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1.
Lasers Med Sci ; 38(1): 44, 2023 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-36656398

RESUMO

To compare the safety and efficacy of en bloc resection of non-muscle-invasive bladder cancer (NMIBC) using a 1470-/980-nm dual-wavelength laser (DwLRBT) compared to the gold standard, transurethral resection (TURBT). The study group included 251 patients with a confirmed diagnosis of NMIBC, 97 in the DwLRBT group and 154 in the TURBT group. Clinical characteristics, complications, and recurrence-free survival were compared between the two groups. There were no differences between the two groups with regard to age, sex, mean tumor size, mean tumor number, tumor location, risk, fever, and reoperation. Compared to TURBT, DwLRBT was associated with a shorter hospitalization time (mean±standard deviation: 5.81±1.48 days vs. 4.96±1.32, respectively, p=0.001), shorter catheterization time (4.98±1.47 vs. 4.20±1.48 days, respectively; p=0.035), and smaller volume of intraoperative bleeding (8.43±6.21 ml vs. 6.15±5.08, respectively; p=0.003). Recurrence-free survival (RFS) was better for DwLRBT than TURBT in the overall cohort (hazard ratio [HR], 0.4323; 95% confidence interval [CI], 0.2852-0.6554; p=0.0004) and for the following subgroups and tumor types: intermediate-risk (HR, 0.2654; 95%CI, 0.1020-0.6904; p=0.0245) and high-risk (HR, 0.4461; 95% CI, 0.2778-0.7162; p=0.0027) groups; and for pedunculate bladder tumors (HR, 0.4158; 95%CI, 0.2401-0.7202; p=0.0063), single bladder tumors (HR, 0.4136; 95%CI, 0.2376-0.7293; p=0.0072), and multiple bladder tumors (HR, 0.2727; 95%CI, 0.1408-0.5282; p=0.0014). DwLRBT is associated with better operative and postoperative outcomes, including, importantly, a longer RFS, compared to TURBT.


Assuntos
Neoplasias da Bexiga Urinária , Humanos , Estudos Retrospectivos , Neoplasias da Bexiga Urinária/cirurgia , Neoplasias da Bexiga Urinária/patologia , Lasers , Recidiva Local de Neoplasia/patologia , Invasividade Neoplásica
2.
BMJ ; 380: e071952, 2023 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-36631148

RESUMO

OBJECTIVE: To assess the recent trends in prevalence and management of hypertension in China, nationally and by population subgroups. DESIGN: Six rounds of a national survey, China. SETTING: China Chronic Disease and Risk Factors Surveillance, 2004-18. PARTICIPANTS: 642 523 community dwelling adults aged 18-69 years (30 501 in 2004, 47 353 in 2007, 90 491 in 2010, 156 836 in 2013, 162 293 in 2015, and 155 049 in 2018). MAIN OUTCOME MEASURES: Hypertension was defined as a blood pressure of ≥140/90 mm Hg or taking antihypertensive drugs. The main outcome measures were hypertension prevalence and proportion of people with hypertension who were aware of their hypertension, who were treated for hypertension, and whose blood pressure was controlled below 140/90 mm Hg. RESULTS: The standardised prevalence of hypertension in adults aged 18-69 years in China increased from 20.8% (95% confidence interval 19.0% to 22.5%) in 2004 to 29.6% (27.8% to 31.3%) in 2010, then decreased to 24.7% (23.2% to 26.1%) in 2018. During 2010-18, the absolute annual decline in prevalence of hypertension among women was more than twice that among men (-0.83 percentage points (95% confidence interval -1.13 to -0.52) v -0.40 percentage points (-0.73 to -0.07)). Despite modest improvements in the awareness, treatment, and control of hypertension since 2004, rates remained low in 2018, at 38.3% (36.3% to 40.4%), 34.6% (32.6% to 36.7%), and 12.0% (10.6% to 13.4%). Of 274 million (95% confidence interval 238 to 311 million) adults aged 18-69 years with hypertension in 2018, control was inadequate in an estimated 240 million (215 to 264 million). Across all surveys, women with low educational attainment had higher prevalence of hypertension than those with higher education, but the finding was mixed for men. The gap in hypertension control between urban and rural areas persisted, despite larger improvements in diagnosis and control in rural than in urban areas. CONCLUSIONS: The prevalence of hypertension in China has slightly declined since 2010, but treatment and control remain low. The findings highlight the need for improving detection and treatment of hypertension through the strengthening of primary care in China, especially in rural areas.


