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1.
Int Wound J ; 21(2): e14778, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38356179

RESUMO

A meta-analysis was conducted to comprehensively evaluate the impact of wound drainage on postoperative wound infection and healing in patients undergoing spinal surgery. Computer searches were performed, from database inception to October 2023, in EMBASE, Google Scholar, Cochrane Library, PubMed, Wanfang and China National Knowledge Infrastructure databases for studies related to the application of wound drainage in spinal surgery. Two researchers independently screened the literature, extracted data and conducted quality assessments. Stata 17.0 software was employed for data analysis. Overall, 11 articles involving 2102 spinal surgery patients were included. The analysis showed that, compared to other treatment methods, the use of wound drainage in spinal surgery patients significantly shortened the wound healing time (standardized mean difference [SMD]: -1.35, 95% confidence intervals [CI]: -1.91 to -0.79, p < 0.001). However, there was no statistical difference in the incidence of wound infection (odds ratio: 1.35, 95% CI: 0.83-2.19, p = 0.226). This study indicates that wound drainage in patients undergoing spinal surgery is effective, can accelerate wound healing and is worth promoting in clinical practice.


Assuntos
Procedimentos Neurocirúrgicos , Infecção da Ferida Cirúrgica , Humanos , Infecção da Ferida Cirúrgica/epidemiologia , Cicatrização , Fatores de Tempo , Drenagem/métodos
2.
Signal Transduct Target Ther ; 9(1): 40, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38355661

RESUMO

Emerging and recurrent infectious diseases caused by human coronaviruses (HCoVs) continue to pose a significant threat to global public health security. In light of this ongoing threat, the development of a broad-spectrum drug to combat HCoVs is an urgently priority. Herein, we report a series of anti-pan-coronavirus ssDNA aptamers screened using Systematic Evolution of Ligands by Exponential Enrichment (SELEX). These aptamers have nanomolar affinity with the nucleocapsid protein (NP) of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and also show excellent binding efficiency to the N proteins of both SARS, MERS, HCoV-OC43 and -NL63 with affinity KD values of 1.31 to 135.36 nM. Such aptamer-based therapeutics exhibited potent antiviral activity against both the authentic SARS-CoV-2 prototype strain and the Omicron variant (BA.5) with EC50 values at 2.00 nM and 41.08 nM, respectively. The protein docking analysis also evidenced that these aptamers exhibit strong affinities for N proteins of pan-coronavirus and other HCoVs (-229E and -HKU1). In conclusion, we have identified six aptamers with a high pan-coronavirus antiviral activity, which could potentially serve as an effective strategy for preventing infections by unknown coronaviruses and addressing the ongoing global health threat.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , Proteínas do Nucleocapsídeo/genética , Antivirais/farmacologia
3.
J Exp Clin Cancer Res ; 43(1): 47, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38342925

RESUMO

In tumor therapeutics, the transition from conventional cytotoxic drugs to targeted molecular therapies, such as those targeting receptor tyrosine kinases, has been pivotal. Despite this progress, the clinical outcomes have remained modest, with glioblastoma patients' median survival stagnating at less than 15 months. This underscores the urgent need for more specialized treatment strategies. Our review delves into the progression toward immunomodulation in glioma treatment. We dissect critical discoveries in immunotherapy, such as spotlighting the instrumental role of tumor-associated macrophages, which account for approximately half of the immune cells in the glioma microenvironment, and myeloid-derived suppressor cells. The complex interplay between tumor cells and the immune microenvironment has been explored, revealing novel therapeutic targets. The uniqueness of our review is its exhaustive approach, synthesizing current research to elucidate the intricate roles of various molecules and receptors within the glioma microenvironment. This comprehensive synthesis not only maps the current landscape but also provides a blueprint for refining immunotherapy for glioma, signifying a paradigm shift toward leveraging immune mechanisms for improved patient prognosis.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Glioma , Células Supressoras Mieloides , Humanos , Glioma/patologia , Glioblastoma/patologia , Imunoterapia , Imunomodulação , Microambiente Tumoral , Neoplasias Encefálicas/tratamento farmacológico
4.
Exp Ther Med ; 27(3): 108, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38356664

