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1.
Int J Biol Sci ; 18(7): 2994-3005, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35541904

RESUMO

Overexpression and/or overactivation of sphingosine kinase 1/2 (SphK1/2) is important for tumorigenesis and progression of cervical cancer. The current study examined the potential activity and signaling mechanisms of SKI-V, a non-lipid small molecule SphK inhibitor, against cervical cancer cells. In different primary and immortalized cervical cancer cells, SKI-V exerted significant anti-cancer activity by inhibiting cell viability, colony formation, proliferation, cell cycle progression and cell migration. Significant apoptosis activation was detected in SKI-V-treated cervical cancer cells. Significantly, SKI-V also provoked programmed necrosis cascade in cervical cancer cells, as it induced mitochondrial p53-cyclophilin-D-adenine nucleotide translocator-1 (ANT1) complexation, mitochondrial membrane potential collapse, reactive oxygen species production and the release of lactate dehydrogenase into the medium. Further, SKI-V blocked SphK activation and induced ceramide accumulation in primary cervical cancer cells, without affecting SphK1/2 expression. SKI-V-induced cytotoxicity in cervical cancer cells was largely inhibited by sphingosine-1-phosphate or the SphK1 activator K6PC-5, but was sensitized by adding the short-chain ceramide C6. Moreover, SKI-V inhibited Akt-mTOR (mammalian target of rapamycin) activation in primary cervical cancer cells, and its cytotoxicity was mitigated by a constitutively-active Akt. In vivo, daily intraperitoneal injection of SKI-V significantly inhibited subcutaneous primary cervical cancer xenograft growth in nude mice. Together, the SphK inhibitor SKI-V suppresses cervical cancer growth in vitro and in vivo.

2.
Appl Ergon ; 103: 103785, 2022 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-35490546

RESUMO

Eye-gaze and head-gaze are two hands-free interaction modes in virtual reality, each of which has demonstrated different strengths. Selecting suitable interaction modes in different scenarios is important to achieve efficient interaction in virtual scenes. This study compared the movement time in an object positioning task by examining eye-gaze interaction and head-gaze interaction in various conditions. In turn, it identified the superior zones for each mode, respectively. Based on this information, we designed a combination mode - utilizing eye-gaze interaction at the acceleration phase and deceleration phase and head-gaze interaction at the correction phase - to achieve the optimal interaction mode, which has allowed us to obtain higher efficiency and subjective satisfaction. This study provides a comprehensive analysis of the characteristics of the eye-gaze and head-gaze interaction modes and provides valuable insights into selecting the appropriate interaction modes for virtual reality applications.

4.
PeerJ ; 10: e13209, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35415016

RESUMO

Here we describe a newly discovered basal ichthyosauromorph from the Lower Triassic of South China, Baisesaurus robustus gen. et sp. nov. The only known specimen of this new species was collected from the Lower Triassic (Olenekian) Luolou Formation in the Zhebao region of Baise City, on the northwest margin of the Nanpanjiang Basin, and comprises a partial skeleton including the ribs, the gastralia, a limb element, 12 centra, and seven neural arches. Comparisons to a wide variety of Early Triassic marine reptiles show Baisesaurus robustus to be a basal ichthyosauromorph based on the following features: neural arches lack transverse processes; dorsal ribs are slender, and not pachyostotic even proximally; and median gastral elements have long, sharp anterior processes. The limb element is long and robust, and is most likely to be a radius. Baisesaurus robustus is large (estimated length more than 3 m) relative to early ichthyosauromorphs previously discovered in China, and shares noteworthy morphological similarities with Utatsusaurus hataii, particularly with regard to body size and the morphology of the probable radius. Baisesaurus robustus also represents the first record of an Early Triassic ichthyosauromorph from Guangxi Autonomous Region, extending the known geographic distribution of ichthyosauromorphs in South China.