Assuntos
Hipertensão , Adulto , Masculino , Humanos , Feminino , Prevalência , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Hipertensão/diagnóstico , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea , China/epidemiologia , Conhecimentos, Atitudes e Prática em Saúde , Conscientização
3.
Cancer Biol Ther ; 24(1): 2162807, 2023 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-36647192

RESUMO

Cholangiocarcinoma (CCA) is an aggressive biliary epithelial tumor with limited therapeutic options and poor prognosis. Curcumin is a promising active natural compound with several anti-cancer properties, though its clinical uses remain hindered due to its poor bioavailability. We recently synthesized curcumin analogs with multifunctional pharmacological and bioactivities with enhanced bioavailability. Among these novel curcumin analogs, WZ26 is a representative molecule. However, the anti-tumor effect of WZ26 against CCA is unclear. In this study, we evaluated the anti-tumor effect of WZ26 in both CCA cells and CCA xenograft mouse model. The underlying molecular anti-cancer mechanism of WZ26 was also studied. Our results show that WZ26 significantly inhibited cell growth and induced mitochondrial apoptosis in CCA cell lines, leading to significant inhibition of tumor growth in xenograft tumor mouse model. Treatment of WZ26 increased reactive oxygen species (ROS) generation, subsequently decreased mitochondrial membrane potential and inhibited the phosphorylation of signal transducer and activator of transcription 3 (STAT3), thereby inducing G2/M cell cycle arrest and cell apoptosis. Pretreatment of N-acetyl cysteine (NAC), an antioxidant agent, could fully reverse the WZ26-induced ROS-mediated changes in CCA cells. Our findings provide experimental evidence that curcumin analog WZ26 could be a potential candidate against CCA via enhancing ROS induction and inhibition of STAT3 activation.


Assuntos
Antineoplásicos , Neoplasias dos Ductos Biliares , Colangiocarcinoma , Curcumina , Humanos , Animais , Camundongos , Curcumina/farmacologia , Curcumina/uso terapêutico , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo , Fator de Transcrição STAT3/metabolismo , Linhagem Celular Tumoral , Morte Celular , Apoptose , Colangiocarcinoma/tratamento farmacológico , Proliferação de Células , Pontos de Checagem da Fase G2 do Ciclo Celular , Ductos Biliares Intra-Hepáticos/metabolismo , Ductos Biliares Intra-Hepáticos/patologia , Neoplasias dos Ductos Biliares/tratamento farmacológico , Neoplasias dos Ductos Biliares/patologia
4.
Artigo em Inglês | MEDLINE | ID: mdl-36695492

RESUMO

Hepatocellular carcinoma (HCC) has a poor response to most available systemic therapies due to intrinsic or acquired resistance to apoptosis. Ferroptosis-based therapy is expected to circumvent those limitations. Therefore, the rational design of ferroptosis-based therapies with targeted delivery of ferroptosis inducers for HCC is in need. In this study, we found that arsenic trioxide (ATO) can efficiently induce ferroptosis in HCC cells, and this effect could be reversed by the iron chelator deferoxamine. On this basis, a drug delivery system was constructed to enhance the therapeutic efficacy of ATO by camouflaging ATO-loaded magnetic nanoparticles (Fe3O4) with HCC cell membranes, termed AFN@CM. After AFN@CM treatment, glutathione peroxidase 4 was strongly inhibited and intracellular lipid peroxide species were significantly increased in HCC cells. In addition, enhanced ferroptosis and tumor suppression were observed both in vitro and in vivo. The bio-safety of AFN@CM was also demonstrated by the in vivo toxicity evaluation. In addition, benefiting from the cell membrane coating, AFN@CM showed enhanced accumulation at tumor sites and achieved continuous tumor elimination in the mouse model. In conclusion, AFN@CM exhibited satisfactory therapeutic efficacy in the treatment of HCC and provided a desirable ferroptosis-based strategy for safe and reliable HCC therapeutics.