RESUMO

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

5.
ACS Nano ; 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38358804

RESUMO

Tumor-associated macrophages (TAMs) are closely related to the progression of glioblastoma multiform (GBM) and its development of therapeutic resistance to conventional chemotherapy. TAM-targeted therapy combined with conventional chemotherapy has emerged as a promising strategy to combat GBM. However, the presence of the blood-brain barrier (BBB) severely limits the therapeutic efficacy. Meanwhile, the lack of ability to distinguish different targeted cells also poses a challenge for precise therapy. Herein, we propose a cathepsin B (CTSB)-responsive programmed brain-targeted delivery system (D&R-HM-MCA) for simultaneous TAM-targeted and GBM-targeted delivery. D&R-HM-MCA could cross the BBB via low density lipoprotein receptor-associated protein 1 (LRP1)-mediated transcytosis. Upon reaching the GBM site, the outer angiopep-2 modification could be detached from D&R-HM-MCA via cleavage of the CTSB-responsive peptide, which could circumvent abluminal LRP1-mediated efflux. The exposed p-aminophenyl-α-d-mannopyranoside (MAN) modification could further recognize glucose transporter-1 (GLUT1) on GBM and macrophage mannose receptor (MMR) on TAMs. D&R-HM-MCA could achieve chemotherapeutic killing of GBM and simultaneously induce TAM polarization from anti-inflammatory M2 phenotype to pro-inflammatory M1 phenotype, thus resensitizing the chemotherapeutic response and improving anti-GBM immune response. This CTSB-responsive brain-targeted delivery system not only can improve brain delivery efficiency, but also can enable the combination of chemo-immunotherapy against GBM. The effectiveness of this strategy may provide thinking for designing more functional brain-targeted delivery systems and more effective therapeutic regimens.

6.
Front Cell Infect Microbiol ; 14: 1332490, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38312743

RESUMO

Anal fistula is a common perianal disease that typically develops from an abscess caused by in-flammation in the area. It has long been believed that intestinal microbes play a significant role in its development, considering its close relation to the intestinal environment. This work attempts to identify the microbiomic signatures of anal fistula, and putative sources of microbes by analyzing microbiomes of 7 anal fistula-associated sites in 12 patients. This study found that microbes in anal fistulas may originate from the skin surface in addition to the intestinal tract. This finding was further validated by NMDS analysis, which also indicated that the microbial communities in the inner and outer openings of the fistula were more similar to their surrounding environments. Using MaAslin2, the characteristics of the microbiome were examined, demonstrating a higher similarity between the abundant bacteria in the anal fistula samples and those found on the skin surface. Moreover, pin-to-pair analysis conducted on all subjects consistently showed a higher abundance of skin-sourced bacteria in anal fistulas. This study identifies the microbiomic signatures of anal fistula, and provides novel insights into the origin of microorganisms in anal fistulas.


Assuntos
Microbiota , Fístula Retal , Humanos , Pele , Resultado do Tratamento
7.
Plant Physiol Biochem ; 207: 108430, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38364632

RESUMO

Copper oxide nanoparticles (CuO NPs) influence the uptake of heavy metal ions by plants, but molecular mechanism is still unknown. Here, we proved the mechanism of CuO NPs affecting Cd absorption in Arabidopsis root. 4-d-old seedlings were treated by 10 and 20 mg/L CuO NPs for 3 d, which decreased the contents of cellulose and hemicellulose in roots. Moreover, the contents of some important monosaccharides were altered by CuO NPs, including arabinose, glucose and mannose. Biosynthesis of cellulose and hemicellulose is regulated by cellulose synthase A complexe (CSC) dynamics. The synthesis of tubulin cytoskeleton was inhibited by CuO NPs, which resulted in the decrease of CSCs bidirectional velocities. Furthermore, the arrangement and network of cellulose fibrillar bundles were disrupted by CuO NPs. CuO NPs treatment significantly increased the influx of Cd2+. The accumulation and translocation of Cd were increased by 10 and 20 mg/L CuO NPs treatment. The subcellular distribution of Cd in root cells indicated CuO NPs decrease the enrichment of Cd in cell wall, but increase the enrichment of Cd in soluble fraction and organelle. In light of these findings, we proposed a mechanistic model in which CuO NPs destroy the ordered structure of the cell wall, alter the uptake and distribution of Cd in Arabidopsis.

