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1.
J Ethnopharmacol ; 298: 115612, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-35987409

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Diabetic dermatopathy is one of the most serious and common complications of diabetes. It has been found that high glucose can lead to abnormal glycometabolism. The skin microenvironment pollution caused by the increase in glucose and the oxidative stress mediated by the deposition of advanced glycation end products can lead to invisible skin injury, and the interaction between them is the key factor that makes the skin wounds of diabetic rats difficult to heal. Therefore, the main task of promoting healing is to reduce blood glucose levels and relieve the deposition of advanced glycation end products. Polygonatum kingianum Collett & Hemsl (PK) of Asparagaceae is planted in Yunnan, China, and is used by the Bai, Hani and Wa nationalities as a traditional medicine for preventing and treating diabetes. AIM OF THE STUDY: To study the effects of PK extract on skin wound healing in diabetic rats and to explore the regulatory mechanism of PK on wound microenvironment pollution, the antioxidative stress signaling pathway and latent injury of wound skin tissue. METHODS: First, wounds were prepared after diabetic rats were given PK extract by gavage for 4 weeks, and then gavage was continued for 2 weeks to observe and calculate the wound healing rate. A scanning electron microscope was used to observe the pathomorphological changes in the skin tissue at the edge of the wound. Western blotting was used to detect protein expression. Immunohistochemistry was used to detect the expression of CD34, AGEs, bFGF and VEGF. The Nrf2/HO-1 signaling pathway in skin tissue was detected by fluorescence quantitative PCR. Serum biochemical indicators and inflammatory cytokine levels were detected by a kit. RESULTS: After PK treatment, the wound healing rate increased significantly (P < 0.001), the infiltration of inflammatory cells in skin tissue of DM lesion rats decreased, the number of new blood vessels increased, and the epidermis and dermis thickened. The content of glucose, AGEs, RAGE protein and RAGE mRNA in skin decreased significantly (P < 0.05, P < 0.01, P < 0.001), while the expression of Nrf2 mRNA, HO-1 mRNA, CD34, bFGF and VEGF increased significantly (P < 0.05, P < 0.01, P < 0.001). The levels of SOD, GSH, MMP-9 and MMP-2 in skin decreased (P < 0.05, P < 0.01, P < 0.001), but the level of TIMP-2 increased (P < 0.001). GSP, GHb and ICAM-1 in plasma decreased (P < 0.05, P < 0.01, P < 0.001), while T-AOC, SOD and FINS increased (P < 0.05, P < 0.01). The levels of MDA, TNF-, IL-6, IL-2 and IFN-γ in plasma and wound skin tissue decreased (P < 0.05, P < 0.01, P < 0.001). CONCLUSION: PK can reduce the infiltration of inflammatory cells and glucose content in the skin tissue at the edge of the wound, reduce inflammatory factors in skin and plasma, and increase angiogenesis, thus improving the wound healing rate. PK can alleviate the microenvironment pollution caused by AGEs and glucose metabolism disorder in diabetic rats and induce antioxidant activity through the Nrf 2/HO-1 signaling pathway, thus reducing oxidative damage and offsetting endogenous skin damage and hidden damage.


Assuntos
Diabetes Mellitus Experimental , Polygonatum , Animais , China , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Glucose/farmacologia , Produtos Finais de Glicação Avançada/metabolismo , Fator 2 Relacionado a NF-E2 , Polygonatum/metabolismo , RNA Mensageiro , Ratos , Rizoma/metabolismo , Superóxido Dismutase , Fator A de Crescimento do Endotélio Vascular/genética , Cicatrização
2.
Preprint em Inglês | bioRxiv | ID: ppbiorxiv-503302

