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1.
Research (Wash D C) ; 2022: 9769803, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35928300

RESUMO

Identification of epitopes targeted following virus infection or vaccination can guide vaccine design and development of therapeutic interventions targeting functional sites, but can be laborious. Herein, we employed peptide microarrays to map linear peptide epitopes (LPEs) recognized following SARS-CoV-2 infection and vaccination. LPEs detected by nonhuman primate (NHP) and patient IgMs after SARS-CoV-2 infection extensively overlapped, localized to functionally important virus regions, and aligned with reported neutralizing antibody binding sites. Similar LPE overlap occurred after infection and vaccination, with LPE clusters specific to each stimulus, where strong and conserved LPEs mapping to sites known or likely to inhibit spike protein function. Vaccine-specific LPEs tended to map to sites known or likely to be affected by structural changes induced by the proline substitutions in the mRNA vaccine's S protein. Mapping LPEs to regions of known functional importance in this manner may accelerate vaccine evaluation and discovery of targets for site-specific therapeutic interventions.

2.
Front Endocrinol (Lausanne) ; 13: 917386, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35909537

RESUMO

Gestational diabetes mellitus (GDM), the most common medical pregnancy complication, has become a growing problem. More and more studies have shown that microRNAs are closely related to metabolic processes. The purpose of this paper is to investigate the role of up-regulation of miR-199a-5p expression in GDM. We found that miR-199a-5p was significantly up-regulated in the placenta of GDM patients compared with normal pregnant women, and expressed in placental villi. miR-199a-5p can regulate the glucose pathway by inhibiting the expression of methyl CpG-binding protein 2 (MeCP2) and down-regulating canonical transient receptor potential 3 (Trpc3). This suggests that miR-199a-5p may regulate the glucose pathway by regulating methylation levels, leading to the occurrence of GDM.


Assuntos
Diabetes Gestacional , MicroRNAs , Diabetes Gestacional/genética , Diabetes Gestacional/metabolismo , Feminino , Glucose/metabolismo , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Placenta/metabolismo , Gravidez , Regulação para Cima
3.
World J Surg ; 2022 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-35913599

RESUMO

BACKGROUND: Retroperitoneal laparoscopic adrenalectomy (RLA) possessing unique superiority with minimal abdominal interference is complicated by the status of periadrenal fat, including its quantity and texture. We hypothesized that an adherent perinephric fat predictor, the Mayo Adhesive Probability score (Mayo score), is associated with the perioperative outcomes of RLA. METHODS: This retrospective study included consecutive patients who underwent RLA for the diagnosis of benign adrenal tumors at our institution between 2017 and 2020. Medical records were reviewed to evaluate the association between Mayo scores obtained from preoperative computed tomography imaging and surgical outcomes as well as complications. Factors independently related to perioperative results were analyzed using multivariable regression models. RESULTS: In total, 186 RLA were included. According to their Mayo scores, the patients were divided as follows: 0 (n = 51, 27.4%), 1 (n = 34, 18.3%), 2 (n = 45, 24.2%), 3 (n = 29, 15.6%), 4 (n = 16, 8.6%) and 5 (n = 11, 5.9%). Longer operative time (92.0 ± 25.0 vs. 114.7 ± 30.6 vs. 137.4 ± 27.1 min, P < 0.001), higher estimated blood loss (42.2 ± 28.1 vs. 70.5 ± 44.9 vs. 132.6 ± 63.4 mL, P < 0.001) and greater decline of hemoglobin (0.7 ± 0.4 vs. 1.0 ± 0.4 vs. 1.3 ± 0.6 g/dL, P < 0.001) were significantly associated with elevated Mayo score risks. No difference in complication rates was found. The score was identified as a unique, independent risk factor for perioperative outcomes on multivariable analysis. CONCLUSIONS: The Mayo score is a vital outcome predictor of RLA. It may be utilized in the preoperative planning for patients undergoing RLA.

