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1.
Genes Dis ; 11(2): 747-759, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37692487

RESUMO

In the mammalian heart, cardiomyocytes are forced to withdraw from the cell cycle shortly after birth, limiting the ability of the heart to regenerate and repair. The development of multimodal regulation of cardiac proliferation has verified that pre-existing cardiomyocyte proliferation is an essential driver of cardiac renewal. With the continuous development of genetic lineage tracking technology, it has been revealed that cell cycle activity produces polyploid cardiomyocytes during the embryonic, juvenile, and adult stages of cardiogenesis, but newly formed mononucleated diploid cardiomyocytes also elevated sporadically during myocardial infarction. It implied that adult cardiomyocytes have a weak regenerative capacity under the condition of ischemia injury, which offers hope for the clinical treatment of myocardial infarction. However, the regeneration frequency and source of cardiomyocytes are still low, and the mechanism of regulating cardiomyocyte proliferation remains further explained. It is noteworthy to explore what force triggers endogenous cardiomyocyte proliferation and heart regeneration. Here, we focused on summarizing the recent research progress of emerging endogenous key modulators and crosstalk with other signaling pathways and furnished valuable insights into the internal mechanism of heart regeneration. In addition, myocardial transcription factors, non-coding RNAs, cyclins, and cell cycle-dependent kinases are involved in the multimodal regulation of pre-existing cardiomyocyte proliferation. Ultimately, awakening the myocardial proliferation endogenous modulator and regeneration pathways may be the final battlefield for the regenerative therapy of cardiovascular diseases.

2.
Talanta ; 266(Pt 2): 125070, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-37591153

RESUMO

There has been a growing concern over the micro/nanoplastics pollution and treatment. The fast qualitative and quantitative analysis of these small plastic particles is the crucial issues. Herein, a novel honeycomb-like AgNPs@TiO2 array-based surface-enhanced Raman scattering (SERS) sensor was developed for efficient identification and analysis of the micro/nanoplastics in the environmental water samples. The plasmonic AgNPs were uniformly anchored within the periodic TiO2 nanocage arrays to form a AgNPs@TiO2 array. The dual enhancement mechanisms in the AgNPs@TiO2 hybrid structure endow the SERS sensor high sensitivity to detect trace amount of micro/nanoplastics down to 50 µg/mL with a hand-held Raman spectrometer. Further, this SERS sensor successfully discerns two-component mixtures of the micro/nanoplastics due to the fingerprint feature. In addition, the superior reproducibility (RSD of 9.69%) of the SERS sensor assures the quantitative detection reliability, realizing quantitative analysis of Polystyrene (PS) microplastics in tap water, lake water, soil water and seawater with detection limits of 100 µg/mL, 100 µg/mL, 100 µg/mL, 100 µg/mL and 250 µg/mL, respectively. The recovery rates of PS microspheres in four water environments ranged from 97.6% to 109.7%, with the RSD ranging from 0.49% to 10.23%. This honeycomb AgNPs@TiO2 array sensor provides a promising application prospect in the detection of micro/nanoplastics contaminants from the environmental water.

3.
Talanta ; 266(Pt 1): 125041, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-37556950

RESUMO

Endowing fluorescent pH sensors with large Stokes shifts promises to resolve interferential background fluorescence in practice, and yet few such method has been reported, owing to lack of luminescent materials with large Stokes shifts used in fluorescent sensors. Herein, we elaborately designed NaGdF4:Ce@NaGdF4:Nd@NaYF4:Eu core-double shells (CDS) lanthanide-doped fluoride nanoparticles (LFNPs), employing Gd3+-mediated energy migration and interfacial energy transfer to realize intense red and NIR emissions under 254 nm irradiation, and pseudo-Stokes shifts of which reached up to striking 361 nm and 610 nm, respectively. The CDS LFNPs collaborated with absorption-based pH indicator bromocresol green to from a novel fluorescent sensor film, and employing low-cost dual chip RGB-NIR camera to precisely record luminescence signals. On the basis of inner-filter effects, this senor system enabled accurate ratiometric read-out of pH value ranging from 5 to 6 (pKa ± 0.5), according to intensity ratios of pH-sensitive red emissions and referenced NIR emissions, avoiding common errors (e.g., fluctuant light sources). Notably, the large pseudo-Stokes shifts allowed red and NIR emissions far from the interfering background fluorescence possessing relatively small Stokes shifts, ensuring elevated signal-to-noise ratio and accurate pH determination. Therefore, the devised pH sensor system based on the CDS LFNPs exhibited sufficient accuracy in autofluorescent real samples (e.g., algae, serum), revealing a novel way of employing large pseudo-Stokes shifts to realize the background-free pH measurement and 2D imaging.

