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1.
Artículo en Inglés | MEDLINE | ID: mdl-38593387

RESUMEN

Upcycling plastic waste into valuable commodity chemicals with clean energy is an appealing strategy for mitigating environmental issues. Polylactic acid (PLA), a biodegradable plastic that is produced annually in millions of tons, can be chemically recycled to valuable products instead of being degraded to carbon dioxide. Here, we demonstrate an electrochemical reforming of PLA hydrolysate to acetate and acetonate using nickel phosphide nanosheets on nickel foam (Ni2P/NF) as the catalyst. The Ni2P/NF catalyst was synthesized by electrochemical deposition and phosphide treatment and showed excellent catalytic activity and ∼100% Faraday efficiency for electroreforming PLA to acetate and acetonate in an H-cell. Moreover, a stable performance of more than 90% Faraday efficiency for value-added organics was achieved for a duration of 100 h in a flow cell at a current density of 100 mA cm-2 and a potential below 1.5 V vs. RHE. In situ characterization revealed that the catalyst underwent electrochemical reforming during the reaction to produce γ-phase NiOOH with high electrochemical activity. This work introduces a new and green solution for the treatment of waste PLA, presenting a low-cost and highly efficient strategy for electrically reforming plastics.

2.
J Med Chem ; 67(7): 5617-5641, 2024 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-38563549

RESUMEN

NIK plays a crucial role in the noncanonical NF-κB signaling pathway associated with diverse inflammatory and autoimmune diseases. Our study presents compound 54, a novel NIK inhibitor, designed through a structure-based scaffold-hopping approach from the previously identified B022. Compound 54 demonstrates remarkable selectivity and potency against NIK both in vitro and in vivo, effectively suppressing pro-inflammatory cytokines and nitric oxide production. In mouse models, compound 54 protected against LPS-induced systemic sepsis, reducing AST, ALT, and AKP liver injury markers. Additionally, it also attenuates sepsis-induced lung and kidney damage. Mechanistically, compound 54 blocks the noncanonical NF-κB signaling pathway by targeting NIK, preventing p100 to p52 processing. This work reveals a novel class of NIK inhibitors with significant potential for sepsis therapy.


Asunto(s)
Proteínas Serina-Treonina Quinasas , Sepsis , Animales , Ratones , Proteínas Serina-Treonina Quinasas/metabolismo , FN-kappa B/metabolismo , Quinasa de Factor Nuclear kappa B , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Sepsis/inducido químicamente , Sepsis/tratamiento farmacológico
3.
Nat Commun ; 15(1): 2083, 2024 Mar 07.
Artículo en Inglés | MEDLINE | ID: mdl-38453952

RESUMEN

Purinergic signaling plays a causal role in the pathogenesis of inflammatory bowel disease. Among purinoceptors, only P2Y14R is positively correlated with inflammatory score in mucosal biopsies of ulcerative colitis patients, nevertheless, the role of P2Y14R in ulcerative colitis remains unclear. Here, based on the over-expressions of P2Y14R in the intestinal epithelium of mice with experimental colitis, we find that male mice lacking P2Y14R in intestinal epithelial cells exhibit less intestinal injury induced by dextran sulfate sodium. Mechanistically, P2Y14R deletion limits the transcriptional activity of cAMP-response element binding protein through cAMP/PKA axis, which binds to the promoter of Ripk1, inhibiting necroptosis of intestinal epithelial cells. Furthermore, we design a hierarchical strategy combining virtual screening and chemical optimization to develop a P2Y14R antagonist HDL-16, which exhibits remarkable anti-colitis effects. Summarily, our study elucidates a previously unknown mechanism whereby P2Y14R participates in ulcerative colitis, providing a promising therapeutic target for inflammatory bowel disease.


