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1.
Nat Commun ; 13(1): 4494, 2022 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-35918380

RESUMO

Enzymes from pathogens often modulate host protein post-translational modifications (PTMs), facilitating survival and proliferation of pathogens. Shigella virulence factors IpaJ and IcsB induce proteolytic cleavage and lysine fatty acylation on host proteins, which cause Golgi stress and suppress innate immunity, respectively. However, it is unknown whether host enzymes could reverse such modifications introduced by pathogens' virulence factors to suppress pathogenesis. Herein, we report that SIRT2, a potent lysine defatty-acylase, is upregulated by the transcription factor CREB3 under Golgi stress induced by Shigella infection. SIRT2 in turn removes the lysine fatty acylation introduced by Shigella virulence factor IcsB to enhance host innate immunity. SIRT2 knockout mice are more susceptible to Shigella infection than wildtype mice, demonstrating the importance of SIRT2 to counteract Shigella infection.


Assuntos
Disenteria Bacilar , Shigella , Acilação , Animais , Disenteria Bacilar/metabolismo , Complexo de Golgi/metabolismo , Lisina/metabolismo , Camundongos , Sirtuína 2/genética , Sirtuína 2/metabolismo , Fatores de Virulência/metabolismo
2.
Rice (N Y) ; 15(1): 41, 2022 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-35920921

RESUMO

Rice bacterial blight, caused by Xanthomonas oryzae pv. oryzae (Xoo), is one of the most serious diseases affecting rice production worldwide. Xa21 was the first disease resistance gene cloned in rice, which encodes a receptor kinase and confers broad resistance against Xoo stains. Dozens of components in the Xa21-mediated pathway have been identified in the past decades, however, the involvement of mitogen-activated protein kinase (MAPK) genes in the pathway has not been well described. To identify MAPK involved in Xa21-mediated resistance, the level of MAPK proteins was profiled using Western blot analysis. The abundance of OsMPK17 (MPK17) was found decreased during the rice-Xoo interaction in the background of Xa21. To investigate the function of MPK17, MPK17-RNAi and over-expression (OX) transgenic lines were generated. The RNAi lines showed an enhanced resistance, while OX lines had impaired resistance against Xoo, indicating that MPK17 plays negative role in Xa21-mediated resistance. Furthermore, the abundance of transcription factor WRKY62 and pathogenesis-related proteins PR1A were changed in the MPK17 transgenic lines when inoculated with Xoo. We also observed that the MPK17-RNAi and -OX rice plants showed altered agronomic traits, indicating that MPK17 also plays roles in the growth and development. On the basis of the current study and published results, we propose a "Xa21-MPK17-WRKY62-PR1A" signaling that functions in the Xa21-mediated disease resistance pathway. The identification of MPK17 advances our understanding of the mechanism underlying Xa21-mediated immunity, specifically in the mid- and late-stages.

3.
Inorg Chem ; 2022 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-35930703

RESUMO

The reactions of CS2 captured by intramolecular geminal G13/P-based (G13 = group 13 elements) and Ga/G15-based (G15 = group 15 elements) frustrated Lewis pairs have been theoretically examined by using density functional theory (DFT) computations. With regard to the nine FLP-related compounds, our DFT calculated results reveal that only Al/P-Rea and Ga/P-Rea can kinetically and thermodynamically precede the energetically feasible combination reactions with CS2 to form the five-membered heterocyclic adducts. Our activation strain model analyses on the nine aforementioned model molecules indicate that the atomic radius of the Lewis acceptor (G13) and the Lewis donor (G15) plays a role in controlling their barrier heights to obtain good orbital overlaps among G13/P-Rea, Ga/G15-Rea, and CS2. Our theoretical observations based on the energy decomposition analysis-natural orbitals for chemical valence (EDA-NOCV) approach strongly indicate that the donor-acceptor bonding (i.e., singlet-singlet bonding) rather than the electron-sharing bonding (i.e., triplet-triplet bonding) plays a central role in determining the bonding conditions of the transition states, G13/P-TS and Ga/G15-TS. In addition, the theoretical evidence obtained by the frontier molecular orbital theory and EDA-NOCV analyses reveals that the best description for the bonding natures of the combination reactions of intramolecular geminal G13/P-Rea and Ga/G15-Rea with CS2 is the lone pair(G15) → p-π*(C) interaction rather than the p-π*(G13) ← p-π(S) interaction. Moreover, our present DFT computations concerning the calculated structures and corresponding relative energetics of the stationary points connected with the aforementioned sophisticated approaches are in accordance with the Hammond postulate.