4.
Talanta ; 266(Pt 1): 124983, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-37542848

RESUMO

An oleanolic acid (OA) surface molecularly imprinted polymer silylated porous composite aerogels (OA-MIP@Si-PC-aerogels) adsorbent material was successfully prepared and characterized. The material not only has a great selectivity for the target molecule OA but also has other noteworthy qualities including high stability, excellent repeatability, and a sizable adsorption capacity. via cellulose and sodium alginate as the main materials, the carrier Si-PC-aerogels were made through ionic cross-linking, chemical cross-linking, and silylation procedures. By adopting a surface molecular imprinting approach on Si-PC-aerogels, OA-MIP@Si-PC-aerogels were effectively created utilizing OA as the template molecule and MAA as the functional monomer. Due to the presence of a specific imprinted layer on the aerogel surface, the adsorption capacity of OA-MIP@Si-PC-aerogels for OA could reach 66.20 mg g-1. OA-MIP@Si-PC-aerogels could achieve a 68.86% yield of OA from the extracts of lingonberry (Vaccinium Vitis-Idaea L.). The adsorption capacity remained at 90% after five consecutive adsorption-desorption cycles. HepG2 cells were exposed to OA that was effectively enriched with OA-MIP@Si-PC-aerogels in lingonberry (Vaccinium Vitis-Idaea L.) fruit homogenates. This OA significantly inhibited the growth of HepG2 cells in vitro. It further demonstrated that OA-MIP@Si-PC-aerogels could efficiently target OA enrichment and separation with good recovery.


Assuntos
Impressão Molecular , Ácido Oleanólico , Vaccinium vitis-Idaea , Polímeros/química , Celulose , Impressão Molecular/métodos , Adsorção
5.
Front Pharmacol ; 14: 1232774, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37654605

RESUMO

Phosphodiesterase-5 inhibitors (PDE5-i) have been widely used in clinical practice for the treatment of erectile dysfunction (ED). However, due to its suboptimal therapeutic effects and side effects, it is necessary to develop new medicines for ED treatment. Botanical drugs have been widely investigated as potential ED treatment drugs and have shown promising therapeutic effects. This review summarized 34 studies, including five botanical drugs with PDE5 inhibitory activity, seven botanical drugs without PDE5 inhibitory activity, and six mixed botanical drugs. The results of clinical studies regarding the aforementioned botanical drugs and relevant mechanisms are summarized in this study. It is necessary to conduct high-quality clinical trials to verify the dosage, targeted patients and therapeutic effects, and further pharmacology experiments are also needed to identify the active compounds.

6.
Asian J Surg ; 2023 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-37657975
7.
Small ; : e2304847, 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37658511

RESUMO

The "shuttle effect" and slow redox reactions of Li-S batteries limit their practical application. To solve these problems, a judicious catalyst design for improved battery cycle life and rate performance is essential. Herein, this issue is addressed by modifying the Li-S battery separator using a 2D Fe2 O3 -CoP heterostructure that combines the dual functions of polar Fe2 O3 and high-conductivity CoP. The synthesized ultrathin nanostructure exposes well-dispersed active sites and shortens the ion diffusion paths. Theoretical calculations, electrochemical tests, and in situ Raman spectroscopy measurements reveal that the heterostructure facilitates the inhibition of polysulfide shuttling and enhances the electrode kinetics. A sulfur cathode constructed using the Fe2 O3 -CoP-based separator provides an astonishing capacity of 1346 mAh g-1 at 0.2 C and a high capacity retention of ≈84.5%. Even at a high sulfur loading of 5.42 mg cm-2 , it shows an area capacity of 5.90 mAh cm-2 . This study provides useful insights into the design of new catalytic materials for Li-S batteries.