Asunto(s)
Colitis Ulcerosa , Colitis , Enfermedades Inflamatorias del Intestino , Humanos , Masculino , Animales , Ratones , Colitis Ulcerosa/patología , Necroptosis , Colitis/patología , Células Epiteliales/metabolismo , Enfermedades Inflamatorias del Intestino/patología , Mucosa Intestinal/metabolismo , Sulfato de Dextran/toxicidad , Ratones Endogámicos C57BL , Modelos Animales de Enfermedad , Colon/patología , Proteína Serina-Treonina Quinasas de Interacción con Receptores/metabolismo
4.
Int J Mol Sci ; 25(5)2024 Mar 04.
Artículo en Inglés | MEDLINE | ID: mdl-38474218

RESUMEN

SMXL genes constitute a conserved gene family that is ubiquitous in angiosperms and involved in regulating various plant processes, including branching, leaf elongation, and anthocyanin biosynthesis, but little is known about their molecular functions in pear branching. Here, we performed genome-wide identification and investigation of the SMXL genes in 16 angiosperms and analyzed their phylogenetics, structural features, conserved motifs, and expression patterns. In total, 121 SMXLs genes were identified and were classified into four groups. The number of non-redundant SMXL genes in each species varied from 3 (Amborella trichopoda Baill.) to 18 (Glycine max Merr.) and revealed clear gene expansion events over evolutionary history. All the SMXL genes showed conserved structures, containing no more than two introns. Three-dimensional protein structure prediction revealed distinct structures between but similar structures within groups. A quantitative real-time PCR analysis revealed different expressions of 10 SMXL genes from pear branching induced by fruit-thinning treatment. Overall, our study provides a comprehensive investigation of SMXL genes in the Rosaceae family, especially pear. The results offer a reference for understanding the evolutionary history of SMXL genes and provide excellent candidates for studying fruit tree branching regulation, and in facilitating pear pruning and planting strategies.


Asunto(s)
Pyrus , Rosaceae , Rosaceae/genética , Pyrus/genética , Familia de Multigenes , Filogenia , Intrones , Regulación de la Expresión Génica de las Plantas , Proteínas de Plantas/genética , Genoma de Planta , Evolución Molecular
5.
Molecules ; 29(6)2024 Mar 11.
Artículo en Inglés | MEDLINE | ID: mdl-38542877

RESUMEN

Disordered gut microbiota (GM) structure and function may contribute to osteoporosis (OP). Nodakenin has been shown to ameliorate osteoporosis; however, its anti-osteoporotic mechanism is unknown. This study aimed to further reveal the mechanism of the anti-osteoporotic action of nodakenin from the perspective of the microbiome and metabolome. An osteoporosis model was induced in mice through ovariectomy (OVX), with bone mass and microstructure assessed using µCT. Subsequently, ELISA and histologic examination were used to detect biochemical indicators of bone conversion and intestinal morphology. Using metabolomics and 16S rRNA sequencing, it was possible to determine the composition and abundance of the gut microbiota in feces. The results revealed that nodakenin treatment improved the bone microstructure and serum levels of bone turnover markers, and increased the intestinal mucosal integrity. 16S rRNA sequencing analysis revealed that nodakenin treatment decreased the relative abundance of Firmicutes and Patescibacteria, as well as the F/B ratio, and elevated the relative abundance of Bacteroidetes in OVX mice. In addition, nodakenin enhanced the relative abundance of Muribaculaceae and Allobaculum, among others, at the genus level. Moreover, metabolomics analysis revealed that nodakenin treatment significantly altered the changes in 113 metabolites, including calcitriol. A correlation analysis revealed substantial associations between various gut microbiota taxa and both the osteoporosis phenotype and metabolites. In summary, nodakenin treatment alleviated OVX-induced osteoporosis by modulating the gut microbiota and intestinal barrier.