5.
Med Biol Eng Comput ; 60(5): 1363-1375, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35359200

RESUMO

Oral cancer is known as one of the relatively common malignancy types worldwide. Despite the easy access of the oral cavity to examination, the invasive biopsy is still essential for final diagnosis, which requires laborious operation and complicated trained specialists. With the development of deep learning, the artificial intelligence (AI) technique is applied for oral cancer examinations and alleviates the workload of manual screening on biopsy. However, existing computer-aided oral cancer diagnostic methods focus on oral cavity environment photos and histology images, which require complicated operations for doctors and are invasive and painful for patients. As a noninvasive, real-time imaging technique, optical coherence tomography (OCT) can express sufficient identical information for oral cancer screening, but it has not been effectively explored for automatic oral cancer diagnosis. This paper proposes a novel deep learning method named Local Residual Adaptation Network (LRAN) for noninvasive oral cancer screening on OCT images, collected from 25 patients in Beijing Stomatological Hospital. Our proposed LRAN consists of a Residual Feature Representation (RFR) module and a Local Distribution Adaptation (LDA) module. Specifically, RFR firstly adopts stacked residual blocks as the backbone network to learn feature representations for training data, optimized by the Cross-Entropy loss, and then deploy Euclidean distance to measure the distribution distance between training and testing OCT images. Finally, LRAN achieves distribution-gap bridging by the LDA module, which integrates local maximum mean discrepancy constraint to estimate and minimize the distribution discrepancy between training and testing sets within the same category. We also collected an OCT-based oral cancer image dataset to evaluate the effectiveness of the proposed method, and it achieves an accuracy of 91.62%, a sensitivity of 91.66%, and a specificity of 92.58% on this self-collected dataset. Furthermore, we conduct a quantitative and qualitative analysis, and the results demonstrate LRAN model has excellent capability to solve the noninvasive oral cancer screening task.


Assuntos
Neoplasias Bucais , Tomografia de Coerência Óptica , Inteligência Artificial , Detecção Precoce de Câncer , Humanos , Neoplasias Bucais/diagnóstico por imagem , Redes Neurais de Computação , Tomografia de Coerência Óptica/métodos
6.
Huan Jing Ke Xue ; 43(4): 2124-2132, 2022 Apr 08.
Artigo em Chinês | MEDLINE | ID: mdl-35393836

RESUMO

Exploring the spatial distribution characteristics and variation law of soil pH and analyzing the impact of environmental factors on the spatial differentiation of soil pH are of great significance to the accurate management of soil pH and the sustainable utilization of soil resources in the complex mountainous environment of Anshun City. Based on 22 851 field sampling points, using the methods of global Moran's I index, cold and hot spot analysis, semi-variance function, and Kriging interpolation, the spatial structure characteristics and distribution law of soil pH in Anshun City were revealed from different angles, and the influence of environmental factors on its spatial differentiation was analyzed with the help of geographic detectors. The results showed that:① the variation range of topsoil pH value in Anshun City was 3.56-8.61, the mean value was 6.28, and the coefficient of variation was 16.33%. ② In the global space, soil pH showed aggregation distribution; in the local space, the west and northwest were hot spots, whereas the east and south were cold spots. The nugget coefficient (40.19%) showed that the spatial variability in soil pH was determined by both structural and random factors, but the role of structural factors was greater. ③ In terms of spatial distribution, soil pH mainly presented a patchy mosaic distribution pattern, in which slightly acidic soil (57.14%) was concentrated in the east, northeast, and south of Anshun City; neutral soil (30.13%) was concentrated in the west, northwest, and southeast; and strongly acidic soil (6.12%) and alkaline soil (6.45%) were embedded in slightly acidic soil and neutral soil, respectively, in a block structure. ④ The geo-detector analysis showed that the explanatory power of various environmental factors to the spatial variation in soil pH was ranked as soil type (9.4%)>soil forming parent rock (7.9%)>altitude (2.1%)>land use (1.8%)>slope (0.1%), in which the q value of the interaction between soil type and parent rock type and other factors was large. Therefore, soil type and parent rock type were the main controlling factors of soil pH spatial variation in Anshun City.