5.
J Clin Transl Hepatol ; 11(2): 295-303, 2023 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-36643051

RESUMO

Background and Aims: Only a small percentage of chronic hepatitis B (CHB) patients effectively respond to treatment with pegylated-interferon alpha (PegIFNα) or nucleos(t)ide analogues (NUCs). We aimed to detect the correlations of complement regulators-associated single-nucleotide polymorphisms (SNPs) with treatment response of hepatitis B e antigen (HBeAg)-positive CHB patients. Methods: A total of 1,763 HBeAg-positive CHB patients were enrolled, 894 received PegIFNα for at least 48 weeks and were followed up for 24 weeks, and 869 received NUCs for 104 weeks. For each patient, nine SNPs in genes encoding for complement regulators were determined and genotyped. To assess the cumulative effect of numerous SNPs, a polygenic score (PGS) was utilized. The correlations of SNPs and PGS with the levels of combined response (CR) and hepatitis B s antigen (HBsAg) loss were also investigated. Results: In PegIFNα-treated patients, an intronic SNP of CD55, rs28371597, was strongly related to CR, and the CR rate in rs28371597_GG genotype carriers was only approximately half that of rs28371597_GT/TT genotype carriers (20.29% vs. 37.10%, p=2.00 × 10-3). A PGS incorporating CD55_rs28371597 and two additional SNPs, CFB_rs12614 and STAT4_rs7574865, which had been considered as predictors for PegIFNα treatment response before, was strongly correlated with the levels of CR (p-trend=7.94×10-6) and HBsAg loss (p-trend=9.40×10-3) in PegIFNα-treated patients. In NUCs-treated individuals, however, none of the nine SNPs were shown to be significantly linked to CHB treatment response. Conclusions: CD55_rs28371597 is a promising biomarker for predicting CHB patients' responsiveness to PegIFNα therapy. The updated PGS may be used for optimizing CHB treatment.

6.
Dev Comp Immunol ; 141: 104634, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36634830

RESUMO

Leucine-rich repeat (LRR) domains mediate multiple innate immune responses via protein-ligand and protein-protein interactions, but their exact roles in invertebrates are poorly understood. Herein, an LRR domain-containing transmembrane protein (BpLRRm) was identified in the rotifer Brachionus plicatilis. The 1069 bp BpLRRm nucleotide sequence contains a 942 bp open reading frame (ORF) encoding a 313 amino acid polypeptide with four LRR motifs harbouring the LXXLXXLXLXXNXLXXL motif, and a transmembrane domain. Treatment with 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) decreased BpLRRm mRNA levels at 3 h, but they increased thereafter and peaked at 12 h. Lipopolysaccharide (LPS) treatment first increased BpLRRm mRNA levels at 3 h, but levels returned to normal at 12 h, then increased and peaked at 24 h. Recombinant BpLRRm protein bound pathogen-related molecular patterns (PAMPs), including LPS, peptidoglycan (PGN), glucan (GLU) and polyinosinic-polycytidylic acid (poly IC), in a dose-dependent manner. Thus, BpLRRm might function as a pattern recognition receptor (PRR) in the innate immunity of B. plicatilis, and mediate responses to environmental pollution.

7.
J Infect Dis ; 2023 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-36705269

RESUMO

From two SARS-CoV-2 household transmission studies (enrolling April 2020 - January 2022) with rapid enrollment and specimen collection for 14 days, 61% (43/70) of primary cases had culturable-virus detected ≥6 days post-onset. Risk of secondary infection among household contacts tended to be greater when primary cases had culturable-virus detected after onset. Regardless of duration of culturable-virus, most secondary infections [70% (28/40)] had serial intervals <6 days, suggesting early transmission. These data examine viral culture as a proxy for infectiousness, reaffirm the need for rapid control measures after infection and highlight the potential for prolonged infectiousness (≥6 days) in many individuals.

