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1.
Cancer Res ; 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39137404

RESUMO

Prostate cancer (PCa) rarely responds to immune-checkpoint blockade (ICB) therapies. Cancer-associated fibroblasts (CAFs) are critical components of the immunologically "cold" tumor microenvironment and are considered a promising target to enhance the immunotherapy response. In this study, we aimed to reveal the mechanisms regulating CAF plasticity to identify potential strategies to switch CAFs from pro-tumorigenic to anti-tumor phenotypes and enhance ICB efficacy in PCa. Integration of four PCa single-cell RNA-sequencing datasets defined pro-tumorigenic and anti-tumor CAFs, and RNA-seq, flow cytometry, and a PCa organoid model demonstrated the functions of two CAF subtypes. Extracellular matrix-associated CAFs (ECM-CAF) promoted collagen deposition and cancer cell progression, and lymphocyte-associated CAFs (Lym-CAF) exhibited an anti-tumor phenotype and induced the infiltration and activation of CD8+ T cells. YAP1 activity regulated the ECM-CAF phenotype, and YAP1 silencing promoted switching to Lym-CAFs. NF-κB p65 was the core transcription factor in the Lym-CAF subset, and YAP1 inhibited nuclear translocation of p65. Selective depletion of YAP1 in ECM-CAFs in vivo promoted CD8+ T-cell infiltration and activation and enhanced the therapeutic effects of anti- PD-1 treatment in PCa. Overall, this study revealed a mechanism regulating CAF identity in PCa and highlighted a therapeutic strategy for altering the CAF subtype to suppress tumor growth and increase sensitivity to ICB.

2.
Nat Commun ; 15(1): 6445, 2024 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-39085263

RESUMO

MuB is a non-specific DNA-binding protein and AAA+ ATPase that significantly influences the DNA transposition process of bacteriophage Mu, especially in target DNA selection for transposition. While studies have established the ATP-dependent formation of MuB filament as pivotal to this process, the high-resolution structure of a full-length MuB protomer and the underlying molecular mechanisms governing its oligomerization remain elusive. Here, we use cryo-EM to obtain a 3.4-Å resolution structure of the ATP(+)-DNA(+)-MuB helical filament, which encapsulates the DNA substrate within its axial channel. The structure categorizes MuB within the initiator clade of the AAA+ protein family and precisely locates the ATP and DNA binding sites. Further investigation into the oligomeric states of MuB show the existence of various forms of the filament. These findings lead to a mechanistic model where MuB forms opposite helical filaments along the DNA, exposing potential target sites on the bare DNA and then recruiting MuA, which stimulates MuB's ATPase activity and disrupts the previously formed helical structure. When this happens, MuB generates larger ring structures and dissociates from the DNA.


Assuntos
Bacteriófago mu , Microscopia Crioeletrônica , DNA Viral , Proteínas de Ligação a DNA , Proteínas Virais , Bacteriófago mu/genética , Bacteriófago mu/metabolismo , Proteínas Virais/metabolismo , Proteínas Virais/genética , Proteínas Virais/química , DNA Viral/genética , DNA Viral/metabolismo , Proteínas de Ligação a DNA/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/química , Modelos Moleculares , Trifosfato de Adenosina/metabolismo , Adenosina Trifosfatases/metabolismo , Adenosina Trifosfatases/genética , Adenosina Trifosfatases/química , Sítios de Ligação , Multimerização Proteica
3.
Adv Sci (Weinh) ; : e2401095, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38946578

RESUMO

Conventional androgen deprivation therapy (ADT) targets the androgen receptor (AR) inhibiting prostate cancer (PCa) progression; however, it can eventually lead to recurrence as castration-resistant PCa (CRPC), which has high mortality rates and lacks effective treatment modalities. The study confirms the presence of high glutathione peroxidase 4 (GPX4) expression, a key regulator of ferroptosis (i.e., iron-dependent program cell death) in CRPC cells. Therefore, inducing ferroptosis in CRPC cells might be an effective therapeutic modality for CRPC. However, nonspecific uptake of ferroptosis inducers can result in undesirable cytotoxicity in major organs. Thus, to precisely induce ferroptosis in CRPC cells, a genetic engineering strategy is proposed to embed a prostate-specific membrane antigen (PSMA)-targeting antibody fragment (gy1) in the macrophage membrane, which is then coated onto mesoporous polydopamine (MPDA) nanoparticles to produce a biomimetic nanoplatform. The results indicate that the membrane-coated nanoparticles (MNPs) exhibit high specificity and affinity toward CRPC cells. On further encapsulation with the ferroptosis inducers RSL3 and iron ions, MPDA/Fe/RSL3@M-gy1 demonstrates superior synergistic effects in highly targeted ferroptosis therapy eliciting significant therapeutic efficacy against CRPC tumor growth and bone metastasis without increased cytotoxicity. In conclusion, a new therapeutic strategy is reported for the PSMA-specific, CRPC-targeting platform for ferroptosis induction with increased efficacy and safety.