Asunto(s)
Cumarinas , Microbioma Gastrointestinal , Glucósidos , Osteoporosis , Femenino , Ratones , Animales , Humanos , ARN Ribosómico 16S/genética , Microbioma Gastrointestinal/genética , Osteoporosis/tratamiento farmacológico , Osteoporosis/etiología , Ovariectomía/efectos adversos
6.
Med Sci Monit ; 30: e944661, 2024 Mar 29.
Artículo en Inglés | MEDLINE | ID: mdl-38551037

RESUMEN

The Editors of Medical Science Monitor wish to inform you that the above manuscript has been retracted from publication due to concerns with the credibility and originality of the study, the manuscript content, and the Figure images. Reference: Tian-Wei Zhang, Li Xing, Jun-Long Tang, Jing-Xiao Lu, Chun-Xiao Liu. Marchantin M Induces Apoptosis of Prostate Cancer Cells Through Endoplasmic Reticulum Stress. Med Sci Monit, 2015; 21: 3570-3576. DOI: 10.12659/MSM.894476.

7.
J Med Econ ; 27(1): 361-369, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38375556

RESUMEN

AIM: This study assessed the treatment patterns, healthcare resource utilization (HRU), costs, and annual prevalence and incidence of metastatic hormone-sensitive prostate cancer (mHSPC) and nonmetastatic castration-resistant prostate cancer (nmCRPC) in China. METHODS: A retrospective study was conducted using electronic medical records (EMR) of patients with prostate cancer from three tertiary-care hospitals in China between January 2014 and March 2021. Descriptive statistics were used to analyze study outcomes. RESULTS: In total, 1086 patients with mHSPC and 679 patients with nmCRPC were included. From 2015 to 2020, the annual percentage of prevalent and incident cases of mHSPC decreased from 22.4% to 20.0% and 11.1% to 6.9%, respectively; for nmCRPC, these increased from 3.8% to 13.6% and 3.3% to 8.4%. Androgen-deprivation therapy and first-generation antiandrogens (bicalutamide or flutamide) were the most frequently prescribed prostate cancer-related medications at baseline and follow-up in patients with mHSPC. Bicalutamide was the most frequently prescribed prostate cancer-related medication during follow-up in patients with nmCRPC. For mHSPC, inpatient admission costs were the highest, with the median (interquartile range) costs per person-month being USD 403.00 (USD 85.50-1226.20), whereas outpatient visit costs were the highest for nmCRPC (USD 372.60 [USD 139.50-818.50]). LIMITATIONS: EMR-based study design did not capture treatment patterns, HRU and associated costs, and healthcare encounters that occurred outside of participating hospitals, which could have led to underestimation of the true disease burden. CONCLUSIONS: A contrasting trend of a decline in the prevalence and incidence of mHSPC and an increase in these for nmCRPC was observed between 2015 and 2020 in China. Androgen-deprivation therapy and first-generation antiandrogens were the most frequently prescribed prostate cancer-related medications. Healthcare resource utilization was driven by inpatient costs in mHSPC and outpatient costs in nmCRPC.


Asunto(s)
Antagonistas de Andrógenos , Anilidas , Nitrilos , Neoplasias de la Próstata Resistentes a la Castración , Compuestos de Tosilo , Masculino , Humanos , Antagonistas de Andrógenos/uso terapéutico , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/patología , Estudios Retrospectivos , Andrógenos/uso terapéutico , Atención a la Salud
8.
Nat Commun ; 15(1): 1009, 2024 Feb 02.
Artículo en Inglés | MEDLINE | ID: mdl-38307859

