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1.
Mediators Inflamm ; 2022: 7924199, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36046763

RESUMO

Alzheimer's disease (AD) is a progressive neurodegenerative disease that primarily manifests as memory deficits and cognitive impairment and has created health challenges for patients and society. In AD, amyloid ß-protein (Aß) induces Toll-like receptor 4 (TLR4) activation in microglia. Activation of TLR4 induces downstream signaling pathways and promotes the generation of proinflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1ß (IL-1ß), which also trigger the activation of astrocytes and influence amyloid-dependent neuronal death. Therefore, TLR4 may be an important molecular target for treating AD by regulating neuroinflammation. Moreover, TLR4 regulates apoptosis, autophagy, and gut microbiota and is closely related to AD. This article reviews the role of TLR4 in the pathogenesis of AD and a range of potential therapies targeting TLR4 for AD. Elucidating the regulatory mechanism of TLR4 in AD may provide valuable clues for developing new therapeutic strategies for AD.


Assuntos
Doença de Alzheimer , Doenças Neurodegenerativas , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Humanos , Microglia/metabolismo , Doenças Neurodegenerativas/metabolismo , Receptor 4 Toll-Like/metabolismo
2.
PLoS Negl Trop Dis ; 16(9): e0010712, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36067140

RESUMO

BACKGROUND: Human immunodeficiency virus (HIV) and enteric parasite co-infection not only aggravates the clinical symptoms of parasites but also accelerates acquired immunodeficiency syndrome (AIDS) progression. However, co-infection research on men who have sex with men (MSM), the predominant high-risk population of HIV/AIDS in China, is still limited. In this study, we investigated the epidemiology of enteric parasites, risk factors, and associations with clinical significance in an MSM HIV/AIDS population in Heilongjiang Province, northeast China. METHODS: We recruited 308 MSMs HIV/AIDS patients and 199 HIV-negative individuals in two designated AIDS hospitals in Heilongjiang between April 2016 and July 2017. Fresh stool samples were collected. DNA extraction, molecular identification, and genotyping of Cryptosporidium species, Entamoeba histolytica, Cyclospora cayetanensis, Enterocytozoon bieneusi, and Blastocystis hominis were performed. Fourteen diarrhea-related pathogens were examined to exclude the influence of other bacterial pathogens on diarrhea incidence. RESULTS: 31.5% of MSM HIV/AIDS participants were infected with at least one parasite species, a significantly higher proportion than that found in the HIV-negative individuals (2.5%). E. bieneusi presented the highest prevalence, followed by B. hominis, E. histolytica, Cryptosporidium spp., and C. cayetanensis. Warm seasons were the risk factor for parasitic infections in this population [odds ratio (OR) = 2.6, 95% CI: 1.47-4.57]. In addition, these individuals showed a higher proportion (35.8%) of present diarrhea (PD) compared with men who have sex with women (MSW) with HIV/AIDS (16.7%). The infection proportions of both Cryptosporidium spp. and E. histolytica were significantly higher in the PD. E. bieneusi infection was more prevalent in the historic diarrhea (HD) group. CD4+ T cell counts in the MSM patients with the above three parasites were significantly lower. New species and genotypes were found, and MSM patients had a wider range of species or genotypes. CONCLUSIONS: Enteric parasitic infection was prevalent in the MSM HIV/AIDS population, especially in patients with present diarrhea during warm seasons. E. histolytica and B. hominis should also be considered high-risk parasites for opportunistic infections in AIDS patients in addition to Cryptosporidium spp.