8.
Lancet Reg Health West Pac ; 37: 100799, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37693879

RESUMO

Background: The systematic comparison of cancer survival between China and the USA is rare. Here we aimed to assess the magnitude of survival disparities and disentangle the impact of the stage at diagnosis between a Chinese metropolitan city and the USA on cancer survival. Methods: We included 11,046 newly diagnosed cancer patients in Dalian Cancer Registry, China, 2015, with the follow-up data for vital status until December 2020. We estimated age-standardised 5-year relative survival and quantified the excess hazard ratio (EHR) of death using generalised linear models for all cancers and 20 individual cancers. We compared these estimates with 17 cancer registries' data from the USA, using the Surveillance, Epidemiology, and End Results database. We further estimated the stage-specific survival for five major cancers by region. Findings: Age-standardised 5-year relative survival for all patients in Dalian was lower than that in the USA (49.9% vs 67.9%). By cancer types, twelve cancers with poorer prognosis were observed in Dalian compared to the USA, with the largest gap seen in prostate cancer (Dalian: 55.8% vs USA: 96.0%). However, Dalian had a better survival for lung cancer, cervical cancer, and bladder cancer. Dalian patients had a lower percentage of stage Ⅰ colorectal cancer (Dalian: 17.9% vs USA: 24.2%) and female breast cancer (Dalian: 40.9% vs USA: 48.9%). However, we observed better stage-specific survival among stage Ⅰ-Ⅱ lung cancer patients in Dalian than in the USA. Interpretation: This study suggests that although the overall prognosis for patients was better in the USA than in Dalian, China, survival deficits existed in both countries. Improvement in cancer early detection and cancer care are needed in both countries. Funding: National Key R&D Program (2021YFC2501900, 2022YFC3600805), Major State Basic Innovation Program of the Chinese Academy of Medical Sciences (2021-I2M-1-010, 2021-I2M-1-046), and Talent Incentive Program of Cancer Hospital of Chinese Academy of Medical Sciences.

9.
Int J Biol Macromol ; : 126794, 2023 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-37699463

RESUMO

Targeted separation of active phytochemicals is urgently needed in the natural medicine field. In this paper, due to the natural porosity and high biocompatibility of cellulose, a nanocellulose membrane combined with surface molecular imprinting was successfully prepared; the efficient nanocellulose-based molecular imprinted membrane (NC-MIM) provided good adsorption for the targeted separation of phytochemicals such as 10-deacetylbaccatin III (10-DAB), an essential intermediate in the synthesis of the anticancer drug paclitaxel. Through a series of characterization and adsorption experiments, the adsorption mechanism of NC-MIM was determined. At pH 8.0 and temperatures of 20 °C-40 °C, the maximum capacity of NC-MIM for adsorption of 10-DAB reached 66.90 mg g - 1, and the content of 10-DAB was dramatically increased 17.5-fold after adsorption. The specific adsorption results showed that NC-MIM had excellent capacity for targeted separation of 10-DAB from among taxane structural analogues. Even after ten cycles, NC-MIM demonstrated a remarkable adsorption capacity of 86.43 %, thereby indicating exceptional selectivity and stability. The successful implementation of NC-MIM for green, safe, and efficient enrichment of phytochemicals from plants provides a promising new approach and valuable insights into its practical application.