4.
Nanomicro Lett ; 14(1): 154, 2022 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-35916945

RESUMO

Large volumetric expansion of cathode hosts and sluggish transport kinetics in the cathode-electrolyte interface, as well as dendrite growth and hydrogen evolution at Zn anode side are considered as the system problems that cause the electrochemical failure of aqueous Zn-vanadium oxide battery. In this work, a multifunctional anti-proton electrolyte was proposed to synchronously solve all those issues. Theoretical and experimental studies confirm that PEG 400 additive can regulate the Zn2+ solvation structure and inhibit the ionization of free water molecules of the electrolyte. Then, smaller lattice expansion of vanadium oxide hosts and less associated by-product formation can be realized by using such electrolyte. Besides, such electrolyte is also beneficial to guide the uniform Zn deposition and suppress the side reaction of hydrogen evolution. Owing to the integrated synergetic modification, a high-rate and ultrastable aqueous Zn-V2O3/C battery can be constructed, which can remain a specific capacity of 222.8 mAh g-1 after 6000 cycles at 5 A g-1, and 121.8 mAh g-1 even after 18,000 cycles at 20 A g-1, respectively. Such "all-in-one" solution based on the electrolyte design provides a new strategy for developing high-performance aqueous Zn-ion battery.

5.
Plast Reconstr Surg ; 2022 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-35939649

RESUMO

SUMMARY: Dental implant placement complications in patients with symphysis cross-arch defect occur following single-barrel fibula mandible reconstruction due to mechanical stress of the implant. The authors compared surgical complications and implant outcomes for patients following single-barrel fibula mandible reconstruction with immediate implant placement or following completion of vertical distraction osteogenesis.

6.
Sci Rep ; 12(1): 13412, 2022 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-35927323

RESUMO

O6-Methylguanine-DNA-methyltransferase (MGMT) promoter methylation was shown in many studies to be an important predictive biomarker for temozolomide (TMZ) resistance and poor progression-free survival in glioblastoma multiforme (GBM) patients. However, identifying the MGMT methylation status using molecular techniques remains challenging due to technical limitations, such as the inability to obtain tumor specimens, high prices for detection, and the high complexity of intralesional heterogeneity. To overcome these difficulties, we aimed to test the feasibility of using a novel radiomics-based machine learning (ML) model to preoperatively and noninvasively predict the MGMT methylation status. In this study, radiomics features extracted from multimodal images of GBM patients with annotated MGMT methylation status were downloaded from The Cancer Imaging Archive (TCIA) public database for retrospective analysis. The radiomics features extracted from multimodal images from magnetic resonance imaging (MRI) had undergone a two-stage feature selection method, including an eXtreme Gradient Boosting (XGBoost) feature selection model followed by a genetic algorithm (GA)-based wrapper model for extracting the most meaningful radiomics features for predictive purposes. The cross-validation results suggested that the GA-based wrapper model achieved the high performance with a sensitivity of 0.894, specificity of 0.966, and accuracy of 0.925 for predicting the MGMT methylation status in GBM. Application of the extracted GBM radiomics features on a low-grade glioma (LGG) dataset also achieved a sensitivity 0.780, specificity 0.620, and accuracy 0.750, indicating the potential of the selected radiomics features to be applied more widely on both low- and high-grade gliomas. The performance indicated that our model may potentially confer significant improvements in prognosis and treatment responses in GBM patients.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Glioma , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Metilação de DNA , Metilases de Modificação do DNA/genética , Metilases de Modificação do DNA/metabolismo , Enzimas Reparadoras do DNA/genética , Enzimas Reparadoras do DNA/metabolismo , Glioblastoma/diagnóstico por imagem , Glioblastoma/genética , Glioma/genética , Humanos , Aprendizado de Máquina , O(6)-Metilguanina-DNA Metiltransferase/genética , Estudos Retrospectivos , Proteínas Supressoras de Tumor/genética
7.
J Integr Plant Biol ; 2022 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-35962716

