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1.
PLoS One ; 19(4): e0301187, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38568913

RESUMO

The literature has confirmed that when managers increase profits through earnings management, the readability of annual reports may be reduced Lo (2017), Ye (2018). Whether this conclusion is suitable for Chinese corporate social responsibility (CSR) reports, however, is still unclear. Based on the panel data of 5083 Chinese non-financial listed companies from 2010 to 2019, this paper adopts multiple linear regression to investigate the impact of earnings management on the readability of Chinese CSR reports. The results show that: (1) There is a significant negative correlation between earnings management and the readability of Chinese CSR reports, with the readability of Chinese annual reports as a mediating variable. (2) The negative effect is more significant when companies are not punished for violations, when the internal control index is low, when companies lack ISO14001 certification and when companies do not have independent third-party authentication for Chinese CSR reports. (3) When earnings management just exceeds zero, the readability of Chinese CSR reports decreases. (4) The economic consequences of reducing the readability of Chinese CSR reports are that financing costs are increased and environmental performance is decreased. To improve the quality of information disclosure of listed companies, the recommendations are as follows: First, the government should issue CSR reporting standards to reduce the manipulation of Chinese CSR reports. Second, Chinese CSR reports disclosed by listed companies must be audited by independent third parties to enhance the credibility of the information. Third, the company needs to strengthen its external and internal supervision to reduce the manipulation space for the readability of Chinese CSR reports. This study extends the negative relationship between earnings management and the readability from annual reports to Chinese CSR reports. To prevent investors from detecting earnings management, the readability of Chinese CSR reports may be reduced. At the same time, the study has definitely added value to the existing literature in the domain of CSR.


Assuntos
Compreensão , Responsabilidade Social , China , Governo , Revelação
2.
Int J Mol Sci ; 25(7)2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38612806

RESUMO

N6-methyladenosine (m6A) is essential for RNA metabolism in cells. The YTH domain, conserved in the kingdom of Eukaryotes, acts as an m6A reader that binds m6A-containing RNA. In plants, the YTH domain is involved in plant hormone signaling, stress response regulation, RNA stability, translation, and differentiation. However, little is known about the YTH genes in tea-oil tree, which can produce edible oil with high nutritional value. This study aims to identify and characterize the YTH domains within the tea-oil tree (Camellia chekiangoleosa Hu) genome to predict their potential role in development and stress regulation. In this study, 10 members of the YTH family containing the YTH domain named CchYTH1-10 were identified from C. chekiangoleosa. Through analysis of their physical and chemical properties and prediction of subcellular localization, it is known that most family members are located in the nucleus and may have liquid-liquid phase separation. Analysis of cis-acting elements in the CchYTH promoter region revealed that these genes could be closely related to abiotic stress and hormones. The results of expression profiling show that the CchYTH genes were differentially expressed in different tissues, and their expression levels change under drought stress. Overall, these findings could provide a foundation for future research regarding CchYTHs in C. chekiangoleosa and enrich the world in terms of epigenetic mark m6A in forest trees.


Assuntos
Camellia , Camellia/genética , Diferenciação Celular , Secas , RNA , Chá
3.
Plants (Basel) ; 13(6)2024 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-38592879

RESUMO

Plants must adapt to the complex effects of several stressors brought on by global warming, which may result in interaction and superposition effects between diverse stressors. Few reports are available on how drought stress affects Xanthomonas albilineans (Xa) infection in sugarcane (Saccharum spp. hybrids). Drought and leaf scald resistance were identified on 16 sugarcane cultivars using Xa inoculation and soil drought treatments, respectively. Subsequently, four cultivars contrasting to drought and leaf scald resistance were used to explore the mechanisms of drought affecting Xa-sugarcane interaction. Drought stress significantly increased the occurrence of leaf scald and Xa populations in susceptible cultivars but had no obvious effect on resistant cultivars. The ROS bursting and scavenging system was significantly activated in sugarcane in the process of Xa infection, particularly in the resistant cultivars. Compared with Xa infection alone, defense response via the ROS generating and scavenging system was obviously weakened in sugarcane (especially in susceptible cultivars) under Xa infection plus drought stress. Collectively, ROS might play a crucial role involving sugarcane defense against combined effects of Xa infection and drought stress.