4.
Nutrients ; 14(15)2022 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-35956340

RESUMO

Akkermansia muciniphila (A. muciniphila) is a mucin-degrading bacterium that resides in the mucus layer, but its potential in intestinal inflammatory diseases has sparked controversy. It is well known that both the consumption of fructose-containing beverages and psychological stress increase the risk of intestinal disease. Our results revealed that a high-fructose diet aggravated the damage to the jejunal mucosal barrier caused by restraint stress, reduced tight junction protein expression and the intestinal digestion and absorption capacity, disrupted the ability of Paneth cells to secrete antimicrobial peptides, and promoted the expression of inflammatory cytokines. A. muciniphila colonization enhanced the defense function of the mucosal barrier by enhancing the function of the NLRP6, promoting autophagy, maintaining the normal secretion of antimicrobial peptides in Paneth cells, promoting the expression of tight junction proteins, negatively regulating the NF-kB signaling pathway and inhibiting the expression of inflammatory cytokines. Our work indicates that A. muciniphila ameliorates the disruption of the intestinal mucosal barrier under high fructose and restraint stress. These results provided a rationale for the development of probiotic colonization for the prevention or treatment of intestinal diseases.


Assuntos
Frutose , Verrucomicrobia , Akkermansia , Citocinas/metabolismo , Frutose/efeitos adversos , Frutose/metabolismo , Mucosa Intestinal/metabolismo
5.
Mol Neurobiol ; 2022 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-35974295

RESUMO

There are sex differences in the severity, mechanisms, and outcomes of neonatal hypoxia-ischemia (HI) brain injury, and apoptosis-inducing factor (AIF) may play a critical role in this discrepancy. Based on previous findings that AIF overexpression aggravates neonatal HI brain injury, we further investigated potential sex differences in the severity and molecular mechanisms underlying the injury using mice that overexpress AIF from homozygous transgenes. We found that the male sex significantly aggravated AIF-driven brain damage, as indicated by the injury volume in the gray matter (2.25 times greater in males) and by the lost volume of subcortical white matter (1.71 greater in males) after HI. As compared to females, male mice exhibited more severe brain injury, correlating with reduced antioxidant capacities, more pronounced protein carbonylation and nitration, and increased neuronal cell death. Under physiological conditions (without HI), the doublecortin-positive area in the dentate gyrus of females was 1.15 times larger than in males, indicating that AIF upregulation effectively promoted neurogenesis in females in the long term. We also found that AIF stimulated carbohydrate metabolism in young males. Altogether, these findings corroborate earlier studies and further demonstrate that AIF is involved in oxidative stress, which contributes to the sex-specific differences observed in neonatal HI brain injury.

6.
Front Vet Sci ; 9: 908862, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35782537

RESUMO

The disparity in fatty acids (FA) composition exhibits a significant impact on meat quality, however, the molecular regulatory mechanisms underlying this trait in chicken are far from clear. In this study, a total of 45 female Beijing-You chicken (BYC) hens, fed on the same diet, were collected at the slaughter age of 150, 300, or 450 days (D150, D300, and D450) from sexual maturation stage to culling stage (15 birds per age). Gas chromatography-mass spectrometry (GC-MS) and tandem mass tag labeling technology based on liquid chromatography mass spectrometry (TMT-LC-MS/MS) analysis strategies were applied to profile FA compositions and to compare differential expressed proteins (DEPs) between these different slaughter ages, respectively. The FA profiling showed that increasing hen ages resulted in increased contents of both saturated and unsaturated fatty acids. Proteomic analyses showed a total of 4,935 proteins in chicken breast muscle with the false discovery rate (FDR) < 1% and 664 of them were differentially expressed (fold change > 1.50 or < 0.67 and P < 0.01). There were 410 up- and 116 down-regulated proteins in D150 vs. D300 group, 32 up- and 20 down-regulated in D150 vs. D450 group, and 72 up- and 241 down-regulated in D300 vs. D450 group. A total of 57 DEPs related to FA/lipid-related metabolisms were obtained according to the enrichment analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). These DEPs were involved in 21 significantly enriched (P < 0.05) pathways, including well-known pathways for FA synthesis (metabolism, desaturation, and elongation) and the signaling pathways for lipid metabolism (PPAR, adipocytokine, calcium, VEGF, MAPK, and Wnt). In addition, there existed several representative DEPs (FABP, FABP3, apoA-I, apoA-IV, apoC-III, apoB, VTG1, and VTG2) involved in the regulation of FA/lipid transportation. The construction of the interaction networks indicated that HADH, ACAA2, HADHA, ACSL1, CD36, CPT1A, PPP3R1, and SPHK1 were the key core nodes. Finally, eight DEPs were quantified using parallel reaction monitoring (PRM) to validate the results from TMT analysis. These results expanded our understanding of how the laying age affects the FA compositions and metabolism in hen breast meat.