RESUMO

Autophagy is an evolutionarily conserved degradation pathway in eukaryotes; it plays a critical role in nutritional stress tolerance. The circadian clock is an endogenous timekeeping system that generates biological rhythms to adapt to daily changes in the environment. Accumulating evidence indicates that the circadian clock and autophagy are intimately interwoven in animals. However, the role of the circadian clock in regulating autophagy has been poorly elucidated in plants. Here, we show that autophagy exhibits a robust circadian rhythm in both light/dark cycle (LD) and in constant light (LL) in Arabidopsis. However, autophagy rhythm showed a different pattern with a phase-advance shift and a lower amplitude in LL compared to LD. Moreover, mutation of the transcription factor LUX ARRHYTHMO (LUX) removed autophagy rhythm in LL and led to an enhanced amplitude in LD. LUX represses expression of the core autophagy genes ATG2, ATG8a, and ATG11 by directly binding to their promoters. Phenotypic analysis revealed that LUX is responsible for improved resistance of plants to carbon starvation, which is dependent on moderate autophagy activity. Comprehensive transcriptomic analysis revealed that the autophagy rhythm is ubiquitous in plants. Taken together, our findings demonstrate that the LUX-mediated circadian clock regulates plant autophagy rhythms. This article is protected by copyright. All rights reserved.

8.
Inflamm Res ; 2022 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-35962796

RESUMO

AIMS: Systemic inflammation plays an important role in cancer cachexia. However, among the systemic inflammatory biomarkers, it is unclear which has optimal prognostic value for cancer cachexia. METHODS: The Kaplan-Meier method was used and the log-rank analysis was performed to estimate survival differences between groups. Cox proportional hazard regression analyses were conducted to assess independent risk factors for all-cause mortality. RESULTS: The C-reactive protein-to-albumin ratio (CAR) was the optimal prognostic assessment tool for patients with cancer cachexia, with 1-, 3-, and 5-year predictive powers of 0.650, 0.658, and 0.605, respectively. Patients with a high CAR had significantly lower survival rates than those with a low CAR. Moreover, CAR can differentiate the prognoses of patients with the same pathological stage. Cox proportional risk regression analyses showed that a high CAR was an independent risk factor for cancer cachexia. For every standard deviation increase in CAR, the risk of poor prognosis for patients with cancer cachexia was increased by 20% (hazard ratio = 1.200, 95% confidence interval = 1.132-1.273, P < 0.001). CONCLUSIONS: CAR is an effective representative of systemic inflammation and a powerful factor for predicting the life function and clinical outcome of patients with cancer cachexia.

9.
Biomed Environ Sci ; 35(7): 613-621, 2022 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-35945176

RESUMO

Objective: To analyze the prevalence of dry and wet age-related macular degeneration (AMD) in patients with diabetes, hypertension and hyperlipidemia, and to analyze the risk factors for AMD. Methods: A population-based cross-sectional epidemiologic study was conducted involving 14,440 individuals. We assessed the prevalence of dry and wet AMD in diabetic and non-diabetic subjects and analyzed the risk factors for AMD. Results: The prevalence of wet AMD in diabetic and non-diabetic patients was 0.3% and 0.5%, respectively, and the prevalence of dry AMD was 17% and 16.4%, respectively. The prevalence of wet AMD in healthy, hypertensive, hyperlipidemic, and hypertensive/hyperlipidemic populations was 0.5%, 0.3%, 0.2%, and 0.7%, respectively. The prevalence of dry AMD in healthy, hypertensive, hyperlipidemic, and hypertensive/hyperlipidemic populations was 16.6%, 16.2%, 15.2%, and 17.2%, respectively. Age, sex, body mass index, and use of hypoglycemic drugs or lowering blood pressure drugs were corrected in the risk factor analysis of AMD. Diabetes, diabetes/hypertension, diabetes/hyperlipidemia, and diabetes/hypertension/hyperlipidemia were analyzed. None of the factors analyzed in the current study increased the risk for the onset of AMD. Conclusion: There was no significant difference in the prevalence of wet and dry AMD among diabetic and non-diabetic subjects. Similarly, there was no significant difference in the prevalence of wet and dry AMD among subjects with hypertension and hyperlipidemia. Diabetes co-existing with hypertension and hyperlipidemia were not shown to be risk factors for the onset of dry AMD.