RESUMEN

Tumor-secreted factors contribute to the development of a microenvironment that facilitates the escape of cancer cells from immunotherapy. In this study, we conduct a retrospective comparison of the proteins secreted by hepatocellular carcinoma (HCC) cells in responders and non-responders among a cohort of ten patients who received Nivolumab (anti-PD-1 antibody). Our findings indicate that non-responders have a high abundance of secreted RNase1, which is associated with a poor prognosis in various cancer types. Furthermore, mice implanted with HCC cells that overexpress RNase1 exhibit immunosuppressive tumor microenvironments and diminished response to anti-PD-1 therapy. RNase1 induces the polarization of macrophages towards a tumor growth-promoting phenotype through activation of the anaplastic lymphoma kinase (ALK) signaling pathway. Targeting the RNase1/ALK axis reprograms the macrophage polarization, with increased CD8+ T- and Th1- cell recruitment. Moreover, simultaneous targeting of the checkpoint protein PD-1 unleashes cytotoxic CD8+ T-cell responses. Treatment utilizing both an ALK inhibitor and an anti-PD-1 antibody exhibits enhanced tumor regression and facilitates long-term immunity. Our study elucidates the role of RNase1 in mediating tumor resistance to immunotherapy and reveals an RNase1-mediated immunosuppressive tumor microenvironment, highlighting the potential of targeting RNase1 as a promising strategy for cancer immunotherapy in HCC.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Animales , Humanos , Ratones , Quinasa de Linfoma Anaplásico , Carcinoma Hepatocelular/metabolismo , Linfocitos T CD8-positivos , Terapia de Inmunosupresión , Neoplasias Hepáticas/metabolismo , Estudios Retrospectivos , Ribonucleasas , Microambiente Tumoral
9.
Mol Ther ; 32(4): 1144-1157, 2024 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-38310354

RESUMEN

The potent immunomodulatory function of mesenchymal stem/stromal cells (MSCs) elicited by proinflammatory cytokines IFN-γ and TNF-α (IT) is critical to resolve inflammation and promote tissue repair. However, little is known about how the immunomodulatory capability of MSCs is related to their differentiation competency in the inflammatory microenvironment. In this study, we demonstrate that the adipocyte differentiation and immunomodulatory function of human adipose tissue-derived MSCs (MSC(AD)s) are mutually exclusive. Mitochondrial reactive oxygen species (mtROS), which promote adipocyte differentiation, were decreased in MSC(AD)s due to IT-induced upregulation of superoxide dismutase 2 (SOD2). Furthermore, knockdown of SOD2 led to enhanced adipogenic differentiation but reduced immunosuppression capability of MSC(AD)s. Interestingly, the adipogenic differentiation was associated with increased mitochondrial biogenesis and upregulation of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PPARGC1A/PGC-1α) expression. IT inhibited PGC-1α expression and decreased mitochondrial mass but promoted glycolysis in an SOD2-dependent manner. MSC(AD)s lacking SOD2 were compromised in their therapeutic efficacy in DSS-induced colitis in mice. Taken together, these findings indicate that the adipogenic differentiation and immunomodulation of MSC(AD)s may compete for resources in fulfilling the respective biosynthetic needs. Blocking of adipogenic differentiation by mitochondrial antioxidant may represent a novel strategy to enhance the immunosuppressive activity of MSCs in the inflammatory microenvironment.


Asunto(s)
Células Madre Mesenquimatosas , Superóxido Dismutasa , Ratones , Humanos , Animales , Diferenciación Celular , Superóxido Dismutasa/genética , Superóxido Dismutasa/metabolismo , Adipocitos , Células Madre Mesenquimatosas/metabolismo
10.
Eur Heart J ; 45(4): 268-283, 2024 Jan 27.
Artículo en Inglés | MEDLINE | ID: mdl-38036416

