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1.
Am J Clin Nutr ; 119(4): 1027-1035, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38569774

RESUMO

BACKGROUND: The postoperative inflammatory response is associated with postoperative recovery in surgery. n-3 (ω-3) polyunsaturated fatty acids have been reported to lower inflammation. The postoperative role of parenteral n-3 polyunsaturated fatty acids supplementation on outcomes in Crohn's disease after bowel resection is unclear. OBJECTIVES: We aimed to investigate the effects of postoperative parenteral n-3 polyunsaturated fatty acids supplementation in Crohn's disease. METHODS: A prospective randomized, unblinded controlled clinical trial was conducted for patients with Crohn's disease who underwent bowel resection between May 2019 and February 2022. Postoperative complications, complete blood count, serum biochemical values, and cytokine concentrations were compared in patients with and without parenteral n-3 polyunsaturated fatty acids supplementation for 5 d postoperatively. RESULTS: There were 268 patients randomly assigned in the analysis, with 134 in the control group (a mix of long-chain and medium-chain fats at 1.0 g/kg/d) and 134 in the treatment group (long-chain, medium-chain, and n-3 polyunsaturated fats at 1.2 g/kg/d). Twenty-six did not complete the allocated treatment, and 8 patients were lost to follow-up. The intention-to-treat analysis and the per-protocol analysis showed that there were a significant reduction in overall complication rates (22.4% compared with 49.3%; P < 0.001 and 21.8% compared with 38.2%; P = 0.006) and postoperative stay (8.8 ± 4.5 d compared with 11.2 ± 6.8 d; P = 0.001 and 8.7 ± 4.0 d compared with 11.5 ± 7.3 d; P < 0.001) in patients with parenteral n-3 polyunsaturated fatty acids supplementation compared with patients in the control group. In the secondary outcomes, the mean ± standard deviation of interleukin (IL)-6 (17.11 ± 2.14 pg/mL compared with 30.50 ± 5.14 pg/mL; P = 0.014), IL-1ß (2.01 ± 0.05 pg/mL compared with 2.24 ± 0.09 pg/mL; P = 0.019), tumor necrosis factor-α (2.09 ± 0.06 pg/mL compared with 2.29 ± 0.06 pg/mL; P = 0.029), and C-reactive protein concentrations (51.3 ± 4.2 mg/L compared with 64.4 ± 5.3 mg/L; P = 0.050) on postoperative day 5 in the treatment group were much lower than those in the control group. CONCLUSIONS: Parenteral n-3 polyunsaturated fatty acids supplementation promotes postoperative recovery in patients with Crohn's disease following bowel resection, with fewer complications and reduced inflammatory cytokines. This trial was registered at clinicaltrials.gov as NCT03901937 at https://classic. CLINICALTRIALS: gov/ct2/show/NCT03901937?term=NCT03901937&cond=Crohn+Disease&draw=2&rank=1.


Assuntos
Doença de Crohn , Ácidos Graxos Ômega-3 , Humanos , Doença de Crohn/tratamento farmacológico , Doença de Crohn/cirurgia , Estudos Prospectivos , Ácidos Graxos Ômega-3/uso terapêutico , Nutrição Parenteral , Citocinas , Interleucina-6 , Suplementos Nutricionais
2.
Small ; : e2400866, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38639306

RESUMO

The scarcity of Te hampers the widespread use of Bi2Te3-based thermoelectric modules. Here, the thermoelectric module potential of PbSe is investigated by improving its carrier mobility. Initially, large PbSe crystals are grown with the temperature gradient method to mitigate grain boundary effects on carrier transport. Subsequently, light doping with <1mole‰ halogens (Cl/Br/I) increases room-temperature carrier mobility to ~1600 cm2 V-1 s-1, achieved by reducing carrier concentration compared to traditional heavy doping. Crystal growth design and light doping enhance carrier mobility without affecting effective mass, resulting in a high power factor ~40 µW cm-1 K-2 in PbSe-Cl/Br/I crystals at 300 K. Additionally, Cl/Br/I doping reduces thermal conductivity and bipolar diffusion, leading to significantly lower thermal conductivity at high temperature. Enhanced carrier mobility and suppressed bipolar effect boost ZT values across the entire temperature range in n-type PbSe-Cl/Br/I crystals. Specifically, ZT values of PbSe-Br crystal reach ~0.6 at 300 K, ~1.2 at 773 K, and the average ZT (ZTave) reaches ~1.0 at 300-773 K. Ultimately, ~5.8% power generation efficiency in a PbSe single leg with a maximum temperature cooling difference of 40 K with 7-pair modules is achieved. These results indicate the potential for cost-effective and high-performance thermoelectric cooling modules based on PbSe.