RESUMO

CD4+ T follicular helper (TFH) cells are required for high-quality antibody generation and maintenance. However, the longevity and functional role of these cells are poorly defined in COVID-19 convalescents and vaccine recipients. Here, we longitudinally investigated the dynamics and functional roles of spike-specific circulating TFH cells and their subsets in convalescents at the 2nd, 5th, 8th, 12th and 24th months after COVID-19 symptom onset and in vaccinees after two and three doses of inactivated vaccine. SARS-CoV-2 infection elicited robust spike-specific TFH cell and antibody responses, of which spike-specific CXCR3+ TFH cells but not spike-specific CXCR3- TFH cells and neutralizing antibodies were persistent for at least two years in more than 80% of convalescents who experienced symptomatic COVID-19, which was well coordinated between spike-specific TFH cell and antibody responses at the 5th month after infection. Inactivated vaccine immunization also induced spike-specific TFH cell and antibody responses; however, these responses rapidly declined after six months with a two-dose standard administration, and a third dose significantly promoted antibody maturation and potency. Functionally, spike-specific CXCR3+ TFH cells exhibited better responsiveness than spike-specific CXCR3- TFH cells upon spike protein stimulation in vitro and showed superior capacity in supporting spike-specific antibody secreting cell (ASC) differentiation and antibody production than spike-specific CXCR3- TFH cells cocultured with autologous memory B cells. In conclusion, spike-specific CXCR3+ TFH cells played a dominant functional role in antibody elicitation and maintenance in SARS-CoV-2 infection and vaccination, suggesting that induction of CXCR3-biased spike-specific TFH cell differentiation will benefit SARS-CoV-2 vaccine development aiming to induce long-term protective immune memory. HighlightsO_LISARS-CoV-2 infection elicited robust spike-specific TFH cell and antibody responses, which persisted for at least two years in the majority of symptomatic COVID-19 convalescent patients. C_LIO_LIInactivated vaccine immunization also elicited spike-specific TFH cell and antibody responses, which rapidly declined over time, and a third dose significantly promoted antibody maturation and potency. C_LIO_LISpike-specific CXCR3+ TFH cells exhibited more durable responses than spike-specific CXCR3- TFH cells, correlated with antibody responses and showed superior capacity in supporting ASC differentiation and antibody production than spike-specific CXCR3- TFH cells. C_LI

3.
Preprint em Inglês | medRxiv | ID: ppmedrxiv-22278764

RESUMO

BackgroundAn exploratory household transmission study was nested in SPECTRA, the phase 2/3 efficacy study of the adjuvanted recombinant protein-based COVID-19 vaccine SCB-2019. We compared occurrence of confirmed COVID-19 infections between households and household contacts of infected SPECTRA participants who were either placebo or SCB-2019 recipients. MethodsSPECTRA trial participants at eight study sites in the Philippines who developed rRT-PCR-confirmed COVID-19 were contacted by a study team blinded to assignment of index cases to vaccine or placebo groups to enroll in this household transmission study. Enrolled households and household contacts were monitored for three weeks using rRT-PCR and rapid antigen testing to detect new COVID-19 infections. ResultsObservation of the households of 154 eligible COVID-19 index cases, 130 symptomatic and 24 asymptomatic at diagnosis, revealed household secondary attack rates for any COVID-19 infection of SCB-2019 index cases of 0.76% (90% CI: 0.15-3.90) compared with 5.88% (90% CI: 3.20-10.8) in placebo index case households, a relative risk reduction of 79% (90% CI: -28-97). The relative risk reduction of symptomatic COVID-19 was 84% (90% CI: 28-97) for household contacts of all COVID-19 infected index cases, and 80% (90% CI: 7-96) for household contacts of index cases with symptomatic COVID-19. ConclusionsIn this prospective household contact study vaccination with SCB-2019 reduced SARS-CoV-2 transmission in households, so decreasing infections of household contacts, compared with placebo.

4.
Artigo em Inglês | MEDLINE | ID: mdl-35945322

RESUMO

The layered double hydroxides (LDHs) have attracted attention in the water treatment field. In this paper, three novel ternary Zn-Co-Ni-LDH adsorbents were prepared successfully through rational construction from 2D to 3D using triethanolamine (TEA) as an alkali source and a structural controlling reagent by hydrothermal technique. Samples were characterized by the SEM, XRD, XPS, FTIR, BET, solid-state UV/vis spectra, and TG. Three Zn-Co-Ni-LDHs exhibited higher crystallinity and surface area which were beneficial to the adsorption for methyl orange (MO). The maximum adsorption capacity of three Zn-Co-Ni-LDH adsorbents can even reach as high as 1871.65 mg·g-1, 1799.56 mg·g-1, and 1646.44 mg·g-1 for MO, respectively, which surpass those of most previously reported LDH-based adsorbents. The pseudo-second-order kinetic equation fitted the kinetic data of adsorption, while the equilibrium adsorption isotherm data followed the Langmuir model. The adsorption mechanism, electrochemical, and the antibacterial properties of three Zn-Co-Ni-LDHs were also discussed. This results not only demonstrates that three Zn-Co-Ni-LDHs are practical interest as an efficient adsorbent for the removal of MO from dye waste water, but also provides a strategy for the rational design through three ternary Zn-Co-Ni-LDHs from 2D to 3D.