8.
J Virol ; 97(1): e0192922, 2023 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-36602362

RESUMO

Classical swine fever (CSF), caused by classical swine fever virus (CSFV), is an important and highly infectious pig disease worldwide. Kinesin-1, a molecular motor responsible for transporting cargo along the microtubule, has been demonstrated to be involved in the infections of diverse viruses. However, the role of kinesin-1 in the CSFV life cycle remains unknown. Here, we first found that Kif5B played a positive role in CSFV entry by knockdown or overexpression of Kif5B. Subsequently, we showed that Kif5B was associated with the endosomal and lysosomal trafficking of CSFV in the early stage of CSFV infection, which was reflected by the colocalization of Kif5B and Rab7, Rab11, or Lamp1. Interestingly, trichostatin A (TSA) treatment promoted CSFV proliferation, suggesting that microtubule acetylation facilitated CSFV endocytosis. The results of chemical inhibitors and RNA interference showed that Rac1 and Cdc42 induced microtubule acetylation after CSFV infection. Furthermore, confocal microscopy revealed that cooperation between Kif5B and dynein help CSFV particles move in both directions along microtubules. Collectively, our study shed light on the role of kinesin motor Kif5B in CSFV endocytic trafficking, indicating the dynein/kinesin-mediated bidirectional CSFV movement. The elucidation of this study provides the foundation for developing CSFV antiviral drugs. IMPORTANCE The minus end-directed cytoplasmic dynein and the plus end-directed kinesin-1 are the molecular motors that transport cargo on microtubules in intracellular trafficking, which plays a notable role in the life cycles of diverse viruses. Our previous studies have reported that the CSFV entry host cell is dependent on the microtubule-based motor dynein. However, little is known about the involvement of kinesin-1 in CSFV infection. Here, we revealed the critical role of kinesin-1 that regulated the viral endocytosis along acetylated microtubules induced by Cdc42 and Rac1 after CSFV entry. Mechanistically, once CSFV transported by dynein met an obstacle, it recruited kinesin-1 to move in reverse to the anchor position. This study extends the theoretical basis of intracellular transport of CSFV and provides a potential target for the control and treatment of CSFV infection.


Assuntos
Vírus da Febre Suína Clássica , Peste Suína Clássica , Animais , Suínos , Cinesinas/genética , Cinesinas/metabolismo , Dineínas/metabolismo , Vírus da Febre Suína Clássica/fisiologia , Endocitose , Microtúbulos/metabolismo
9.
Signal Transduct Target Ther ; 8(1): 18, 2023 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-36642705

RESUMO

Enhancer of zeste homolog 2 (EZH2), an enzymatic subunit of PRC2 complex, plays an important role in tumor development and progression through its catalytic and noncatalytic activities. Overexpression or gain-of-function mutations of EZH2 have been significantly associated with tumor cell proliferation of triple-negative breast cancer (TNBC) and diffuse large B-cell lymphoma (DLBCL). As a result, it has gained interest as a potential therapeutic target. The currently available EZH2 inhibitors, such as EPZ6438 and GSK126, are of benefit for clinical using or reached clinical trials. However, certain cancers are resistant to these enzymatic inhibitors due to its noncatalytic or transcriptional activity through modulating nonhistone proteins. Thus, it may be more effective to synergistically degrade EZH2 in addition to enzymatic inhibition. Here, through a rational design and chemical screening, we discovered a new irreversible EZH2 inhibitor, IHMT-337, which covalently bounds to and degrades EZH2 via the E3 ligase CHIP-mediated ubiquitination pathway. Moreover, we revealed that IHMT-337 affects cell cycle progression in TNBC cells through targeting transcriptional regulating of CDK4, a novel PRC2 complex- and enzymatic activity-independent function of EZH2. More significantly, our compound inhibits both DLBCL and TNBC cell proliferation in different preclinical models in vitro and in vivo. Taken together, our findings demonstrate that in addition to enzymatic inhibition, destroying of EZH2 by IHMT-337 could be a promising therapeutic strategy for TNBC and other malignancies that are independent of EZH2 enzymatic activity.


Assuntos
Linfoma Difuso de Grandes Células B , Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/metabolismo , Linhagem Celular Tumoral , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Inibidores Enzimáticos , Proliferação de Células/genética , Linfoma Difuso de Grandes Células B/genética , Quinase 4 Dependente de Ciclina
11.
ACS Omega ; 8(1): 1476-1485, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36643557

RESUMO

The threshold dilution ratio of acetaldehyde is much larger than those of other odor compounds generated during the spontaneous combustion process and so it is the most important odorant. Studying the mechanism by which acetaldehyde is generated can provide the necessary theoretical support for acetaldehyde-based odor analysis. In the present work, the release of acetaldehyde was monitored while heating lignite, long-flame coal, and coking coal specimens under either air or nitrogen. The data show that acetaldehyde was primarily produced by the oxidation of active sites in the coal rather than by the pyrolysis of oxygen-containing functional groups. Based on quantum chemistry and coal-oxygen reaction theory, the transition state approach was used to further study the formation of acetaldehyde during the low-temperature oxidation of coal. Using density functional theory, three different coal molecule structures were modeled and optimized structures for acetaldehyde formation and the energies, bond lengths, and virtual frequencies of each reaction stagnation point were obtained at the B3LYP-D3/6-311G** and M062X-D3/Def2-TZVP levels. The results indicate that the low-temperature oxidation of coal to generate acetaldehyde involves the capture of H atoms from aliphatic side chains to generate peroxy radicals. These radicals then attack unsaturated C atoms through complex inversions to generate peroxides. In the third step of this process, the O-O single bonds in the peroxides break in response to thermal energy to form carbonyl groups. Finally, specific C-C or C-O bonds on the aliphatic side chains are thermally cleaved to generate acetaldehyde.