3.
Front Pharmacol ; 15: 1371574, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38576492

RESUMO

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, resulting in a huge medical burden worldwide. Accumulating evidence suggests that the gut microbiome and bile acids play pivotal roles during the development of NAFLD. Patients with NAFLD exhibit unique signatures of the intestinal microbiome marked by the priority of Gram-negative bacteria, decreased ratio of Firmicutes/Bacteroidetes (F/B), and increased Prevotella and Lachnospiraceae. The intestinal microbiota is involved in the metabolism of bile acids. Ursodeoxycholic acid (UDCA) is a key determinant in maintaining the dynamic communication between the host and gut microbiota. It generally shows surprising therapeutic potential in NAFLD with several mechanisms, such as improving cellular autophagy, apoptosis, and mitochondrial functions. This action is based on its direct or indirect effect, targeting the farnesoid X receptor (FXR) and various other nuclear receptors. This review aims to discuss the current studies on the involvement of the microbiome-UDCA interface in NAFLD therapy and provide prospective insights into future preventative and therapeutic approaches for NAFLD.

4.
Sci Rep ; 14(1): 5700, 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38459121

RESUMO

In contemporary large wind farms, the combination of condition-based maintenance (CBM) and time-based maintenance (TBM) has become a prevalent approach in preventive maintenance, which is an indispensable part to ensure the safe, stable and environmental operation of equipment. However, the utilization of an inappropriate maintenance strategy may result in over-maintenance or under-maintenance, leading to unstable equipment operation. Furthermore, the majority of preventive maintenance involves replacement maintenance, which may have adverse effects on the performance of wind turbines with excessive maintenance time. Therefore, this paper takes the gearbox as a case study to introduce the incomplete maintenance parameters into the failure rate function to establish a state model based on the stochastic differential equation (SDE) and describing the state change of incomplete maintenance. And then simulating the state model of the gearbox and the joint preventive maintenance strategy of TBM and CBM through examples, resulting the time-based incomplete maintenance (TBIM) is proposed based on the TBM and the incomplete maintenance, and a new joint preventive maintenance strategy incorporating TBIM and CBM is proposed. Through developing the decision-making process of the maintenance strategy to optimize the inappropriate maintenance which including over-maintenance and under-maintenance and simulating the optimized preventive maintenance strategy to compare with that of TBM and CBM and verify the superiority and effectiveness of the proposed maintenance method.

5.
Biomedicines ; 12(3)2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38540274

RESUMO

The emergence of castration-resistant prostate cancer (CRPC) following androgen deprivation therapy (ADT) is associated with increased malignancy and limited treatment options. This study aims to investigate potential connections between immune cell infiltration and inflammatory cytokines with the YAP1/AR/PSA axis by exploring their interactions with autophagy. Our research reveals heightened levels of Yes-associated protein 1 (YAP1) expression in CRPC tissues compared with tissues from androgen-dependent prostate cancer (ADPC) and benign prostate hyperplasia (BPH). Additionally, a correlation was observed between YAP1 and PSA expressions in CRPC tissues, suggesting that YAP1 may exert a regulatory influence on PSA expression within CRPC. Enhanced YAP1 expression in C4-2 cells resulted in the upregulation of androgen receptor (AR) nuclear translocation and intracellular prostate-specific antigen (PSA) levels. Conversely, the suppression of YAP1 led to a decrease in PSA expression, suggesting that YAP1 may positively regulate the PSA in castration-resistant prostate cancer (CRPC) by facilitating AR nuclear import. The modulation of the autophagy activity exerts a significant impact on the expression levels of YAP1, the AR, and the PSA. Moreover, recent advancements in immunity and inflammation studies present promising avenues for potential therapies targeting prostate cancer (PC).