5.
Preprint em Inglês | medRxiv | ID: ppmedrxiv-22275010

RESUMO

BackgroundOngoing outbreaks of COVID-19 are driven by waning immunity following primary immunizations and emergence of new SARS-CoV-2 variants which escape vaccine-induced neutralizing antibodies. It has been suggested that heterologous boosters could enhance and potentially maintain population immunity. MethodsWe assessed immunogenicity and reactogenicity of booster doses of different formulations of alum-adjuvanted SCB-2019 vaccine (9 g SCB-2019 with or without CpG-1018 adjuvant, or 30 g SCB-2019 with CpG-1018) in Brazilian adults primed with ChAdOx1-S vector vaccine. S-protein antibodies and ACE2-binding inhibition were measured by ELISA on Days 1, 15 and 29. Participants self-reported solicited adverse events and reactions. ResultsAll SCB-2019 formulations increased S-protein ELISA antibodies and ACE2 binding inhibition to a greater extent than ChAdOx1-S. After 30 g SCB-2019+CpG+alum titers against wild-type S-protein were significantly higher than after ChAdOx1-S on Days 15 and 29, as were titers of neutralizing antibodies against wild-type strain and Beta, Gamma, Delta, and Omicron variants. Boosting with SCB-2019 or ChAdOx1-S was well tolerated with no vaccine-related serious or severe adverse events. ConclusionsBoosting ChAdOx1-S-primed adults with SCB-2019 induced higher levels of antibodies against a wild-type strain and SARS-CoV-2 variants than a homologous ChAdOx1-S booster, highest responses being with the 30 g SCB-2019+CpG+alum formulation.

6.
Endocr J ; 2022 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-35718445

RESUMO

We enrolled 264 patients with papillary thyroid carcinoma (PTC). We performed immunohistochemical detection of p16 and determined the degree of interstitial fibrosis (IF). The expression of p16 was associated with pathological tumor-node-metastasis (pTNM) stage and age (p < 0.05). The overall survival was longer in p16-negative patients (195.73 vs. 181.78 months, p = 0.007). p16 was significantly related to the degree of IF (r = 0.130, p = 0.035). PTC patients with no or mild fibrosis tended to have a larger tumor (p = 0.045). The degree of fibrosis was related to the proportion of papillary structure components (p = 0.025). Univariate and multivariate survival analyses showed that relapse-free survival was longer in patients with moderate/severe IF (p < 0.05). In summary, p16 was correlated with prognosis and IF of PTC. Patients with moderate/severe IF tend to have better prognosis in RFS.

7.
Preprint em Inglês | medRxiv | ID: ppmedrxiv-22273829

RESUMO

The SARS-CoV-2 pandemic poses a great threat to global health, particularly in solid organ transplant recipients (SOTRs). Although a 3-dose mRNA vaccination protocol has been implemented for the majority of SOTRs, its effectiveness was still largely unknown. We analyzed 113 vaccinated SOTRs, and 30 healthy controls (HCs), some of whom had recovered from COVID, for their immune responses against the original vaccine strain and variants of concern (VOC), including the highly mutated-omicron variant. Here, we report that 3 doses of the mRNA vaccine had only a modest effect in eliciting anti-viral responses against all viral strains in the fully vaccinated SOTRs who did not contract the virus. Only 34.0% (16/47) of this group of patients demonstrated both detectable anti-RBD IgG and neutralization activities against alpha, beta, and delta variants, and only 8.5% (4/47) of them showed additional omicron-neutralizing capacities. In contrast, 79.5% (35/44) of the vaccinated recovered-SOTRs demonstrated both higher anti-RBD IgG levels and neutralizing activities against all VOC, including omicron. These findings illustrate a significant impact of previous infection on the development of anti-COVID immune responses in vaccinated SOTRs and highlight the need for alternative strategies to protect a subset of a lesser-vaccine responsive population.