RESUMEN

BACKGROUND AND AIMS: Macrophage-derived foam cells play a causal role during the pathogenesis of atherosclerosis. P2Y6 receptor (P2Y6R) highly expressed has been considered as a disease-causing factor in atherogenesis, but the detailed mechanism remains unknown. This study aims to explore P2Y6R in regulation of macrophage foaming, atherogenesis, and its downstream pathways. Furthermore, the present study sought to find a potent P2Y6R antagonist and investigate the feasibility of P2Y6R-targeting therapy for atherosclerosis. METHODS: The P2Y6R expression was examined in human atherosclerotic plaques and mouse artery. Atherosclerosis animal models were established in whole-body P2Y6R or macrophage-specific P2Y6R knockout mice to evaluate the role of P2Y6R. RNA sequencing, DNA pull-down experiments, and proteomic approaches were performed to investigate the downstream mechanisms. High-throughput Glide docking pipeline from repurposing drug library was performed to find potent P2Y6R antagonists. RESULTS: The P2Y6R deficiency alleviated atherogenesis characterized by decreasing plaque formation and lipid deposition of the aorta. Mechanically, deletion of macrophage P2Y6R significantly inhibited uptake of oxidized low-density lipoprotein through decreasing scavenger receptor A expression mediated by phospholipase Cß/store-operated calcium entry pathways. More importantly, P2Y6R deficiency reduced the binding of scavenger receptor A to CALR, accompanied by dissociation of calreticulin and STIM1. Interestingly, thiamine pyrophosphate was found as a potent P2Y6R antagonist with excellent P2Y6R antagonistic activity and binding affinity, of which the pharmacodynamic effect and mechanism on atherosclerosis were verified. CONCLUSIONS: Macrophage P2Y6R regulates phospholipase Cß/store-operated calcium entry/calreticulin signalling pathway to increase scavenger receptor A protein level, thereby improving foam cell formation and atherosclerosis, indicating that the P2Y6R may be a potential therapeutic target for intervention of atherosclerotic diseases using P2Y6R antagonists including thiamine pyrophosphate.


Asunto(s)
Aterosclerosis , Células Espumosas , Receptores Purinérgicos P2 , Humanos , Ratones , Animales , Células Espumosas/metabolismo , Células Espumosas/patología , Calcio/metabolismo , Calreticulina/metabolismo , Calreticulina/farmacología , Proteómica , Tiamina Pirofosfato/metabolismo , Tiamina Pirofosfato/farmacología , Aterosclerosis/genética , Macrófagos/metabolismo , Lipoproteínas LDL/metabolismo , Receptores Depuradores/metabolismo , Ratones Noqueados , Fosfolipasas/metabolismo , Fosfolipasas/farmacología
11.
BMC Anesthesiol ; 23(1): 418, 2023 12 19.
Artículo en Inglés | MEDLINE | ID: mdl-38114893

RESUMEN

BACKGROUND: Bicarbonate Ringer's (BR) solution is a direct liver and kidney metabolism-independent HCO3- buffering system. We hypothesized that BR solution would be more effective in improving acid-base equilibrium and more conducive to better liver function than Acetate Ringer's (AR) solution in conventional orthotopic liver transplantation (OLT) patients. METHODS: Sixty-nine adult patients underwent OLT. Patients in the bicarbonate and acetate groups received BR solution or AR solution as infused crystalloids and graft washing solution, respectively. The primary outcome was the effect on pH and base excess (BE) levels. The secondary outcome measures were the incidence and volume of intraoperative 5% sodium bicarbonate infusion and laboratory indicates of liver and kidney function. RESULTS: The pH and absolute BE values changed significantly during the anhepatic phase and immediately after transplanted liver reperfusion in the bicarbonate group compared with the acetate group (all P < 0.05). The incidence and volume of 5% sodium bicarbonate infusion were lower in the bicarbonate group than in the acetate group (all P < 0.05). The aspartate transaminase (AST) level at 7 postoperative days and the creatine level at 30 postoperative days were significantly higher in the acetate group than in the bicarbonate group (all P < 0.05). CONCLUSION: Compared with AR solution, BR solution was associated with improved intraoperative acid-base balance and potentially protected early postoperative liver graft function and reduced late-postoperative renal injury.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Trasplante de Hígado , Adulto , Humanos , Equilibrio Ácido-Base , Solución de Ringer , Bicarbonatos , Bicarbonato de Sodio , Donadores Vivos , Soluciones Isotónicas , Acetatos
13.
Eur J Pharmacol ; 960: 176121, 2023 Dec 05.
Artículo en Inglés | MEDLINE | ID: mdl-37866743

