in celery, can be esterified with carboxylic acids generated during frying leading to the consequently change of its antioxidant activity, we prepared a group of apigenin esters using fatty acids of varying chain lengths (C3:0-C18:0) and further checked their presence in celeries fried in soybean oil, rapeseed oil, and palm oil. Apigenin-7, 4'-O-dioctanoate was detected in celeries fried in soybean and rapeseed oil. Apigenin-7, 4'-O-dilaurinate was detected in celeries fried in all the three oils. In addition, all the apigenin esters exhibited lower ABTS and DPPH radical scavenging activity but improved lipophilicity and stronger cellular antioxidant activity than the parent compound, apigenin. These results demonstrated for the first time that apigenin could be esterified by carboxylic acids generated from lipid peroxidation under thermal processing, and these esters showed enhanced lipophilicity and cellular antioxidant activity.

7.
J Appl Clin Med Phys ; : e13502, 2022 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-35045204

RESUMO

PURPOSE: Radiation-induced lung injury (RILI) is a common side effect in patients with non-small cell lung cancer (NSCLC) treated with radiotherapy. Minimizing irradiation into highly functional areas of the lung may reduce the occurrence of RILI. The aim of this study is to evaluate the feasibility and utility of hyperpolarized xenon-129 magnetic resonance imaging (MRI), an imaging tool for evaluation of the pulmonary function, to guide radiotherapy planning. METHODS: Ten locally advanced NSCLC patients were recruited. Each patient underwent a simulation computed tomography (CT) scan and hyperpolarized xenon-129 MRI, then received 64 Gyin 32 fractions for radiotherapy. Clinical contours were drawn on CT. Lung regions with good ventilation were contoured based on the MRI. Two intensity-modulated radiation therapy plans were made for each patient: an anatomic plan (Plan-A) based on CT alone and a function-based plan (Plan-F) based on CT and MRI results. Compared to Plan-A, Plan-F was generated with two additional steps: (1) beam angles were carefully chosen to minimize direct radiation entering well-ventilated areas, and (2) additional optimization criteria were applied to well-ventilated areas to minimize dose exposure. V20Gy , V10Gy , V5Gy , and the mean dose in the lung were compared between the two plans. RESULTS: Plan-A and Plan-F were both clinically acceptable and met similar target coverage and organ-at-risk constraints (p > 0.05) except for the ventilated lungs. Compared with Plan-A, V5Gy (Plan-A: 30.7 ± 11.0%, Plan-F: 27.2 ± 9.3%), V10Gy (Plan-A: 22.0 ± 8.6%, Plan-F: 19.3 ± 7.0%), and V20Gy (Plan-A: 12.5 ± 5.6%, Plan-F: 11.0 ± 4.1%) for well-ventilated lung areas were significantly reduced in Plan-F (p < 0.05). CONCLUSION: In this pilot study, function-based radiotherapy planning using hyperpolarized xenon-129 MRI is demonstrated to be feasible in 10 patients with NSCLC with the potential to reduce radiation exposure in well-ventilated areas of the lung defined by hyperpolarized xenon-129 MRI.

8.
Metabolites ; 12(1)2022 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-35050197

RESUMO

Plants produce numerous structurally and functionally diverse signaling metabolites, yet only relatively small fractions of which have been discovered. Multi-omics has greatly expedited the discovery as evidenced by increasing recent works reporting new plant signaling molecules and relevant functions via integrated multi-omics techniques. The effective application of multi-omics tools is the key to uncovering unknown plant signaling molecules. This review covers the features of multi-omics in the context of plant signaling metabolite discovery, highlighting how multi-omics addresses relevant aspects of the challenges as follows: (a) unknown functions of known metabolites; (b) unknown metabolites with known functions; (c) unknown metabolites and unknown functions. Based on the problem-oriented overview of the theoretical and application aspects of multi-omics, current limitations and future development of multi-omics in discovering plant signaling metabolites are also discussed.