Assuntos
Síndrome de Imunodeficiência Adquirida , Coinfecção , Criptosporidiose , Cryptosporidium , Infecções por HIV , Parasitos , Doenças Parasitárias , Minorias Sexuais e de Gênero , Síndrome de Imunodeficiência Adquirida/complicações , Síndrome de Imunodeficiência Adquirida/epidemiologia , Animais , Coinfecção/complicações , Coinfecção/epidemiologia , Criptosporidiose/epidemiologia , Cryptosporidium/genética , Diarreia/parasitologia , Fezes/parasitologia , Feminino , HIV , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Homossexualidade Masculina , Humanos , Masculino , Prevalência
3.
Dis Markers ; 2022: 3201600, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36046378

RESUMO

Objective: The mitochondrial energy metabolic pathway (MEMP) is the primary energy metabolism of tumor cells, and its disruption may promote cancer emergence, spreading, and immune escape. However, there is a lack of studies to determine the relationship between relevant functional mechanisms and lung adenocarcinoma (LUAD) prognosis. Methods: Gene set enrichment analysis (GSEA) was employed to determine MEMP pathway-related genes. Then, a prognostic model was created using the MEMP key genes that were found by LASSO-Cox regression analysis. The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases provided the training and validation sets. Furthermore, the infiltration of immune cells was examined by ssGSEA. Finally, a screening of candidate therapeutic compounds for LUAD patients was performed using DrugBank, Protein Data Bank (PDB), and AutoDock Vina databases. Results: First, 266 MEMP pathway-related genes that exhibited aberrant activity in tumors were identified. Then, 19 MEMP key genes were used to build a prognostic model, which can successfully predict the survival rates of LUAD patients after 1, 3, and 5 years, respectively. The Kaplan-Meier curve showed that patients in the high-risk group had considerably lower survival outcomes than those in the low-risk group. Furthermore, it was discovered that the high-risk group had the majority of activated T cells, while the low-risk group tended to have more other activated immune cells. The majority of immunological checkpoints expressed themselves more strongly in the high-risk group as well. Finally, 11 prospective medication small molecules were obtained from the projected potential therapeutic drugs, with DB0980 being regarded as the most promising of them for the treatment of LUAD. Conclusion: This current study developed reliable prognostic signature, called MEMP score, which provides new guidance for prognostic assessment, immunotherapy, and drug development in LUAD. Thereby, DB0980 appears to be the most likely approach for the treatment of LUAD.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Adenocarcinoma de Pulmão/patologia , Metabolismo Energético/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/patologia , Prognóstico , Estudos Prospectivos
4.
Arch Microbiol ; 204(9): 586, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36048288

RESUMO

Members of the genus Marinomonas are known for their environmental adaptation and metabolically versatility, with abundant proteins associated with antifreeze, osmotic pressure resistance, carbohydrase and multiple secondary metabolites. Comparative genomic analysis focusing on secondary metabolites and orthologue proteins was conducted with 30 reference genome sequences in the genus Marinomonas. In this study, a Gram-stain-negative, rod-shaped, non-flagellated and strictly aerobic bacterium, designated as strain E8T, was isolated from the red algae (Gelidium amansii) in the coastal of Weihai, China. Optimal growth of the strain E8T was observed at temperatures 25-30 °C, pH 6.5-8.0 and 1-3% (w/v) NaCl. The DNA G + C content was 42.8 mol%. The predominant isoprenoid quinone was Q-8 and the major fatty acids were C16:0, summed feature 3 and summed feature 8. The major polar lipids were phosphatidylglycerol (PG) and phosphatidylethanolamine (PE). Based on data obtained from this polyphasic taxonomic study, strain E8T should be considered as a novel species of the genus Marinomonas, for which the name Marinomonas algarum is proposed. The type strain is E8T (= KCTC 92201T = MCCC 1K07070T).


Assuntos
Marinomonas , Rodófitas , Técnicas de Tipagem Bacteriana , DNA Bacteriano/genética , Ácidos Graxos/química , Genômica , Marinomonas/genética , Fosfolipídeos/química , Filogenia , RNA Ribossômico 16S/genética , Rodófitas/genética , Rodófitas/microbiologia , Análise de Sequência de DNA , Ubiquinona/química
5.
Dis Markers ; 2022: 1360954, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36051356