4.
Gen Physiol Biophys ; 43(2): 153-162, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38477605

RESUMO

Endothelial damage caused by persistent glucose and lipid metabolism disorders is the main reason of diabetic vascular diseases. Daidzein exerts positive effects on vascular dysfunction. Peroxisome proliferator-activated receptors (PPARs) regulate critically glucose and lipid metabolism. However, the interaction of daidzein to PPARs is still insufficiently explored. In this study, the cell proliferation was detected by EdU. The intrinsic activity and binding affinity of daidzein for human PPARs (hPPARs) were estimated by transactivation reporter gene test and HPLC-UV method, respectively. Daidzein significantly reversed high glucose (HG, at 30 mmol/l)-induced injury in HUVECs, which was inhibited by both PPARα and PPARγ antagonist, but no PPARß antagonist. Daidzein selectively activated hPPARα and hPPARγ1, but weakly hPPARß. Additionally, daidzein also bound to both hPPARα and hPPARγ1. The findings suggested that daidzein may be a PPARα and PPARγ dual-agonist. The amelioration of daidzein on HUVECs from hyperglycemia may be mediated by the activation of PPARα and PPARγ receptors.


Assuntos
Isoflavonas , PPAR alfa , PPAR gama , Humanos , PPAR alfa/metabolismo , Células Endoteliais , Glucose
5.
Mol Cell Endocrinol ; 580: 112103, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38450475

RESUMO

BACKGROUND: Osteoporosis (OP) can be caused by an overactive osteoclastic function. Anti-osteoporosis considerable therapeutic effects in tissue repair and regeneration because bone resorption is a unique osteoclast function. In this study, we mainly explored the underlying mechanisms of osteoclasts' effects on osteoporosis. METHODS: RAW264.7 cells were used and induced toward osteoclast and iron accumulation by M-CSF and RANKL administration. We investigated Hepcidin and divalent metal transporter 1 (DMT1) on iron accumulation and osteoclast formation in an ovariectomy (OVX)-induced osteoporosis. Osteoporosis was induced in mice by OVX, and treated with Hepcidin (10, 20, 40, 80 mg/kg, respectively) and overexpression of DMT1 by tail vein injection. Hepcidin, SPI1, and DMT1 were detected by immunohistochemical staining, western blot and RT-PCR. The bioinformatics assays, luciferase assays, and Chromatin Immunoprecipitation (ChIP) verified that Hepcidin was a direct SPI1 transcriptional target. Iron accumulation was detected by laser scanning confocal microscopy, Perl's iron staining and iron content assay. The formation of osteoclasts was assessed using tartrate-resistant acid phosphatase (TRAP) staining. RESULTS: We found that RAW264.7 cells differentiated into osteoclasts when exposed to M-CSF and RANKL, which increased the protein levels of osteoclastogenesis-related genes, including c-Fos, MMP9, and Acp5. We also observed higher concentration of iron accumulation when M-CSF and RANKL were administered. However, Hepcidin inhibited the osteoclast differentiation cells and decreased intracellular iron concentration primary osteoclasts derived from RAW264.7. Spi-1 proto-oncogene (SPI1) transcriptionally repressed the expression of Hepcidin, increased DMT1, facilitated the differentiation and iron accumulation of mouse osteoclasts. Overexpression of SPI1 significantly declined luciferase activity of HAMP promoter and increased the enrichment of HAMP promoter. Furthermore, our results showed that Hepcidin inhibited osteoclast differentiation and iron accumulation in mouse osteoclasts and OVX mice. CONCLUSION: Therefore, the study revealed that SPI1 could inhibit Hepcidin expression contribute to iron accumulation and osteoclast formation via DMT1 signaling activation in mouse with OVX.