9.
Aquat Toxicol ; 243: 106080, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-35065452

RESUMO

As a representative polycyclic aromatic hydrocarbon with low ring numbers, phenanthrene (Phe) is ubiquitously present in the environment. In this study, zebrafish embryos were exposed to Phe at 0.05, 0.5, 5 and 50 nmol/L for 96 h, and then cultured to adulthood in clean water, the developmental defects of craniofacial cartilage were observed in F1 larvae produced by adult males and females mated with untreated fish. Delayed development of craniofacial cartilage, including a shorter and wider Meckel's cartilage and mandibular arch were observed in F1 larvae from adult fish of both sexes. Maternal F1 larvae showed a greater impact on the lower jaw than paternal F1 larvae, this may be connected with greater downregulation of the transcription of genes related to the development of craniofacial cartilage such as runt-related transcription factor 2 (runx2), fibroblast growth factor 8 (fgf8), sonic hedgehog (shh), Indian hedgehog (ihh). Further results indicated that the modification DNA methylation levels in the promotors of gene runx2 and shh in maternal and paternal F1 larvae were inherited from embryonic F0 larvae, and might be linked with the toxicity of craniofacial cartilage in F1 larvae. This study illustrated that embryonic exposure to Phe could induce adverse effects on craniofacial development in F1 offspring, emphasizing the importance of transgenerational toxicology studies in risk assessment.

10.
J Ethnopharmacol ; : 114998, 2022 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-35063590

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Chronic pain management represents a serious healthcare problem worldwide. The use of opioid analgesics for pain has always been hampered by their side effects; in particular, the addictive liability associated with chronic use. Finding a morphine replacement has been a long-standing goal in the field of analgesia. In traditional Chinese medicine, processed Buthus martensii Karsch (BmK) scorpion has been used as a painkiller to treat chronic inflammatory arthritis and spondylitis, so called "Scorpio-analgesia". However, the molecular basis and the underline mechanism for the Scorpio-analgesia are still unclear. AIM OF THE STUDY: The study aims to investigate the molecular basis of "Scorpio analgesia" and identify novel analgesics from BmK scorpion. MATERIALS AND METHODS: In this study, the analgesic abilities were determined using formalin-, acetic acid- and complete Freund's adjuvant-induced pain models. The effect of BmK venom and processed BmK venom on Nav1.7 were detected by whole-cell voltage-clamp recordings on HEK293-hNav1.7 stable cell line. Action potentials in Dorsal root ganglion (DRG) neurons induced by Makatoxin-3-R58A were recorded in current-clamp mode. The content of Makatoxin-3 was detected using competitive enzyme-linked immunosorbent assay based on the Makatoxin-3 antibody. High performance liquid chromatography, western blot and circular dichroism spectroscopy were used to analysis the stability of Makatoxin-3. RESULTS: Here we demonstrate that Makatoxin-3, an α-like toxin in BmK scorpion venom targeting Nav1.7 is the critical component in Scorpio-analgesia. The analgesic effect of Makatoxin-3 could not be reversed by naloxone and is more potent than Nav1.7-selective inhibitors and non-steroidal anti-inflammatory drugs in inflammatory models. Moreover, a R58A mutant of Makatoxin-3 is capable of eliciting analgesia effect without inducing pain response. CONCLUSIONS: This study advances ion channel biology and proposes Nav1.7 agonists, rather than the presumed Nav1.7-only blockers, for non-narcotic relief of chronic pain.