Assuntos
Solo , China , Cidades , Concentração de Íons de Hidrogênio , Solo/química , Análise Espacial
7.
Sci Total Environ ; 836: 155466, 2022 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-35472356

RESUMO

Currently, the characteristics of volatile organic compounds (VOC) released from coking industry are still vague, and the widely used VOC emission factors (EFs) were still from the measurements of 1990s. Hence, focusing on coking industry, we conducted an in-situ measurement campaign in several typical plants, developed a set of VOC EFs for various release units, and estimated the current emission amounts and future reduction potentials of VOC in China. The measurements show that the levels of VOC in stationary units were 63.82-9563.93 µg·m-3, and those surrounding fugitive units were 111.37-1436.36 µg·m-3. VOC emissions from stationary units were directly calculated, which deducing EFs of 11.57, 15.51, 127.13, 0.28, 0.16 g·t-1 coke respectively for coke charging, coke pushing, coke oven chimney, dry quenching, and wastewater treatment processes. Meanwhile, VOC emissions from fugitive units were simulated following the inverse dispersion method, which achieving EFs of 443.34 ± 66.31, 352.12 ± 65.81, and 718.56 ± 132.69 g·t-1 coke respectively for the coke oven leakage, byproduct recovery with VOC treatment system, and byproduct recovery without VOC treatment system. Generally, the coking plants installing VOC treatment system had total VOC EF of 953.76 g·t-1 coke, about 37.1% lower than those never considering VOC treatment (1516.25 g·t-1 coke). According to these developed EFs, the VOC emission amount from coking industry in China were estimated, slightly decreasing from 623.54 to 578.17 Gg per year, although the coke production increasing from 410.86 to 418.26 Tg during 2015-2019. In future, according to the national industrial policies, regulations and standards, technical guidelines, the VOC reduction potential of this industry in China could reach 336.9 Gg, to which headstream adjustment, process improvement, and end-of-pipe control contributed about 21.4%, 31.6%, and 47.0%, respectively.

8.
Theranostics ; 12(6): 2860-2893, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35401835

RESUMO

Carbon dots (CDs), as one new class of carbon nanomaterials with various structure and extraordinary physicochemical properties, have attracted tremendous interest for their potential applications in tumor theranostics, especially in targeted bioimaging and therapy. In these areas, CDs and its derivatives have been employed as highly efficient imaging agent for photoluminescence bioimaging of tumors cells. With unique structure, optical and/or dose attention properties, CDs have been harnessed in various nanotheranostic strategies for diverse tumors through integrating with other functional nanoparticles or utilizing their inherent physical properties. Up to now, CDs have been approved as novel biomaterials by their excellent performances in precise targeted bioimaging and therapy for tumors. Herein, the latest progress in the development of CDs in targeted bioimaging and tumor therapy are reviewed. Meanwhile, the challenges and future prospects of the application of CDs in promising nanotheranostic strategies are discussed and proposed.


Assuntos
Nanoestruturas , Neoplasias , Pontos Quânticos , Carbono/química , Humanos , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Pontos Quânticos/química , Nanomedicina Teranóstica/métodos
9.
Phytother Res ; 2022 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-35445769