Assuntos
Osteoclastos , Osteoporose , Feminino , Animais , Camundongos , Fator Estimulador de Colônias de Macrófagos , Hepcidinas , Luciferases
6.
Int Urol Nephrol ; 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38528290

RESUMO

Men are inevitably plagued by prostate disease throughout their lives. However, the understanding of the pathogenesis of prostate diseases is still limited. In the 1960s, McNeal proposed the theory of prostate zones: the prostate was divided into three main zones: transition zone, central zone, and peripheral zone. Over the past 50 years, significant differences between different prostate zones have been gradually revealed. We summarized the most significant differences in different zones of the prostate. For the first time, we proposed the "apparent difference in prostate zones" concept. This new concept has been proposed to understand the different zones of the prostate better. It also provided new ideas for exploring the susceptibility of lesions in different prostate zones. Despite the reported differences between zones, the treatment of prostate-related diseases remains partition agnostic. Therefore, we also discussed the clinical significance of the "apparent difference in the prostate zone" and emphasized the necessity of prostate zones.

7.
Waste Manag ; 177: 169-176, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38325017

RESUMO

Chemical looping gasification (CLG) is a promising technology that utilizes lattice oxygen for partial oxidation of solid organic waste to produce high-quality syngas. The utilization of low-cost and high-performance oxygen carriers (OCs) is important for the success of this technology. The red mud from aluminum production was mixed with calcium and manganese oxides to prepare CaMn0.5Fe0.5O3-δ perovskite OCs. The comparative redox tests were carried out to analyze the reactivity using a thermogravimetric analyzer (TGA). Multiple cycle CLG experiments were conducted on a wet municipal sludge in a lab-scale fluidized bed to produce the hydrogen-rich gas. The results showed that the CaMn0.5Fe0.5O3-δ-washed demonstrated higher oxygen transfer capacity and better cycling stability with a maximum weight loss of 7.3096 %. After the 5th cycle in CLG, the syngas obtained using CaMn0.5Fe0.5O3-δ-washed maintained a H2 volume fraction exceeding 40%. However, an increase in CO2 production was also observed, which could be due to the catalytic effect of MnO in the OC on the steam-reforming reaction. The XRD curves showed that fresh CaMn0.5Fe0.5O3-δ-washed exhibited prominent diffraction peaks characteristic of perovskite. It was observed that after undergoing 5 cycles, the presence of iron calcium silicate structures containing Mn became evident due to the attachment of sludge ash, leading to the increased impurities on the surface of OCs with a decrease in the specific surface area. Additionally, some of the reacted OC particles exhibited a hollow structure, facilitating the fluidization. This preliminary study provides the basis for the improvement of the OC performance in sludge gasification.


Assuntos
Compostos de Cálcio , Óxidos , Esgotos , Titânio , Alumínio , Oxigênio , Resíduos Sólidos
8.
Chemosphere ; 352: 141457, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38378050

RESUMO

This study assessed the impact of different plant-derived biochar (cornstalk, rice husk, and sawdust) on bacterial community and functions for compost maturity and gaseous emissions during the composting of food waste. Results showed that all biochar strengthened organic biotransformation and caused a higher germination index on day 12 (over 100%), especially for rice husk biochar to enhance the growth of Thermobifida related to aerobic chemoheterotrophy. Rice husk biochar also achieved a relatively higher reduction efficiency of methane (85.8%) and ammonia (82.7%) emissions since its greater porous structure. Besides, the growth of Pseudomonas, Pusillimonas, and Desulfitibacter was restricted to constrict nitrate reduction, nitrite respiration, and sulfate respiration by optimized temperature and air permeability, thus reducing nitrous oxide and hydrogen sulfide emissions by 48.0-57.3% by biochar addition. Therefore, rice husk biochar experienced the optimal potential for maturity increment and gaseous emissions mitigation.


Assuntos
Compostagem , Eliminação de Resíduos , Gases , 60659 , Nitrogênio/análise , Alimentos , Solo/química , Carvão Vegetal , Esterco
9.
Int J Mol Sci ; 25(3)2024 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-38338907

RESUMO

WUSCHEL-related homeobox (WOX) transcription factors (TFs) play a crucial role in regulating plant development and responding to various abiotic stresses. However, the members and functions of WOX proteins in Pinus massoniana remain unclear. In this study, a total of 11 WOX genes were identified, and bioinformatics methods were used for preliminary identification and analysis. The phylogenetic tree revealed that most PmWOXs were distributed in ancient and WUS clades, with only one member found in the intermediate clade. We selected four highly conserved WOX genes within plants for further expression analysis. These genes exhibited expressions across almost all tissues, while PmWOX2, PmWOX3, and PmWOX4 showed high expression levels in the callus, suggesting their potential involvement in specific functions during callus development. Expression patterns under different abiotic stresses indicated that PmWOXs could participate in resisting multiple stresses in P. massoniana. The identification and preliminary analysis of PmWOXs lay the foundation for further research on analyzing the resistance molecular mechanism of P. massoniana to abiotic stresses.