7.
Front Chem ; 10: 928806, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35783206

RESUMO

In recent years, unsupported MoS2-based catalysts have been reported as promising candidates in the hydrodeoxygenation (HDO) of bio-oil. However, preparing MoS2-based catalysts with both high activity and good stability for HDO reaction is still challenging and of great importance. Hence, this mini-review is focused on the recent development of unsupported MoS2-based HDO catalysts from the understanding of catalyst design. The three aspects including morphology and defect engineering, metal doping, and deactivation mechanism are highlighted in adjusting the HDO performance of MoS2-based catalysts. Finally, the key challenges and future perspectives about how to design efficient catalysts are also summarized in the conclusions.

8.
Front Mol Biosci ; 9: 907148, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35832736

RESUMO

In recent years, the studies of the role of microRNAs in adipogenesis and adipocyte development and the corresponding molecular mechanisms have received great attention. In this work, we investigated the function of miR-140 in the process of adipogenesis and the molecular pathways involved, and we found that adipogenic treatment promoted the miR-140-5p RNA level in preadipocytes. Over-expression of miR-140-5p in preadipocytes accelerated lipogenesis along with adipogenic differentiation by transcriptional modulation of adipogenesis-linked genes. Meanwhile, silencing endogenous miR-140-5p dampened adipogenesis. Platelet-derived growth factor receptor alpha (PDGFRα) was shown to be a miR-140-5p target gene. miR-140-5p over-expression in preadipocyte 3T3-L1 diminished PDGFRα expression, but silencing of miR-140-5p augmented it. In addition, over-expression of PDGFRα suppressed adipogenic differentiation and lipogenesis, while its knockdown enhanced these biological processes of preadipocyte 3T3-L1. Altogether, our current findings reveal that miR-140-5p induces lipogenesis and adipogenic differentiation in 3T3-L1 cells by targeting PDGFRα, therefore regulating adipogenesis. Our research provides molecular targets and a theoretical basis for the treatment of obesity-related metabolic diseases.

9.
Front Med (Lausanne) ; 9: 896451, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35836941

RESUMO

Background: Identifying a high-risk group of older people before surgical procedures is very important. The study aimed to explore the association between the age-adjusted Charlson comorbidity index (ACCI) and all-cause mortality and readmission among older Chinese surgical patients (age ≥65 years). Methods: A large-scale cohort study was performed in 25 general public hospitals from six different geographic regions of China. Trained registered nurses gathered data on clinical and sociodemographic characteristics. All-cause mortality was recorded when patients died during hospitalization or during the 90-day follow-up period. Readmission was also tracked from hospital discharge to the 90-day follow-up. The ACCI, in assessing comorbidities, was categorized into two groups (≥5 vs. <5). A multiple regression model was used to examine the association between the ACCI and all-cause mortality and readmission. Results: There were 3,911 older surgical patients (mean = 72.46, SD = 6.22) in our study, with 1,934 (49.45%) males. The average ACCI score was 4.77 (SD = 1.99), and all-cause mortality was 2.51% (high ACCI = 5.06% vs. low ACCI = 0.66%, P < 0.001). After controlling for all potential confounders, the ACCI score was an independent risk factor for 90-day hospital readmission (OR = 1.18, 95% CI: 1.14, 1.23) and 90-day all-cause mortality (OR = 1.26, 95% CI: 1.16-1.36). Furthermore, older surgical patients with a high ACCI (≥5) had an increased risk of all-cause mortality (OR = 6.13, 95% CI: 3.17, 11.85) and readmission (OR = 2.13, 95% CI: 1.78, 2.56) compared to those with a low ACCI (<5). The discrimination performance of the ACCI was moderate for mortality (AUC:0.758, 95% CI: 0.715-0.80; specificity = 0.591, sensitivity = 0.846) but poor for readmission (AUC: 0.627, 95% CI: 0.605-0.648; specificity = 0.620; sensitivity = 0.590). Conclusions: The ACCI is an independent risk factor for all-cause mortality and hospital readmission among older Chinese surgical patients and could be a potential risk assessment tool to stratify high-risk older patients for surgical procedures.