4.
Tissue Cell ; 90: 102478, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39053131

RESUMO

Nimbolide has been demonstrated to possess protective properties against gestational diabetes mellitus and diabetic retinopathy. However, the role and molecular mechanism of nimbolide in diabetic cardiomyopathy (DCM) remain unknown. Diabetes was induced in rats via a single injection of streptozotocin (STZ) and then the diabetic rats were administered nimbolide (5 mg/kg and 20 mg/kg) or dimethyl sulfoxide daily for 12 weeks. H9c2 cardiomyocytes were exposed to high glucose (25 mM glucose) to mimic DCM in vitro. The protective effects of nimbolide against DCM were evaluated in vivo and in vitro. The potential molecular mechanism of nimbolide in DCM was further explored. We found that nimbolide dose-dependently decreased blood glucose and improved body weight of diabetic rats. Additionally, nimbolide dose-dependently improved cardiac function, alleviated myocardial injury/fibrosis, and inhibited endoplasmic reticulum (ER) stress and apoptosis in diabetic rats. Moreover, nimbolide dose-dependently improved mitochondrial function and activated the Akt/mTOR signaling. We consistently demonstrated the cardioprotective effects of nimbolide in an in vitro model of DCM. The involvement of ER stress and mitochondrial pathways were further confirmed by using inhibitors of ER stress and mitochondrial division. By applying a specific Akt inhibitor SC66, the cardioprotective effects of nimbolide were partially blocked. Our study indicated that nimbolide alleviated DCM by activating Akt/mTOR pathway. Nimbolide may be a novel therapeutic agent for DCM treatment.


Assuntos
Diabetes Mellitus Experimental , Cardiomiopatias Diabéticas , Estresse do Retículo Endoplasmático , Limoninas , Mitocôndrias , Proteínas Proto-Oncogênicas c-akt , Transdução de Sinais , Serina-Treonina Quinases TOR , Animais , Cardiomiopatias Diabéticas/metabolismo , Cardiomiopatias Diabéticas/tratamento farmacológico , Cardiomiopatias Diabéticas/patologia , Cardiomiopatias Diabéticas/prevenção & controle , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/patologia , Serina-Treonina Quinases TOR/metabolismo , Transdução de Sinais/efeitos dos fármacos , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , Limoninas/farmacologia , Masculino , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Ratos Sprague-Dawley , Linhagem Celular , Apoptose/efeitos dos fármacos , Cardiotônicos/farmacologia
5.
Langmuir ; 40(27): 14188-14196, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38940399

RESUMO

Surfactants are widely used as foaming agents to remove liquid accumulation in gas wells, enhancing natural gas production. The surfactant used in traditional foam sticks was dissolved and released as foam in a short period, especially at elevated downhole temperatures. This often requires the addition of foam sticks to maintain foam. To solve this problem, this study studies the utilization of nano silica to incorporate the amphoteric surfactant, cocamidopropyl betaine (CAB), into the mesoporous structure of silica nanocomposite as foam sticks for controlled release of CAB. Mesoporous nano silica was prepared by a sol-gel acid-catalyzed process with a silica precursor. The formation of nanocomposite solid sticks containing the amphoteric surfactant was achieved by aging and drying. The composite was characterized by various techniques: infrared spectroscopy, thermogravimetric analysis, energy-dispersive spectrometry, scanning electron microscopy, transmission electron microscopy, and small-angle X-ray diffraction. Results showed that 49.3% of CAB was encapsulated within the mesoporous structure of 30-50 nm nano silica. CAB release over time in aqueous solution at 130 °C exhibited 10.1% surfactant left in the nanocomposite after 72 h, as determined by thermal analysis. Surfactant release was systematically evaluated through foam performance tests. The study revealed that CAB could be control-released over 168 h via CAB diffusion from mesoporous silica. This study provides a longer-lasting foam method to enhance gas production by utilizing mesoporous silica as a control release medium for gas well deliquification.