8.
Int J Surg Pathol ; : 10668969221097389, 2022 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-35477307

RESUMO

Mixed epithelial and stromal tumors of the kidney (MESTK) are rare and recently defined entities that comprise both epithelial and stromal cells. MESTK is mostly benign; however, to date, 18 borderline or malignant cases have been reported. In this study, we report a case of carcinosarcoma exhibiting a large carcinoma and small sarcoma component, and review the relevant literature. The patient was a 59-year-old woman who presented with a large mass in the left kidney having solid and focal cystic components. The patient underwent left radical nephrectomy. The tumor was gray-white and solid-cystic, with a relatively clear boundary. Microscopically, the tumor revealed benign and malignant components. The benign component consisted of multiple tubules, variable-sized cysts lined with benign epithelium, and hyalinized stroma. The malignant component was composed of predominantly small cell neuroendocrine carcinoma and a small quantity of adenocarcinoma, squamous cell carcinoma, and sarcoma. Finally, a diagnosis of the malignant MESTK was made. Certain cases of borderline or malignant transformation of MESTK have been published, so it is important to enhance findings made by other studies.

9.
Biotechnol Bioeng ; 119(7): 1768-1780, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35383880

RESUMO

Currently, whole-cell catalysts face challenges due to the complexity of reaction systems, although they have a cost advantage over pure enzymes. In this study, cytarabine was synthesized by purified purine phosphorylase 1 (PNP1) and uracil phosphorylase (UP), and the conversion of cytarabine from adenine arabinoside reached 72.3 ± 4.3%. However, the synthesis was unsuccessful by whole-cell catalysis due to interference from unnecessary proteins (UNPs) in cells. Thus, we carried out a large-scale gene editing involving 377 genes in the genome of Escherichia coli to reduce the negative effect of UNPs on substrate conversion and cytarabine production. Finally, the PNP1 and UP activities of the obtained mutant were increased significantly compared with the parental strain, and more importantly, the conversion rate of cytarabine by whole-cell catalysis reached 67.4 ± 2.5%. The lack of 148 proteins and downregulation of 783 proteins caused by gene editing were equivalent to partial purification of the enzymes within cells, and thus, we provided inspiration to solve the problem caused by UNP interference, which is ubiquitous in the field of whole-cell catalysis.


Assuntos
Escherichia coli , Purina-Núcleosídeo Fosforilase , Citarabina/metabolismo , Escherichia coli/metabolismo , Fosforilases/metabolismo , Purina-Núcleosídeo Fosforilase/química , Purina-Núcleosídeo Fosforilase/genética , Purina-Núcleosídeo Fosforilase/metabolismo , Purinas/metabolismo , Uracila/metabolismo
10.
World J Clin Cases ; 10(5): 1572-1579, 2022 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-35211594

RESUMO

BACKGROUND: Nodular fasciitis (NF) is a self-limiting tumor that mostly occurs in the subcutaneous superficial fascia. NF originating from the appendicular periosteum is extremely rare. A large NF lesion of periosteal origin can be misdiagnosed as a malignant bone tumor and may cause overtreatment. CASE SUMMARY: A right axillary mass was found in a 46-year-old man and was initially diagnosed intraoperatively as low-grade sarcoma, but later diagnosed as NF after post-resection histopathological evaluation. Furthermore, fluorescence in situ hybridization analysis revealed a USP6 gene rearrangement that confirmed the diagnosis. To the best of our knowledge, this is the first case of NF in the humeral periosteum. CONCLUSION: NF poses a diagnostic challenge as it is often mistaken for sarcoma. Postoperative histopathological examination of whole sections can be combined with immunohistochemical staining and, if necessary, the diagnosis can be confirmed by molecular detection, and thus help avoid overtreatment.

11.
Neoplasma ; 2022 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-35144475

RESUMO

miR-200c-3p is aberrantly expressed in numerous cancers, but its underlying mechanisms in nephroblastoma are unknown. In our study, the differentially regulated miRNAs between the nephroblastoma tissues and adjacent non-neoplastic renal tissues were screened based on microarray analysis. The miR-200c-3p expression in nephroblastoma tissues and cells was detected by qRT-PCR. Then, the effects of miR-200c-3p mimic or inhibitor on cell proliferation, invasion, and migration were evaluated by CCK-8 assay, plate colony formation assay, soft agar assay, Transwell, and wound-healing assay in SK-NEP-1 and G401 cells. Afterward, the target gene of miR-200c-3p was predicted by TarBase, miRTarBase, miRDB softwares, and then verified by dual-luciferase reporter gene assay. The in vivo effects of miR-200c-3p on pathological changes and tumor volume were investigated in tumor xenograft mice by H&E staining and in vivo fluorescence imaging. ChIP assay was used to evaluate the relationship between histone acetyltransferase E1A-binding protein p300 (EP300) and P27, and the relationship of the role of miR-200c-3p in nephroblastoma and the AKT/FOXO1/p27 signaling pathways was evaluated by western blotting. Our study shows that miR-200c-3p was downregulated in nephroblastoma tissues and cells, and EP300 was a target gene of miR-200c-3p. Furthermore, miR-200c-3p mimic decreased cell proliferation and inhibited cell migration and invasion in nephroblastoma. Mechanistically, miR-200c-3p could inhibit p-AKT activity and enhance p-FOXO1 and p27 expression. Notably, the transcription factor P27 could bind to the EP300 promoter. This study demonstrates a new approach to treat nephroblastoma.