Assuntos
Diabetes Mellitus , Hiperlipidemias , Hipertensão , Degeneração Macular , Estudos Transversais , Diabetes Mellitus/epidemiologia , Humanos , Hiperlipidemias/complicações , Hiperlipidemias/epidemiologia , Hipertensão/complicações , Hipertensão/epidemiologia , Degeneração Macular/epidemiologia , Degeneração Macular/etiologia , Fatores de Risco
10.
Sci Adv ; 8(32): eabj3725, 2022 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-35947672

RESUMO

Mechanisms of implantation such as determination of the attachment pole, fetal-maternal communication, and underlying causes of implantation failure are largely unexplored. Here, we performed single-cell RNA sequencing on peri-implantation embryos from both humans and mice to explore trophectoderm (TE) development and embryo-endometrium cross-talk. We found that the transcriptomes of polar and mural TE diverged after embryos hatched from the zona pellucida in both species, with polar TE being more mature than mural TE. The implantation poles show similarities in cell cycle activities, as well as in expression of genes critical for implantation and placentation. Embryos that either fail to attach in vitro or fail to implant in vivo show abnormalities in pathways related to energy production, protein metabolism, and 18S ribosomal RNA m6A methylation. These findings uncover the gene expression characteristics of humans and mice TE differentiation during the peri-implantation period and provide new insights into embryo implantation.

11.
J Am Chem Soc ; 2022 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-35948064

RESUMO

Mollanol A is the first isolated member of the mollane-type grayanoids which possesses an unprecedented C-nor-D-homograyanane carbon skeleton and an 5,8-epoxide. Due to its transcriptional activation effects on the Xbp1 upstream promoters in different cell types, it has a potential therapeutic effect on inflammatory bowel disease. Here we report the first total synthesis of mollanol A, which constitutes a 15-step synthesis from commercially available materials via a convergent strategy. The synthesis involves an InCl3-catalyzed Conia-ene cyclization reaction to construct the bicyclo[3.2.1]octane moiety and a vinylogous aldol reaction/intramolecular oxa-Michael addition sequence to rapidly assemble the oxa-bicyclo[3.2.1] core.

12.
Drug Des Devel Ther ; 16: 2407-2422, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35923932

RESUMO

Purpose: To investigate the effective components and possible mechanism of action of Lavandula angustifolia Mill. essential oil (LEO) in preventing vomiting through the olfactory pathway. Materials and Methods: A new network pharmacology-based method was established to analyze main components and pathways of LEO involved in antiemetic effects by introducing component content; biological activities of key proteins of the olfactory pathway and their corresponding compounds were verified by molecular docking technique; and finally pica in a rat model was established to verify the molecular mechanism of antiemetic effects of LEO by enzyme-linked immunosorbent assay (ELISA) to determine the serum 5-HT, substance P, and DA levels in each group and by immunohistochemistry to determine the contents of 5-HT3R, CaMKII and ERK1/2 proteins in the medulla oblongata tissue. Results: Network pharmacology combined with molecular docking analysis showed that the mechanism of the antiemetic effect of LEO may be related to (2Z)-3,7-dimethyl-2,6-octadienyl acetate, linalyl acetate, butanoic acid, hexyl ester, 4-hexen-1-ol, 5-methyl-2-(1-methylethenyl)-, acetate, .tau.-cadinol and other active ingredients, which regulate the cyclic adenosine monophosphate (cAMP) signaling pathway and the expression of BRAF, PDE and other targets on the pathway. An ELISA revealed that LEO reduced the levels of 5-hydroxytryptamine (5-HT), substance P, and dopamine in serum compared with the model group (P <0.05). Immunohistochemical analysis showed that LEO decreased the expression of 5-HT3R, CaMKII, and ERK1/2 proteins in the medulla oblongata of rats compared with the model group (P <0.01). Conclusion: LEO may achieve the antiemetic effect by reducing the content of 5-HT and inhibiting its related receptors, thereby regulating downstream Ca2+/CaMKII/ERK1/2 pathway of the cAMP signaling pathway.