Assuntos
Pinus , Fatores de Transcrição , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Família Multigênica , Filogenia , Pinus/genética , Pinus/metabolismo , Estresse Fisiológico/genética , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/metabolismo
10.
Cancer Immunol Immunother ; 73(3): 60, 2024 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-38400933

RESUMO

Over the past decade, US Food and Drug Administration (FDA)-approved immune checkpoint inhibitors that target programmed death-1 (PD-1) have demonstrated significant clinical benefit particularly in patients with PD-L1 expressing tumors. Toripalimab is a humanized anti-PD-1 antibody, approved by FDA for first-line treatment of nasopharyngeal carcinoma in combination with chemotherapy. In a post hoc analysis of phase 3 studies, toripalimab in combination with chemotherapy improved overall survival irrespective of PD-L1 status in nasopharyngeal carcinoma (JUPITER-02), advanced non-small cell lung cancer (CHOICE-01) and advanced esophageal squamous cell carcinoma (JUPITER-06). On further characterization, we determined that toripalimab is molecularly and functionally differentiated from pembrolizumab, an anti-PD-1 mAb approved previously for treating a wide spectrum of tumors. Toripalimab, which binds the FG loop of PD-1, has 12-fold higher binding affinity to PD-1 than pembrolizumab and promotes significantly more Th1- and myeloid-derived inflammatory cytokine responses in healthy human PBMCs in vitro. In an ex vivo system employing dissociated tumor cells from treatment naïve non-small cell lung cancer patients, toripalimab induced several unique genes in IFN-γ and immune cell pathways, showed different kinetics of activation and significantly enhanced IFN-γ signature. Additionally, binding of toripalimab to PD-1 induced lower levels of SHP1 and SHP2 recruitment, the negative regulators of T cell activation, in Jurkat T cells ectopically expressing PD-1. Taken together, these data demonstrate that toripalimab is a potent anti-PD-1 antibody with high affinity PD-1 binding, strong functional attributes and demonstrated clinical activity that encourage its continued clinical investigation in several types of cancer.


Assuntos
Anticorpos Monoclonais Humanizados , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Neoplasias Pulmonares , Neoplasias Nasofaríngeas , Humanos , Anticorpos Monoclonais/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/patologia , Antígeno B7-H1 , Receptor de Morte Celular Programada 1 , Neoplasias Pulmonares/tratamento farmacológico , Carcinoma Nasofaríngeo , Neoplasias Esofágicas/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Linfócitos T/patologia
11.
Emerg Med Int ; 2024: 5215977, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38380077