10.
Cancer Sci ; 2023 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-37702298

RESUMO

Although PARP inhibitor (PARPi) has been proven to be a promising anticancer drug in cancer patients harboring BRCA1/2 mutation, it provides limited clinical benefit in colorectal cancer patients with a low prevalence of BRCA1/2 mutations. In our study, we found PARPi talazoparib significantly induced cellular senescence via inhibiting p53 ubiquitination and activating p21. Furthermore, CDK4/6i palbociclib amplified this therapy-induced senescence (TIS) in vitro and in vivo. Mechanistically, talazoparib and palbociclib combination induced senescence-associated secretory phenotype (SASP), and characterization of SASP components revealed type I interferon (IFN)-related mediators, which were amplified by cGAS/STING signaling. More importantly, RNA sequencing data indicated that combination therapy activated T cell signatures and combination treatment transformed the tumor microenvironment (TME) into a more antitumor state with increased CD8 T cells and natural killer (NK) cells and decreased macrophages and granulocytic myeloid-derived suppressor cells (G-MDSCs). Moreover, clearance of the TIS cells by αPD-L1 promoted survival in immunocompetent mouse colorectal cancer models. Collectively, we elucidated the synergistic antitumor and immunomodulatory mechanisms of the talazoparib-palbociclib combination. Further combination with PD-L1 antibody might be a promising "one-two punch" therapeutic strategy for colorectal cancer patients.

11.
Adv Sci (Weinh) ; : e2300993, 2023 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-37697644

RESUMO

Hereditary primary hypogonadism (HPH), caused by gene mutation related to testosterone synthesis in Leydig cells, usually impairs male sexual development and spermatogenesis. Genetically corrected stem Leydig cells (SLCs) transplantation may provide a new approach for treating HPH. Here, a novel nonsense-point-mutation mouse model (LhcgrW495X ) is first generated based on a gene mutation relative to HPH patients. To verify the efficacy and feasibility of SLCs transplantation in treating HPH, wild-type SLCs are transplanted into LhcgrW495X mice, in which SLCs obviously rescue HPH phenotypes. Through comparing several editing strategies, optimized PE2 protein (PEmax) system is identified as an efficient and precise approach to correct the pathogenic point mutation in Lhcgr. Furthermore, delivering intein-split PEmax system via lentivirus successfully corrects the mutation in SLCs from LhcgrW495X mice ex vivo. Gene-corrected SLCs from LhcgrW495X mice exert ability to differentiate into functional Leydig cells in vitro. Notably, the transplantation of gene-corrected SLCs effectively regenerates Leydig cells, recovers testosterone production, restarts sexual development, rescues spermatogenesis, and produces fertile offspring in LhcgrW495X mice. Altogether, these results suggest that PE-based gene editing in SLCs ex vivo is a promising strategy for HPH therapy and is potentially leveraged to address more hereditary diseases in reproductive system.

12.
Molecules ; 28(17)2023 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-37687149

RESUMO

To improve the utilization value of raspberry leaves, the extraction and purification conditions of phenolic compounds from raspberry leaves were optimized, and the contents of phenolic compounds and the biological activities of extracts were studied. After steam explosion pretreatment at 115 °C for 15 min, raspberry leaf extract with a total phenolic content (TPC) of 136.30~140.51 mg GAE/g was obtained via homogenization and ultrasound-assisted extraction. In addition, the adsorption relationship between raspberry leaf polyphenols and middle polar XDA-6 macroporous resin was best described by the Langmuir model, and tended to be monolayer adsorption. Its adsorption kinetics best resembled the pseudo second-order kinetic model, and it was speculated that this was influenced by multiple factors. According to the optimal integrated extraction-purification process, the TPC of the extracts increased to 738.98 mg GAE/g after one application of purification and 905.27 mg GAE/g after two applications of purification. Moreover, the latter case showed the highest antioxidant activity and α-glucosidase inhibition activity, and the content of the most typical compound, quercetin-3-glucuronide, reached 199.69 mg/g. SE has a double-edged effect, and is more conducive to the release of active substances as a pre-treatment method. This study provides a theoretical basis for the efficient use of raspberry leaves, further improving their medicinal and economic value.