12.
ACS Nano ; 2023 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-36656264

RESUMO

Antimony (Sb) has been pursued as a promising anode material for sodium-ion batteries (SIBs). However, it suffers from severe volume expansion during the sodiation-desodiation process. Encapsulating Sb into a carbon matrix can effectively buffer the volume change of Sb. However, the sluggish Na+ diffusion kinetics in traditional carbon shells is still a bottleneck for achieving high-rate performance in Sb/C composite materials. Here we design and synthesize a yolk-shell Sb@Void@graphdiyne (GDY) nanobox (Sb@Void@GDY NB) anode for high-rate and long cycle life SIBs. The intrinsic in-plane cavities in GDY shells offer three-dimensional Na+ transporting channels, enabling fast Na+ diffusion through the GDY shells. Electrochemical kinetics analyses show that the Sb@Void@GDY NBs exhibit faster Na+ transport kinetics than traditional Sb@C NBs. In situ transmission electron microscopy analysis reveals that the hollow structure and the void space between Sb and GDY successfully accommodate the volume change of Sb during cycling, and the plastic GDY shell maintains the structural integrity of NBs. Benefiting from the above structural merits, the Sb@Void@GDY NBs exhibit excellent rate capability and extraordinary cycling stability.

13.
PLoS One ; 18(1): e0279945, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36607967

RESUMO

Research on underwater image processing has increased significantly in the past decade due to the precious resources that exist underwater. However, it is still a challenging problem to restore degraded underwater images. Existing prior-based methods show limited performance in many cases due to their reliance on hand-crafted features. Therefore, in this paper, we propose an effective unsupervised generative adversarial network(GAN) for underwater image restoration. Specifically, we embed the idea of contrastive learning into the model. The method encourages two elements (corresponding patches) to map the similar points in the learned feature space relative to other elements (other patches) in the data set, and maximizes the mutual information between input and output through PatchNCE loss. We design a query attention (Que-Attn) module, which compares feature distances in the source domain, and gives an attention matrix and probability distribution for each row. We then select queries based on their importance measure calculated from the distribution. We also verify its generalization performance on several benchmark datasets. Experiments and comparison with the state-of-the-art methods show that our model outperforms others.


Assuntos
Aumento da Imagem , Aprendizagem , Generalização Psicológica , Processamento de Imagem Assistida por Computador , Benchmarking
15.
Pediatr Surg Int ; 39(1): 93, 2023 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-36705764

RESUMO

OBJECTIVE: To evaluate the efficacy and safety of lauromacrogol foam sclerotherapy in the treatment of children with lip venous malformation. METHODS: Fifty-two children (27 males and 25 females) aged from 6 months to 17 years with lip VM who underwent lauromacrogol foam injection with ultrasonic guidance from July 2018 to December 2020 in our hospital were retrospectively recruited for this study. All the children were examined by MRI, ultrasound, blood routine and coagulation before operation. We were guided by ultrasound to locate the blood flow area (nests), injecting lauromacrogol foam to fill the venous malformation. The follow-up time was 14.31 ± 5.96 (6-24) months. Follow-up items include clinical manifestations, imaging data, efficacy and complications. RESULTS: This group of children was treated 3-5 times, an average of 4 times/case. The total effective rate was 90.38%. Pain in 4 cases, fever in 4 cases, infection in 2 cases, ulcer in 1 case. There were no serious complications such as cardiopulmonary accident. CONCLUSION: Ultrasound guiding foam sclerotherapy with lauromacrogol is effective and safe for children with lip venous malformation.