Assuntos
Antieméticos , Lavandula , Óleos Voláteis , Acetatos , Animais , Antieméticos/farmacologia , Cálcio/metabolismo , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina , Lavandula/química , Sistema de Sinalização das MAP Quinases , Simulação de Acoplamento Molecular , Óleos Voláteis/química , Óleos Voláteis/farmacologia , Ratos , Serotonina , Substância P
13.
Curr Med Chem ; 2022 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-35946097

RESUMO

Long-term diabetes can lead to renal injury known as diabetic nephropathy (DN), which is a major cause of end-stage renal disease (ESRD). However, its pathogenesis has not been well explained. Adipose tissue is recognized as an important energy storage device for the body. Interestingly, many studies have shown that adipose tissue can also act as an endocrine organ by secreting a variety of adipokines to maintain homeostasis. Here, we summarize some of the adipokines that have been identified thus far to, more specifically, to emphasize their role in DN progression and propose that the "adipose-renal axis" may be a potential target for the treatment of DN.

14.
PLoS Genet ; 18(8): e1010310, 2022 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-35939513

RESUMO

Chromosomal mosaicism is common throughout human pre- and post-implantation development. However, the incidence and characteristics of mosaicism in human blastocyst remain unclear. Concerns and confusions still exist regarding the interpretation of chromosomal mosaicism on preimplantation genetic testing for aneuploidy (PGT-A) results and embryo development. Here, we aimed to estimate the genetic concordance between trophectoderm (TE), inner cell mass (ICM) and the corresponding human embryonic stem cells (hESCs), and to explore the characteristics of mosaicism in human blastocyst and hESCs on a single cell level. The single cell sequencing results of TE cells indicated that 65.71% of the blastocysts were mosaic (23 in 35 embryos), while the ICM sequencing results suggested that 60.00% of the blastocysts were mosaic (9 in 15 embryos). The incidence of mosaicism for the corresponding hESCs was 33.33% (2 in 6 embryos). No significant difference was observed between the mosaic rate of TE and that of ICM. However, the mosaic rate of the corresponding hESCs was significantly lower than that of TE and ICM cells, suggesting that the incidence of mosaicism may decline during embryonic development. Upon single cell sequencing, we found several "complementary" copy number variations (CNVs) that were usually not revealed in clinical PGT-A which used multi-cell DNA sequencing (or array analysis). This indicates the potential diagnostic risk of PGT-A based multi-cell analysis routinely in clinical practice. This study provided new insights into the characteristics, and considerable influences, of mosaicism on human embryo development, as well as the clinical risks of PGT-A based on multi-cell biopsies and bulk DNA assays.

15.
Front Immunol ; 13: 912095, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35958591

RESUMO

Background: The heterogeneity of RSV-infected pathology phenotype in early life is strongly associate with increased susceptibility of asthma in later life. However, the inner mechanism of this heterogeneity is still obscure. ITGB4 is a down-regulated adhesion molecular in the airway epithelia of asthma patients which may participate in the regulation of RSV infection related intracellular pathways. Object: This study was designed to observe the involvement of ITGB4 in the process of RSV infection and the effect of ITGB4 deficiency on anti-RSV responses of airway epithelia. Results: RSV infection caused a transient decrease of ITGB4 expression both in vitro and in vivo. Besides, ITGB4 deficiency induced not only exacerbated RSV infection, but also enhanced HDM sensitivity in later life. Moreover, IFN III (IFN-λ) was significantly suppressed during RSV infection in ITGB4 deficient airway epithelial cells. Furthermore, the suppression of IFN-λ were regulated by IRF-1 through the phosphorylation of EGFR in airway epithelial cells after RSV infection. Conclusion: These results demonstrated the involvement of ITGB4 deficiency in the development of enhance RSV infection in early life and the increased HDM sensitivity in later life by down-regulation of IFN-λ through EGFR/IRF-1 pathway in airway epithelial cells.