10.
J Gastrointest Oncol ; 13(3): 1444-1453, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35837197

RESUMO

Background: Pancreatic cancer (PC) is among the most prevalent and deadliest endocrine tumors, yet the mechanisms governing its pathogenesis remain to be fully clarified. While ubiquitin-conjugating enzyme E2C (UBE2C) has been identified as an important oncogene in several cancers, its importance in PC has yet to be established. Methods: UBE2C expression in PC tumor samples and cell lines was examined via quantitative real-time polymerase chain reaction (qRT-PCR), while appropriate commercial kits were used to assess lactate production, ATP generation, and the uptake of glucose. Results: UBE2C was found to be upregulated in PC patient tumors and correlated with poorer survival outcomes. In PC cell lines, the silencing of this gene suppressed the malignant activity of cells, thus supporting its identification as an oncogene in this cancer type. Mechanistically, UBE2C was found to promote enhanced matrix metalloproteinase (MMP) protein expression via activating the PI3K-Akt pathway. Moreover, it was found to bind to the epidermal growth factor receptor (EGFR), stabilizing it and driving additional PI3K-Akt pathway activation. UBE2C knockdown in PC cells impaired their uptake of glucose and their ability to produce lactate and ATP. Conclusions: In conclusion, the results of this study support a role for UBE2C as a driver of metastatic PC progression owing to its ability to bind to EGFR and to induce signaling via the PI3K-Akt pathway.

11.
J Gastrointest Oncol ; 13(3): 1330-1339, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35837203

RESUMO

Background: It remains unclear whether diabetic medications, such as metformin and insulin, affect the post-liver resection prognosis of hepatocellular carcinoma (HCC) patients complicated with diabetes mellitus (DM). This study try to find out the prognostic factors in HCC patients with DM and provide a better antidiabetic therapy after liver resection. Methods: Patients presenting with HCC complicated with DM undergoing liver resection were enrolled in this study. They were examined and followed up every 3-6 months after surgery. Patients were divided into the antidiabetic treatment group and no antidiabetic treatment group according to whether they received medications for diabetes or not. Then patients in the antidiabetic treatment group were further divided into insulin group, metformin group, insulin plus metformin group and others group, according to the medications they received. Overall survival (OS) and recurrence-free survival (RFS) were compared among two groups and four subgoups. Comparative and multivariate analyses were performed to investigate the effects of DM medication on the prognosis of these HCC patients, using Cox proportional hazards model. Results: The 1-, 3-, 5-, and 7-year OS rates for the antidiabetic treatment group were 87.5%, 75.5%, 48.7%, and 29.1%, respectively, and for the no antidiabetic treatment group, the OS rates were 85.4%, 57.7%, 33.6%, and 19.1%, respectively (P=0.007). The 1-, 3-, 5-, 7-year RFS rates for the antidiabetic treatment group were 76.4%, 53.5%, 28.5%, and 17.5%, respectively, and for the no antidiabetic treatment group, the RFS rates were 69.5%, 32.5%, 16.5%, and 10.7%, respectively (P=0.001). In subgroup analysis, There was no significant difference in either RFS (P=0.934) nor OS (P=0.412) among the different types of antidiabetic treatment regimens. Cox proportional hazard regression analysis revealed that tumor size (HR: 1.048), tumor number (HR: 1.626), vascular invasion (HR: 2.074, P=0.003), satellite tumor (HR: 1.592), Edmondson classification (HR: 1.468) and antidiabetic treatment (HR: 0.722) were independent prognostic factors of DFS, while tumor size (HR: 1.048), tumor number (HR: 1.779), vascular invasion (HR: 2.545), Edmondson classification (HR: 1.596) and antidiabetic treatment (HR: 0.713) were independent prognostic factors of OS. Conclusions: For HCC patients with DM, antidiabetic treatment should be recommended aggressively in order to improve the surgical outcome, regardless of which antidiabetic drugs are used.