8.
Int Wound J ; 21(2): e14777, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38361227

RESUMO

In knee osteoarthritis surgery, managing postoperative wound healing and minimizing scar formation are pivotal for patient recovery and satisfaction. These aspects are particularly challenging due to the nature of the surgical procedure and patient demographics. Physiotherapy interventions are increasingly recognized for their role in improving these postoperative outcomes. This meta-analysis sought to evaluate the efficacy of physiotherapy in enhancing wound healing, as measured by REEDA scores, and reducing scar formation, as indicated by Manchester Scar Scale (MSS) scores, following knee osteoarthritis surgery. Analysing data from eight studies, we found that physiotherapy significantly improved wound healing, evidenced by lower REEDA scores (SMD = -19.58, 95% CI: [-22.49, -16.66], p < 0.01), and reduced scar formation, reflected in lower MSS scores (SMD = -24.79, 95% CI: [-30.03, -19.55], p < 0.01). These findings highlight the crucial role of physiotherapy in postoperative care for knee osteoarthritis patients, emphasizing its impact on enhancing recovery and improving surgical outcomes.


Assuntos
Osteoartrite do Joelho , Humanos , Osteoartrite do Joelho/cirurgia , Cicatriz , Modalidades de Fisioterapia , Cicatrização , Cuidados Pós-Operatórios
9.
Biochem Biophys Rep ; 37: 101655, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38333051

RESUMO

Background: Previous studies have shown that the nicotinamide adenine dinucleotide (NAD+) precursors, nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR), protect against endogenously or exogenously induced DNA damage. However, whether the two compounds have the same or different efficacy against DNA damage is not clear. In the current study, we systematically compared the effects of NMN and NR on cisplatin-induced DNA damage in HeLa cells. Methods: To evaluate the protective effects of NMN or NR, HeLa cells were pretreated with different doses of NMN or NR followed with 10 µM of cisplatin treatment. Cell viability was examined by Trypan blue staining assay. For observing the DNA damage repair process, HeLa cells were treated with 10 µM of cisplatin for 12 h, followed with 10 mM NMN or NR treatment for another 8, 16, 24, or 32 h, DNA damage levels were assessed for each time point by immunofluorescent staining against phosphor-H2AX (γH2AX) and alkaline comet assay. The effects of NMN and NR on intracellular NAD+ and reactive oxygen species (ROS) levels were also determined. Results: NMN and NR treatment alone did not have any significant effects on cell viability, however, both can protect HeLa cells from cisplatin-induced decrease of cell viability with similar efficacy in a dose-dependent manner. On the other hand, while both can reduce the DNA damage levels in cisplatin-treated cells, NR exhibited better protective effect. However, both appeared to boost the DNA damage repair process with similar efficacy. NMN or NR treatment alone could increase cellular NAD+ levels, and both can reverse cisplatin-induced decrease of NAD+ levels. Finally, while neither NMN nor NR affected cellular ROS levels, both inhibited cisplatin-induced increase of ROS with no significant difference between them. Conclusion: NR have a better protective effect against cisplatin-induced DNA damage than NMN.

11.
Polymers (Basel) ; 16(3)2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38337254

RESUMO

Despite their effectiveness in preventing icing, hydrophobic coatings possess drawbacks such as susceptibility to detachment and limited wear resistance, leading to inadequate longevity in melting ice/snow. To enhance the surface stability and durability of superhydrophobic coatings, nanoparticle/epoxy formulations were developed using three types of nanoparticles, two dispersion techniques, three application methods, and two epoxy resin introduction approaches. Testing encompassed water contact angle measurements, assessment of ice adhesion force, and determination of icing rates on asphalt concrete coated with these hydrophobic formulations. Fourier-transform infrared spectroscopy was employed to analyze the molecular structures of the coatings, while scanning electron microscopy facilitated observation of the surface morphology of the hydrophobic coatings. The findings indicated that nano-ZnO, TiO2, and SiO2 particles could be modified into hydrophobic forms using stearic acid. Application of the hydrophobic coating improved the concrete's hydrophobicity, reduced ice adhesion strength on both concrete and asphalt, and delayed the onset of icing. Furthermore, optimal dosages of stearic acid, nanoparticles, and epoxy resin were identified as crucial parameters within specific ranges to ensure the optimal hydrophobicity and durability of the coatings.