RESUMEN

Osteoporosis, a systemic bone disease defined by decreased bone mass and deterioration of bone microarchitecture, is becoming a global concern. Nodakenin (NK) is a furanocoumarin-like compound isolated from the traditional Chinese medicine Radix Angelicae biseratae (RAB). NK has been reported to have various pharmacological activities, but osteoporosis has not been reported to be affected by NK. In this study, we used network pharmacology, molecular docking and molecular dynamics simulation techniques to identify potential targets and pathways of NK in osteoporosis. We found that NK treatment significantly promoted osteogenic differentiation of BMSCs while activating the PI3K/AKT/mTOR signalling pathway by measuring alkaline phosphatase activity and the expression of various osteogenic markers. In contrast, LY294002, an inhibitor of PI3K, reversed these changes and inhibited the osteogenic differentiation-enabling effect of NK. Meanwhile, prevent the Akt and NFκB signalling pathways by down-regulating c-Src and TRAF6 thereby effectively inhibiting RANKL-induced osteoclastogenesis. In addition, oral administration of NK to mice significantly elevated bone mass and ameliorated ovariectomized (OVX)-mediated bone microarchitectural disorders. In conclusion, these data suggest that NK attenuates OVX-induced bone loss by enhancing osteogenesis and inhibiting osteoclastogenesis.


Asunto(s)
Osteogénesis , Osteoporosis , Femenino , Ratones , Animales , Humanos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Simulación del Acoplamiento Molecular , Osteoporosis/tratamiento farmacológico , Osteoporosis/etiología , Osteoporosis/metabolismo , Ovariectomía/efectos adversos , Osteoclastos , Diferenciación Celular , Ligando RANK/farmacología
14.
Front Cardiovasc Med ; 10: 1168180, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37692046

RESUMEN

Objective: The main purpose of this study was to evaluate the safety and efficacy of Castor single-branched stent-graft combined with fenestrated technique in treatment of thoracic aortic disease (TAD) with unfavorable proximal landing area (PLZ) and isolated left vertebral artery (ILVA). Methods: From January 2018 to March 2022, 8 patients with TAD (6 patients with type B aortic dissections, 1 patient with type B intramural hematomas, and 1 patient with thoracic aortic aneurysm) underwent thoracic endovascular aortic repair with fenestrated Castor stent-graft due to the existence of ILVA and unfavorable PLZ. Demographic characteristics, surgical details, postoperative complications, follow-up and postoperative CTA imaging results were collected and analyzed. Results: The primary technical success rate was 100%. The mean operation time was 115 min (range, 70-180 min). All the left subclavian arteries (LSAs) and ILVAs of the eight patients were revascularized by fenestrated Castor stent-grafts. During the follow-up period, no deaths and complications were observed. No internal leakage, aortic rupture, retrograde type A dissection were found on computed tomography angiography. All of the LSAs and ILVAs maintained patency without stenosis. Conclusion: Castor single-branched stent-graft implantation combined with fenestration technique may be safe and feasible for TAD patients with ILVA and unfavorable PLZ.

15.
Funct Integr Genomics ; 23(4): 291, 2023 Sep 07.
Artículo en Inglés | MEDLINE | ID: mdl-37676513

RESUMEN

Folate metabolism is critical for the maintenance of genomic stability due to its regulatory ability to methylation, nucleotide metabolism, and reduction capabilities in cancer cells. However, the prognostic value of folate metabolism-related genes has not been clarified, especially in bladder cancer (BLCA). 91 folate metabolism-related genes were retrieved from the public database. TCGA-BLCA cohort, obtained from the Cancer Genome Atlas, was selected for training, while GSE13507, GSE31684, and GSE32894, downloaded from the Gene Expression Omnibus, and 35 BLCA samples collected from the local hospital were used for external validation. Through genomic difference detection, protein-protein interaction network analysis, LASSO regression, and Cox regression, a three-gene signature, including ATIC, INS, and MTHFD1L, was constructed. The signature was a reliable prognosis predictor across multiple independent cohorts (pooled hazard ratio = 2.79, 95% confidence interval = 1.79-4.33). The signature was associated with the BLCA malignant degree, which was validated in the local clinical samples (P < 0.01) and multiple cell lines (all P < 0.05). Additionally, the TIDE algorithm, GSE111636 cohort, and IMvigor210 cohort indicated that the signature was a promising tool to evaluate the immunotherapeutic response. Collectively, a folate metabolism-related gene signature was constructed to predict the prognosis and immunotherapeutic sensitivity in BLCA, which was verified in multiple large-scale cohorts, clinical samples, and cellular experiments, providing novel insights into the biological mechanisms.