RESUMO

Objective: Large-scale studies on the characteristics and management of abdominal trauma in megacities in China are lacking. The aim of this study was to analyze and present the clinical patterns and treatment status of abdominal trauma in regional medical centers. Methods: Cases of abdominal trauma treated at seven medical centers in Beijing from 2010 to 2021 were collected. Clinical information about age, sex, injury cause, geographic distribution, abbreviated injury scale/injury severity score (AIS/ISS) value, injury-hospital time, preoperative time, surgically identified organ injuries, type of surgery, causes of reoperation and 90-day mortality was included in this study. Clinical characteristics, treatment methods, and short-term prognoses (90-days survival) were compared between blunt abdominal trauma (BAT) and penetrating abdominal trauma (PAT) cases. Non-normally distributed data are described as medians (IQR), and the Mann‒Whitney U test was performed; qualitative data were analyzed using the X2 test. Univariate and multivariate survival analyses were performed by the Cox proportional hazards model. Results: A total of 553 patients (86.98% male) with a median age of 36.50 (27.00-48.00) years were included. The BAT group had a significantly higher proportion of serious injury (P=0.001), lower initial hemoglobin level (P=0.001), and a lower laparoscopy surgery rate (P=0.044) compared to the PAT group. Additionally, more BAT cases were from the area around Beijing (P=0.008) and a longer injury-regional hospital time (10.47 (5.18-22.51) hours vs. 7.00 (3.80-15.38) hours, P=0.001). In the hollow viscus injury subgroup, the BAT group had a significantly longer injury-regional hospital time and preoperative time compared to the PAT group (injury-regional hospital time: 10.23 (6.00-21.59) hours vs. 7.07 (3.99-13.85) hours, P=0.002; preoperative time: 3.02 (2.01-5.58) hours vs. 2.81 (1.85-3.63) hours, P=0.047). The overall 90-day mortality was 11.9%, and longer injury-regional hospital time (HR: 1.01, 95% CI: 1.00-1.02, P=0.008), receipt of ICU treatment (HR: 4.69, 95% CI: 2.54-8.65, P=0.001), and severe ISSs (ISS > 25 vs. ISS < 16, HR: 2.78, 95% CI: 1.38-5.601, P=0.004) had a worse impact on survival. Conclusion: More patients with BAT were transferred to higher-level hospital, leading to significantly longer prehospital and preoperation time. In the subgroup of hemodynamically stable individuals, more patients with BAT experienced hollow viscus injuries. For those patients, aggressive diagnostic laparoscopic exploration may be beneficial. Patients with longer injury-regional hospital intervals, the need for ICU care, and higher injury severity scores (ISSs) suffered from worse prognoses.

12.
Endocr Relat Cancer ; 31(4)2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38261313

RESUMO

Pralsetinib has demonstrated efficacious activity in various solid tumors, including medullary thyroid cancer (MTC), as observed in the phase 1/2 global ARROW study (BLU-667-1101; NCT03037385). We evaluated the safety and efficacy of pralsetinib in Chinese patients with advanced RET-mutant MTC. In the extension cohort of ARROW, adult patients with advanced MTC, who had not received systemic therapy (except for cytotoxic chemotherapy), were treated with pralsetinib (400 mg once daily, orally). The primary endpoints were blinded independent central-reviewed (BICR) objective response rate (ORR) and safety. Between October 9, 2019, and April 29, 2020, 34 patients were enrolled at 12 centers across China. Among them, 28 patients tested positive for RET mutations in the central laboratory, and 26 of these, with measurable disease at baseline per BICR, were included in the analysis set for tumor response. As of April 12, 2021 (data cutoff), the ORR was 73.1% (95% CI: 52.2-88.4), and the median duration of response was not reached. The most common (≥15%) grade ≥3 treatment-related adverse events (TRAEs) in the 28 patients with RET-mutant MTC were neutrophil count decreased (8/28, 28.6%), blood creatine phosphokinase increased (6/28, 21.4%), and lymphocyte count decreased (5/28, 17.9%). Serious TRAEs were reported by six patients (21.4%), with the most common event being pneumonia (3/28, 10.7%). No patient discontinued treatment or died from pralsetinib-related adverse events. Pralsetinib demonstrated broad, deep, and durable efficacy, as well as a manageable and acceptable safety profile in Chinese patients with advanced RET-mutant MTC.


Assuntos
Carcinoma Neuroendócrino , Proteínas Proto-Oncogênicas c-ret , Pirazóis , Pirimidinas , Neoplasias da Glândula Tireoide , Adulto , Humanos , Proteínas Proto-Oncogênicas c-ret/genética , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/patologia , Piridinas/uso terapêutico
13.
J Orthop Surg Res ; 19(1): 59, 2024 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-38216929