12.
Cureus ; 16(1): e52063, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38344586

RESUMO

Hypokalemic Periodic Paralysis Type 2 (HOKPP2) is a rare autosomal dominant disorder characterized by recurrent episodes of muscle weakness, paralysis, and hypokalemia. In this case report, we present the clinical details of a 49-year-old female diagnosed with HOKPP2. Genetic testing revealed a heterozygous mutation in the Sodium Voltage-Gated Channel Alpha Subunit 4 (SCN4A) gene, confirming the diagnosis of HOKPP2. Management strategies, including potassium supplementation and lifestyle modifications, were implemented, resulting in a significant decrease in the frequency of symptomatic episodes. This case highlights the importance of considering HOKPP2 in patients with recurrent muscle weakness, particularly those with a familial history of similar symptoms. Furthermore, it underscores the crucial role of genetic testing in guiding patient management and facilitating genetic counseling.

13.
Parasite Immunol ; 46(2): e13023, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38372452

RESUMO

Toxoplasmosis is one of the most dangerous zoonotic diseases, causing serious economic losses worldwide due to abortion and reproductive problems. Vaccination is the best way to prevent disease; thus, it is imperative to develop a candidate vaccine for toxoplasmosis. BAG1 and ROP8 have the potential to become vaccine candidates. In this study, rTgBAG1, rTgROP8, and rTgBAG1-rTgROP8 were used to evaluate the immune effect of vaccines in each group by detecting the humoral and cellular immune response levels of BABL/c mice after immunization and the ability to resist acute and chronic infection with Toxoplasma gondii (T. gondii). We divided the mice into vaccine groups with different proteins, and the mice were immunized on days 0, 14, and 28. The protective effects of different proteins against T. gondii were analysed by measuring the cytokines, serum antibodies, splenocyte proliferation assay results, survival time, and number and diameter of brain cysts of mice after infection. The vaccine groups exhibited substantially higher IgG, IgG1, and IgG2a levels and effectively stimulated lymphocyte proliferation. The levels of IFN-γ and IL-2 in the vaccine group were significantly increased. The survival time of the mice in each vaccine group was prolonged and the diameter of the cysts in the vaccine group was smaller; rTgBAG1-rTgROP8 had a better protection. Our study showed that the rTgBAG1, rTgROP8, and rTgBAG1-rTgROP8 recombinant protein vaccines are partial but effective approaches against acute or chronic T. gondii infection. They are potential candidates for a toxoplasmosis vaccine.

14.
Nanomicro Lett ; 16(1): 122, 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38372850

RESUMO

Compared with traditional piezoelectric ultrasonic devices, optoacoustic devices have unique advantages such as a simple preparation process, anti-electromagnetic interference, and wireless long-distance power supply. However, current optoacoustic devices remain limited due to a low damage threshold and energy conversion efficiency, which seriously hinder their widespread applications. In this study, using a self-healing polydimethylsiloxane (PDMS, Fe-Hpdca-PDMS) and carbon nanotube composite, a flexible optoacoustic patch is developed, which possesses the self-healing capability at room temperature, and can even recover from damage induced by cutting or laser irradiation. Moreover, this patch can generate high-intensity ultrasound (> 25 MPa) without the focusing structure. The laser damage threshold is greater than 183.44 mJ cm-2, and the optoacoustic energy conversion efficiency reaches a major achievement at 10.66 × 10-3, compared with other carbon-based nanomaterials and PDMS composites. This patch is also been successfully examined in the application of acoustic flow, thrombolysis, and wireless energy harvesting. All findings in this study provides new insight into designing and fabricating of novel ultrasound devices for biomedical applications.

15.
Br J Cancer ; 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38316994

RESUMO

The "undruggable" MYC oncoproteins are deregulated in 70% human cancers. The approval of DFMO, an irreversible inhibitor of ornithine oxidase (ODC1) that is a direct transcriptional target of MYC, demonstrates that patients can benefit from targeting MYC activity via an indirect approach. However, the mechanism of action of DFMO needs further studies to understand how it works in post-immunotherapy neuroblastomas. Efforts to develop a more potent and safer drug to block MYC function will continue despite challenges.