12.
Mol Breed ; 42(2): 6, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35103045

RESUMO

Leaf thickness is an important trait in rice (Oryza sativa L.). It affects both photosynthesis and sink-resource efficiency. However, compared to leaf length and length width, reports seldom focused on leaf thickness due to the complicated measurement and minor difference. To identify the quantitative trait loci (QTL) and explore the genetic mechanism regulating the natural variation of leaf thickness, we crossed a high leaf thickness variety Aixiuzhan (AXZ) to a thin leaf thickness variety Yangdao No.6 (YD 6) and evaluated 585 F2 individuals. We further use bulked sergeant analysis with whole-genome resequencing (BSA-seq) to identify five genomic regions, including chromosomes 1, 6, 9, 10, and 12. These regions represented significant allele frequency differentiation between thick and thin leaf thickness among the mixed pool offspring. Moreover, we conducted a linkage mapping using 276 individuals derived from the F2 population. We fine-mapped and confirmed that chromosome 9 contributed the primary explanation of phenotypic variance. We fine-mapped the candidate regions and confirmed that the chromosome 9 region contributed to flag leaf thickness in rice. We observed the virtual cellular slices and found that the bundle sheath cells in YD 6 flag leaf veins are fewer than AXZ. We analyzed the potential regions on chromosome 9 and narrowed the QTL candidate intervals in the 928-kb region. Candidate genes of this major QTL were listed as potentially controlled leaf thickness. These results provide promising evidence that cloning leaf thickness is associated with yield production in rice. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11032-022-01275-y.

13.
Autophagy ; 18(5): 1152-1173, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-34432562

RESUMO

Excessive macroautophagy/autophagy is one of the causes of cardiomyocyte death induced by cardiovascular diseases or cancer therapy, yet the underlying mechanism remains unknown. We and other groups previously reported that autophagy might contribute to cardiomyocyte death caused by sunitinib, a tumor angiogenesis inhibitor that is widely used in clinic, which may help to understand the mechanism of autophagy-induced cardiomyocyte death. Here, we found that sunitinib-induced autophagy leads to apoptosis of cardiomyocyte and cardiac dysfunction as the cardiomyocyte-specific Atg7-/+ heterozygous mice are resistant to sunitinib. Sunitinib-induced maladaptive autophagy selectively degrades the cardiomyocyte survival mediator CCN2 (cellular communication network factor 2) through the TOLLIP (toll interacting protein)-mediated endosome-related pathway and cardiomyocyte-specific knockdown of Ccn2 through adeno-associated virus serotype 9 (AAV9) mimics sunitinib-induced cardiac dysfunction in vivo, suggesting that the autophagic degradation of CCN2 is one of the causes of sunitinib-induced cardiotoxicity and death of cardiomyocytes. Remarkably, deletion of Hmgb1 (high mobility group box 1) inhibited sunitinib-induced cardiomyocyte autophagy and apoptosis, and the HMGB1-specific inhibitor glycyrrhizic acid (GA) significantly mitigated sunitinib-induced autophagy, cardiomyocyte death and cardiotoxicity. Our study reveals a novel target protein of autophagic degradation in the regulation of cardiomyocyte death and highlights the pharmacological inhibitor of HMGB1 as an attractive approach for improving the safety of sunitinib-based cancer therapy.