Assuntos
Polifenóis , Rubus , Polifenóis/farmacologia , Fenóis , Adsorção , Extratos Vegetais/farmacologia
13.
Artigo em Inglês | MEDLINE | ID: mdl-37689589

RESUMO

BACKGROUND: The role of mitophagy in various cancer-associated biological processes is well recognized. Nonetheless, the comprehensive implications of mitophagy in clear cell renal cell carcinoma (ccRCC) necessitate further exploration. METHODS: Based on the transcriptomic data encompassing 25 mitophagy-related genes (MRGs), we identified the distinct mitophage patterns in 763 ccRCC samples. Subsequently, a mitophage-related predictive signature with machine learning algorithms was constructed, designated as RiskScore, to quantify the individual mitophagy status in ccRCC patients. Employing multispectral immunofluorescence (mIF) and immunohistochemistry (IHC) staining, we detected the effect of PTEN-induced putative kinase 1 (PINK1) in the prognosis and immune microenvironment of ccRCC. RESULTS: Our analysis initially encompassed a comprehensive assessment of the expression profiling, genomic variations, and interactions among the 25 MRGs in ccRCC. Subsequently, the consensus clustering algorithm was applied to stratify ccRCC patients into three clusters with distinct prognostic outcomes, tumor microenvironment (TME) characteristics, and underlying biological pathways. We screened eight pivotal genes (CLIC4, PTPRB, SLC16A12, ENPP5, FLRT3, HRH2, PDK4, and SCD5) to construct a mitophagy-related predictive signature, which showed excellent prognostic value for ccRCC patients. Moreover, patient subgroups divided by the RiskScore showed contrasting expression levels of immune checkpoints (ICPs), abundance of immune cells, and immunotherapy response. Additionally, a nomogram was established with robust predictive power integrating the RiskScore and clinical features. Notably, we observed that PINK1 expression markedly correlated with favorable treatment response and advanced maturation stages of tertiary lymphoid structures, which potentially shed light on enhancing anti-tumor immunity of ccRCC. CONCLUSION: Collectively, this study initially developed a signature associated with mitophagy, which demonstrated an excellent ability to predict the clinical prognosis, TME characterization, and responsiveness to targeted therapy and immunotherapy for ccRCC patients. Of particular note is the pivotal role of PINK1 in mediating the treatment response and immune microenvironment for ccRCC patients.

15.
Asian J Androl ; 2023 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-37695210

RESUMO

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), also known as National Institutes of Health (NIH) type III prostatitis, is a common disorder with an unclear etiology and no known curative treatments. Based on the presence or absence of leukocytes in expressed prostatic secretion (EPS), CP/CPPS is classified further into IIIa (inflammatory) and IIIb (noninflammatory) subtypes. However, the severity of symptoms is not entirely consistent with the white blood cell (WBC) count. Following the preliminary finding of a link between inflammatory cytokines and CP/CPPS, we performed this clinical study with the aim of identifying cytokines that are differentially expressed according to whether the prostatitis subtype is IIIa or IIIb. We found that granulocyte colony-stimulating factor (G-CSF), interleukin-18 (IL-18), and monocyte chemoattractant protein-1 (MCP-1) levels were significantly elevated and interferon-inducible protein-10 (IP-10) and platelet-derived growth factor-BB (PDGF-BB) levels were downregulated in the EPS of patients with type IIIa prostatitis. In a word, it is a meaningful study in which we investigate the levels of various cytokines in EPS according to whether prostatitis is the IIIa or IIIb subtype. The combination of G-CSF, IL-18, MCP-1, IP-10, and PDGF-BB expression levels could form a basis for classification, diagnosis, and therapeutic targets in clinical CP/CPPS.