RESUMO

Colorectal cancer (CRC) is becoming increasingly prevalent worldwide. Fluoropyrimidine drugs are the primary chemotherapy regimens in routine clinical practice of CRC. However, the survival rate of patients on fluoropyrimidine-based chemotherapy varies significantly among individuals. Biomarkers of fluoropyrimidine drugs'' efficacy are needed to implement personalized medicine. This review summarized fluoropyrimidine drug-related microRNA (miRNA) by affecting metabolic enzymes or showing the relevance of drug efficacy. We first outlined 42 miRNAs that may affect the metabolism of fluoropyrimidine drugs. Subsequently, we filtered another 41 miRNAs related to the efficacy of fluoropyrimidine drugs based on clinical trials. Bioinformatics analysis showed that most well-established miRNA biomarkers were significantly enriched in the cancer pathways instead of the fluoropyrimidine drug metabolism pathways. The result also suggests that the miRNAs screened from metastasis patients have a more critical role in cancer development than those from non-metastasis patients. There are five miRNAs shared between these two lists. The miR-21, miR-215, and miR-218 can suppress fluoropyrimidine drugs'' catabolism. The miR-326 and miR-328 can reduce the efflux of fluoropyrimidine drugs. These five miRNAs could jointly act by increasing intracellular levels of fluoropyrimidine drugs'' cytotoxic metabolites, leading to better chemotherapy responses. In conclusion, we demonstrated that the dynamic changes in the transcriptional regulation via miRNAs might play significant roles in the efficacy and toxicity of the fluoropyrimidine drug. The reported miRNA biomarkers would help evaluate the efficacy of fluoropyrimidine drug-based chemotherapy and improve the prognosis of colorectal cancer patients.


Assuntos
Antineoplásicos , Neoplasias Colorretais , MicroRNAs , Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Prognóstico
6.
Dis Markers ; 2022: 5038847, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36051361

RESUMO

Objective: Elevated intraocular pressure (IOP) has significant impacts on different stages in the progression of chronic glaucoma. In this study, we investigated changes in the material properties of sclera and lamina cribrosa (LC) in a nonhuman primate model with elevated IOP. Methods: Normal adult Tibetan macaques were selected for the construction of elevated IOP model. After 40 days of stable maintenance on the ocular hypertension, the binocular eyeballs were obtained for the measurement of macroscopic parameters of the eyeballs. Posterior scleral tissue strips were obtained in circumferential and axial directions, and thickness was measured, respectively. Biomechanical parameters were obtained with stress relaxation, creep, and tensile test. The nanoindentation test was performed on the LC and scleral tissue around optic nerve head (ONH) to obtain compressive modulus. Results: In the presence of elevated IOP, variations of the axial diameter of the eyeball were greater than those of the transverse diameter, and the mean scleral thickness around ONH was smaller in the experimental group than control group. The elastic modulus and stress relaxation modulus of sclera were larger, and the creep rate was lower in the experimental group than control group. In the control group, the elastic modulus and stress relaxation modulus of the circumferential sclera were larger in the axial direction, and creep rate was smaller. In the experimental group, there was no significant difference in biomechanical characteristics between the two directions. Compared to the control group, the compression modulus of the LC was smaller, and the compression modulus of sclera around ONH was larger in the experimental group. Conclusion: Elevated IOP alters the viscoelasticity and anisotropy of sclera and LC. These may contribute to reduction of the organizational resistance to external forces and decline in the ability of self-recovery.


Assuntos
Glaucoma , Disco Óptico , Animais , Fenômenos Biomecânicos/fisiologia , Haplorrinos , Pressão Intraocular , Disco Óptico/fisiologia , Esclera/fisiologia
7.
Front Neurosci ; 16: 975131, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36051640

RESUMO

Feature extraction is a key task in the processing of surface electromyography (SEMG) signals. Currently, most of the approaches tend to extract features with deep learning methods, and show great performance. And with the development of deep learning, in which supervised learning is limited by the excessive expense incurred due to the reliance on labels. Therefore, unsupervised methods are gaining more and more attention. In this study, to better understand the different attribute information in the signal data, we propose an information-based method to learn disentangled feature representation of SEMG signals in an unsupervised manner, named Layer-wise Feature Extraction Algorithm (LFEA). Furthermore, due to the difference in the level of attribute abstraction, we specifically designed the layer-wise network structure. In TC score and MIG metric, our method shows the best performance in disentanglement, which is 6.2 lower and 0.11 higher than the second place, respectively. And LFEA also get at least 5.8% accuracy lead than other models in classifying motions. All experiments demonstrate the effectiveness of LEFA.