RESUMO

The activation of thermogenic programs in brown adipose tissue (BAT) and white adipose tissue (WAT) provides a promising approach to increasing energy expenditure during obesity and diabetes treatment. Although evidence has been found that rutin activates BAT against obesity and type 2 diabetes mellitus (T2DM), its potential mechanism is not completely understood. In this study, we focused on the potential modulating effect of rutin on short-chain fatty acids (SCFAs) and the thermogenesis of BAT and WAT, aiming to elucidate the molecular mechanism of rutin in the treatment of obesity and T2DM. The results showed that rutin could significantly reduce the body weight and fasting blood glucose, inhibit fat accumulation, relieve hepatic steatosis and ameliorate the disorder of glycolipid metabolism in db/db mice. Moreover, rutin also increased the expression of uncoupling protein 1 (Ucp1) and other thermogenic genes and proteins in BAT and inguinal WAT (IWAT), indicating that rutin activated BAT and induced browning of IWAT. Importantly, rutin markedly enhanced the concentration of SCFAs (acetate, propionate and butyrate) and SCFA-producing enzymes (acetate kinase (ACK), methylmalonyl-CoA decarboxylase (MMD) and butyryl-CoA (BUT)) in feces of db/db mice. In addition, rutin significantly increased the mRNA expression of monocarboxylate transporter 1 (Mct1), catabolic enzyme acyl-CoA medium-chain synthetase 3 (Acsm3), carnitine palmitoyl transferase 1α (Cpt-1α) and Cpt-1ß genes in BAT and IWAT of db/db mice, which is conducive to inducing adipocyte thermogenesis. In summary, our findings revealed that rutin played a variety of regulatory roles in improving glucose and lipid metabolism disorders, reducing hepatic steatosis, inducing browning of IWAT and activating BAT, which has potential therapeutic significance for the treatment of obesity and T2DM. Mechanistically, rutin activates the thermogenesis of BAT and IWAT, which may be associated with increasing the concentration of SCFAs.

10.
Front Neurosci ; 16: 844519, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35401094

RESUMO

There is abundant evidence that early onset schizophrenia (EOS) is associated with abnormalities in widespread regions, including the cortical, striatal, and limbic areas. As a main component of the ventral striatum, the nucleus accumbens (NAc) is implicated in the pathology of schizophrenia. However, functional connection patterns of NAc in patients with schizophrenia, especially EOS, are seldom explored. A total of 78 first-episode, medication-naïve patients with EOS and 90 healthy controls were recruited in the present study, and resting-state, seed-based functional connectivity (FC) analyses were performed to investigate temporal correlations between NAc and the rest of the brain in the two groups. Additionally, correlation analyses were done between regions showing group differences in NAc functional integration and clinical features of EOS. Group comparison found enhanced FC of the NAc in the EOS group relative to the HCs with increased FC in the right superior temporal gyrus and left superior parietal gyrus with the left NAc region of interest (ROI) and elevated FC in left middle occipital gyrus with the right NAc ROI. No significant associations were found between FC strength and symptom severity as well as the age of the patients. Our findings reveal abnormally enhanced FC of the NAc with regions located in the temporal, parietal, and occipital areas, which were implicated in auditory/visual processing, sensorimotor integration, and cognitive functions. The results suggest disturbed relationships between regions subserving reward, salience processing, and regions subserving sensory processing as well as cognitive functions, which may deepen our understanding of the role of NAc in the pathology of EOS.

11.
Front Vet Sci ; 9: 850715, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35464392

RESUMO

Yucca contains high a content of saponin that has a glucocorticord-like effect in animals, e.g., anti-inflammation and anti-microbiota. The objective of the present study was to test the hypothesis that dietary supplementation of yucca powder may alleviate heat stress and improve growth performance of growing broilers subjected to cycling high ambient temperature. A total of 240 male broiler chicks (yellow feathered chicken) aged 28 days, with body weight (BW) of 792 ± 43.7 g, were randomly allocated to one of four treatments (6 replicates per treatment): control (normal temperature, 24 ± 2°C, 24 h), fed diets supplemented with 100 mg/kg yucca under normal temperature (Y), high ambient temperature exposure (HT, 34 ± 2°C, 11 h), fed diets supplemented with 100 mg/kg yucca (HT+Y) under high ambient temperature. After 7 days of adaption, the experiment was conducted for 4 weeks (aged 28-56 days). HT significantly reduced feed intake, BW, and average daily gain (ADG) of broiler, but yucca improved the feed intake under HT condition. Yucca supplementation reduced (P < 0.05) the HT-induced increase in temperature of rectum and leg skin. Supplementation of yucca increased the hypothalamic mRNA expression of TRPV2, TRPV4, and TRPM8 (P < 0.05). Yucca reduced (P < 0.05) the plasma lipid oxidation product malondialdehyde (MDA), but did not affect the activities of antioxidant enzyme superoxide oxidase (SOD) and glutathione peroxidase (Gpx). Yucca did not affect the plasma neuro peptide Y (NPY), which was reduced by HT, yucca reduced circulation cholecystokinin (CCK) and hypothalamic mRNA expression of CCK. Supplementation of yucca increased the mRNA expression of both heat and cool sensing receptors. The results of the present study indicate that yucca could improve antioxidant status and attenuate the heat stress response by regulating hypothalamic temperature-sensing genes in growing chickens. Besides, yucca supplementation improved feed intake probably through modulating CCK in growing broilers under high ambient temperature.