16.
Sci Rep ; 13(1): 14359, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-37658132

RESUMO

Oxaliplatin is widely used in chemotherapy for colorectal cancer (CRC), but its sensitivity has become a major obstacle to limiting efficacy. Many literatures reported that Nrf2 activation promoted tumor chemoresistance. In this study, we explored the role and mechanism of Nrf2 inhibition in oxaliplatin-based chemosensitivity of CRC. In vitro experiments, we applied 4-octyl itaconate (4-OI) to activate Nrf2, and used lentivirus to knock down Nrf2 in CRC cell lines. By measuring cell viability, colony formation, apoptosis, reactive oxygen species production, and western blot, we found that oxaliplatin and lobaplatin suppressed the growth of HCT-116 and LOVO cells in a dose-dependent manner, and promoted the expression of Nrf2. 4-OI, an Nrf2 activator, reduced the sensibility of CRC cells to oxaliplatin and lobaplatin, while the knockdown of Nrf2 promoted the sensibility of CRC cells to oxaliplatin and lobaplatin. Through the public databases, we found that the expression of GPX4 in normal tissues was lower compared with cancer tissues in CRC, and the high GPX4 expression predicted a poor prognosis. Meanwhile, we found that oxaliplatin reduced the expression of GPX4 in vitro. The knockdown of Nrf2 enhanced the effects of oxaliplatin to reduce the expression of GPX4 and GSH content, and increase the MDA content, which enhanced oxaliplatin-induced ferroptosis. Subsequently, we found that oxaliplatin promoted the expression of GSDME-N, and induced LDH, IL-1ß, and TNF-a release, and the knockdown of Nrf2 aggravated the occurrence of GSMDE-mediated pyroptosis. Finally, we found that the knockdown of Nrf2 enhanced the inhibition of oxaliplatin on HCT116 xenograft tumor growth in vivo. Thus, our study showed that Nrf2 inhibition improved sensitivity to oxaliplatin of CRC cells by promoting ferroptosis and pyroptosis, which provided a new target for overcoming chemoresistance in CRC.


Assuntos
Neoplasias Colorretais , Ferroptose , Humanos , Piroptose , Fator 2 Relacionado a NF-E2/genética , Oxaliplatina/farmacologia , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética
17.
Sci Rep ; 13(1): 14536, 2023 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-37666872

RESUMO

The seed oil of Echium plantagineum L. is rich in unsaturated fatty acids. With the gradual development of the value of echium oil in food, medical care and cosmetics, the corresponding market demand has also increased. The selection of suitable cultivars and the increase of yield per unit area has also become one of the main objectives of current breeding and cultivation of E. plantagineum. To effectively use the local photothermal resources, to improve the use of light energy by E. plantagineum, and to enhance the growth and yield of E. plantagineum. E. plantagineum cultivars Blue Bedder and Mixed Bedding were used as research subjects to study the effects of different sowing dates (1 May, 8 May, 15 May, 22 May and 29 May) on the photosynthetic characteristics and yield of E. plantagineum. Under the same cultivar conditions, with the delay in sowing date, the leaf chlorophyll content (SPAD), photosynthetic rate (Pn), transpiration rate (Tr), stomatal limitation value (Ls), photochemical quenching (qP), electron transfer rate (ETR), actual photochemical efficiency (ΦpsII) and yield of Blue Bedder decreased and reached a maximum at T1, while the SPAD, Pn, Tr, water use efficiency (WUE), Ls, initial fluorescence (Fo), maximum fluorescence (Fm), qP, ETR, ΦpsII and yield of Mixed Bedding reached the maximum at T4. Blue Bedder should be sown early at T1 and Mixed Bedding late at T4 during planting, which will help to improve the photosynthetic characteristics and grain yield of E. plantagineum.


Assuntos
Echium , Humanos , Fluorescência , Melhoramento Vegetal , Clorofila , Grão Comestível
18.
Heliyon ; 9(9): e19244, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37674841

RESUMO

Infantile hemangioma (IH) is among the most prevalent benign vascular tumours in infants. The pathogenesis of IH mainly involves abnormal proliferation of vascular endothelial cells and the formation of new vessels. Itraconazole was shown to be effective in treating IH; however, the mechanism underlying its action is still unclear. The purpose of this study was to examine the effects of itraconazole on the proliferation, apoptosis, and angiogenesis of hemangioma endothelial cells (HemECs); human umbilical vein endothelial cells served as the control group. The expression of genes involved in the hedgehog (HH) signaling pathway (SHH, PTCH1, SMO, and GLI1) was determined using real-time quantitative polymerase chain reaction. Western blotting was used to determine the expression of related proteins. In this study, itraconazole significantly dose- and time-dependently inhibited the viability of HemECs. Itraconazole suppressed the expression of PCNA, Ki67, and vascular endothelial growth factor (VEGF), demonstrating that this treatment inhibited cell proliferation and angiogenesis. Moreover, itraconazole induced apoptosis of HemECs by activating the expression of BAX and inhibiting the expression of BCL2. Itraconazole inhibited SHH, PTCH1, SMO, and GLI1 expression. Activation of the HH pathway by recombinant human sonic hedgehog (rhSHH) protein attenuated the effect of itraconazole on HemECs. In conclusion, itraconazole inhibits proliferation, induces apoptosis, and reduces angiogenesis of HemECs via the downregulation of the HH signaling pathway. Therefore, itraconazole may be an alternative choice for the treatment of IH.