8.
Am J Hematol ; 2022 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-36054786

RESUMO

Myelofibrosis (MF) is associated with several constitutional symptoms. Currently, there are few therapeutic options for MF. Jaktinib, a novel, small-molecule inhibitor of JAK, is currently being studied for its potential to treat MF. This phase 2 trial investigated efficacy and safety of jaktinib in the treatment of MF patients. The primary end point was the proportion of patients with ≥ 35% reduction in spleen volume (SVR35, proportion of patients with ≥ 35% reduction in spleen volume) at week 24. The secondary end points included improvement of anemia, rates of symptom response, and safety profile. Between January 8, 2019 and August 29, 2020, 118 patients were recruited and treated with either jaktinib 100 mg BID or 200 mg QD. At week 24, 54.8% (34/62) of patients in the 100 mg BID group and 31.3% (15/48) in the 200 mg QD group achieved SVR35 (P = 0.0199). Jaktinib treatment increased hemoglobin level to ≥ 20 g/L in 35.6% (21/59) of patients with hemoglobin ≤ 100 g/L at baseline. The proportion of patients who achieved a ≥ 50% improvement in total symptom score at week 24 was 69.6% (39/56) in the BID group and 57.5% (23/40) in the QD group. The most common ≥ grade 3 hematological treatment-emergent adverse events (TEAEs; ≥ 10%) were anemia (100 mg BID: 24.2%, 200 mg QD: 28.8%), thrombocytopenia (16.7%, 11.5%), and neutropenia (3.0%, 11.5%). All non-hematological TEAEs were mild. These results indicate that jaktinib can shrink the spleen, improve anemia, and other clinical symptoms with good tolerability. This article is protected by copyright. All rights reserved.

9.
Immunology ; 2022 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-36053796

RESUMO

AKI (acute kidney injury) with maladaptive repair plays exacerbated role in renal fibrosis characterized by tubulointerstitial fibrosis. Previously, we reported that IKKα contributed to kidney regeneration and inhibited inflammation. Here, we first identified the role and mechanism of IKKα on TGF-ß1-induced fibrosis in human tubular epithelial cells and fibrotic kidneys. IKKα was up-regulated in kidney tubular epithelium in unilateral ureteral obstruction (UUO) and unilateral ischemic reperfusion injury (UIRI) mice. Immunohistochemical staining showed that IKKα was positively correlated with the extent of kidney fibrosis in tissue biopsies from chronic kidney disease (CKD) patients. Compared with wild-type controls, Ksp-IKKα-/- mice exhibited inactivated Wnt/ß-catenin pathway, decreased serum creatinine and interstitial fibrosis in the kidney after IRI. In TGF-ß1-stimulated human tubular epithelial cells, IKKα overexpression enhanced ß-catenin nuclear translocation. Blocking IKKα by siRNA specifically suppressed ß-catenin activation and downstream profibrotic genes such as fibronectin and α-smooth muscle actin (α-SMA). Taken together, our study demonstrated that IKKα aggravated renal fibrogenesis by activating Wnt/ß-catenin signalling pathway, providing a new target for the treatment of kidney fibrosis.