6.
Int J Surg ; 110(5): 2757-2764, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38349216

RESUMO

BACKGROUND: This prospective cohort study, conducted at a high-volume esophageal cancer center from July 2019 to July 2022, aimed to investigate the link between the right gastroepiploic artery (RGEA) length and anastomotic leakage (AL) rates following minimally invasive esophagectomy (MIE). Real-world data on stomach blood supply in the Chinese population were examined. MATERIALS AND METHODS: A total of 516 cases were enrolled, categorized into two groups based on the Youden index-determined optimal cut-off value for the relative length of RGEA (length of RGEA/length of gastric conduit, 64.69%) through ROC analysis: Group SR (short RGEA) and Group LR (long RGEA). The primary observation parameter was the relationship between AL incidence and the ratio of direct blood supply from RGEA. Secondary parameters included the mean length of the right gastroepiploic artery, greater curvature, and the connection type between right and left gastroepiploic vessels. Patient data were prospectively recorded in electronic case report forms. RESULTS: The study revealed median lengths of 43.60 cm for greater curvature, 43.16 cm for the gastric conduit, and 26.75 cm for RGEA. AL, the most common postoperative complication, showed a significant difference between groups (16.88 vs. 8.84%, P =0.01). Multivariable binary logistic regression identified Group SR and LR (odds ratio: 2.651, 95% CI: 1.124-6.250, P =0.03) and Neoadjuvant therapy (odds ratio: 2.479, 95% CI: 1.374-4.473, P =0.00) as independent predictors of AL. CONCLUSIONS: The study emphasizes the crucial role of RGEA length in determining AL incidence in MIE for esophageal cancer. Preserving RGEA and fostering capillary arches between RGEA and LGEA are recommended strategies to mitigate AL risk.


Assuntos
Fístula Anastomótica , Neoplasias Esofágicas , Esofagectomia , Artéria Gastroepiploica , Humanos , Esofagectomia/efeitos adversos , Neoplasias Esofágicas/cirurgia , Fístula Anastomótica/etiologia , Fístula Anastomótica/epidemiologia , Masculino , Estudos Prospectivos , Feminino , Pessoa de Meia-Idade , Idoso , Procedimentos Cirúrgicos Minimamente Invasivos/efeitos adversos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , China/epidemiologia
7.
Chemosphere ; 349: 140785, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38016524

RESUMO

Residual antibiotics in swine wastewater pose a critical challenge for stable anaerobic digestion (AD). This study offers fresh insights into the anaerobic treatment of swine wastewater. The results showed that the presence of three typical antibiotics (sulfamethoxazole (SMX), oxytetracycline (OTC) and ciprofloxacin (CIP)) in swine wastewater could promote methane production by stimulating the production and conversion of ethanol. Among them, SMX exhibited the strongest methane promotion effect, with the cumulative methane production increasing from 138.47 to 2204.19 mL/g VS. According to the microbial community structure, antibiotics could promote the growth of Corynebacterium, Lutispora and hydrogenotrophic methanogens (Methanosassiliicoccus, Methanobrevibacter, and Methanobacterium), but inhibit the enrichment of acetoclastic methanogen (Methanosaeta). The relative abundance of Methanosaeta decreased from 2.93-19.80% to 0.52-2.58% under antibiotic stress. Furthermore, there were significant differences in the influence of different antibiotic types on methanogenic pathways. Specifically, OTC and CIP promoted the acetoclastic and hydrogenotrophic pathways, respectively, to enhance methane production. However, SMX could promote both acetoclastic and hydrogenotrophic pathways.


Assuntos
Antibacterianos , Águas Residuárias , Animais , Suínos , Antibacterianos/farmacologia , Anaerobiose , Reatores Biológicos/microbiologia , Ciprofloxacina , Metano
8.
Front Chem ; 11: 1351829, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38156019

RESUMO

[This corrects the article DOI: 10.3389/fchem.2022.845363.].