12.
Antioxidants (Basel) ; 11(7)2022 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-35883709

RESUMO

Light pollution is one of the most serious public problems, especially the night light. However, the effect of dim blue light at night (dLAN-BL) on cognitive function is unclear. In this study, we evaluated the effects of exposure to dLAN-BL in C57BL/6J mice for 4 consecutive weeks. Our results showed dLAN-BL significantly impaired spatial learning and memory and increased plasma corticosterone level in mice. Consistent with these changes, we observed dLAN-BL significantly increased the numbers and activation of microglia and the levels of oxidative stress product MDA in the hippocampus, decreased the levels of antioxidant enzymes Glutathione peroxidase (GSH-Px), Superoxide dismutase (SOD), Gluathione reductase (Gsr), total antioxidants (T-AOC) and the number of neurons in the hippocampus, up-regulated the mRNA expression levels of IL6, TNF-α and the protein expression levels of iNOS, COX2, TLR4, p-p65, Cleaved-Caspase3 and BAX, and down-regulated the mRNA expression levels of IL4, IL10, Psd95, Snap25, Sirt1, Dcx and the protein expression level of BCL2. In vitro results further showed corticosterone (10uM)-induced BV2 cell activation and up-regulated content of IL6, TNF-α in the cell supernatant and the protein expression levels of iNOS, COX2, p-p65 in BV2 cells. Our findings suggested dLAN-BL up-regulated plasma corticosterone level and hippocampal microglia activation, which in turn caused oxidative stress and neuroinflammation, leading to neuronal loss and synaptic dysfunction, ultimately leading to spatial learning and memory dysfunction in mice.

13.
BMC Psychiatry ; 22(1): 448, 2022 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-35790936

RESUMO

BACKGROUND: The prevalence of comorbid depressive and anxiety disorders in people living with HIV (PLWH) is high. However, it is unclear which symptom is the bridge symptom between depression and anxiety in PLWH. This study aimed to develop symptom networks for depression and anxiety and explore the bridge symptoms and interconnectedness between these disorders in PLWH with comorbid depressive and anxiety disorders. METHODS: A multisite, hospital-based cross-sectional study was conducted from March 2020 to November 2021. Depression and anxiety were measured with the Hospital Anxiety and Depression Scale. We visualized the symptom network using the qgraph package and computed the bridge expected influence of each node. The GLASSO layout was used to generate undirected association networks. RESULTS: A total of 2016 individuals were included in the analysis. In the anxiety cluster, "not feeling relaxed" had the highest bridge expected influence and strength (rbridge expected influence = 0.628, rstrength = 0.903). In the depression cluster, "not feeling cheerful" was identified as having a high bridge expected influence (rbridge expected influence = 0.385). "Not feeling cheerful" and "not feeling relaxed" were the strongest edges across the depression and anxiety clusters (r = 0.30 ± 0.02). CONCLUSIONS: Healthcare professionals should take note when PLWH report severe bridge symptoms. To enhance the levels of perceived cheerfulness and relaxation, positive psychology interventions could be implemented.