10.
Microbiol Spectr ; : e0134822, 2022 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-36094217

RESUMO

Vancomycin remains the mainstay of treatment for methicillin-resistant Staphylococcus aureus (MRSA) pneumonia. This study assessed risk factors for vancomycin failure in 63 patients with MRSA pneumonia through detailed clinical, microbiological, pharmacokinetic/pharmacodynamic, and genetic analyses of prospective multicenter studies conducted from February 2012 to July 2018. Therapeutic drug monitoring was performed during vancomycin treatment, and the 24-h area under the curve (AUC0-24) was calculated. All baseline strains were collected for MIC determination, heterogeneous vancomycin-intermediate S. aureus (hVISA) screening, and biofilm determination. Whole-genome sequencing was performed on the isolates to analyze their molecular typing and virulence and adhesion genes. Clinical signs and symptoms improved in 44 patients (44/63, 69.8%), with vancomycin daily dose (P = 0.045), peak concentration (P = 0.020), and sdrC (P = 0.047) being significant factors. Isolates were eradicated in 51 patients (51/63, 81.0%), with vancomycin daily dose (P = 0.009), cardiovascular disease (P = 0.043), sequence type 5 (ST5; P = 0.017), tst (P = 0.050), and sec gene (P = 0.044) associated with bacteriological failure. Although the AUC0-24/MIC was higher in the groups with bacterial eradication, the difference was not statistically significant (P = 0.108). Multivariate analysis showed that no variables were associated with clinical efficacy; ST5 was a risk factor for bacterial persistence (adjusted odds ratio, 4.449; 95% confidence interval, 1.103 to 17.943; P = 0.036). ST5 strains had higher frequencies of the hVISA phenotype, biofilm expression, and presence of some adhesion and virulence genes such as fnbB, tst, and sec than non-ST5 strains. Our study suggests that ST5 is a possible predictor of bacterial persistence in MRSA pneumonia treated with vancomycin. IMPORTANCE Few studies have simultaneously examined the influence of clinical characteristics of patients with pneumonia, the vancomycin pharmacokinetic/pharmacodynamic (PK/PD) index, and the phenotypic and genetic characteristics of methicillin-resistant Staphylococcus aureus (MRSA) strains. We assessed risk factors for vancomycin failure in patients with MRSA pneumonia by analyzing these influences in a prospective multicenter study. Sequence type 5 (ST5) was a possible predictor of bacterial persistence in adult patients with MRSA pneumonia (adjusted odds ratio, 4.449). We found that this may be related to ST5 strains having higher levels of vancomycin heterogeneous resistance, biofilms, and the presence of adhesion and virulence genes such as fnbB, tst, and sec.

11.
Mol Plant Pathol ; 2022 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-36094814

RESUMO

Tobacco black shank caused by Phytophthora nicotianae is a serious disease in tobacco cultivation. We found that naringenin is a key factor that causes different sensitivity to P. nicotianae between resistant and susceptible tobacco. The level of basal flavonoids in resistant tobacco was distinct from that in susceptible tobacco. Of all flavonoids with different content, naringenin showed the best antimicrobial activity against mycelial growth and sporangia production of P. nicotianae in vitro. However, naringenin showed very low or no antimicrobial activity to other plant pathogens. We found that naringenin induced not only the accumulation of reactive oxygen species, but also the expression of salicylic acid biosynthesis-related genes. Naringenin induced the expression of the basal pathogen resistance gene PR1 and the SAR8.2 gene that contributes to plant resistance to P. nicotianae. We then interfered with the expression of the chalcone synthase (NtCHS) gene, the key gene of the naringenin synthesis pathway, to inhibit naringenin biosynthesis. NtCHS-RNAi rendered tobacco highly sensitive to P. nicotianae, but there was no change in susceptibility to another plant pathogen, Ralstonia solanacearum. Finally, exogenous application of naringenin on susceptible tobacco enhanced resistance to P. nicotianae and naringenin was very stable in this environment. Our findings revealed that naringenin plays a core role in the defence against P. nicotianae and expanded the possibilities for the application of plant secondary metabolites in the control of P. nicotianae.

12.
World Neurosurg ; 2022 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-36087911

RESUMO

Spinal cord injury is the commonest problem encountered in spinal surgery. After the initial trauma the disruption of the blood-brain barrier, and subsequent microglia activation result in extensive inflammatory responses. Inflammasomes are large protein complexes that are essential during inflammation. One of the most studied inflammasome components, NLRP (NOD-, LRR-, and pyrin domain-containing 3), is widely expressed in the central nervous system. Previous research has shown that the micro-RNA, miR-451, may play a role in regulating inflammatory conditions. Using bioinformatics analysis we found that NLRP3 was a direct target of miR-451. This in silico prediction was confirmed in Dual-Luciferase reporter gene assays. To further demonstrate that miR-451 influenced microglial NLRP3 production we activated microglial cells with lipopolysaccharides (LPS). This intervention resulted in the production of NLRP3 inflammasomes and the secretion of the pro-inflammatory cytokines IL-1ß and IL-18. We were able to demonstrate that the overexpression of miR-451 suppressed this NLRP3-induced pro-inflammatory cascade of events. These findings highlight a potential anti-inflammatory role of miR-451 in reducing secondary neuronal damage after SCI.