Asunto(s)
Neoplasias de la Vejiga Urinaria , Humanos , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/terapia , Algoritmos , Línea Celular , Inmunoterapia , Ácido Fólico
16.
Cell Death Discov ; 9(1): 283, 2023 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-37532687

RESUMEN

Warburg effect plays a crucial role in bladder cancer (Bca) development. However, the mechanism by which glycolysis is involved in Bca remains poorly understood. CircRNAs commonly play a regulatory role in tumor progression. Our study discovered and identified a novel circRNA, hsa_circ_0000235 (circ235), and investigated its role in the glycolytic process, which further results in the progression of Bca. We applied qRT-PCR to assess its clinicopathological relevance and evaluated its proliferation, migration, and glycolytic capacity. We investigated its mechanism using RNA immunoprecipitation, dual-luciferase reporters, and fluorescence in situ hybridization. The findings demonstrated that circ235 was dramatically increased in Bca tissues and was related to a worse prognosis. In vitro studies revealed that circ235 accelerated the rate of extracellular acidification and promoted glucose uptake and lactate manufacture in Bca cells. Additionally, it strengthened the proliferative and migratory capacities. Experiments on animals revealed that downregulating circ235 dramatically reduced carcinogenesis and tumor growth. Circ235 activates monocarboxylate transporter 4 (MCT4) by sponging miR-330-5p, which promotes glycolysis and tumor growth. In conclusion, these findings suggest that circ235 may be a viable molecular marker and therapeutic target for Bca.

17.
Artículo en Inglés | MEDLINE | ID: mdl-37464818

RESUMEN

The birth of a child is a critical and potentially traumatic experience for women, entailing multiple physiological and psychosocial changes. The psychological effects of childbirth pain can have both immediate and long-term effects on the mother's health and her bond with her child. Many studies investigated the different ranges of synthetic drugs available for pain control in labour, inclusive of neuraxial analgesics, inhaled analgesics, and various opioids. The inadequate efficacy and unfavourable side effects of these synthetic drugs prevent appropriate pharmacotherapy, resulting in a quest for natural therapies for reducing labour pain. Herbal therapies (aromatherapy) using several essential oils obtained from various natural plants are another alternative that calms and manages the mind and body through aromatic compounds that have neurological and physiological effects. The review discussed the safety profile of various synthetic drugs with their dosage information and also deliberated on the mechanism and safety profile of various natural plants that are used in aromatherapy. The review also briefly highlighted the other non-pharmacological miscellaneous techniques such as TENS, hypnosis, immersion in water, acupuncture, massage, and different other tactics that aim to assist women in coping with pain in labour.

18.
Nano Lett ; 23(15): 7046-7053, 2023 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-37470490

RESUMEN

Selective electroreduction of CO2 to C1 feed gas provides an attractive avenue to store intermittent renewable energy. However, most of the CO2-to-CO catalysts are designed from the perspective of structural reconstruction, and it is challenging to precisely design a meaningful confining microenvironment for active sites on the support. Herein, we report a local sulfur doping method to precisely tune the electronic structure of an isolated asymmetric nickel-nitrogen-sulfur motif (Ni1-NSC). Our Ni1-NSC catalyst presents >99% faradaic efficiency for CO2-to-CO under a high current density of -320 mA cm-2. In situ attenuated total reflection surface-enhanced infrared absorption spectroscopy and differential electrochemical mass spectrometry indicated that the asymmetric sites show a significantly weaker binding strength of *CO and a lower kinetic overpotential for CO2-to-CO. Further theoretical analysis revealed that the enhanced CO2 reduction reaction performance of Ni1-NSC was mainly due to the effectively decreased intermediate activation energy.