RESUMO

OBJECTIVE: Iron accumulation is associated with osteoporosis. This study aims to explore the effect of chronic iron accumulation induced by hepcidin1 deficiency on aging osteoporosis. METHODS: Iron accumulation in hepcidin1 knockout aging mice was assessed by atomic absorption spectroscopy and Perl's staining. Bone microarchitecture was observed using Micro-CT. Hepcidin, ferritin, oxidative stress, and markers of bone turnover in serum were detected by enzyme-linked immunosorbent assay. Bone formation and resorption markers were measured by real-time quantitative PCR. Cell aging was induced by D-galactose treatment. CCK-8, flow cytometry, EdU assays, and Alizarin red staining were performed to reveal the role of hepcidin1 knockout in cell model. Iron Colorimetric Assay Kit and western blot were applied to detect iron and ferritin levels in cells, respectively. RESULTS: In hepcidin1-knockout mice, the ferritin and iron contents in liver and tibia were significantly increased. Iron accumulation induced by hepcidin1 knockout caused a phenotype of low bone mass and deteriorated bone microarchitecture. Osteogenic marker was decreased and osteoclast marker was increased in mice, accompanied by increased oxidative stress level. The mRNA expression levels of osteoclast differentiation markers (RANKL, Mmp9, OPG, Trap, and CTSK) were up-regulated, while bone formation markers (OCN, ALP, Runx2, SP7, and Col-1) were down-regulated in model group, compared to wild type mice. In vitro, hepcidin1 knockdown inhibited proliferation and osteogenic differentiation, while promoted apoptosis, with increased levels of iron and ferritin. CONCLUSION: Iron accumulation induced by hepcidin1 deficiency aggravates the progression of aging osteoporosis via inhibiting osteogenesis and promoting osteoclast genesis.


Assuntos
Osteogênese , Osteoporose , Camundongos , Animais , Osteoporose/genética , Osteoporose/metabolismo , Ferro , Ferritinas/farmacologia , Diferenciação Celular/genética , Envelhecimento
14.
J Org Chem ; 89(1): 784-792, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38096498

RESUMO

A novel methodology for the synthesis of indanone derivates has been developed. The palladium-catalyzed annulation reaction of o-bromobenzaldehydes with norbornene derivatives is achieved through extremely concise reaction processes. The indanone skeleton was established directly via C-H activation of the aldehyde group under a mild reaction condition. This method is simple and practical, which simplified the traditional synthesis method for the rapid construction of indanone.

15.
ACS Nano ; 17(23): 23535-23544, 2023 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-38084419

RESUMO

Of patients bearing unresectable tumors at advanced stages, most undergo serious pain. For unresectable tumors adjacent to vital organs or nerves, eliminating local cancer pain without adverse effects remains a formidable challenge. Interventional ablative therapies (IATs), such as radio frequency ablation (RFA), microwave ablation, and irreversible electroporation, have been clinically adopted to treat various carcinomas. In this study, we established another palliative interventional therapy to eliminate local cancer pain, instead of relieving nociception temporarily. Here, we developed another interventional ablative therapy (termed nanoparticle-mediated microknife ablation) to locoregionally eliminate cancer pain and tumors. The IAT system was composed of self-assembled nanodrugs, infusion catheters, puncture needles, injection pump, and an empirical tumor ablation formula. Notably, the ablation formula established in the IAT system enables us to predict the essential nanoparticle (NP) numbers used for completely destroying tumors. In a mouse model of cancer pain, tumor-targeted nanodrugs made of Paclitaxel and Hematoporphyrin, which have an extremely high drug-loading efficiency (more than 60%), were infused into tumors through injection pumps under imaging guidance. In conclusion, when compared to classic chemotherapeutic agents, IAT showed significantly higher effectiveness in cancer pain removal. It also presented no damage to the nervous, sensory, and motor capabilities of the treated mice. All of these merits resulted from NPs' long-lasting retention, targeted ablation, and confined diffusion in tumor stroma. Therefore, this safe treatment modality has great potential to eradicate local cancer pain in the clinic.


Assuntos
Dor do Câncer , Neoplasias Pancreáticas , Humanos , Animais , Camundongos , Dor do Câncer/tratamento farmacológico , Neoplasias Pancreáticas/patologia
16.
Signal Transduct Target Ther ; 8(1): 417, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37907503