16.
Proc Natl Acad Sci U S A ; 121(7): e2314085121, 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38330013

RESUMO

Cancer therapy, including immunotherapy, is inherently limited by chronic inflammation-induced tumorigenesis and toxicity within the tumor microenvironment. Thus, stimulating the resolution of inflammation may enhance immunotherapy and improve the toxicity of immune checkpoint inhibition (ICI). As epoxy-fatty acids (EpFAs) are degraded by the enzyme soluble epoxide hydrolase (sEH), the inhibition of sEH increases endogenous EpFA levels to promote the resolution of cancer-associated inflammation. Here, we demonstrate that systemic treatment with ICI induces sEH expression in multiple murine cancer models. Dietary omega-3 polyunsaturated fatty acid supplementation and pharmacologic sEH inhibition, both alone and in combination, significantly enhance anti-tumor activity of ICI in these models. Notably, pharmacological abrogation of the sEH pathway alone or in combination with ICI counter-regulates an ICI-induced pro-inflammatory and pro-tumorigenic cytokine storm. Thus, modulating endogenous EpFA levels through dietary supplementation or sEH inhibition may represent a unique strategy to enhance the anti-tumor activity of paradigm cancer therapies.


Assuntos
Epóxido Hidrolases , Neoplasias , Camundongos , Humanos , Animais , Epóxido Hidrolases/metabolismo , Ácidos Graxos/metabolismo , Inflamação/metabolismo , Neoplasias/terapia , Imunoterapia , Microambiente Tumoral
17.
Heliyon ; 10(2): e24371, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38298695

RESUMO

Purpose: The aim of this study is to investigate a new method that combines radiological and pathological breast cancer information to predict discrepancies in pathological responses for individualized treatment planning. We used baseline multiparametric magnetic resonance imaging and hematoxylin and eosin-stained biopsy slides to extract quantitative feature information and predict the pathological response to neoadjuvant chemotherapy in breast cancer patients. Methods: We retrospectively collected data from breast cancer patients who received neoadjuvant chemotherapy in our hospital from August 2016 to January 2018; multiparametric magnetic resonance imaging (contrast-enhanced T1-weighted imaging and diffusion-weighted imaging) and whole slide image of hematoxylin and eosin-stained biopsy sections were collected. Quantitative imaging features were extracted from the multiparametric magnetic resonance imaging and the whole slide image were used to construct a radiopathomics signature model powered by machine learning methods. Models based on multiparametric magnetic resonance imaging or whole slide image alone were also constructed for comparison and referred to as the radiomics signature and pathomics signature models, respectively. Four modeling methods were used to establish prediction models. Model performances were evaluated using receiver operating characteristic curve analysis and the area under the curve, accuracy, sensitivity, specificity, positive predictive value, and negative predictive value. Results: The radiopathomics signature model had favourable performance for the prediction of pathological complete response in the training set (the best value: area under the curve 0.83, accuracy 0.84, and sensitivity 0.87), and in the test set (the best value: area under the curve 0.91, accuracy 0.90, and sensitivity 0.88). In the test set, the radiopathomics signature model also significantly outperformed the radiomics signature (the best value: area under the curve 0.83, accuracy 0.64, and sensitivity 0.62), pathomics signature (the best value: area under the curve 0.60, accuracy 0.74, and sensitivity 0.62) (p > 0.05). Decision curve analysis and calibration curves confirmed the excellent performance of these prediction models in discrimination, calibration, and clinical usefulness. Conclusions: The results of this study suggest that radiopathomics, the combination of both radiological information regarding the whole tumor and pathological information at the cellular level, could potentially predict discrepancies in pathological response and provide evidence for rational treatment plans.

18.
Aesthetic Plast Surg ; 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38315230

RESUMO

BACKGROUND: With an increasing number of East Asians undergoing blepharoplasty, the number of patients with secondary upper eyelid deformities is increasing. The sunken eyelid deformity is a common deformity after upper blepharoplasty in Asians due to over-resection, retraction, or atrophy of the nasal and central orbital fat pads. Herein, we present a novel procedure, the pendulum movement of orbital fat and retro-orbicularis oculi fat ("POR" technique), for correction of sunken eyelid deformity in secondary Asian blepharoplasty. METHODS: Patients who underwent secondary upper blepharoplasty with the POR technique by the senior author between January 2020 and October 2021 were identified retrospectively. Those with fewer than 6 months of follow-up were excluded. Patient charts and images were reviewed for demographic data, comorbidities, concomitant eyelid deformities, and postoperative complications. Pre- and postoperative aesthetics, including degree of sunken eyelid deformity, were assessed by two independent raters and by self-reported patient satisfaction. RESULTS: Forty-nine consecutive patients were identified, all of whom were female and had grade I or II sunken eyelid deformity. Median follow-up was 8 months. Concomitant deformities included high tarsal crease (N = 31 patients, 63.3%), ptosis (N = 13, 26.5%), and upper eyelid retraction (N = 5, 10.2%). Almost patients had improvement in their eyelid volume, and 95.9% had improvement in their aesthetic rating. Approximately 93.9% of patients were satisfied with the outcome. CONCLUSIONS: The POR technique is an effective technique for correction of sunken eyelid deformity and can be utilized in conjunction with other techniques during secondary blepharoplasty. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