Assuntos
Depressão , Infecções por HIV , Ansiedade/complicações , Ansiedade/diagnóstico , Ansiedade/epidemiologia , Transtornos de Ansiedade/complicações , Transtornos de Ansiedade/epidemiologia , Estudos Transversais , Depressão/complicações , Depressão/diagnóstico , Depressão/epidemiologia , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Infecções por HIV/psicologia , Humanos
14.
Theranostics ; 12(10): 4753-4766, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35832084

RESUMO

Rationale: Cisplatin nephrotoxicity is an important cause of acute kidney injury (AKI), limiting cisplatin application in cancer therapy. Growing evidence has suggested that genome instability, telomeric dysfunction, and DNA damage were involved in the tubular epithelial cells (TECs) damage in cisplatin-induced AKI (cAKI). However, the exact mechanism is largely unknown. Methods: We subjected miR-155-/- mice and wild-type controls, as well as HK-2 cells, to cAKI models. We assessed kidney function and injury with standard techniques. The cell apoptosis and DNA damage of TECs were evaluated both in vivo and in vitro. Telomeres were measured by the fluorescence in situ hybridization. Results: The expression level of miR-155 was upregulated in cAKI. Inhibition of miR-155 expression protected cisplatin-induced AKI both in vivo and in vitro. Compared with wild-type mice, miR-155-/- mice had reduced mortality, improved renal function and pathological damage after cisplatin intervention. Moreover, inhibition of miR-155 expression attenuated TECs apoptosis and DNA damage. These protective effects were caused by increasing expression of telomeric repeat binding factor 1 (TRF1) and cyclin-dependent kinase 12 (CDK12), thereby limiting the telomeric dysfunction and the genomic DNA damage in cAKI. Conclusion: We demonstrated that miR-155 deficiency could significantly attenuate pathological damage and mortality in cAKI through inhibition of TECs apoptosis, genome instability, and telomeric dysfunction, which is possibly regulated by the increasing expression of TRF1 and CDK12. This study will provide a new molecular strategy for the prevention of cAKI.


Assuntos
Injúria Renal Aguda , Dano ao DNA , MicroRNAs , Injúria Renal Aguda/metabolismo , Injúria Renal Aguda/patologia , Injúria Renal Aguda/prevenção & controle , Animais , Apoptose/efeitos dos fármacos , Cisplatino/toxicidade , Células Epiteliais/efeitos dos fármacos , Instabilidade Genômica , Genômica , Hibridização in Situ Fluorescente , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/metabolismo , Telômero/metabolismo
15.
Front Immunol ; 13: 849780, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35903105

RESUMO

Emerging data demonstrated that the gut microbiota plays an important role in protecting the integrity of the epithelial barrier, forming a mucosal immune system, and maintaining intestinal homeostasis through its metabolites. However, the intestinal microbiota community can be affected by environmental factors, such as litter, photoperiod, or temperature. Thus, we investigated the effect of different monochromatic light combinations on cecal microbiota composition as well as explored the molecular mechanism by how the external light color information mediate cecal tonsil T lymphocyte proliferation. In this study, a total of 160 chicks were exposed to monochromatic light [red (R), green (G), blue (B), or white (W) light] or green and blue monochromatic light combination (G→B) from P0 to P42. The 16S rRNA microbial sequencing results showed that the richness and diversity of the cecum microbiota and the abundance of Faecalibacterium and Butyricicoccus were significantly increased in the G→B. With consistency in the upregulation of antioxidant enzyme ability and downregulation of pro-inflammation levels in the cecum, we observed an increase in the number of goblet cells, secretory IgA+ cells, tight junction protein (occludin, ZO-1, and claudin-1) and MUC-2 expression in the cecum of the G→B. The metabolomics analysis revealed that the relative abundance of metabolites related to butyrate was significantly increased in G→B. In an in vitro experiment, we found that butyrate could effectively induce T lymphocyte proliferation and cyclin D1 protein expression. However, these butyrate responses were abrogated by HDAC3 agonists, STAT3 antagonists, or mTOR antagonists but were mimicked by GPR43 agonists or HDAC3 antagonists. Thus, we suggested that G→B can indirectly affect the composition of cecal microbiota as well as increase the relative abundance of Faecalibacterium and Butyricicoccus and butyrate production by reducing the level of oxidative stress in the cecum. Exogenous butyrate could promote the T lymphocyte proliferation of cecal tonsil by activating the GPR43/HDAC3/p-STAT3/mTOR pathways.