RESUMO

Immunity-and-matrix-regulatory cells (IMRCs) derived from human embryonic stem cells have unique abilities in modulating immunity and regulating the extracellular matrix, which could be mass-produced with stable biological properties. Despite resemblance to mesenchymal stem cells (MSCs) in terms of self-renew and tri-lineage differentiation, the ability of IMRCs to repair the meniscus and the underlying mechanism remains undetermined. Here, we showed that IMRCs demonstrated stronger immunomodulatory and pro-regenerative potential than umbilical cord MSCs when stimulated by synovial fluid from patients with meniscus injury. Following injection into the knees of rabbits with meniscal injury, IMRCs enhanced endogenous fibrocartilage regeneration. In the dose-escalating phase I clinical trial (NCT03839238) with eighteen patients recruited, we found that intra-articular IMRCs injection in patients was safe over 12 months post-grafting. Furthermore, the effective results of magnetic resonance imaging (MRI) of meniscus repair and knee functional scores suggested that 5 × 107 cells are optimal for meniscus injury treatment. In summary, we present the first report of a phase I clinical trial using IMRCs to treat meniscus injury. Our results demonstrated that intra-articular injection of IMRCs is a safe and effective therapy by providing a permissive niche for cartilage regeneration.


Assuntos
Menisco , Transplante de Células-Tronco Mesenquimais , Animais , Humanos , Coelhos , Diferenciação Celular , Matriz Extracelular , Transplante de Células-Tronco Mesenquimais/métodos
17.
Int J Mol Sci ; 24(21)2023 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-37958919

RESUMO

Pinus massoniana is an important coniferous tree species for barren mountain afforestation with enormous ecological and economic significance. It has strong adaptability to the environment. TEOSINTE BRANCHED 1/CYCLOIDEA/PCF (TCP) transcription factors (TFs) play crucial roles in plant stress response, hormone signal transduction, and development processes. At present, TCP TFs have been widely studied in multiple plant species, but research in P. massoniana has not been carried out. In this study, 13 PmTCP TFs were identified from the transcriptomes of P. massoniana. The phylogenetic results revealed that these PmTCP members were divided into two categories: Class I and Class II. Each PmTCP TF contained a conserved TCP domain, and the conserved motif types and numbers were similar in the same subgroup. According to the transcriptional profiling analysis under drought stress conditions, it was found that seven PmTCP genes responded to drought treatment to varying degrees. The qRT-PCR results showed that the majority of PmTCP genes were significantly expressed in the needles and may play a role in the developmental stage. Meanwhile, the PmTCPs could respond to several stresses and hormone treatments at different levels, which may be important for stress resistance. In addition, PmTCP7 and PmTCP12 were nuclear localization proteins, and PmTCP7 was a transcriptional suppressor. These results will help to explore the regulatory factors related to the growth and development of P. massoniana, enhance its stress resistance, and lay the foundation for further exploration of the physiological effects on PmTCPs.


Assuntos
Pinus , Fatores de Transcrição , Fatores de Transcrição/metabolismo , Transcriptoma , Filogenia , Pinus/genética , Pinus/metabolismo , Regulação da Expressão Gênica de Plantas , Hormônios/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Estresse Fisiológico/genética
18.
Environ Sci Technol ; 57(48): 19463-19472, 2023 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-37943691

RESUMO

Prebiotics may stimulate beneficial gut microorganisms. However, it remains unclear whether they can lower the oral bioavailability of early life arsenic (As) exposure via regulating gut microbiota and altering As biotransformation along the gastrointestinal (GI) tract. In this study, weanling mice were exposed to arsenate (iAsV) via diet (7.5 µg As g-1) amended with fructooligosaccharides (FOS), galactooligosaccharides (GOS), and inulin individually at 1% and 5% (w/w). Compared to As exposure control mice, As concentrations in mouse blood, liver, and kidneys and As urinary excretion factor (UEF) were reduced by 43.7%-74.1% when treated with 5% GOS. The decrease corresponded to a significant proliferation of Akkermansia and Psychrobacter, reduced percentage of inorganic arsenite (iAsIII) and iAsV by 47.4% and 65.4%, and increased proportion of DMAV in intestinal contents by 101% in the guts of mice treated with 5% GOS compared to the As control group. In contrast, FOS and inulin either at l% or 5% did not reduce As concentration in mouse blood, liver, and kidneys or As UEF. These results suggest that GOS supplementation may be a gut microbiota-regulating approach to lower early life As exposure via stimulating the growth of Akkermansia and Psychrobacter and enhancing As methylation in the GI tract.