11.
Talanta ; 237: 122894, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34736710

RESUMO

In this paper, a facile hydrothermal combined with subsequent two-step post-calcination method was used to fabricate hematite (α-Fe2O3) nanoarrays on fluorine-doped SnO2 glass (FTO). The morphology, crystalline phase, optical property and surface chemical states of the fabricated α-Fe2O3 photoelectrode were characterized by scanning electron microscopy, X-ray diffraction, ultraviolet visible spectroscopy and X-ray photoelectron spectroscopy correspondingly. The α-Fe2O3 photoelectrode exhibits excellent photoelectrochemical (PEC) response toward hydrogen peroxide (H2O2) in aqueous solutions, with a low detection limit of 20 µM (S/N = 3) and wide linear range (0.01-0.09, 0.3-4, and 6-16 mM). Additionally, the α-Fe2O3 photoelectrode shows satisfying reproducibility, stability, selectivity and good feasibility for real samples. Mechanism analysis indicates, comparing with H2O, H2O2 possesses much more fast reaction kinetics over α-Fe2O3 surface, thus the recombination of photogenerated charges are reduced, followed by much more photogenerated electrons are migrated to the counter electrode via external circuit. The insight on the enhanced photocurrent, which is corelative to the concentration of H2O2 in aqueous solution, will stimulate us to further optimize the surface structure of α-Fe2O3 to gain highly efficient α-Fe2O3 based sensors.

12.
Carbohydr Polym ; 275: 118691, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34742418

RESUMO

Fucosylated chondroitin sulfates (FCS) are a sulfated polysaccharide exclusively existing in the body wall of sea cucumber. FCS possesses a mammalian chondroitin sulfate like backbone, namely repeating disaccharides units composed of GlcA and GalNAc, with fucosyl branches linked to GlcA and/or GalNAc residues. It is found that FCS can prevent unhealthy dietary pattern-induced metabolic syndromes, including insulin resistance and ß-cell function improvement, anti-inflammation, anti-hyperlipidemia, and anti-adipogenesis. Further studies show that those activities of FCS might be achieved through positively modulating gut microbiota composition. Besides, FCS also show therapeutic efficacy in cancer, HIV infection, and side effects of cyclophosphamide. Furthermore, bioactivities of FCS are closely affected by their molecular weights, sulfation pattern of the fucosyl branches, and chain conformations. This review summarizes the recent 20 years studies to provide references for the future studies and applications of FCS in functional foods or drugs.

13.
EMBO Mol Med ; 14(1): e14502, 2022 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-34898004

RESUMO

Impressive clinical benefit is seen in clinic with PD-1 inhibitors on portion of cancer patients. Yet, there remains an urgent need to develop effective synergizers to expand their clinical application. Tumor-associated macrophage (TAM), a type of M2-polarized macrophage, eliminates or suppresses T-cell-mediated anti-tumor responses. Transforming TAMs into M1 macrophages is an attractive strategy of anti-tumor therapy. Here, we conducted a high-throughput screening and found that Carfilzomib potently drove M2 macrophages to express M1 cytokines, phagocytose tumor cells, and present antigens to T cells. Mechanistically, Carfilzomib elicited unfolded protein response (UPR), activated IRE1α to recruit TRAF2, and activated NF-κB to transcribe genes encoding M1 markers in M2 macrophages. In vivo, Carfilzomib effectively rewired tumor microenvironment through reprogramming TAMs into M1-like macrophages and shrank autochthonous lung cancers in transgenic mouse model. More importantly, Carfilzomib synergized with PD-1 antibody to almost completely regress autochthonous lung cancers. Given the safety profiles of Carfilzomib in clinic, our work suggested a potentially immediate application of combinational treatment with Carfilzomib and PD-1 inhibitors for patients with solid tumors.

14.
Food Chem ; 375: 131859, 2022 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-34933234

RESUMO

The effects of different kinds of chitosan, oligomer (ChiO) and monomer (Gluco), and the combinations of polymer (Chi) or ChiO with flavonoid aglycones and glycosides against the formation of major HAs were investigated to find out potential combination partners for enhanced suppression of HA formation. Results in roast beef patties showed ChiO and Gluco significantly inhibited PhIP and MeIQx formation by 43-80% and 31-57%, respectively. Of which, ChiO was the most effective. In combinations with flavonoid glycosides (phloridzin, rutin and hesperidzin, respectively), Chi, but not ChiO, generated enhanced inhibitory effects. Further analysis showed Chi and phloridzin combined at a ratio of 1:1 was the most promising, especially in inhibiting PhIP, and the mechanism behind involved: 1) water retention by Chi, and 2) reduction of phenylalanine availability by phloridzin. These findings suggest that appropriate combination of Chi and flavonoid glycosides contributes to significant improvement in the safety of meat products.