Assuntos
Soluções Esclerosantes , Malformações Vasculares , Masculino , Feminino , Humanos , Criança , Polidocanol , Soluções Esclerosantes/uso terapêutico , Estudos Retrospectivos , Lábio , Ultrassom , Resultado do Tratamento , Escleroterapia/métodos , Malformações Vasculares/diagnóstico por imagem , Malformações Vasculares/terapia
16.
Emerg Microbes Infect ; 12(1): e2161422, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36594261

RESUMO

The rapid evolution of SARS-CoV-2 Omicron sublineages mandates a better understanding of viral replication and cross-neutralization among these sublineages. Here we used K18-hACE2 mice and primary human airway cultures to examine the viral fitness and antigenic relationship among Omicron sublineages. In both K18-hACE2 mice and human airway cultures, Omicron sublineages exhibited a replication order of BA.5 ≥ BA.2 ≥ BA.2.12.1 > BA.1; no difference in body weight loss was observed among different sublineage-infected mice. The BA.1-, BA.2-, BA.2.12.1-, and BA.5-infected mice developed distinguishable cross-neutralizations against Omicron sublineages, but exhibited little neutralization against the index virus (i.e. USA-WA1/2020) or the Delta variant. Surprisingly, the BA.5-infected mice developed higher neutralization activity against heterologous BA.2 and BA.2.12.1 than that against homologous BA.5; serum neutralizing titres did not always correlate with viral replication levels in infected animals. Our results revealed a distinct antigenic cartography of Omicron sublineages and support the bivalent vaccine approach.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , Animais , Camundongos , SARS-CoV-2/genética , Melfalan , Anticorpos Antivirais , Anticorpos Neutralizantes
17.
Foods ; 12(2)2023 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-36673516

RESUMO

As primary coffee by-products, Arabica coffee husks are largely discarded during coffee-drying, posing a serious environmental threat. However, coffee husks could be used as potential material for extracting pectin polysaccharides, with high bioactivities and excellent processing properties. Thus, the present study aimed to extract the pectin polysaccharide from Arabica coffee husk(s) (CHP). The CHP yield was calculated after vacuum freeze-drying, and its average molecular weight (Mw) was detected by gel permeation chromatography (GPC). The structural characteristics of CHP were determined by Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), proton nuclear magnetic resonance (1H NMR), and scanning electron microscopy (SEM). Additionally, the rheological and antioxidant properties of CHP and the inhibition capacities of advanced glycation end products (AGEs) with different concentrations were evaluated. The interaction mechanisms between galacturonic acid (GalA) and the AGE receptor were analyzed using molecular docking. The results demonstrated that the CHP yield was 19.13 ± 0.85%, and its Mw was 1.04 × 106 Da. The results of the structural characteristics results revealed that CHP was an amorphous and low-methoxyl pectic polysaccharide linked with an α-(1→6) glycosidic bond, and mainly composed of rhamnose (Rha, 2.55%), galacturonic acid (GalA, 45.01%), ß-N-acetyl glucosamine (GlcNAc, 5.17%), glucose (Glc, 32.29%), galactose (Gal, 6.80%), xylose (Xyl, 0.76%), and arabinose (Ara, 7.42%). The surface microstructure of CHP was rough with cracks, and its aqueous belonged to non-Newtonian fluid with a higher elastic modulus (G'). Furthermore, the results of the antioxidant properties indicated that CHP possessed vigorous antioxidant activities in a dose manner, and the inhibition capacities of AGEs reached their highest of 66.0 ± 0.35% at 1.5 mg/mL of CHP. The molecular docking prediction demonstrated that GalA had a good affinity toward AGE receptors by -6.20 kcal/mol of binding energy. Overall, the study results provide a theoretical basis for broadening the application of CHP in the food industry.

18.
Cell Discov ; 9(1): 1, 2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36596774

RESUMO

Unraveling cell fate plasticity during tissue homeostasis and repair can reveal actionable insights for stem cell biology and regenerative medicine. In the pancreas, it remains controversial whether lineage transdifferentiation among the exocrine cells occur under pathophysiological conditions. Here, to address this question, we used a dual recombinase-mediated genetic system that enables simultaneous tracing of pancreatic acinar and ductal cells using two distinct genetic reporters, avoiding the "ectopic" labeling by Cre-loxP recombination system. We found that acinar-to-ductal transdifferentiation occurs after pancreatic duct ligation or during caerulein-induced pancreatitis, but not during homeostasis or after partial pancreatectomy. On the other hand, pancreatic ductal cells contribute to new acinar cells after significant acinar cell loss. By genetic tracing of cell proliferation, we also quantify the cell proliferation dynamics and deduce the turnover rate of pancreatic exocrine lineages during homeostasis. Together, these results suggest that the lineage transdifferentiation happens between acinar cells and ductal cells in the pancreatic exocrine glands under specific conditions.