Assuntos
Arsênio , Microbioma Gastrointestinal , Camundongos , Animais , Inulina/metabolismo , Prebióticos , Fígado/metabolismo
19.
Front Microbiol ; 14: 1264670, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38029152

RESUMO

Introduction: The average carbon storage of Pinus massoniana is much higher than the average carbon storage of Chinese forests, an important carbon sink tree species in subtropical regions of China. However, there are few studies on the differences in rhizosphere microorganisms of P. massoniana with different carbon storages. Methods: To clarify the relationships between plant carbon storage level, environmental parameters and microbial community structure, we identified three carbon storage levels from different P. massoniana provenances and collected rhizosphere soil samples. We determined chemical properties of soil, extracellular enzyme activity, and microbial community structures at different carbon storage levels and examined how soil factors affect rhizosphere microorganisms under different carbon storage levels. Results: The results revealed that soil organic carbon (SOC), nitrate nitrogen (NO3--N), ammonium nitrogen (NH4+-N) contents all increased with increasing carbon storage levels, while pH decreased accordingly. In contrast, the available phosphorus (AP) content did not change significantly. The soil AP content was within the range of 0.91 ~ 1.04 mg/kg. The microbial community structure of P. massoniana changed with different carbon storage, with Acidobacteria (44.27%), Proteobacteria (32.57%), and Actinobacteria (13.43%) being the dominant bacterial phyla and Basidiomycota (73.36%) and Ascomycota (24.64%) being the dominant fungal phyla across the three carbon storage levels. Soil fungi were more responsive to carbon storage than bacteria in P. massoniana. C/N, NH4+-N, NO3--N, and SOC were the main drivers (p < 0.05) of changes in rhizosphere microbial communities. Discussion: The results revealed that in the rhizosphere there were significant differences in soil carbon cycle and microorganism nutrient preferences at different carbon storages of P. massoniana provenance, which were significantly related to the changes in rhizosphere microbial community structure. Jiangxi Anyuan (AY) provenance is more suitable for the construction of high carbon storage plantation.

20.
Immun Inflamm Dis ; 11(11): e1069, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38018571

RESUMO

BACKGROUND: Ulcerative colitis (UC), a chronic inflammatory disease, is caused by abnormal immune system reactions resulting in inflammation and ulcers in the large intestine. Phillygenin (PHI) is a natural compound found in Forsythia suspensa (Thunb.) Vahl, which is known for its antipyretic, anti-inflammatory, antiobesity, and other biological activities. However, the therapeutic role and molecular mechanisms of PHI on UC are still insufficiently researched. METHODS: In this study, dextran sulfate sodium (DSS) and 2.5% 2,4,6-trinitro-Benzenesulfonic acid (TNBS)-induced acute UC were used to investigate the therapeutic effects of PHI. We evaluated the effects of PHI on disease activity index (DAI), body weight, mortality, intestinal mucosal barrier, cytokine secretion, and macrophage infiltration into colon tissue using various techniques such as flow cytometry, immunofluorescence, enzyme-linked immunosorbent assay (ELISA), RT-qPCR, and Western blot analysis. RESULTS: Our findings revealed that PHI has therapeutic properties in UC treatment. PHI was able to maintain body weight, reduce DAI and mortality, restore the intestinal mucosal barrier, and inhibit cytokine secretion. Flow cytometry assay and immunofluorescence indicated that PHI reduces macrophage infiltration into colon tissue. Mechanistically, PHI may exert anti-inflammatory effects by downregulating the TLR4/MyD88/NF-κB pathway and inhibiting the activation of NLRP3 inflammasome. CONCLUSION: In conclusion, PHI possesses significant anti-inflammatory properties and is expected to be a potential drug for UC treatment. Our study delves into the underlying mechanisms of PHI therapy and highlights the potential for further research in developing PHI-based treatments for UC.


Assuntos
Colite Ulcerativa , Forsythia , NF-kappa B/metabolismo , Colite Ulcerativa/tratamento farmacológico , Inflamassomos/efeitos adversos , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Fator 88 de Diferenciação Mieloide/metabolismo , Fator 88 de Diferenciação Mieloide/farmacologia , Receptor 4 Toll-Like/metabolismo , Forsythia/metabolismo , Transdução de Sinais , Anti-Inflamatórios/efeitos adversos , Citocinas/metabolismo , Peso Corporal
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