Assuntos
Quitosana , Compostos Heterocíclicos , Aminas/análise , Animais , Bovinos , Culinária , Flavonoides , Glicosídeos , Compostos Heterocíclicos/análise , Carne/análise
15.
Mol Med Rep ; 25(2)2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34935053

RESUMO

Targeting excessive osteoclast differentiation and activity is considered a valid therapeutic approach for osteoporosis. Zoledronic acid (ZOL) plays a pivotal role in regulating bone mineral density. However, the exact molecular mechanisms responsible for the inhibitory effects of ZOL on receptor activator of nuclear factor (NF)­κB ligand (RANKL)­induced osteoclast formation are not entirely clear. The present study aimed to investigate the role of ZOL in osteoclast differentiation and function, and to determine whether NF­κB and mitogen­activated protein kinase, and their downstream signalling pathways, are involved in this process. RAW264.7 cells were cultured with RANKL for differentiation into osteoclasts, in either the presence or absence of ZOL. Osteoclast formation was observed by tartrate­resistant acid phosphatase staining and bone resorption pit assays using dentine slices. The expression of osteoclast­specific molecules was analysed using reverse transcription­quantitative polymerase chain reaction and western blotting assays to deduce the molecular mechanisms underlying the role of ZOL in osteoclastogenesis. The results showed that ZOL significantly attenuated osteoclastogenesis and bone resorptive capacity in vitro. ZOL also suppressed the activation of NF­κB and the phosphorylation of c­Jun N­terminal kinase. Furthermore, it inhibited the expression of the downstream factors c­Jun, c­Fos and nuclear factor of activated T cells c1, thereby decreasing the expression of dendritic cell­specific transmembrane protein and other osteoclast­specific markers. In conclusion, ZOL may have therapeutic potential for osteoporosis.

16.
Cancer Cell Int ; 21(1): 654, 2021 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-34876128

RESUMO

BACKGROUND: Tumor migration and invasion is a complex and diverse process that involves the epithelial-mesenchymal transition (EMT) of tumor cells and degradation of the extracellular matrix by matrix metalloproteases (MMPs). Mortalin is an important oncogene. It has been reported to play an important role in tumor migration and invasion through various signaling pathways, but the underlying mechanism is not fully understood. METHODS: Here, we investigated the role of mortalin in the migration of the hepatocellular carcinoma (HCC) cell lines HepG2 and HCCLM3. RESULTS: The overexpression of mortalin in HepG2 cells decreased the protein level of reversion-inducing cysteine-rich protein with Kazal motifs (RECK) and activated the phosphorylation and acetylation of STAT3, thereby up-regulating matrix metalloproteinase 9 (MMP9) and promoting cell migration and invasion. In contrast, in HCCLM3 cells, mortalin knockdown increased the expression of RECK, inhibited the STAT3 pathway and the activity of MMP9, and inhibited cell migration and invasion. Furthermore, we found that salvianolic acid B, a caffeic acid phenethyl ester analog, specifically bound to mortalin and increased the degradation of mortalin proteasomes through ubiquitination, thereby up-regulating RECK, inhibiting STAT3, and finally inhibiting the migration and invasion of HCC cells. CONCLUSION: Our work suggested that mortalin is a potential therapeutic target for hepatocellular carcinoma.

17.
New Phytol ; 2021 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-34877653

RESUMO

Plants and microbes coinhabit the earth and coevolve during environmental changes over time. Root metabolites are the key to mediating the dynamic association of plants with microbes, yet the underlying functions and mechanisms behind which remain largely illusive. Knowledge in metabolite-mediated altering of root microbiota in response to environmental stress will open avenues for engineering root microbiota for improved plant stress resistance and health. Here, we synthesize recent advances connecting environmental stresses, root metabolome and microbiota and propose integrated synthetic biology-based strategies for tuning plant root metabolome in situ for microbe-assisted stress resistance, offering potential solutions to combat climate change. Current limitations, challenges and perspectives for engineering plant root metabolome for modulating microbiota were collectively discussed.