12.
Int J Gen Med ; 15: 3933-3941, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35431572

RESUMO

Background: Hepatocellular carcinoma (HCC) is the reason for the world's second largest cancer-related death. It is clinically valuable to study the molecular mechanisms of HCC occurrence and development for formulating more effective diagnosis and treatment strategies. Methods: The five microarray data sets GSE45267, GSE101685, GSE84402, GSE62232 and GSE45267 were downloaded from Gene Expression Omnibus (GEO) database, including 165 HCC tissues and 73 normal tissues. Differential expressed genes (DEGs) between HCC tissues and normal tissues were determined by GEO2R. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and the protein-protein interaction network (PPI) network analysis were employed to identify DEGs and to evaluate the clinical significance in prognosis of HCC. Results: A total of 152 genes differentially expressed in HCC tissues and normal tissues were identified. GO and KEGG functional enrichment analysis revealed that 39 up-regulated genes were mainly enriched in mitosis, cell cycle and oocyte meiosis, while those down-regulated genes (113) were concentrated in exogenous drug catabolism and the metabolism of cytochrome P450 on exogenous drugs. Totally, 19 hub genes were chosen by PPI network and module analysis and verified by The Cancer Genome Atlas (TCGA) database. Finally, 8 hub genes were selected, including CDK1, CYP2C8, CCNB1, AURKA, CYP2C9, BUB1B, MAD2L1 and TTK, which were associated with the overall survival rate of HCC patients. Conclusion: This study presented eight target genes connected to the prognosis of HCC patients. Those mainly exists in cell cycle and drug catabolism, which may be latent targets for clinical treatment.

13.
Artigo em Inglês | MEDLINE | ID: mdl-35482077

RESUMO

BACKGROUND: Tumor vaccines for hepatocellular carcinoma (HCC) is an area of intense interest. Tremendous clinical trials have been conducted globally, but the efficacy and security of tumor vaccines are elusive. The aim of our study was to evaluate the efficacy and security of tumor vaccines. METHODS: All relevant studies were identified in PubMed, EMBASE, Web of science and Cochrane Library databases. Objective response rate (ORR), median overall survival (OS), or median progression-free survival (PFS) and 95% CI were meta-analyzed based on the random-effects model. The individual-level data of OS, PFS were pooled by conducting survival analysis. All observed adverse events were collected. RESULTS: 31 studies containing 35 eligible cohorts with 932 HCC patients were included. The pooled ORR were 7% (95% CI 3-14%), while ORR of dendritic cell (DC) vaccine (19%, 95% CI 11-29%) were highly significant than ORR of peptide vaccine (1%, 95% CI 0-5%). The pooled median OS and PFS were 13.67 months (95% CI 8.20-22.80) and 6.19 months (95% CI 2.97-12.91), respectively. The pooled median OS (DC vaccine: median OS = 21.77 months, 95% CI 18.33-25.86; Peptide vaccine: median OS = 10.08 months, 95% CI 5.23-19.44) and PFS (DC vaccine: median PFS = 11.01 months, 95% CI 5.25-23.09; Peptide vaccine: median PFS = 1.97 months, 95% CI 1.53-2.54) of DC vaccine were also longer than that of peptide vaccine. HBV-related HCC may acquire more benefits from tumor vaccines than HCV-related HCC. In almost all studies, the observed toxicities were moderate even tiny. CONCLUSIONS: Tumor vaccines for HCC, especially DC vaccine, are safe and worth exploring. More high-quality prospective studies are warranted.