9.
J Orthop Traumatol ; 24(1): 48, 2023 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-37709959

RESUMO

BACKGROUND: This study aimed to analyze the clinical efficacy of one-stage anterior debridement of lower cervical tuberculosis using iliac crest bone graft fusion and internal fixation. MATERIALS AND METHODS: A retrospective analysis was performed on 48 patients with lower cervical tuberculosis admitted to multiple medical centers from June 2018 to June 2021. Among them, 36 patients had lesions involving two vertebrae and 12 patients had lesions involving more than three vertebrae. All patients were treated with quadruple antituberculosis drugs for more than 2 weeks before the operation, and then treated with one-stage anterior debridement and autogenous iliac bone graft fusion combined with titanium plate internal fixation. After the operation, antituberculosis drugs were continued for 12-18 months. The patients were followed-up to observe the improvement in clinical symptoms, bone graft fusion, Cobb angle, visual analog score (VAS), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), wound healing, and neurological function. RESULTS: The patients were followed-up for 13-43 months, with an average of 21.46 ± 1.52 months. The clinical symptoms significantly improved after the operation. The bone graft was completely fused in all patients, and the bone fusion time was 3-6 months, with an average of 4.16 ± 0.47 months. At the last follow-up, the Cobb angle, VAS, ESR, and CRP level were significantly lower than those before surgery (P < 0.05). None of the patients had loosening, detachment, or rupture of the internal fixation, and no recurrence occurred. All surgical incisions healed in one stage without infection or sinus formation. The preoperative Frankel neurological function classification was grade B in 7 cases, grade C in 13, grade D in 18, and grade E in 10. At the last follow-up, 8 cases recovered to grade D and 40 recovered to grade E. CONCLUSIONS: For patients with lower cervical tuberculosis, based on oral treatment with quadruple antituberculosis drugs, direct decompression through anterior debridement, followed by autologous iliac bone graft fusion combined with internal fixation can completely remove tuberculosis foci, rebuild the stability of the cervical spine, and obtain good clinical efficacy. Level of evidence Level 3.


Assuntos
Ílio , Tuberculose , Humanos , Estudos Retrospectivos , Desbridamento , Antituberculosos/uso terapêutico , Vértebras Cervicais/cirurgia
10.
Surg Endosc ; 37(9): 6908-6914, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37322359

RESUMO

BACKGROUND: To compare the perioperative outcomes from McKeown minimally invasive esophagectomy (MIE) when performed in three-dimensional versus two-dimensional visualization system, and investigate the learning curve of a single surgeon who implemented three-dimensional McKeown MIE. METHODS: A total of 335 consecutive cases (three-dimensional or two-dimensional) were identified. Perioperative clinical parameters were compared and cumulative sum learning curve was plotted. Propensity score matching was used to reduce selection bias from confounding factors. RESULTS: Patients in three-dimensional group were associated with more chronic obstructive pulmonary disease (23.9% vs 3.0%, p < 0.01). After propensity score matching (108 matched patients in each groups), this finding was no longer statistically significant. Comparing to two-dimensional group, significant improvement in total retrieved lymph nodes (28 vs 33, p = 0.003) was observed in three-dimensional group. In addition, more lymph nodes around the right recurrent laryngeal nerve were harvested in three-dimensional group than that in two-dimensional group (p = 0.045). However, there were no significantly differences were found between the two groups in terms of other intraoperative parameters (e.g., operative time) and postoperative relevant outcomes (e.g., lung infection). Furthermore, the change point in the cumulative sum learning curves for intraoperative blood loss and thoracic procedure time was 33 procedures, respectively. CONCLUSION: Three-dimensional visualization system appears to be superior in performing lymphadenectomy during McKeown MIE to that of a two-dimensional technique. For surgeons proficient in performing two-dimensional McKeown MIE, the learning curve for a three-dimensional procedure appears to begin near proficiency after more than 33 cases.


Assuntos
Neoplasias Esofágicas , Complicações Pós-Operatórias , Humanos , Resultado do Tratamento , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Esofagectomia/métodos , Estudos de Viabilidade , Neoplasias Esofágicas/cirurgia , Neoplasias Esofágicas/patologia , Estudos Retrospectivos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos
11.
Surg Endosc ; 37(9): 7073-7082, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37380741