Assuntos
Asma , Infecções por Vírus Respiratório Sincicial , Asma/patologia , Epitélio/patologia , Receptores ErbB , Humanos , Integrina beta4/genética , Infecções por Vírus Respiratório Sincicial/patologia , Sistema Respiratório/patologia
16.
Front Psychol ; 13: 918447, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35910983

RESUMO

The purpose of business sentiment analysis is to determine the emotions or attitudes expressed toward the company, products, services, personnel, or events. Text analysis are the simplest and most developed types of sentiment analysis so far. The text-based business sentiment analysis still has some unresolved challenges. For example, the machine learning algorithms are unable to recognize double meanings, jokes and allusions. The regional differences between language and non-native speech structures cannot be explained. To solve this problem, an undirected weighted graph is constructed for news topics. The sentences in an article are modeled as nodes, and the normalized sentence similarity is used as the link of the nodes, which can help avoid the influence of sentence length on the summary results. In the topic extraction process, the keywords are not limited to a single word, to achieve the purpose of improving the readability of the abstract. To improve the accuracy of sentiment classification, this work proposes a robust news mining-based business sentiment analysis framework, called BuSeD. It contains two main stages: (1) news collection and preprocessing, and (2) feature extraction and sentiment classification. In the first stage, the news is collected by using crawler tools. The news dataset is then preprocessed by reducing noises. In the second stage, topics in each article is extracted by using traditional topic extraction tools. And then a convolutional neural network (CNN)-based text analyzing model is designed to analyze news from sentence level. We conduct comprehensive experiments to evaluate the performance of BuSeD for sentiment classification. Compared with four classical classification algorithms, the proposed CNN-based classification model of BuSeD achieves the highest F1 scores. We also present a quantitative trading application based on sentiment analysis to validate BuSeD, which indicates that the news-based business sentiment analysis has high economic application value.

17.
J Cancer ; 13(9): 2872-2883, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35912012

RESUMO

Purpose: Liver kinase B1 (LKB1), also known as serine/threonine kinase 11, was considered as a tumor suppressor, which exhibited anti-cancer activity in a variety of cancers. However, the effect of LKB1 in thyroid cancer remains unclear. Methods: In the study, MTT assay, colony formation assay, flow cytometry, western blot analysis, wound healing assay, transwell assays, quantitative real-time PCR, HUVEC migration assay, ELISA assay, tube formation assay and nude mice xenograft were used to investigate the anti-cancer capacity of LKB1 in thyroid cancer in vitro and in vivo. Results: In the present study, we found that the expression of LKB1 was lower in thyroid cancer tissues and cell lines, compared with the adjacent normal tissue and thyroid epithelial cell. After construction of stable clone cells with ectopic LKB1 overexpression, the findings revealed that LKB1 overexpression exerted anti-proliferative and pro-apoptotic property in thyroid cancer TPC-1 and BCPAP cells. In addition, LKB1 overexpression could inhibit migration and invasion, downregulate MMP2 and MMP9 expressions, and reverse EMT in thyroid cancer cells. Furthermore, overexpression of LKB1 attenuated HUVEC recruitment, decreased the expression of VEGFA and inhibited the formation of new vessels in thyroid cancer cells. To validate the underlying mechanism of LKB1 in thyroid cancer, the results showed that LKB1 could positively regulate SIK1 in thyroid cancer TPC-1 and BCPAP cells. Additionally, the SIK1 inhibitor HG-9-91-01 could partially abrogate the anti-proliferative and anti-metastatic effect of LKB1, and reverse MET (mesenchymal-to-epithelial transition) mediated by LKB1 overexpression. Ultimately, the results in vivo revealed that LKB1 overexpression exhibited a strong inhibitory effect of tumorigenicity and presented anti-angiogenic characteristic in nude mice xenograft model. Conclusion: the results demonstrated that LKB1 could inhibit proliferation, metastasis phenotype and angiogenesis, and reverse EMT in thyroid cancer in vitro and vivo via the upregulation of SIK1, suggesting that LKB1 could be considered as a potential therapeutic target for the treatment of thyroid cancer.