18.
Front Oncol ; 11: 758698, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34868971

RESUMO

Purpose: To retrospectively and comparatively evaluate the improvement of the efficacy and safety on the addition of 252Cf neutron intracavitary brachytherapy (ICBT), individualized or individualized with intrarectal peritumoral injection of amifostine (IPIA) to external-beam radiotherapy (EBRT) or concurrent chemo-EBRT in 314 patients with T2N0-1 or T3N0-1 low-lying rectal adenocarcinoma. Methods: Phase I: from 2009 to 2011, 157 patients were treated with additional 252Cf neutron ICBT for four fixed fractions with a total dose of 40-45 Gy-eq during the EBRT. Phase II: from 2011 to 2013, 75 patients were treated with individualized neutron ICBT delivered for two to five fractions with a total dose of 26-45 Gy-eq according to the response of tumor after concurrent chemo-EBRT. Phase III: from 2013 to 2014, 82 patients were treated with individualized ICBT protected by pretreatment IPIA. Results: The 4-year local control rates for the entire T2 and T3 patients were 69.4, 72.0, and 79.3%, while the 4-year overall survival rates were 63.1, 54.7, and 72.0% (P=0.08), and the 4-year disease-free survival rates were 55.4, 52.0, and 69.5% (P=0.053) in Phases I, II, and III, respectively. The late complication (LAC, ≥G2) rates were 33.8, 26.7, and 15.9%, respectively (P=0.012), and the serious LAC (≥G3) rates were 4.5, 4.2, and 0%, respectively, in Phases I, II, and III. Conclusion: Concurrent chemo-EBRT combined with individualized 252Cf neutron ICBT protected by IPIA shows promising efficacy and safety in treating low-lying T2 and T3 rectal adenocarcinoma patients without surgery opportunity or willing.

19.
Front Cell Dev Biol ; 9: 768238, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34869363

RESUMO

Pleckstrin-2 is a member of pleckstrin family with well-defined structural features that was first identified in 1999. Over the past 20 years, our understanding of PLEK2 biology has been limited to cell spreading. Recently, increasing evidences support that PLEK2 plays important roles in other cellular events beyond cell spreading, such as erythropoiesis, tumorigenesis and metastasis. It serves as a potential diagnostic and prognostic biomarker as well as an attractive target for the treatment of cancers. Herein, we summary the protein structure and molecular interactions of pleckstrin-2, with an emphasis on its regulatory roles in tumorigenesis.

20.
Inorg Chem ; 2021 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-34855375

RESUMO

Photochromic materials are constructed with molecules accompanied by structural change after triggering by light, which are of great importance and necessity for various applications. However, because of space-confinement effects, molecule stacking of these photoresponsive chromophores within coordination polymers (CPs) always results in an efficiency decrement and a response delay, and this phenomenon will lead to a poor photochromic property. Herein, a CP (named CIT-E) with a 3-fold-interpenetrating network structure, which was prepared with (Z)-1,2-diphenyl-1,2-bis[4-(pyridin-3-ylmethoxy)phenyl]ethene (1Z) and a CuI cluster, showed fast reversible photochromic behavior. Under UV-light illumination, the color of CIT-Z changed from pale yellow to reddish brown. With the illumination of green light, the polymer could return to its initial color within 10 s. To reveal the mechanism of reversible photochromic behavior of CIT-Z, single-crystal structures of each color state were fully studied, and other scientific study methods were also used, such as time-dependent density functional theory calculation and control experiments. It was found that, with light illumination, this behavior of CIT-Z was the result of a ligand-to-metal charge-transfer process, and this process was triggered by subtle molecular conformation variation of tetraphenylethylene. It should be noted that CIT-Z has high thermal and chemical stability, which are excellent advantages as smart photoresponsive materials. As a proof of concept, a uniform thin film with such a fascinating photochromic property allows applications in invisible anticounterfeiting and dynamic optical data storage. Overall, the present study opens up a new avenue toward reversible photochromic materials.

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