6.
Nutr Rev ; 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38553410

RESUMO

Context: Research regarding the treatment of inflammatory bowel disease (IBD) with probiotics has not yielded consistent results. OBJECTIVE: The aim of this meta-analysis was to evaluate the efficacy of probiotics supplementation in patients with IBD. DATA SOURCES: Randomized controlled trials (RCTs) evaluating the efficacy of probiotics in patients with IBD were searched in PubMed, the Google Scholar database, Web of Science, and CrossRef for the period July 2003 to June 2023. DATA EXTRACTION: The RCTs were extracted, independently by 2 authors, according to the PICOS criteria. DATA ANALYSIS: Seven studies, including a total of 795 patients, met the study criteria. Five end points were selected to evaluate the efficacy. Of these, 3 indicators showed a statistically significant difference in efficacy: C-reactive protein (odds ratio [OR]: -2.45, 95% confidence interval [CI]: -3.16, -1.73, P < .01), the number of fecal Bifidobacterium (OR: 3.37, 95% CI: 3.28, 3.47, P < .01), and Lactobacillus(OR: 2.00, 95% CI: 1.91, 2.09, P < .01). The other 2 indicators (disease activity for Crohn's disease and for ulcerative colitis) showed no statistically significant difference, while the OR reflected a positive correlation. CONCLUSION: Probiotics supplementation may have a positive effect on IBD by reducing clinical symptoms, reducing the serological inflammatory markers, and increasing favorable gut flora in patients with IBD. Additional RCTs are needed to evaluate the therapeutic effect of probiotics in IBD.

7.
J Innate Immun ; 16(1): 188-202, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38442696

RESUMO

BACKGROUND: Although substantial efforts have been made by researchers to develop drugs, a disappointing reality is that the emergence of drug resistance is an unavoidable reality for the majority of patients. In recent years, emerging evidence suggests a connection between drug resistance and immune dysregulation. SUMMARY: As a ubiquitously distributed, versatile innate immune cell, macrophages play essential roles in maintaining tissue homeostasis in a steady state. Nevertheless, it is becoming aware that macrophages undermine the action of therapeutic drugs across various disease types. Reprogramming macrophage function has been proven to be effective in restoring patient responsiveness to treatment. Herein, we comprehensively reviewed how macrophages respond to drugs and the mechanisms by which they contribute to treatment unresponsiveness in cancer, inflammatory diseases, and metabolic diseases. In addition, future prospects in macrophage-based combination therapy were discussed. KEY MESSAGES: Targeting macrophages is a promising strategy for overcoming drug resistance in immune disorders.


Assuntos
Imunidade Inata , Macrófagos , Humanos , Macrófagos/imunologia , Animais , Neoplasias/imunologia , Neoplasias/terapia , Neoplasias/tratamento farmacológico , Resistência a Medicamentos , Inflamação/imunologia , Homeostase
8.
Clin Respir J ; 18(3): e13741, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38450981

RESUMO

Histiocytic sarcoma is an aggressive haematopoietic malignancy accounting for less than 1% of haematolymphoid neoplasms with a diagnosis based on morphology and immunophenotype of tissue biopsies with a very poor prognosis. Here, we report a 45-year-old man who was diagnosed with primary pulmonary histiocytic sarcoma with systemic metastases, with partial remission (PR) treated with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) chemotherapy, but it relapsed soon after therapy above. Tests demonstrated that TMB was 21 Muts/Mb PD-L1 expression was 90% positive, and the disease has been well-controlled over 3 years using immune checkpoint inhibitors (nivolumab and pembrolizumab). Bioinformatic pan-cancer analysis verified that there was the highest genetic alteration frequency of PD-L1 in which amplification accounted for the majority of sarcoma tumour samples. Following that, we found that the genetic alteration of PD-L1 was associated with poor prognosis in sarcoma patients in terms of overall survival (OS) (p = 1.51 × 10-4 ), progress-free survival (PFS) (p = 4.90 × 10-2 ) and disease-specific survival (DSS) (p = 4.90 × 10-2 ). To our knowledge, this may be the first reported case with high PD-L1 expression in primary pulmonary histiocytic sarcoma who may benefit from immunotherapy such as nivolumab and pembrolizumab significantly and safely.