Assuntos
Microbiota , Tonsila Palatina , Butiratos , Ceco/microbiologia , Proliferação de Células , RNA Ribossômico 16S/análise , Linfócitos T/química , Serina-Treonina Quinases TOR
16.
Glob Chang Biol ; 2022 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-35833875

RESUMO

Elucidating the response mechanism of soil respiration (Rs) to silvicultural practices is pivotal to evaluating the effects of management practices on soil carbon cycling in planted forest ecosystems. However, as common management practices, how thinning, understory plant removal, and their interactions affect Rs and its autotrophic and heterotrophic components (Ra and Rh) remains unclear. Therefore, we investigated Rs, Ra and Rh by the trenching method from 2011 to 2015 in a Pinus tabuliformis plantation in northern China, subjecting to four treatments (intact control plots [CK], thinning [T], understory removal [UR], and thinning with understory removal [TUR]). Mean annual Rs was significantly increased by thinning (by 15.3%), whereas decreased by UR (by 17.4%), compared with CK. These variations in Rs were mainly attributed to changes in Ra. The increments of Ra were caused by the enhanced growth of fine root biomass after thinning. However, UR led to lower Ra compared with CK (p < .05), indicating that understory growth is inadequate to compensate for the decreased respiring root biomass induced by understory removal. Rs was unchanged between TUR and the intact control plot due to the opposite effects of thinning and UR on the Ra. Changes in Rh exhibited no significant differences among the treatments, partly because of the stable microbial biomass carbon (MBC) and forest floor mass (litter and fine woody debris). No interaction effect between thinning and understory removal was detected on Rs, Ra, and Rh. The lowest temperature sensitivity (Q10 ) value of Ra was found in CK. This study highlights the necessity of incorporating understory plant effects on soil CO2 efflux in assessing forest management practices on soil carbon cycling.

17.
Life Sci ; 306: 120839, 2022 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-35902029

RESUMO

AIMS: Electroacupuncture (EA) is a potentially useful treatment for inflammatory pain. Receptor-interacting protein 3 (RIP3) triggers the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome; activation independent of necroptosis has been reported. However, the role of RIP3 in inflammatory pain and its EA-induced analgesic effects remains unclear. MAIN METHODS: Mice were treated with EA (2 Hz, 2 mA) after complete Freund's adjuvant (CFA) pain models were established. Inhibition or activation of spinal RIP3 was achieved by intrathecal administration of GSK-843 (a specific RIP3 inhibitor) or microinjection of lentivirus-RIP3, respectively. Mechanical analgesiometry and thermal analgesiometry were used to assess paw withdrawal threshold and paw withdrawal latency in mice. Quantitative polymerase chain reaction (qRT-PCR) and Western blotting were used to evaluate the expression of RIP3 and NLPR3 in spinal dorsal horn (SDH) of mice. KEY FINDINGS: The expression of spinal RIP3 and NLPR3 increased significantly after CFA injection. Both intrathecal administration of GSK-843 and EA alleviated mechanical and thermal pain behaviors induced by CFA and inhibited the expression of RIP3 and NLRP3 in the SDH of CFA mice. Over-expression of RIP3 induces pain-like symptoms in mice and inhibits the regulatory effects of EA on inflammatory pain. SIGNIFICANCE: Our results indicate that the EA analgesia effect may be related to suppression of RIP3 and NLRP3 expression in the SDH. This study could provide potential insights into the underlying spinal mechanisms involved in the analgesic effect of EA.