13.
Zootaxa ; 5134(2): 238-260, 2022 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-36101067

RESUMO

Eight new species of Otacilia Thorell, 1897 from China are described and illustrated, all with both sexes: O. furcata sp. nov., O. guoi sp. nov., O. jiajinshan sp. nov. and O. menghuo sp. nov. from Sichuan Province, O. triangula sp. nov. from Chongqing City; O. shunhuangshan sp. nov. from Hunan Province; and O. subkomurai sp. nov. from Hubei Province, O. xueshanensis sp. nov. from Guizhou Provice.


Assuntos
Aranhas , Distribuição Animal , Animais , China , Feminino , Masculino
14.
Zootaxa ; 5129(3): 412-421, 2022 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-36101129

RESUMO

The representation of the Clubiona reclusa species-group in China is here established in two species: Clubiona qianlei sp. nov. from Central China and C. interjectaL. Koch, 1879, which is mainly distributed in northern China. Detailed description, diagnosis, photographs of the new species are given. DNA barcodes (a partial fragment of the mitochondrial cytochrome oxidase subunit I gene, COI) of the new species were obtained to confirm matching of the sexes and for future use in molecular studies. Supplementary micrographs of C. interjecta are provided for the first time, alongside an emended diagnosis, to demonstrate the validity of C. qianlei sp. nov.. A distribution map of the reclusa group species in China is given.


Assuntos
Aranhas , Animais , China , Genes Mitocondriais , Microscopia , Aranhas/genética
15.
Front Microbiol ; 13: 957849, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36060787

RESUMO

Senecavirus A (SVA) is an emerging picornavirus. Its genome is one positive-sense, single-stranded RNA. The viral protein (VPg) is covalently linked to the extreme 5' end of the SVA genome. A complex hairpin-pseudoknot-hairpin (HPH) RNA structure was computationally predicted to form at the 5' end of the SVA genome. A total of three extra "U" residues (UUU) served as a linker between the HPH structure and the VPg, causing putative UUU-HPH formation at the extreme 5' end of the SVA genome. It is unclear how the UUU-HPH structure functions. One SVA cDNA clone (N0) was constructed previously in our laboratory. Here, the N0 was genetically tailored for reconstructing a set of 36 modified cDNA clones (N1 to N36) in an attempt to rescue replication-competent SVAs using reverse genetics. The results showed that a total of nine viruses were successfully recovered. Out of them, five were independently rescued from the N1 to N5, reconstructed by deleting the first five nucleotides (TTTGA) one by one from the extreme 5' end of N0. Interestingly, these five viral progenies reverted to the wild-type or/and wild-type-like genotype, suggesting that SVA with an ability to repair nucleotide defects in its extreme 5' end. The other four were independently rescued from the N26 to N29, containing different loop-modifying motifs in the first hairpin of the HPH structure. These four loop-modifying motifs were genetically stable after serial passages, implying the wild-type loop motif was not a high-fidelity element in the first hairpin during SVA replication. The other genetically modified sequences were demonstrated to be lethal elements in the HPH structure for SVA recovery, suggesting that the putative HPH formation was a crucial cis-acting replication element for SVA propagation.