Assuntos
Sarcoma Histiocítico , Neoplasias Pulmonares , Sarcoma , Masculino , Humanos , Pessoa de Meia-Idade , Sarcoma Histiocítico/tratamento farmacológico , Sarcoma Histiocítico/genética , Antígeno B7-H1/genética , Nivolumabe/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Imunoterapia , Biologia Computacional
9.
J Am Chem Soc ; 146(12): 8727-8736, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38487899

RESUMO

The practical application of thermoelectric devices requires both high-performance n-type and p-type materials of the same system to avoid possible mismatches and improve device reliability. Currently, environmentally friendly SnTe thermoelectrics have witnessed extensive efforts to develop promising p-type transport, making it rather urgent to investigate the n-type counterparts with comparable performance. Herein, we develop a stepwise optimization strategy for improving the transport properties of n-type SnTe. First, we improve the n-type dopability of SnTe by PbSe alloying to narrow the band gap and obtain n-type transport in SnTe with halogen doping over the whole temperature range. Then, we introduce additional Pb atoms to compensate for the cationic vacancies in the SnTe-PbSe matrix, further enhancing the electron carrier concentration and electrical performance. Resultantly, the high-ranged thermoelectric performance of n-type SnTe is substantially optimized, achieving a peak ZT of ∼0.75 at 573 K with a high average ZT (ZTave) exceeding 0.5 from 300 to 823 K in the (SnTe0.98I0.02)0.6(Pb1.06Se)0.4 sample. Moreover, based on the performance optimization on n-type SnTe, for the first time, we fabricate an all-SnTe-based seven-pair thermoelectric device. This device can produce a maximum output power of ∼0.2 W and a conversion efficiency of ∼2.7% under a temperature difference of 350 K, demonstrating an important breakthrough for all-SnTe-based thermoelectric devices. Our research further illustrates the effectiveness and application potential of the environmentally friendly SnTe thermoelectrics for mid-temperature power generation.

10.
Int Immunopharmacol ; 130: 111742, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38452414

RESUMO

BACKGROUND: Cerebral ischemia/reperfusion injury (IRI) is pathologically associated with protein damage. The flavonoid fisetin has good therapeutic effects on cerebral IRI. However, the role of fisetin in regulating protein damage during cerebral IRI development remains unclear. This study investigated the pharmacological effects of fisetin on protein damage during cerebral IRI progression and defined the underlying mechanism of action. METHODS: In vivo and in vitro models of cerebral IRI were established by middle cerebral artery occlusion/reperfusion (MACO/R) and oxygen-glucose deprivation/reperfusion (OGD/R) treatment, respectively. Triphenyl tetrazolium chloride staining was performed to detect cerebral infarct size, and the modified neurologic severity score was used to examine neurological deficits. LDH activity and protein damage were assessed using kits. HT22 cell vitality and apoptosis were examined using CCK-8 assay and TUNEL staining, respectively. Interactions between Foxc1, Ubqln1, Sirt1, and Ezh2 were analyzed using CoIP, ChIP and/or dual-luciferase reporter gene assays. RESULTS: Fisetin alleviated protein damage and ubiquitinated protein aggregation and neuronal death caused by MCAO/R and OGD/R. Ubqln1 knockdown abrogated the inhibitory effect of fisetin on OGD/R-induced protein damage, ubiquitinated protein aggregation, and neuronal death in HT22 cells. Further experiments demonstrated that Foxc1 functions as a transcriptional activator of Ubqln1 and that Sirt1 promotes Foxc1 expression by deacetylating Ezh2 and inhibiting its activity. Furthermore, Sirt1 knockdown abrogated fisetin-mediated biological effects on OGD/R-treated HT22 cells. CONCLUSION: Fisetin improved proteostasis during cerebral IRI by regulating the Sirt1/Foxc1/Ubqln1 signaling axis. Our findings strongly suggest that fisetin-mediated inhibition of protein damage after ischemic stroke is a part of the mechanism through which fisetin is neuroprotective in cerebral IRI.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal , Proteínas Relacionadas à Autofagia , Isquemia Encefálica , Flavonóis , Fatores de Transcrição Forkhead , Proteostase , Traumatismo por Reperfusão , Sirtuína 1 , Apoptose , Isquemia Encefálica/tratamento farmacológico , Flavonóis/farmacologia , Flavonóis/uso terapêutico , Infarto da Artéria Cerebral Média/tratamento farmacológico , Agregados Proteicos , Proteostase/efeitos dos fármacos , Traumatismo por Reperfusão/tratamento farmacológico , Sirtuína 1/metabolismo , Masculino , Animais , Camundongos , Camundongos Endogâmicos C57BL , Fatores de Transcrição Forkhead/metabolismo , Proteínas Relacionadas à Autofagia/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismo
11.
Adv Mater ; : e2401828, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38466123