19.
Orthop Surg ; 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38316415

RESUMO

PURPOSE: Multilevel cervical spondylotic myelopathy poses significant challenges in selecting optimal surgical approaches, warranting a comprehensive understanding of their biomechanical impacts. Given the lack of consensus regarding the most effective technique, this study aims to fill this critical knowledge gap by rigorously assessing and comparing the biomechanical properties of three distinct surgical interventions, including anterior controllable antedisplacement and fusion (ACAF), anterior cervical corpectomy decompression and fusion (ACCF), and anterior cervical discectomy and fusion (ACDF). The study offers pivotal insights to enhance treatment precision and patient outcomes. METHODS: The construction of the cervical spine model involved a detailed process using CT data, specialized software (Mimics, Geomagic Studio, and Hypermesh) and material properties obtained from prior studies. Surgical instruments were modeled (titanium mesh, anterior cervical plate, interbody cage, and self-tapping screws) to simulate three surgical approaches: ACAF, ACCF, and ACDF, each with specific procedures replicating clinical protocols. A 75-N follower load with 2 Nm was applied to simulate biomechanical effects. RESULTS: The range of motion decreased more after surgery for ACAF and ACDF than for ACCF, especially in flexion and lateral bending. ACCF have higher stress peaks in the fixation system than those of ACAF and ACDF, especially in flexion. The maximum von Mises stresses of the bone-screw interfaces at C3 of ACCF were higher than those of ACAF and ACDF. The maximum von Mises stresses of the bone-screw interfaces at C6 of ACDF were much higher than those of ACAF and ACCF. The maximum von Mises stresses of the grafts of ACCF and ACAF were much higher than those of ACDF. The maximum von Mises stresses of the endplate of ACCF were much higher than those of ACAF and ACDF. CONCLUSION: The ACAF and ACDF models demonstrated superior cervical reconstruction stability over the ACCF model. ACAF exhibited lower risks of internal fixation failure and cage subsidence compared to ACCF, making it a promising approach. However, while ACAF revealed improved stability over ACCF, higher rates of subsidence and internal fixation failure persisted compared to ACDF, suggesting the need for further exploration of ACAF's long-term efficacy and potential improvements in clinical outcomes.

20.
Biochem Pharmacol ; 221: 116040, 2024 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-38311257

RESUMO

Paclitaxel is widely used to treat cancer, however, drug resistance limits its clinical utility. STAT3 is constitutively activated in some cancers, and contributes to chemotherapy resistance. Currently, several STAT3 inhibitors including WP1066 are used in cancer clinical trials. However, whether WP1066 reverses paclitaxel resistance and the mechanismremains unknown. Here, we report that in contrast to paclitaxel-sensitive parental cells, the expressions of several pro-survival BCL2 family members such as BCL-2, BCL-XL and MCL-1 are higher in paclitaxel-resistant ovarian cancer cells. Meanwhile, STAT3 is constitutively activated while stathmin loses its activity in paclitaxel-resistant cells. Importantly, WP1066 amplifies the inhibition of cell proliferation, colony-forming ability and apoptosis of ovarian cancer cells induced by paclitaxel. Mechanistically, WP1066, on the one hand, interferes the STAT3/Stathmin interaction, causing unleash of STAT3/Stathmin from microtubule, thus destroying microtubule stability. This process results in reduction of Ac-α-tubulin, further causing MCL-1 reduction. On the other hand, WP1066 inhibits phosphorylation of STAT3 by JAK2, and blocks its nuclear translocation, therefore repressing the transcription of pro-survival targets such as BCL-2, BCL-XL and MCL-1. Finally, the two pathways jointly promote cell death. Our findings reveal a new mechanism wherein WP1066 reverses paclitaxel-resistance of ovarian cancer cells by dually inhibiting STAT3 activity and STAT3/Stathmin interaction, which may layfoundation for WP1066 combined with paclitaxel in treating paclitaxel-resistant ovarian cancer.

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