18.
Artigo em Inglês | MEDLINE | ID: mdl-35975336

RESUMO

BACKGROUND: This study aimed to explore the relationship between the modified advanced lung cancer inflammation index (mALI) and the survival of overweight or obese patients with lung cancer (LC). METHODS: The mALI was defined as the appendix skeletal muscle index× the albumin/neutrophil -lymphocyte ratio. The cut-off values for male and female were assessed separately. Survival curves were estimated using the Kaplan-Meier method and statistical differences determined using the log-rank test. Univariate and multivariate Cox proportional hazards models were used for the survival analysis. The area under the receiver operating characteristic curve was used to compare the prognostic value of mALI with other nutritional assessment indicators. RESULTS: The mALI cut-offs for male and female were 8.59 and 8.26, respectively. Malnutrition, high systemic inflammation, and advanced stage for overweight or obese LC patients were found to be correlated with a low mALI. The median survival of patients with a low mALI was significantly lower than patients with a high mALI by approximately 25 months. In addition, the mALI can be used as an effective supplement to the traditional pathological stage. Multivariable analysis found that mALI was an independent prognostic factor of overall survival (hazard ratio = 0.531, 95% confidence interval = 0.402-0.700, p < 0.001). The prognostic predictive performance of mALI was superior to that of other nutritional assessment indicators. CONCLUSIONS: The mALI was an independent risk factor for the prognosis of overweight or obese LC patients, and a useful supplement to the pathological stage. This article is protected by copyright. All rights reserved.

19.
J Cosmet Dermatol ; 2022 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-35976065

RESUMO

BACKGROUND: Cetirizine, a widely-used agent for allergic disorders, has recently been topically used for treating androgenetic alopecia (AGA). We aimed to summarize the current evidence regarding the effectiveness and safety of topical cetirizine for treating AGA. METHODS: We searched Ovid MEDLINE, Embase, and Cochrane Central Register of Controlled Trials. We included both randomized controlled trials (RCTs) and non-randomized clinical trials. FINDINGS: We initially identified 102 records, of which, we included two RCTs and one non-randomized clinical trial, which were of moderate-to-high risk of bias. All included trials used 1% topical cetirizine as the intervention with various regimens. Topical cetirizine was likely to be more effective than a placebo for treating AGA. In comparison with topical minoxidil, topical cetirizine appears to be less effective for improving total and vellus hair density, but it might have a longer-lasting effect. Further, cetirizine might be as effective as minoxidil in improving hair diameter. CONCLUSION: 1% topical cetirizine may serve as a choice for treating AGA, especially for patients with a negative response to topical minoxidil. In order to fully understand the role of topical cetirizine for AGA, additional well-designed RCTs are needed.

20.
G3 (Bethesda) ; 2022 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-35976114

RESUMO

Along with specialized functions, cells of multicellular organisms also perform essential functions common to most if not all cells. Whether diverse cells do this by using the same set of genes, interacting in a fixed coordinated fashion to execute essential functions, or a subset of genes specific to certain cells, remains a central question in biology. Here, we focus on gene co-expression to search for a core cellular network across a whole organism. Single-cell RNA-sequencing (scRNA-seq) measures gene expression of individual cells, enabling researchers to discover gene expression patterns that contribute to the diversity of cell functions. Current efforts to study cellular functions focus primarily on identifying differentially expressed genes across cells. However, patterns of co-expression between genes are probably more indicative of biological processes than are the expression of individual genes. We constructed cell type-specific gene co-expression networks using single-cell transcriptome datasets covering diverse cell types from the fruit fly, Drosophila melanogaster. We detected a set of highly coordinated genes preserved across cell types and present this as the best estimate of a core cellular network. This core is very small compared with cell type-specific gene co-expression networks and shows dense connectivity. Gene members of this core tend to be ancient genes and are enriched for those encoding ribosomal proteins. Overall, we find evidence for a core cellular network in diverse cell types of the fruit fly. The topological, structural, functional and evolutionary properties of this core indicate that it accounts for only a minority of essential functions.

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