Assuntos
Cardiotoxicidade , Fator de Crescimento do Tecido Conjuntivo , Proteína HMGB1 , Cardiopatias , Sunitinibe , Animais , Apoptose , Autofagia , Cardiotoxicidade/patologia , Fator de Crescimento do Tecido Conjuntivo/genética , Proteína HMGB1/metabolismo , Cardiopatias/induzido quimicamente , Cardiopatias/patologia , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Camundongos , Miócitos Cardíacos/metabolismo , Sunitinibe/farmacologia
14.
Environ Sci Pollut Res Int ; 29(16): 24098-24111, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34822088

RESUMO

Based on panel data from 30 provinces in China from 2008 to 2017, this paper constructs a quantile regression econometric model to analyze whether China's environmental regulation has an impact on export trade and to verify whether the Porter hypothesis has been valid in China in recent years. The results show that in the short term, environmental regulations have a restraining effect on export trade, while in the long run, due to the existence of innovation efficiency, environmental regulations will change from having a restraining effect to a promoting effect on export trade. Strict environmental regulations will reduce the production cost of Chinese products, further improve the export competitiveness of Chinese enterprises, and promote export trade. The empirical results verify the conclusion that the Porter hypothesis is confirmed in China. The following three suggestions are proposed for China's exports to promote the win-win of China's green development and export trade: promote the realization of international and domestic double circulation, avoid becoming "pollution shelters" and support technological innovation in environmental protection industries.


Assuntos
Poluição Ambiental , Indústrias , China , Conservação dos Recursos Naturais , Desenvolvimento Econômico , Eficiência , Poluição Ambiental/análise , Invenções
15.
IEEE J Biomed Health Inform ; 26(4): 1826-1834, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34520381

RESUMO

Physically-coupled bimanual tasks (activities where a force effect occurs between two human limbs) involve the coordination and cooperation of bilateral arms. Such uncertain contribution of two arms is often studied under static configuration, which is not sufficient to typify all activities of daily life (ADLs). This study aims to investigate people's bilateral force production and control in dynamic tasks. Experiments were conducted with a customized robotic system that is characterized with two handles and programmable force fields between them. Fourteen healthy right-handed human volunteers were instructed to generate force with each hand when performing predefined trajectory tracking tasks, in which the sum of forces contributed by the left and the right hand is required to equal a target force. Significant asymmetry was found in the force output between bilateral hands. With the homologous muscles activated synchronously, the contribution of the left hand was larger, while when the non-homogenous muscles were activated synchronously, the laterality was subject to the moving direction. In addition, when considering the force difference between two hands in terms of direction and magnitude, the former decreased with the increase of the target force, but the latter was more sensitive to moving directions. The results reveal the unique characteristics of non-isometric force control tasks compared with isometric ones.


Assuntos
Mãos , Desempenho Psicomotor , Atividades Cotidianas , Lateralidade Funcional/fisiologia , Força da Mão/fisiologia , Humanos , Desempenho Psicomotor/fisiologia
16.
Virchows Arch ; 480(3): 577-585, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34757486

RESUMO

UbiquitinC-terminal hydrolase-L1 (UCH-L1) is a cysteine hydrolase. It functions as a ubiquitin hydrolase, stabilizes the ubiquitin monomer, and affects cell division through cell cycle protein deubiquitination. Abnormal UCH-L1 expression is closely related to the occurrence and development of several tumors. Although some in vitro studies have demonstrated the significance of UCH-L1 in non-small-cell lung cancer (NSCLC), only few clinical studies have focused on the UCH-L1 expression in NSCLC, and the results are controversial and non-uniform. We investigated the UCH-L1 expression in 401 cases of surgically resected NSCLC, including 286 cases of adenocarcinoma (ADC) and 65 cases of squamous cell carcinoma. The associations between the UCH-L1 expression and clinicopathological features, programmed cell death-ligand 1 (PD-L1) expression, and prognostic significance were analyzed. For NSCLC, the UCH-L1 expression is associated with sex, smoking history, tumor size (>3 cm), lymphocyte infiltration, advanced pathological stages, and shortened overall survival (OS; 89.72 vs. 114.55 months; P = 0.005), but not PD-L1 expression. The UCH-L1 expression in ADC is associated with advanced pathological stages, pleural invasion, and shortened OS (90.38 vs. 118.55 months; P = 0.010). Multivariate analysis confirmed that UCH-L1 expression was an independent poor prognostic factor for NSCLC (OS: hazard ratio [HR], 1.854; 95% confidence interval [CI], 1.132-3.038; P = 0.014). Our results suggest that the UCH-L1 expression differs across tumors with different clinicopathological features, and it is related to poor prognosis.