16.
Front Nutr ; 9: 960670, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36061885

RESUMO

Background: Malnutrition and sarcopenia are common in elderly gastric cancer patients, which are also interrelated and affect each other. We aimed to determine the characteristics of coexistence of malnutrition and sarcopenia in the elderly gastric cancer patients and investigate the predictive roles of malnutrition and sarcopenia on clinical outcomes. Methods: Between 2014 and 2019, a total of 742 elderly gastric cancer patients were enrolled. Malnutrition and sarcopenia were diagnosed according to the most recent diagnostic criteria. Patients were divided into four groups according to presence of these two symptoms. Clinical characteristics, short- and long-term outcomes were compared among four groups. The independent risk factors for complications and survival were evaluated using univariate and multivariate analyses. Results: Of all patients, 34.8% were diagnosed with malnutrition and 34.0% were diagnosed with sarcopenia. Patients with both malnutrition and sarcopenia had the highest rate of total (P < 0.001), surgical (P = 0.003), and medical complications (P = 0.025), and the highest postoperative hospital stays (P < 0.001) and hospitalization costs (P < 0.001). They also had the worst overall survival (P < 0.0001) and disease-free survival (P < 0.0001). Sarcopenia and Charlson Comorbidity Index (≥2) were independent risk factors for total complications. Hypoalbuminemia and malnutrition were non-tumor-related independent risk factors for overall survival and disease-free survival. Conclusions: Malnutrition and sarcopenia had superimposed negative effects on elderly gastric cancer patients. Preoperative geriatric evaluation including screening for malnutrition and sarcopenia are recommended for all elderly gastric cancer patients for accurate treatment strategy.

17.
Microsyst Nanoeng ; 8: 96, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36065436

RESUMO

Neural electrode interfaces are essential to the stimulation safety and recording quality of various bioelectronic therapies. The recently proposed hierarchical platinum-iridium (Pt-Ir) electrodes produced by femtosecond lasers have exhibited superior electrochemical performance in vitro, but their in vivo performance is still unclear. In this study, we explored the electrochemical performance, biological response, and tissue adhesion of hierarchical Pt-Ir electrodes by implantation in adult rat brains for 1, 8, and 16 weeks. Regular smooth Pt-Ir electrodes were used as a control. The results showed that the electrochemical performance of both electrodes decreased and leveled off during implantation. However, after 16 weeks, the charge storage capacity of hierarchical electrodes stabilized at ~16.8 mC/cm2, which was 15 times that of the smooth control electrodes (1.1 mC/cm2). Moreover, the highly structured electrodes had lower impedance amplitude and cutoff frequency values. The similar histological response to smooth electrodes indicated good biocompatibility of the hierarchically structured Pt-Ir electrodes. Given their superior in vivo performance, the femtosecond laser-treated Pt-Ir electrode showed great potential for neuromodulation applications.

18.
Environ Pollut ; 313: 120122, 2022 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-36089147

RESUMO

Dioxins and dioxin-like polychlorinated biphenyls (dl-PCBs) in fish fillet counteract the health benefits of fish products. In this study, food waste was used as a protein alternative to replacing fishmeal commonly used in the commercial fish feed, aiming to cultivate Sabah grouper with acceptable levels of dioxins and dl-PCBs. The concentrations of dioxins and dl-PCBs, as well as the fish growth performance, were compared between the fish groups fed with food waste-based feed (FWBF) and commercial feed (Nanyu®, control). The results showed that the concentrations of polychlorinated dibenzo-p-dioxins (PCDDs) (1.22 pg/g dry weight (d.w.)) and non-ortho-dl-PCBs (13.0 pg/g d.w.) were significantly lower (p < 0.05) in the FWBF than in the control feed (commercial feed) (PCDDs: 2.35 pg/g d.w.; non-ortho-dl-PCBs: 27.2 pg/g d.w.). The growth performance of the fish group fed with the FWBF was comparable to that fed with the control feed. There were no significant differences between the WHO2005-TEQ values of different fish fillets (1.00, 1.11, and 1.10 pg WHO2005-TEQ/g d.w. for FWBF group, control feed group, and local market fish, respectively). Based on the guidelines provided by European Food Safety Authority (ESFA) and U.S. Environmental Protection Agency (USEPA), the fish fed with the FWBF were safe for human consumption (hazard index values: 0.284-0.522; cancer risk range: 2.59-2.97 × 10-5). The findings of this study suggest that food waste could serve as an alternative protein source for cultivating Sabah grouper with acceptable levels of dioxins and dl-PCBs.