RESUMO

BACKGROUND: To evaluate effectiveness of concurrent radiotherapy in esophageal cancer patient treated with neoadjuvant therapy. METHODS: The data of 1026 consecutive esophageal squamous cell carcinoma (ESCC) patients who underwent minimally invasive esophagectomy (MIE) were retrospectively collected. The main inclusion criteria were patients with locally advanced (cT2-4N0-3M0) ESCC who underwent neoadjuvant chemoradiotherapy (NCRT) or neoadjuvant chemotherapy (NCT) followed by MIE, and divided into two groups according to different neoadjuvant strategies. Propensity score matching was performed to improve the comparability between the two groups. RESULTS: After exclusion and matching, 141 patients were enrolled retrospectively: 92 received NCT, and 49 received NCRT. No difference in clinicopathologic characteristics or incidence of adverse events between groups. A shorter operation time (215.7 ± 35.5 min) (p < 0.001), less blood loss (111.2 ± 67.7 ml) (p = 0.0007) and a greater number of lymph nodes retrieved (33.8 ± 11.7) (p = 0.002) were observed in NCT group than in NCRT group. The incidence of postoperative complications was similar between groups. Although patients in NCRT group had better pathological complete response (16, 32.7%) (p = 0.0026) and ypT0N0 (10, 20.4%) (p = 0.0002) rates, there was no significant difference in 5-year progression-free survival (p = 0.1378) or disease-specific survival (p = 0.1258) between groups. CONCLUSIONS: Compared with NCRT, NCT has certain advantages in that it can simplify the surgical procedure and decrease the surgical technique required without compromising the surgical oncological outcomes and long-term survival of patients.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Terapia Neoadjuvante/métodos , Neoplasias Esofágicas/patologia , Estudos Retrospectivos , Esofagectomia/métodos , Taxa de Sobrevida , Quimiorradioterapia
12.
Otolaryngol Head Neck Surg ; 169(4): 1070-1079, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37191322

RESUMO

OBJECTIVE: Autonomic dysfunction is an independent risk factor for cardiovascular disease (CVD). Both obesity and obstructive sleep apnea (OSA) are associated with heart rate variability (HRV) (a hall marker of sympathetic arousal) and increased risk of CVD. This study aims to investigate whether anthropometric parameters could predict reduced HRV in adult OSA during wakefulness. STUDY DESIGN: Cross-sectional study. SETTING: Sleep center of Shanghai Jiao Tong University Affiliated Sixth Hospital from 2012 to 2017. METHODS: Total of 2134 subjects (503 non-OSA and 1631 OSA) were included. Anthropometric parameters were recorded. HRV was recorded during a 5-minute wakefulness period and analyzed by using time-domain method and frequency-domain method. Multiple step-wise linear regressions were performed to determine significant predictors of HRV with and without adjustments. Multiplicative interactions between gender, OSA, and obesity on HRV were also determined and evaluated. RESULTS: Waist circumference (WC) was significant negative determinant of root mean square of successive NN intervals (ß = -.116, p < .001) and high-frequency power (ß = -.155, p < .001). Age was the strongest determining factor of HRV. Significant multiplicative interactions between obesity and OSA on HRV, gender, and obesity on cardiovascular parameters were observed. CONCLUSION: Anthropometric parameters could predict reduced HRV during wakefulness in patients with OSA, especially WC was the strongest influenceable factor. Obesity and OSA had significant multiplicative interaction on HRV. Gender and obesity had significant multiplicative interaction on cardiovascular parameters. Early intervention for obesity, especially centripetal obesity, may improve reduction of autonomic function and risk of CVD.


Assuntos
Doenças Cardiovasculares , Apneia Obstrutiva do Sono , Adulto , Humanos , Estudos Transversais , Polissonografia , China/epidemiologia , Frequência Cardíaca/fisiologia , Doenças Cardiovasculares/complicações , Obesidade/complicações
13.
J Orthop Surg Res ; 18(1): 177, 2023 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-36890588

RESUMO

BACKGROUND: Increasing evidence suggests that mitophagy is responsible for the pathogenesis of intervertebral disk (IVD) degeneration. Previous studies have shown that Duhuo Jisheng Decoction (DHJSD), a classic Fangji of traditional Chinese medicine, can delay IVD degeneration; however, its specific mechanism of action is unknown. In this study, we investigated the mechanism by which DHJSD treatment prevented IVD degeneration in IL-1ß-treated human nucleus pulposus (NP) cells in vitro. METHODS: Cell Counting Kit-8 was performed to explore the effects of DHJSD on the viability of NP cells exposed to IL-1ß. The mechanism by which DHJSD delays IVD degeneration was explored using luciferase reporter assay, RT-qPCR, western blotting, TUNEL assay, mitophagy detection assay, Mito-SOX, Mitotracker and in situ hybridization. RESULTS: We observed that DHJSD enhanced the viability of NP cells treated with IL-1ß in a concentration-time dependent approach. Moreover, DHJSD lessened IL-1ß-induced NP apoptosis and mitochondrial dysfunction and activated mitophagy in NP cells treated with IL-1ß. Mitophagy suppressor cyclosporin A reversed the beneficial impacts of DHJSD in NP cells. In addition, the differential expression of miR-494 regulated IL-1ß-induced NP apoptosis and mitochondrial dysfunction, and the protective impact of miR-494 on NP cells treated with IL-1ß was achieved by mitophagy activation, which was regulated by its target gene, sirtuin 3 (SIRT3). Finally, we observed that DHJSD treatment could effectively delay IL-1ß-induced NP apoptosis by affecting the miR-494/SIRT3/mitophagy signal axis. CONCLUSIONS: These results show that the miR-494/SIRT3/mitophagy signaling pathway is responsible for the apoptosis and mitochondrial dysfunction of NP cells and that DHJSD may exert protective effects against IVD degeneration by regulating the miR-494/SIRT3/mitophagy signal axis.