RESUMO

Thermoelectrics has applications in power generation and refrigeration. Since only commercial Bi2 Te3 has a low abundance Te, PbSe gets attention. This work enhances the near-room temperature performance of p-type PbSe through enhancing carrier mobility via lattice plainification. Composition controlled and Cu-doped p-type PbSe crystals are grown through physical vapor deposition. Results exhibit an enhanced carrier mobility ≈2578 cm2  V-1  s-1 for Pb0.996 Cu0.0004 Se. Microstructure characterization and density functional theory calculations verify the introduced Cu atoms filled Pb vacancies, realizing lattice plainification and enhancing the carrier mobility. The Pb0.996 Cu0.0004 Se sample achieves a power factor ≈42 µW cm-1  K-2 and a ZT ≈ 0.7 at 300 K. The average ZT of it reaches ≈0.9 (300-573 K), resulting in a single-leg power generation efficiency of 7.1% at temperature difference of 270 K, comparable to that of p-type commercial Bi2 Te3 . A 7-pairs device paired the p-type Pb0.996 Cu0.0004 Se with the n-type commercial Bi2 Te3 shows a maximum cooling temperature difference ≈42 K with the hot side at 300 K, ≈65% of that of the commercial Bi2 Te3 device. This work highlights the potential of p-type PbSe for power generation and refrigeration near room temperature and hope to inspire researchers on replacing commercial Bi2 Te3 .

12.
Clin. transl. oncol. (Print) ; 26(3): 756-764, mar. 2024.
Artigo em Inglês | IBECS | ID: ibc-230805

RESUMO

There are controversial about the application of cancer-directed surgery (CDS) in patients with liver metastases from gastric cancer, with improved responses to chemotherapy and targeted treatments, the role of CDS in metastatic gastric cancer to the liver needs to be revisited. This study aimed to evaluate the effect of CDS on patients with liver metastases from gastric cancer. Data for patients with liver metastases from gastric cancer were extracted from the population-based Surveillance, Epidemiology, and End Results (SEER) database. A total of 958 individuals were enrolled, 285 in the CDS group and 673 in the non-cancer guided surgery (Non-CDS) group. Following propensity score matching (PSM) analysis at 1:1 in the two groups,285 were included in the survival analysis for each group. Kaplan–Meier values and Cox proportional risk models were used to estimate the effect of CDS on patients' prognoses. Compared with the Non-CDS group, the CDS group significantly prolonged the median overall survival from 4 months (95% confidence interval [CI] 3–5) to 11 months (95% CI 8–12), p value < 0.001. Overall survival (OS) at 1 year was higher in the CDS group than in the Non-CDS group, at 44% (95 CI 38–50) and 25% (95 CI 20–30), respectively. OS at 3 years was also higher in the CDS group than in the Non-CDS group, at 24% (95 CI 19–29) and 6% (95 CI 3–9), respectively. Multivariate analysis showed that Non-CDS (hazard ratio[HR] = 2.26, 95% CI 1.88–2.72, p value < 0.001) was an adverse independent prognostic factor for patients (AU)


Assuntos
Humanos , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Estudos Retrospectivos , Estudos Prospectivos , Qualidade de Vida , Prognóstico
13.
Pharmacol Res ; : 107162, 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38554788

RESUMO

In American men, the incidence of prostate cancer (PC) is the highest among all types of cancer, making it the second leading cause of mortality associated with cancer. For advanced or metastatic PC, antiandrogen therapies are standard treatment options. The administration of these treatments unfortunately carries the potential risk of inducing neuroendocrine prostate cancer (NEPC). Neuroendocrine differentiation (NED) serves as a crucial indicator of prostate cancer development, encompassing various factors such as phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR), Yes-associated protein 1 (YAP1), AMP-activated protein kinase (AMPK), miRNA. The processes of autophagy and ferroptosis (an iron-dependent form of programmed cell death) play pivotal roles in the regulation of various types of cancers. Clinical trials and preclinical investigations have been conducted on many signaling pathways during the development of NEPC, with the deepening of research, autophagy and ferroptosis appear to be the potential target for regulating NEPC. Due to the dual nature of autophagy and ferroptosis in cancer, gaining a deeper understanding of the developmental programs associated with achieving autophagy and ferroptosis may enhance risk stratification and treatment efficacy for patients with NEPC.