19.
Pathol Oncol Res ; 28: 1610199, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36091935

RESUMO

The heterogeneity of hepatocellular carcinoma (HCC) highlights the importance of precision therapy. In recent years, single-cell RNA sequencing has been used to reveal the expression of genes at the single-cell level and comprehensively study cell heterogeneity. This study combined big data analytics and single-cell data mining to study the influence of genes on HCC prognosis. The cells and genes closely related to the HCC were screened through single-cell RNA sequencing (71,915 cells, including 34,414 tumor cells) and big data analysis. Comprehensive bioinformatics analysis of the key genes of HCC was conducted for molecular classification and multi-dimensional correlation analyses, and a prognostic model for HCC was established. Finally, the correlation between the prognostic model and clinicopathological features was analyzed. 16,880 specific cells, screened from the single-cell expression profile matrix, were divided into 20 sub-clusters. Cell typing revealed that 97% of these cells corresponded to HCC cell lines, demonstrating the high specificity of cells derived from single-cell sequencing. 2,038 genes with high variability were obtained. The 371 HCC samples were divided into two molecular clusters. Cluster 1 (C1) was associated with tumorigenesis, high immune score, immunotherapy targets (PD-L1 and CYLA-4), high pathological stage, and poor prognosis. Cluster 2 (C2) was related to metabolic and immune function, low immune score, low pathological stage, and good prognosis. Seven differentially expressed genes (CYP3A4, NR1I2, CYP2C9, TTR, APOC3, CYP1A2, and AFP) identified between the two molecular clusters were used to construct a prognostic model. We further validated the correlation between the seven key genes and clinical features, and the established prognostic model could effectively predict HCC prognosis. Our study identified seven key genes related to HCC that were used to construct a prognostic model through single-cell sequencing and big data analytics. This study provides new insights for further research on clinical targets of HCC and new biomarkers for clinical application.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Prognóstico
20.
J Gastrointest Oncol ; 13(4): 1616-1625, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36092329

RESUMO

Background: An adequate resection margin and lymph node dissection are important factors for successful radical gastrectomy. The presence of near-infrared camera imaging with indocyanine green (ICG) gives new insight into radical gastrectomy. Laparoscopic radical gastrectomy with ICG is still in its initial stages and requires more evidence-based medical research. The aim of the present study was to evaluate the safety and availability of lymph node dissection and precise gastrectomy for gastric cancer patients undergoing radical resection under laparoscope with ICG, in the hope of providing evidence of application of ICG tracer fluorescence technique in radical gastrectomy. Methods: A retrospective cohort study was performed with 56 patients who underwent laparoscopic radical gastrectomy. The patients were categorized into the ICG (n=18) or the non-ICG (n=38) group based on whether preoperative endoscopic mucosal ICG injection was performed. Their clinical characteristics (age, tumor size, location, TNM stage and so on) were compared as baseline data. Perioperative outcomes (blood loss, time of first intestinal exhaust, early or long-term complications and so on) were used to assess safety. The status of lymph node dissection and tumor localization were analyzed to testify efficacy. SPSS version 26.0 was used for the statistical analysis. Results: There was no difference in clinical data at baseline. From the safety point of view, there was no difference in perioperative outcomes (operative time, blood loss, time of first intestinal exhaust and so on) between the two groups (all P>0.05). From the efficacy point of view, the number of lymph nodes <5 mm (21.84±1.86 vs. 16.24±2.10, P<0.001), the total number of lymph nodes (34.61±5.87 vs. 29.92±5.27, P=0.004), the number of lymph nodes dissected in perigastric regions (groups 1-7, 22.89±3.64 vs. 20.29±3.00, P=0.007), and the number of lymph nodes in extraperigastric regions (groups 8-12, 11.72±3.06 vs. 9.61±3.18, P=0.022) were greater in ICG group compared with non-ICG group. In ICG group, the average vertical distances between the top and bottom of the fluorescent edge and neoplastic edge were 2.65±0.58 and 2.67±0.65 cm, respectively. Fluorescent edge pathology was negative. Conclusions: ICG fluorescence could be conducive to lymph node dissection and precise gastrectomy in laparoscopic radical gastrectomy.

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