Assuntos
Degeneração do Disco Intervertebral , MicroRNAs , Núcleo Pulposo , Sirtuína 3 , Humanos , Sirtuína 3/genética , Sirtuína 3/metabolismo , Mitofagia , Células Cultivadas , Degeneração do Disco Intervertebral/patologia , Apoptose , MicroRNAs/metabolismo , Mitocôndrias/genética
14.
Front Pharmacol ; 14: 1121586, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36744260

RESUMO

Background: Cancer-associated fibroblasts (CAFs) promote tumor progression through extracellular matrix (ECM) remodeling and extensive communication with other cells in tumor microenvironment. However, most CAF-targeting strategies failed in clinical trials due to the heterogeneity of CAFs. Hence, we aimed to identify the cluster of tumor-promoting CAFs, elucidate their function and determine their specific membrane markers to ensure precise targeting. Methods: We integrated multiple single-cell RNA sequencing (scRNA-seq) datasets across different tumors and adjacent normal tissues to identify the tumor-promoting CAF cluster. We analyzed the origin of these CAFs by pseudotime analysis, and tried to elucidate the function of these CAFs by gene regulatory network analysis and cell-cell communication analysis. We also performed cell-type deconvolution analysis to examine the association between the proportion of these CAFs and patients' prognosis in TCGA cancer cohorts, and validated that through IHC staining in clinical tumor tissues. In addition, we analyzed the membrane molecules in different fibroblast clusters, trying to identify the membrane molecules that were specifically expressed on these CAFs. Results: We found that COL11A1+ fibroblasts specifically exist in tumor tissues but not in normal tissues and named them cancer-specific fibroblasts (CSFs). We revealed that these CSFs were transformed from normal fibroblasts. CSFs represented a more activated CAF cluster and may promote tumor progression through the regulation on ECM remodeling and antitumor immune responses. High CSF proportion was associated with poor prognosis in bladder cancer (BCa) and lung adenocarcinoma (LUAD), and IHC staining of COL11A1 confirmed their specific expression in tumor stroma in clinical BCa samples. We also identified that CSFs specifically express the membrane molecules LRRC15, ITGA11, SPHK1 and FAP, which could distinguish CSFs from other fibroblasts. Conclusion: We identified that CSFs is a tumor specific cluster of fibroblasts, which are in active state, may promote tumor progression through the regulation on ECM remodeling and antitumor immune responses. Membrane molecules LRRC15, ITGA11, SPHK1 and FAP could be used as therapeutic targets for CSF-targeting cancer treatment.

15.
Surg Endosc ; 37(3): 1727-1734, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36214915

RESUMO

BACKGROUND: The extent to which the presence of pleural adhesions affects the surgical and oncological outcomes of patients undergoing McKeown minimally invasive esophagectomy (MIE) for esophageal cancer (EC) has not previously been studied. METHODS: Data of consecutive EC patients undergoing McKeown MIE by a single surgeon in the Department of Thoracic Surgery at Daping Hospital from November 2015 to December 2020 were collected. Patients were grouped according to the presence or absence of pleural adhesions when entering the chest cavity. Propensity score matching (PSM) was used to reduce selection bias from confounding factors. Kaplan-Meier was used to assess the survival differences. RESULTS: A total of 617 consecutive EC patients underwent McKeown MIE were enrolled. There were 116 patients with pleural adhesions (Group A) and 501 patients without pleural adhesions (Group B). Patients in Group A were more likely to be older than those of patients in Group B: (66.26 vs. 63.27, P = 0.001). In addition, Group A had more patients with chronic obstructive pulmonary disease (COPD) (24.1% vs. 16.8%, P = 0.04). After propensity score matching (102 matched patients in Group A and 185 matched patients in Group B), these findings were no longer statistically significant. Postoperative pulmonary infection occurred in 57 patients in Group A and in 15 patients in Group B (53.9% vs. 13.0%, P < 0.001). In addition, the presence of pleural adhesions was significantly associated with the prolonged operation time (232 min vs. 210 min, P < .001), length of stay (12 days vs. 10 days, P = 0.001), and hydrothorax requiring drainage (12.7% vs. 5.4%, P = 0.04). However, the disease-specific survival and disease-free survival rates were comparable between the two groups (P = 0.40 and 0.13, respectively). CONCLUSIONS: The presence of pleural adhesions predicted an increased operation time, length of stay, postoperative pneumonia, and hydrothorax requiring drainage of EC patients undergoing McKeown MIE, but did not exert unfavourable effect on long-term survival.