14.
ACS Nano ; 2022 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-35446560

RESUMO

The combination of small coercive fields and weak magnetic anisotropy makes soft ferromagnetic films extremely useful for nanoscale devices that need to easily switch spin directions. However, soft ferromagnets are relatively rare, particularly in ultrathin films with thicknesses of a few nanometers or less. We have synthesized large-area, high-quality, ultrathin freestanding LaMnO3 films on Si and found unexpected soft ferromagnetism along both the in-plane and out-of-plane directions when the film thickness was reduced to 4 nm. We argue that the vanishing magnetic anisotropy between the two directions is a consequence of two coexisting magnetic easy axes in different atomic layers of the LaMnO3 film. Spectroscopy measurements reveal a change in Mn valence from 3+ in the film interior to approximately 2+ at the surfaces where considerable hydrogen infiltration occurs due to the water dissolving process. First-principles calculations show that protonation of LaMnO3 decreases the Mn valence and switches the magnetic easy axis from in-plane to out-of-plane as the Mn valence approaches 2+ from its 3+ bulk value. Our work demonstrates that ultrathin freestanding films can exhibit functional properties that are absent in homogeneous materials, concomitant with their convenient compatibility with Si-based devices.

15.
J Agric Food Chem ; 70(12): 3745-3756, 2022 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-35312309

RESUMO

This work provided an interesting finding of lysine (Lys) control on skeletal muscle growth besides protein synthesis. According to the isobaric tag for relative and absolute quantitation and molecular docking analyses, we found both in in vivo skeletal muscle and in vitro muscle satellite cells (MuSCs) that the frizzled7 (FZD7) expression level was positively correlated with Lys levels and this was consistent with the activation of the Wnt/ß-catenin pathway. On the other hand, FZD7 inhibition suppressed the Lys-rescued Wnt/ß-catenin pathway, FZD7 knockdown caused cell proliferation, and Wnt/ß-catenin pathway restrictions could not be compensated for by Lys or Wnt3a. Furthermore, the combination between Lys and recombinant pig frizzled7 (rpFZD7) protein was confirmed by isothermal titration calorimetry. This finding displayed concrete evidence that Lys is not only a molecular block of protein synthesis but is also a ligand for FZD7 to activate ß-catenin to stimulate MuSCs in promoting skeletal muscle growth.


Assuntos
Lisina , beta Catenina , Animais , Lisina/metabolismo , Simulação de Acoplamento Molecular , Músculo Esquelético/metabolismo , Suínos , Via de Sinalização Wnt , beta Catenina/genética , beta Catenina/metabolismo
16.
Materials (Basel) ; 15(5)2022 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-35269008

RESUMO

In order to monitor the synthesis processes or characterize nanoparticles for application, a new method that allows in situ determination of the two-dimensional size distribution and concentration of Au-Ag alloy nanospheroids, based on their extinction spectrum, is developed. Non-negative Tikhonov regularization and T-matrix method were used to solve the inverse problem. The effects of the two-dimensional size steps, wavelength range, and measurement errors of extinction spectrum on the retrieval results were analyzed to verify the feasibility and accuracy of the retrieval algorithm. Through comparative analysis, the size steps and wavelength range that make the retrieval error smaller are found. After adding 0.1% random noise to the extinction spectrum, a small variation in the retrieval error of the mean size is observed. The results showed that the error of the mean size is smaller than 2% and the error of the concentration is smaller than 3%. This method is simple, fast, cheap, nondestructive, and can be done in situ during the growth process of nanoparticles.

17.
Science ; 375(6587): eabj1711, 2022 03 25.
Artigo em Inglês | MEDLINE | ID: mdl-35324280

RESUMO

Jeon et al. (Reports, 29 January 2021, p. 498) reported reversible fluctuations between disordered and crystalline states during nucleation. We argue that the adoption of "magic numbers" for separation of the size range into three parts is misleading when using the sigmoid functions and that their figure 3B was wrongly illustrated. The crystal shape effect was neglected during theoretical analysis.