Assuntos
Adenocarcinoma , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Ubiquitina Tiolesterase , Antígeno B7-H1/metabolismo , Biomarcadores Tumorais/análise , Carcinoma Pulmonar de Células não Pequenas/patologia , Humanos , Neoplasias Pulmonares/patologia , Ubiquitina , Ubiquitina Tiolesterase/metabolismo
17.
ACS Appl Mater Interfaces ; 13(37): 44440-44450, 2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34499478

RESUMO

A phase junction fabricated by two crystalline phases of the same semiconductor is a promising photocatalyst with efficient charge transfer and separation. However, the weak light absorption and uncontrolled phase junction interface limit the generation and separation of photogenerated carriers. Herein, a two-dimensional (2D)/2D phase junction was prepared by growing orthorhombic WO3 ultrathin nanosheets on hexagonal WO3 nanosheets through a one-step hydrothermal method. The orthorhombic/hexagonal WO3 possesses large-area phase junction interfaces, rich reactive sites, and built-in electric field, which greatly accelerate the photogenerated charge separation and transfer. Thus, the orthorhombic/hexagonal WO3 displayed excellent photocatalytic hydrogen generation activity from water splitting under light irradiation (λ > 420 nm), which is 2.16 and 2.85 times those of orthorhombic and hexagonal WO3 phase components. Furthermore, Au nanoparticles (about 4.5 nm in diameter) were deposited on both orthorhombic and hexagonal WO3 nanosheets to form a plasmon-mediated phase junction. The hybrids exhibit prominent visible-light absorption and efficient charge transfer, leading to a further improved photocatalytic hydrogen generation activity. Further characterization studies demonstrate that superior photoactivity arises from the excellent visible-light-harvesting ability, appropriate band structure, and high-efficiency and multichannel transferring processes of photogenerated carriers.

18.
Cancer Med ; 10(21): 7650-7664, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34581023

RESUMO

PURPOSE: Some studies have indicated that using 500 mg/m2 rituximab combined with CHOP-14 may be beneficial for elderly men but not women with diffuse large B-cell lymphoma (DLBCL). The purpose of this study was to investigate the potential benefit of escalated doses of rituximab with CHOP-21 as the first-line treatment in male patients with DLBCL. METHODS: We performed a retrospective cohort study to analyze the survival benefit of rituximab 500 mg/m2 plus the CHOP-21 regimen (Escalated-R-CHOP-21) as the first-line treatment compared with using rituximab 375 mg/m2 plus the CHOP-21 regimen (Standard-R-CHOP-21) in men with DLBCL. We used propensity score matching to maximize the balance of the observed covariables. The primary endpoints of this study were the progression-free survival (PFS) rate and overall survival (OS) rate at 3 years. RESULTS: After a median follow-up of 47 months (IQR 31-65), no significant difference in PFS and OS was found for men treated with Escalated-R-CHOP-21 compared with Standard-R-CHOP-21 [3-year PFS: 69.7% versus 71.9%, p = 0.867; 3-year OS: 83.0% versus 82.4%, p = 0.660]. After 1:1 propensity score matching, we found that the patients using Escalated-R-CHOP-21 had statistically significant survival benefits relative to Standard-R-CHOP-21 among the 96 matched elderly male patients for 3-year PFS [75.5% (95% CI 62.8-88.2) versus 58.2% (95% CI 44.3-72.1); p = 0.019] and 3-year OS [86.6% (95% CI 76.4-96.8) versus 65.8% (95% CI 52.1-79.5); p = 0.017]. However, no differences in survival were observed for younger male patients. Furthermore, the dose effect in PFS of Escalated-R-CHOP-21 was more obvious for elderly male patients with no high-risk extranodal sites (p = 0.005 and interaction p = 0.030). CONCLUSION: Escalated-R-CHOP-21 could be a safe and effective option for treating elderly male patients with DLBCL. This study provides new insight into optimizing the standard treatment regimen, which may have important therapeutic implications in elderly male patients with DLBCL.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Rituximab/administração & dosagem , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ciclofosfamida/efeitos adversos , Ciclofosfamida/uso terapêutico , Doxorrubicina/efeitos adversos , Doxorrubicina/uso terapêutico , Esquema de Medicação , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prednisona/efeitos adversos , Prednisona/uso terapêutico , Intervalo Livre de Progressão , Pontuação de Propensão , Estudos Retrospectivos , Fatores de Risco , Rituximab/efeitos adversos , Fatores Sexuais , Análise de Sobrevida , Vincristina/efeitos adversos , Vincristina/uso terapêutico
19.
BMC Cancer ; 21(1): 913, 2021 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-34380457