14.
Biomed Pharmacother ; 173: 116354, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38442673

RESUMO

Angiogenesis is the growth of new blood vessels on preexisting ones. It is the outcome of a multifactorial effect involving several cells, which can be brought on by different stress reactions.The accumulation of unfolded proteins in the endoplasmic reticulum occurs when cells are stressed due to environmental changes, where physical or chemical stimuli induce endoplasmic reticulum stress, thereby activating the unfolded protein response (UPR), a homeostasis response designed to re-establish protein balance. Ferroptosis is a planned death of lipid peroxidation and anomalies in metabolism that is dependent on iron. Large concentrations of iron ions accumulate there, along with high concentrations of lipid peroxides and reactive oxygen species, all of which can contribute to the development of several diseases. Through the production of growth factors, adhesion factors, and inflammatory factors that trigger the start of angiogenesis, both UPR and Ferroptosis can be implicated in angiogenesis.To set the stage for further research on angiogenesis, this work concentrated on the effects of Ferroptosis and UPR on angiogenesis, respectively.


Assuntos
Ferroptose , 60489 , Resposta a Proteínas não Dobradas , Estresse do Retículo Endoplasmático/fisiologia , Ferro
15.
Exp Ther Med ; 27(3): 108, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38356664

RESUMO

[This retracts the article DOI: 10.3892/etm.2014.2135.].

16.
Proc Natl Acad Sci U S A ; 121(7): e2313002121, 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38319965

RESUMO

It is known that pre-mRNAs in eukaryotic cells can be processed to circular RNAs by a backsplicing mechanism. Circular RNAs have great stability and can sequester proteins or small RNAs to exert functions on cellular pathways. Because viruses often exploit host pathways, we explored whether the RNA genome of the cytoplasmic hepatitis C virus is processed to yield virus-derived circRNAs (vcircRNAs). Computational analyses of RNA-seq experiments predicted that the viral RNA genome is fragmented to generate hundreds of vcircRNAs. More than a dozen of them were experimentally verified by rolling-circle amplification. VcircRNAs that contained the viral internal ribosome entry site were found to be translated into proteins that displayed proviral functions. Furthermore, two highly abundant, nontranslated vcircRNAs were shown to enhance viral RNA abundance. These findings argue that novel vcircRNA molecules modulate viral amplification in cells infected by a cytoplasmic RNA virus.


Assuntos
Hepatite C , RNA Circular , Humanos , Hepacivirus/genética , RNA Viral/genética , Provírus/genética
17.
Mol Biol Rep ; 51(1): 365, 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38409611

RESUMO

A low-frequency variant of sushi, von Willebrand factor type A, EGF, and pentraxin domain-containing protein 1 (SVEP1) is associated with the risk of coronary artery disease, as determined by a genome-wide association study. SVEP1 induces vascular smooth muscle cell proliferation and an inflammatory phenotype to promote atherosclerosis. In the present study, qRT‒PCR demonstrated that the mRNA expression of SVEP1 was significantly increased in atherosclerotic plaques compared to normal tissues. Bioinformatics revealed that EGR1 was a transcription factor for SVEP1. The results of the luciferase reporter assay, siRNA interference or overexpression assay, mutational analysis and ChIP confirmed that EGR1 positively regulated the transcriptional activity of SVEP1 by directly binding to its promoter. EGR1 promoted human coronary artery smooth muscle cell (HCASMC) proliferation and migration via SVEP1 in response to oxidized low-density lipoprotein (ox-LDL) treatment. Moreover, the expression level of EGR1 was increased in atherosclerotic plaques and showed a strong linear correlation with the expression of SVEP1. Our findings indicated that EGR1 binding to the promoter region drive SVEP1 transcription to promote HCASMC proliferation and migration.


Assuntos
MicroRNAs , Placa Aterosclerótica , Humanos , Placa Aterosclerótica/metabolismo , Vasos Coronários/metabolismo , Estudo de Associação Genômica Ampla , Movimento Celular , Lipoproteínas LDL/farmacologia , Células Cultivadas , Proliferação de Células/genética , Miócitos de Músculo Liso/metabolismo , MicroRNAs/genética , Proteína 1 de Resposta de Crescimento Precoce/genética , Proteína 1 de Resposta de Crescimento Precoce/metabolismo , Moléculas de Adesão Celular/genética
18.
J Dig Dis ; 25(1): 27-35, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38342693