19.
Int J Surg ; 2023 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-37678274

RESUMO

BACKGROUND: Cholangitis is common in patients with biliary atresia following Kasai portoenterostomy (KPE). The prompt use of empiric antibiotics is essential due to the lack of identified microorganisms. The authors aimed to validate a severity grading system to guide empiric antibiotic therapy in the management of post-KPE cholangitis. MATERIALS AND METHODS: This multicenter, prospective, randomized, open-label study recruited patients with post-KPE cholangitis and was conducted from January 2018 to December 2019. On admission, patients were categorized into mild, moderate, and severe cholangitis according to the severity grading system. Patients in the mild cholangitis group were randomized to receive cefoperazone sodium tazobactam sodium (CSTS) or meropenem (MEPM). Patients with severe cholangitis were randomized to treatment with MEPM or a combination of MEPM plus immunoglobulin (MEPM+IVIG). Patients with moderate cholangitis received MEPM. RESULTS: The primary endpoint was duration of fever (DOF). Secondary outcomes included blood culture, length of hospital stay, incidence of recurrent cholangitis, jaundice clearance rate, and native liver survival (NLS). For mild cholangitis, DOF, and length of hospital stay were similar between those treated with CSTS or MEPM (all P>0.05). In addition, no significant difference in recurrence rate, jaundice clearance rate, and NLS was observed between patients treated with CSTS and MEPM at 1-month, 3-month, and 6-month follow-up. In patients with moderate cholangitis, the DOF was 36.00 (interquartile range: 24.00-48.00) h. In severe cholangitis, compared with MEPM, MEPM+IVIG decreased DOF and improved liver function by reducing alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, and direct bilirubin at 1-month follow-up. However, recurrence rate, jaundice clearance rate, and NLS did not differ significantly between MEPM+IVIG and MEPM at 1-month, 3-month, and 6-month follow-up. CONCLUSIONS: In patients with post-KPE cholangitis, MEPM is not superior to CSTS for the treatment of mild cholangitis. However, MEPM+IVIG treatment was associated with better short-term clinical outcomes in patients with severe cholangitis.

20.
Artigo em Inglês | MEDLINE | ID: mdl-37668661

RESUMO

BACKGROUND: The optimal internal fixation for non-displaced femoral neck fractures remains controversial. This study aimed to compare the clinical results of the percutaneous compression plate (PCCP) with parallel screws (PS) in treating femoral neck fractures in elderly patients. MATERIALS AND METHODS: A total of 218 patients who underwent internal fixation were randomized to receive either a percutaneous compression plate (PCCP group) or parallel screws (PS group) using a computerized random sequence generator which was used to assign the order of randomization. Patients were assessed by the operating time, intraoperative blood loss, hemoglobin level drop, postoperative hospital stay, the time to full weight-bearing, reduction quality, fracture healing time, Harris hip score, and postoperative complications. RESULTS: There was no significant difference between PCCP and PS groups regarding operative time, intraoperative blood loss, hemoglobin level drop, postoperative hospital stays, reduction quality, and Harris hip score (p > 0.05). The time to full weight-bearing and the fracture healing time in the PCCP group were shorter than those in the PS group (p < 0.05). The overall complication rates were slightly lower in the PCCP compared to the PS patients, but there was no significant difference (p > 0.05). However, the implant failure rate was significantly higher in the PS group compared to the PCCP group (p < 0.05). CONCLUSIONS: The present study suggests that the PCCP is superior to the parallel screws fixation in the treatment of non-displaced elderly femoral neck fractures in terms of earlier full weight-bearing, shorter fracture healing time, and lower implant failure rate. Therefore, it may be a better therapeutic strategy for non-displaced femoral neck fractures in elderly patients.

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