19.
Ann Hematol ; 102(9): 2387-2395, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37278748

RESUMEN

B-cell lymphoma is the most prevalent type of non-Hodgkin lymphoma, for which the standard treatment regimen includes rituximab combined with CHOP. However, some patients may develop interstitial pneumonitis (IP), which can be caused by various factors; one of the most important factors is Pneumocystis jirovecii. It is crucial to investigate the pathophysiology of IP and implement preventive measures since IP can be fatal for some people. The data were collected from the First Affiliated Hospital, Zhejiang University School of Medicine, where patients with B-cell lymphoma received the R-CHOP/R-CDOP regimen with or without prophylactic use of trimethoprim-sulfamethoxazole (TMP-SMX). Multivariable logistic regression and propensity score matching (PSM) were used to investigate any potential association. Eight hundred thirty-one patients with B-cell lymphoma were classified into two groups: the non-prophylaxis group without TMP-SMX (n=699) and the prophylaxis group with TMP-SMX (n = 132). IP occurred in 66 patients (9.4%, all in the non-prophylaxis group), with an onset median of three cycles of chemotherapy. Multiple logistic regression analysis demonstrated that IP incidence was associated with pegylated liposome doxorubicin (OR=3.29, 95% CI 1.84-5.90, P<0.001). After utilizing a 1:1 matching algorithm for PSM, 90 patients from each group were obtained. There was a statistical difference between the two cohorts in the IP incidence (non-prophylaxis 12.2% vs prophylaxis 0.0%, P <0.001). The prophylactic use of TMP-SMX could prevent the occurrence of IP whose risk factor was pegylated liposome doxorubicin after chemotherapy for B-cell lymphoma.


Asunto(s)
Enfermedades Pulmonares Intersticiales , Linfoma de Células B , Neumonía por Pneumocystis , Humanos , Combinación Trimetoprim y Sulfametoxazol/efectos adversos , Neumonía por Pneumocystis/etiología , Neumonía por Pneumocystis/prevención & control , Liposomas , Puntaje de Propensión , Rituximab/efectos adversos , Vincristina/efectos adversos , Prednisona , Doxorrubicina/efectos adversos , Enfermedades Pulmonares Intersticiales/inducido químicamente , Enfermedades Pulmonares Intersticiales/prevención & control , Enfermedades Pulmonares Intersticiales/complicaciones , Ciclofosfamida , Polietilenglicoles , Linfoma de Células B/tratamiento farmacológico , Linfoma de Células B/complicaciones , Estudios Retrospectivos
20.
Nat Commun ; 14(1): 3382, 2023 Jun 08.
Artículo en Inglés | MEDLINE | ID: mdl-37291114

RESUMEN

Electrochemical CO2 conversion to methane, powered by intermittent renewable electricity, provides an entrancing opportunity to both store renewable electric energy and utilize emitted CO2. Copper-based single atom catalysts are promising candidates to restrain C-C coupling, suggesting feasibility in further protonation of CO* to CHO* for methane production. In theoretical studies herein, we find that introducing boron atoms into the first coordination layer of Cu-N4 motif facilitates the binding of CO* and CHO* intermediates, which favors the generation of methane. Accordingly, we employ a co-doping strategy to fabricate B-doped Cu-Nx atomic configuration (Cu-NxBy), where Cu-N2B2 is resolved to be the dominant site. Compared with Cu-N4 motifs, as-synthesized B-doped Cu-Nx structure exhibits a superior performance towards methane production, showing a peak methane Faradaic efficiency of 73% at -1.46 V vs. RHE and a maximum methane partial current density of -462 mA cm-2 at -1.94 V vs. RHE. Extensional calculations utilizing two-dimensional reaction phase diagram analysis together with barrier calculation help to gain more insights into the reaction mechanism of Cu-N2B2 coordination structure.


Asunto(s)
Dióxido de Carbono , Cobre , Boro , Electricidad , Metano
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