Assuntos
Neoplasias Esofágicas , Hidrotórax , Doenças Pleurais , Humanos , Resultado do Tratamento , Esofagectomia/efeitos adversos , Pontuação de Propensão , Hidrotórax/etiologia , Hidrotórax/cirurgia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Doenças Pleurais/cirurgia , Procedimentos Cirúrgicos Minimamente Invasivos/efeitos adversos , Estudos Retrospectivos
16.
Aging Clin Exp Res ; 35(1): 85-90, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36260215

RESUMO

BACKGROUND: Anxiety is common in older patients suffering from lumbar disc herniation. Postoperative delirium is related to poor prognosis. But the relationship between preoperative anxiety and postoperative delirium among older patients undergoing elective surgery for lumbar disc herniation is not clear. AIMS: The study aimed to investigate if preoperative anxiety is an independent risk factor of postoperative delirium among older patients undergoing elective surgery for lumbar disc herniation. METHODS: The medical records of 1290 patients undergoing elective surgery for lumbar disc herniation at a single institution from 2016 through 2021 were reviewed. Of 863 eligible patients, 225 (26.1%) patients had been diagnosed with anxiety by a board-certified psychiatrist and constituted the Anxiety group; the remaining 638 patients constituted the no-anxiety group. The demographics, baseline, operative variable and postoperative complications were collected and compared between the two groups. The primary outcome of this study was the incidence of delirium, according to the Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition, during a hospital stay after surgery for lumbar disc herniation. The relationship between anxiety and postoperative delirium was determined through multivariate logistic regression analysis. RESULTS: The demographics and comorbidity were similar between the two groups, except for age, sex, alcohol use and cerebrovascular disease. The operative variables were different between the two groups. The incidence of postoperative complications other than postoperative delirium was also similar between the two groups. In total, 86 patients (9.97%) had an episode of postoperative delirium, with anxiety group patients experiencing approximately a twofold higher rate (15.6% vs 7.99%). In a multivariate logistic regression analysis, anxiety was an independent predictor of postoperative delirium in older patients undergoing elective surgery for lumbar disc herniation (OR 2.228, 95% CI 1.494-3.416, p = 0.009). CONCLUSION: This study suggests that anxiety is an independent risk factor of postoperative delirium among older patients undergoing elective surgery for lumbar disc herniation. Preoperative anxiety assessment can help to identify older patients at high risk of postoperative delirium and facilitate perioperative management of older patients undergoing elective surgery for lumbar disc herniation.


Assuntos
Delírio do Despertar , Deslocamento do Disco Intervertebral , Humanos , Idoso , Deslocamento do Disco Intervertebral/complicações , Deslocamento do Disco Intervertebral/cirurgia , Deslocamento do Disco Intervertebral/epidemiologia , Vértebras Lombares/cirurgia , Ansiedade , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Fatores de Risco
17.
Front Genet ; 13: 1021163, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36338999

RESUMO

Purpose: To establish an effective prognostic model for patients with clear cell renal cell carcinoma (ccRCC). Methods: We identified four hub differentially expressed genes (DEGs) in Gene Expression Omnibus (GEO) database and verified them in the Cancer Gene Atlas (TCGA), STRING, UALCAN, TIMER, and Gene Expression Profiling Interactive Analysis (GEPIA) databases. We then used TCGA and International Cancer Genome Consortium (ICGC) to identify tumor pathway molecules highly correlated with hub DEGs. And by further LASSO and Cox regression analysis, we successfully identified five genes as prognostic factors. Results: We successfully identified a risk prediction model consisting of five genes: IGF2BP3, CDKN1A, GSDMB, FABP5, RBMX. We next distributed patients into low-risk and high-risk groups using the median as a cutoff. The low-risk group obviously had better survival than those in the predicted high-risk group. The results showed discrepancies in tumor-associated immune cell infiltration between risk groups. We also combined the risk model with clinical variables to create a nomogram. Conclusion: Our model has a satisfactory predictive effect on the prognosis of ccRCC patients and may provide new ideas for future immune therapy.