Assuntos
Registros , Cristalização
19.
Cell Death Dis ; 13(3): 211, 2022 03 07.
Artigo em Inglês | MEDLINE | ID: mdl-35256590

RESUMO

The present study was performed to explore whether and how impaired autophagy could modulate calcium/calmodulin-dependent protein kinase II (CAMKII)-regulated necrosis in the pathogenesis of acute pancreatitis (AP). Wistar rats and AR42J cells were used for AP modeling. When indicated, genetic regulation of CAMKII or ATG7 was performed prior to AP induction. AP-related necrotic injury was positively regulated by the incubation level of CAMKII. ATG7 positively modulated the level of CAMKII and necrosis following AP induction, indicating that there might be a connection between impaired autophagy and CAMKII-regulated necrosis in the pathogenesis of AP. microRNA (miR)-30b-5p was predicted and then verified as the upstream regulator of CAMKII mRNA in our setting of AP. Given that the level of miR-30b-5p was negatively correlated with the incubation levels of ATG7 after AP induction, a rescue experiment was performed and indicated that the miR-30b-5p mimic compromised ATG7 overexpression-induced upregulation of CAMKII-regulated necrosis after AP induction. In conclusion, our results indicate that ATG7-enhanced impaired autophagy exacerbates AP by promoting regulated necrosis via the miR-30b-5p/CAMKII pathway.


Assuntos
MicroRNAs , Pancreatite , Doença Aguda , Animais , Autofagia/genética , Proteína 7 Relacionada à Autofagia/genética , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Necrose , Pancreatite/induzido quimicamente , Pancreatite/genética , Ratos , Ratos Wistar
20.
Cancer Biol Ther ; 23(1): 89-95, 2022 12 31.
Artigo em Inglês | MEDLINE | ID: mdl-35230928

RESUMO

This study aimed to compare the treatment efficacy and tolerance between drug-eluting beads transarterial chemoembolization (DEB-TACE) and conventional transarterial chemoembolization (cTACE) in hepatocellular carcinoma (HCC) patients with arterioportal fistula (APF). A total of 44 HCC patients with APF scheduled for DEB-TACE (N = 24, as DEB-TACE group) or cTACE (N = 20, as cTACE group) were recruited. Treatment response, hepatic function, and adverse events were assessed or recorded. Besides, progression-free survival (PFS) and overall survival (OS) were calculated. Total treatment response was better in the DEB-TACE group compared with the cTACE group (P = .012). Meanwhile, the objective response rate (87.5% versus 60.0%) was higher (P = .013), while the disease control rate (95.8% versus 85.0%) was similar in the DEB-TACE group compared to the cTACE group (P = .213). Besides, PFS (mean value: 12.2 (95%CI: 9.9-14.6) months versus 7.8 (95%CI: 5.6-10.0) months) (P = .037), but not OS (mean value: 20.0 (95%CI: 18.1-21.9) months versus. 18.6 (95%CI: 15.4-21.8) months) (P = .341) was prolonged in DEB-TACE group compared with cTACE group. Regarding the safety, Child-Pugh stage, albumin level, and bilirubin level after treatment were all similar between the DEB-TACE group and cTACE group (all P > .05); moreover, no difference was found in the occurrence of adverse events during or after treatment between the two groups (all P > .05). Moreover, subsequent analyses found that embolic materials for APF (microspheres) in the DEB-TACE group did not affect the treatment efficacy (all P > .05). DEB-TACE promotes treatment response and PFS compared with cTACE and shows good safety in HCC patients with APF.


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Fístula , Neoplasias Hepáticas , Carcinoma Hepatocelular/patologia , Quimioembolização Terapêutica/efeitos adversos , Fístula/terapia , Humanos , Neoplasias Hepáticas/patologia , Estudos Retrospectivos , Resultado do Tratamento
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