RESUMO

OBJECTIVE: To investigate the clinical potential and safety of Moluodan to reverse gastric precancerous lesions. METHODS: Patients aged 18-70 years diagnosed with moderate-to-severe atrophy and/or moderate-to-severe intestinal metaplasia, with or without low-grade dysplasia, and negative for Helicobacter pylori were recruited in this randomized, double-blind, parallel-controlled trial. The primary outcome was the improvement of global histological diagnosis at 1-year follow-up endoscopy using the operative link for gastritis assessment, the operative link for gastric intestinal metaplasia assessment, and the disappearance rate of dysplasia. RESULTS: Between November 3, 2017 and January 27, 2021, 166 subjects were randomly assigned to the Moluodan group, 168 to the folic acid group, 84 to the combination group, and 84 to the high-dose Moluodan group. The improvement in global histological diagnosis was achieved in 60 (39.5%) subjects receiving Moluodan, 59 (37.8%) receiving folic acid, 26 (32.1%) receiving the combined drugs, and 36 (47.4%) receiving high-dose Moluodan. Moluodan was non-inferior to folic acid (95% confidence interval: -9.2 to 12.5; P = 0.02). High-dose Moluodan had a trend for better protective efficacy, though there was no statistical significance. The disappearance rate of dysplasia was 82.8% in the Moluodan group, which was superior to folic acid (53.9%; P = 0.006). No drug-related serious adverse events were observed. CONCLUSIONS: One pack of Moluodan three times daily for 1 year was safe and effective in reversing gastric precancerous lesions, especially dysplasia. Doubling its dose showed a better efficacy trend.


Assuntos
Medicamentos de Ervas Chinesas , Gastrite Atrófica , Infecções por Helicobacter , Helicobacter pylori , Lesões Pré-Cancerosas , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Gastrite Atrófica/tratamento farmacológico , Gastrite Atrófica/patologia , Infecções por Helicobacter/complicações , Infecções por Helicobacter/tratamento farmacológico , Lesões Pré-Cancerosas/tratamento farmacológico , Lesões Pré-Cancerosas/patologia , Metaplasia , Ácido Fólico/uso terapêutico , Mucosa Gástrica/patologia
19.
Talanta ; 271: 125739, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38309115

RESUMO

Fluorescent sensors have been widely applied for biosensing, but probes for both multiple analytes sensing and photodynamic therapy (PDT) effect are less reported. In this article, we reported three AIE-based probes anchored with different mass-weight polyethylene glycol (PEG) tails, i.e., TPE-PEG160, TPE-PEG350, and TPE-PEG750, for both adenosine-5'-triphosphate (ATP) and hydrogen sulfide (H2S) detection and also cancer cells photodynamic therapy. TPE-PEGns (n = 160, 350 and 750) contain the tetraphenylethylene-based fluorophore core, the pyridinium and amide anion binding sites, the H2S cleavable disulfide bond, and the hydrophilic PEG chain. They exhibit a good amphiphilic property and can self-assemble nona-aggregation with a moderated red emission in an aqueous solution. Importantly, the size of aggregation, photophysical property, sensing ability and photosensitivity of these amphiphilic probes can be controlled by tuning the PEG chain length. Moreover, the selected probe TPE-PEG160 has been successfully used to detect environmental H2S and image ATP levels in living cells, and TPE-PEG750 has been used for photodynamic therapy of tumor cells under light irradiation.


Assuntos
Neoplasias , Fotoquimioterapia , Humanos , Amidas , Polietilenoglicóis , Células HeLa , Neoplasias/tratamento farmacológico
20.
Sci Rep ; 14(1): 2390, 2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38287024

RESUMO

The components of wind turbines are complex in structure and the working environment is harsh, which makes wind turbines face problems such as high failure rates and high maintenance costs. In this paper, the stochastic differential equation model has been established for the harsh operating environment of wind turbines, and used Brownian motion to simulate random disturbances; aiming at the problem of high failure rate of wind turbines, based on Weibull distribution, a new model has been established by combining operating time and equipment state to calculate the failure rate; in the analysis of monitoring data, the Higher-Order Moment method and Bayesian method were used to solve the parameters. The opportunity maintenance threshold curve and preventive maintenance threshold curve were obtained by analyzing Time-Based Maintenance and Condition-Based Maintenance. Therefore, the Condition-Based Opportunistic Maintenance strategy was obtained. The effectiveness of the proposed method was finally verified by arithmetic examples.

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