18.
Front Med (Lausanne) ; 9: 979542, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36186809

RESUMO

Background: Bladder cancer patients have a high recurrence and poor survival rates worldwide. Early diagnosis and intervention are the cornerstones for favorable prognosis. However, commonly used predictive tools cannot meet clinical needs because of their insufficient accuracy. Methods: We have developed an enhancer RNA (eRNA)-based signature to improve the prediction for bladder cancer prognosis. First, we analyzed differentially expressed eRNAs in gene expression profiles and clinical data for bladder cancer from The Cancer Genome Atlas database. Then, we constructed a risk model for prognosis of bladder cancer patients, and analyzed the correlation between this model and tumor microenvironment (TME). Finally, regulatory network of downstream genes of eRNA in the model was constructed by WGCNA and enrichment analysis, then Real-time quantitative PCR verified the differentiation of related genes between tumor and adjacent tissue. Results: We first constructed a risk model composed of eight eRNAs, and found the risk model could be an independent risk factor to predict the prognosis of bladder cancer. Then, the log-rank test and time-dependent ROC curve analysis shown the model has a favorable ability to predict prognosis. The eight risk eRNAs may participate in disease progression by regulating cell adhesion and invasion, and up-regulating immune checkpoints to suppress the immunity in TME. mRNA level change in related genes further validated regulatory roles of eRNAs in bladder cancer. In summary, we constructed an eRNA-based risk model and confirmed that the model could predict the prognosis of bladder cancer patients.

19.
Artigo em Chinês | MEDLINE | ID: mdl-36217653

RESUMO

Objective:To investigate the clinical effect of one-stage sternohyoid musculocutaneous flap after total laryngectomy for reconstruction of epiglottis function and vocalization. Methods:A retrospective analysis of 8 patients who underwent total laryngectomy from November 2019 to September 2020. The sternohyoid myocutaneous flap was designed after total laryngectomy. The lower edge of the flap was sewed with the posterior upper edge of the tracheostomy opening, and the lateral and medial edges of the flap were anastomosed to create a vocal tube. The lateral edge of the upper end of tube was sutured with the anterolateral wall of the hypopharynx, then made full use of residual epiglottis and tongue root tissue to reconstruct epiglottis function. Results:None of the 8 patients had serious complications after total laryngectomies. Fifteen months after operation,the vocal tube flaps survived and had intact structure under fiberoptic laryngoscope. All patients could speak clearly and forcefully, and the swallowing function was intact. Conclusion:The use of adjacent myocutaneous flap to construct the vocal canal and reconstruct the epiglottis function is a simple and effective technique that can be completed in one stage and improve the voicing of patients undergoing total laryngectomy.


Assuntos
Neoplasias Laríngeas , Retalho Miocutâneo , Procedimentos de Cirurgia Plástica , Epiglote/cirurgia , Humanos , Neoplasias Laríngeas/cirurgia , Laringectomia/métodos , Retalho Miocutâneo/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Estudos Retrospectivos , Tecnologia
20.
ACS Omega ; 7(36): 31954-31960, 2022 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-36120002

RESUMO

Low porosity and permeability of oil and gas reservoirs make it difficult to develop these resources. To address these problems, we developed and evaluated a novel, environmentally friendly waterproof locking agent, which was prepared using dimethyl silicone oil and octadecyltrimethylammonium chloride and characterized by Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, and particle size measurement. The waterproof locking performance of the agent was evaluated in a low-permeability reservoir using surface tension and contact angle measurements, and thermodynamic calculations were performed. The average particle size or median diameter (D 50) of a 1% mother liquor was 325 nm at 20 °C and 470.8 nm at 70 °C. The contact angle of clean water on the core surface increased from 10 to 110°. At 70 °C, the surface tension of water was reduced to 24 mN·m-1, indicating good waterproof locking performance. The interaction parameters were calculated in accordance with the Langmuir adsorption theory. The increase in temperature from 20 to 70 °C reduced Γmax from 4.59 × 10-6 to 1.36 × 10-6 mol·m-2 and ΔG θ from -40.93 to -56.54 kJ·mol-1. Thus, the adsorption behavior of the developed locking agent is believed to improve the productivity of oil wells.

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