RESUMO

BACKGROUND: Although spread through air spaces (STAS) is a robust biomarker in surgically resected lung cancer, its application to biopsies is challenging. Moreover, limited resection is not an effective treatment for STAS-positive lung adenocarcinoma. This study aimed to identify histologic features from preoperative percutaneous transthoracic needle biopsies (PTNBs) to predict STAS status in the subsequently resected specimens, and thus help in selecting the surgical extent. METHODS: Between January 2014 and December 2015, 111 PTNB specimens and subsequent resection specimens from consecutive lung adenocarcinoma patients were retrospectively examined. Histopathologic features of PTNB specimens and presence of STAS in subsequent resection specimens were evaluated and correlations between them were analyzed statistically. RESULTS: The study participants had a mean age of 59 years (range, 35-81) and included 50 men and 61 women. Thirty-six patients were positive for STAS whereas 75 were negative. The micropapillary/solid histologic subtypes of lung adenocarcinoma (26 of 39; 66.7%; P <  0.001), necrotic/tumor debris (31 of 42; 73.8%; P <  0.001), intratumoral budding (ITB) (20 of 33; 60.6%; P <  0.001), desmoplasia (35 of 41; 85.4%; P <  0.001), and grade 3 nuclei (12 of 14; 85.7%; P <  0.001) were more common in STAS-positive tumors. Micropapillary/solid histologic subtype (OR, 1.35; 95% CI: 1.06, 1.67), ITB (OR, 1.64; 95% CI: 1.09, 2.83), desmoplasia (OR, 1.83; 95% CI: 1.36, 3.12), and N stage (N1 stage: OR, 1.37; 95% CI: 1.19, 1.87) (N2 stage: OR, 1.29; 95% CI: 1.07, 1.73) were independent predictors of STAS. CONCLUSIONS: Micropapillary/solid histologic subtype, ITB, and desmoplasia in preoperative PTNB specimens were independently associated with STAS in the subsequent resection specimens. Therefore, these can predict STAS and may help to optimize therapeutic planning.


Assuntos
Adenocarcinoma de Pulmão/diagnóstico , Biópsia/efeitos adversos , Cuidados Pré-Operatórios , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/cirurgia , Biópsia/métodos , Feminino , Humanos , Imuno-Histoquímica , Masculino , Gradação de Tumores , Metástase Neoplásica , Estadiamento de Neoplasias , Razão de Chances , Prognóstico , Estudos Retrospectivos
20.
Plant Physiol Biochem ; 166: 964-973, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34256250

RESUMO

Elevated CO2 concentrations and persistent drought are predicted to inhibit the photosynthetic performance and yield of crops. Such effects vary considerably between species groups. Modern cultivated (Triticum aestivum L., AABBDD) and wild (Triticum dicoccoides Korn L., AABB and Triticum monococcum L., AA) species of wheat were subjected to elevated CO2 concentration (ambient concentration +200 µmol mol-1) and drought (well watered: 75-85% of the field water capacity; drought: 50-60% of the field water capacity) at open-top chamber experimental facilities. Elevated CO2 concentration decreased the limitation of stomatal morphology traits on stomatal conductance regulation. This could compensate the disadvantage of plants who has low stomatal density and large single stomatal area as well as low leaf water use efficiency such as modern wheat Z9023 in drought acclimation in the future CO2 rising world. Moreover, elevated CO2 concentration largely increased the dependence of light harvesting and electron transportation performance per photosynthesis system II reaction center, maximum rubisco carboxylation rate, and maximum Ribulose-1,5-bisphosphate regeneration rate on leaf nitrogen concentration across the selected wheat species and water regimes. Modern cultivated cultivars Z9023 and CH58 have higher photosynthetic performance per unit of leaf nitrogen than wild species under elevated CO2 concentrations. The increasing CO2 may present opportunities to breeders and possibly allow them to select for cultivars with better photosynthetic nitrogen use efficiency response to future CO2 rising climate.


Assuntos
Nitrogênio , Triticum , Dióxido de Carbono , Secas , Fotossíntese , Folhas de Planta
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