19.
Theranostics ; 13(1): 77-94, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36593968

RESUMO

Rationale: microRNAs (miRNAs) are frequently deregulated and play important roles in the pathogenesis and progression of acute myeloid leukemia (AML). miR-182 functions as an onco-miRNA or tumor suppressor miRNA in the context of different cancers. However, whether miR-182 affects the self-renewal of leukemia stem cells (LSCs) and normal hematopoietic stem progenitor cells (HSPCs) is unknown. Methods: Bisulfite sequencing was used to analyze the methylation status at pri-miR-182 promoter. Lineage-negative HSPCs were isolated from miR-182 knockout (182KO) and wild-type (182WT) mice to construct MLL-AF9-transformed AML model. The effects of miR-182 depletion on the overall survival and function of LSC were analyzed in this mouse model in vivo. Results: miR-182-5p (miR-182) expression was lower in AML blasts than normal controls (NCs) with hypermethylation observed at putative pri-miR-182 promoter in AML blasts but unmethylation in NCs. Overexpression of miR-182 inhibited proliferation, reduced colony formation, and induced apoptosis in leukemic cells. In addition, depletion of miR-182 accelerated the development and shortened the overall survival (OS) in MLL-AF9-transformed murine AML through increasing LSC frequency and self-renewal ability. Consistently, overexpression of miR-182 attenuated AML development and extended the OS in the murine AML model. Most importantly, miR-182 was likely dispensable for normal hematopoiesis. Mechanistically, we identified BCL2 and HOXA9 as two key targets of miR-182 in this context. Most importantly, AML patients with miR-182 unmethylation had high expression of miR-182 followed by low protein expression of BCL2 and resistance to BCL2 inhibitor venetoclax (Ven) in vitro. Conclusions: Our results suggest that miR-182 is a potential therapeutic target for AML patients through attenuating the self-renewal of LSC but not HSPC. miR-182 promoter methylation could determine the sensitivity of Ven treatment and provide a potential biomarker for it.


Assuntos
Antineoplásicos , Leucemia Mieloide Aguda , MicroRNAs , Animais , Camundongos , Linhagem Celular Tumoral , DNA , Regulação Leucêmica da Expressão Gênica , Células-Tronco Hematopoéticas/metabolismo , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , MicroRNAs/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo
20.
Artigo em Inglês | MEDLINE | ID: mdl-36592286

RESUMO

Toxicological studies suggest that organophosphate esters (OPEs) may impair thyroid function. Epidemiological evidence, related to children and adolescents, has not been reported, and little is known about the combined effects of exposure to OPE mixtures. In this study, we collected information of 1156 children and adolescents (aged 6-18 years, 48.4% males) from a cross-sectional study in Liuzhou, China, and measured the levels of 15 urinary OPE metabolites and 5 serum thyroid hormones. Multivariate linear regression and quantile g-computation (QGC) approach were used to examine the associations which adjusted for demographic and lifestyle characteristics. Few participants had levels of triiodothyronine (T3) and free thyroxine (FT4) outside age-specific pediatric ranges. QGC analyses showed that individuals in the second, third, and fourth quartiles (Q2-Q4) of exposure had 3.93% (2.14%, 5.75%), 8.01% (4.32%, 11.8%), and 12.3% (6.54%, 18.3%) higher T3 than those in the first quartile (Q1), with similar pattern for free triiodothyronine (FT3). Individuals in Q2 and Q3 had higher thyroid-stimulating hormone (TSH) than those in Q1, but no differences were observed in TSH between Q1-Q4. In contrast, compared to the lowest quartile, FT4 was lower for those in Q2 (- 1.54%; 95% CI: - 3.02%, -0.04%), Q3 (-3.07%; 95% CI: -5.95%, -0.09%), and Q4 (-4.56%; 95% CI: - 8.80%, - 0.13%). These associations were consistent with the results from multivariate linear regression. When stratified by sex, OPE exposure (individual or mixtures) was associated with increased T3 and FT3 in males and decreased FT4 in females. This study provides the first evidence to characterize the thyroid-disrupting effects of OPE exposure in children and adolescents.

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