18.
J Chemother ; : 1-8, 2022 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-35881409

RESUMO

This study aimed to assess the efficacy and safety of hypomethylating agent (HMA)-based regimens in the treatment of older adult patients with acute myeloid leukaemia (AML), unfit for standard induction chemotherapy. Treatment outcomes and prognostic factors of 140 older adult patients with AML who were unfit for intensive chemotherapy and were treated with HMA-based therapies were retrospectively analysed. The median age of the group was 70 years, and poor-risk cytogenetics and secondary/treatment-related AML (s/t-AML) accounted for 45.6% and 34.3% of these patients, respectively. The overall response rate was 48.6%, and 40.1% for patients who achieved complete remission (CR) or CR with incomplete blood count recovery. The median overall survival (OS) was 10.4 months, and the 1-, 2-, and 5-year OS rates were 42.6%, 19.9%, and 4.9%, respectively. Early mortality accounted for 4.3% of all cases, and infection occurred in 87.1% of all patients during induction therapy. Patients who received HMA and low-dose chemotherapy presented with significantly superior response and long-term survival rates compared to those who received HMA alone. They also showed comparable outcomes to those treated with the azacitidine plus venetoclax protocol. Low-dose chemotherapy in combination with decitabine or azacitidine showed a similar response rate and prognosis. Age ≥ 75years and a white blood cell (WBC) count ≥ 10 × 109 cells/L were identified as independent adverse prognostic factors for OS, while poor-risk cytogenetics, percentage of bone marrow blasts, and s/tAML had no significant impact on OS when patients were treated with HMA-based regimens. In conclusion, HMA combined with low-dose chemotherapy was effective and safe in older adults with AML who were unfit for intensive chemotherapy, and no difference was observed between decitabine and azacitidine.

19.
Physiol Behav ; 254: 113897, 2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-35788009

RESUMO

Food resource availability is one of the most important factors affecting interindividual competition in a variety of animal species. However, the energy budget and territory aggression strategy of small mammals during periods of food restriction remain uncertain. In this study, metabolic rate, body temperature, territory aggression behavior, and fat deposit were measured in male striped hamster (Cricetulus barabensis) restricted by 20% of ad libitum food intake with or without supplementary methimazole. Serum thyroid hormone (tri-iodothyronine, T3 and thyroxine, T4), and cytochrome c oxidase (COX) activity in liver, brown adipose tissue, and skeletal muscle, were also measured. Attack latency, total attack times and duration, and the interval duration between attacks of resident hamsters were not significantly changed during food restriction, which was not significantly affected by supplementary methimazole. Metabolic rate and body temperature was significantly increased in food-restricted hamsters following introduction of an intruder, which was not completely blocked by supplementary methimazole. Serum T3 and T4 levels and BAT COX activity were not significantly changed following aggression, and were significantly decreased by supplementary methimazole. These findings suggest that striped hamsters increase energy expenditure for territory aggression during food restriction, and consequently lead to excessive energy depletion. Territory aggression behavior may decrease the capacity to cope with food shortage, which may be independent of thyroid hormone.


Assuntos
Tecido Adiposo Marrom , Metimazol , Tecido Adiposo Marrom/fisiologia , Agressão , Animais , Cricetinae , Cricetulus , Metabolismo Energético/fisiologia , Masculino , Metimazol/metabolismo , Hormônios Tireóideos
20.
Adv Mater ; : e2203209, 2022 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-35796130

RESUMO

Neuromorphic computing provides a means for achieving faster and more energy efficient computations than conventional digital computers for artificial intelligence (AI). However, its current accuracy is generally less than the dominant software-based AI. The key to improving accuracy is to reduce the intrinsic randomness of memristive devices, emulating synapses in the brain for neuromorphic computing. Here using a planar device as a model system, the controlled formation of conduction channels is achieved with high oxygen vacancy concentrations through the design of sharp protrusions in the electrode gap, as observed by X-ray multimodal imaging of both oxygen stoichiometry and crystallinity. Classical molecular dynamics simulations confirm that the controlled formation of conduction channels arises from confinement of the electric field, yielding a reproducible spatial distribution of oxygen vacancies across switching cycles. This work demonstrates an effective route to control the otherwise random electroforming process by electrode design, facilitating the development of more accurate memristive devices for neuromorphic computing.

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