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1.
ACS Nano ; 2024 Jun 12.
Article En | MEDLINE | ID: mdl-38864540

Drug-resistant bacterial infections pose a serious threat to human health; thus, there is an increasingly growing demand for nonantibiotic strategies to overcome drug resistance in bacterial infections. Mild photothermal therapy (PTT), as an attractive antibacterial strategy, shows great potential application due to its good biocompatibility and ability to circumvent drug resistance. However, its efficiency is limited by the heat resistance of bacteria. Herein, Cu2O@MoS2, a nanocomposite, was constructed by the in situ growth of Cu2O nanoparticles (NPs) on the surface of MoS2 nanosheets, which provided a controllable photothermal therapeutic effect of MoS2 and the intrinsic catalytic properties of Cu2O NPs, achieving a synergistic effect to eradicate multidrug-resistant bacteria. Transcriptome sequencing (RNA-seq) results revealed that the antibacterial process was related to disrupting the membrane transport system, phosphorelay signal transduction system, oxidative stress response system, as well as the heat response system. Animal experiments indicated that Cu2O@MoS2 could effectively treat wounds infected with methicillin-resistant Staphylococcus aureus. In addition, satisfactory biocompatibility made Cu2O@MoS2 a promising antibacterial agent. Overall, our results highlight the Cu2O@MoS2 nanocomposite as a promising solution to combating resistant bacteria without inducing the evolution of antimicrobial resistance.

2.
Free Radic Biol Med ; 221: 245-256, 2024 May 26.
Article En | MEDLINE | ID: mdl-38806104

Low back pain (LBP) may profoundly impact the quality of life across the globe, and intervertebral disc degeneration (IVDD) is the major cause of LBP; however, targeted pharmaceutical interventions for IVDD are still lacking. Ferroptosis is a novel form of iron-dependent programmed cell death. Studies have showed that ferroptosis may closely associate with IVDD; thus, targeting ferroptosis may have great potential for IVDD therapy. Non-steroidal anti-inflammatory drugs (NSAIDs) are the first-line medications for LBP, while nuclear factor-erythroid 2-related factor-2 (Nrf2) is a key inhibitory protein for ferroptosis. In the current study, we conducted a molecular docking screening between NSAIDs library and Nrf2 protein. Tinoridine was shown to have a high binding affinity to Nrf2. The in vitro study in nucleus pulposus (NP) cells showed that Tinoridine may promote the expression and activity of Nrf2, it may also rescue RSL3-induced ferroptosis in NP cells. Knockdown of Nrf2 reverses the protective effect of Tinoridine on RSL3-induced ferroptosis in NP cells, suggesting that the inhibitory effect of Tinoridine on ferroptosis is through Nrf2. In vivo study demonstrated that Tinoridine may attenuate the progression of IVDD in rats. As NSAIDs are already clinically used for LBP therapy, the current study supports Tinoridine's application from the view of ferroptosis inhibition.

3.
Article En | MEDLINE | ID: mdl-38779728

OBJECTIVE: Current cisplatin (CDDP) resistance remains a major challenge in the treatment of advanced gastric cancer. To address the issue of drug resistance, we explored the regulatory functions of PDZ and LIM structural domain protein 1 (PDLIM1) in CDDP chemotherapy for gastric cancer. METHODS: In this study, we analyzed PDLIM1 expression and prognosis using bioinformatics on publicly available data. PDLIM1 expression in a gastric mucosal epithelial cell line (GSE-1), CDDP- sensitive (SGC7901, BGC823) and CDDP-resistant gastric cancer cells was detected by RTqPCR and Western blotting. Cell proliferative capacity was assessed by knockdown of PDLIM1 and overexpression of PDLIM1 in cells administered in combination with cisplatin, and apoptotic levels were measured by CCK-8 and colony formation assay and by flow cytometry. Expression of breast cancer susceptibility gene 1 (BRCA1) and γH2AX was determined by Western blotting or immunofluorescence staining. RESULTS: Downregulation of PDLIM1 was found in tumor tissues and cells, which was associated with poor clinical outcomes. Knockdown of PDLIM1 enhanced proliferation and attenuated apoptosis in gastric cancer cells. In addition, the therapeutic effects of CDDP on proliferation, apoptosis, and DNA damage repair were attenuated by PDLIM1 deletion.PDLIM1 expression was downregulated in CDDP-resistant tumor cells. Overexpression of PDLIM1 overcomes CDDP resistance in tumor cells as BRCA1 expression decreases and γH2AX expression increases. CONCLUSION: Our findings demonstrate that PDLIM1 enables to alleviate gastric cancer progression and resistance to cisplatin via impeding DNA damage repair.

4.
Cancer Med ; 13(7): e7132, 2024 Apr.
Article En | MEDLINE | ID: mdl-38606892

BACKGROUND: Fertility-sparing surgery (FSS) is an alternative choice of young patients who have not completed their family planning and still have fertility needs. The aims of this study were to compare the outcomes of early-stage epithelial ovarian cancer (EOC) patients undergoing FSS and radical comprehensive staging surgery (RCS), and the suitability of FSS. METHODS: A total of 1297 patients aged between 20 and 44 years with newly diagnosed early-stage EOC were recruited from the Taiwan Cancer Registry database between 2009 and 2017. Site-specific surgery codes were used to distinguish patients in FSS group or RCS group. Cancer-specific survival (CSS) was evaluated using Kaplan-Meier method with log-rank test and Cox regression model. RESULTS: There were 401 and 896 patients in FSS and RCS group. Patients in FSS group were with younger age and mostly had Stage I disease. In contrast, patients in RCS group were older. There were more Stage II, high-grade (Grade 3) disease, and adjuvant chemotherapy in RCS group. Stage and tumor grade were two independent factors correlating with CSS and the type of surgery showed no effect on CSS (HR: 1.09, 95% CI: 0.66-1.77, p = 0.73) in multivariable analysis. In multivariable analysis, the clear cell carcinoma group who underwent FSS demonstrated better CSS compared to those in the RCS group (HR: 0.28, 95% CI: 0.06-0.82, p = 0.04). A total of 17 women who underwent FSS developed second malignancies of the uterine corpus or contralateral ovary. CONCLUSION: FSS can be a safe alternative procedure in selected young patients of Stage I EOC who have fertility desire. Endometrial biopsy before or during FSS and regular surveillance to detect recurrence are mandatory for ovarian cancer patients undergoing FSS.


Fertility Preservation , Ovarian Neoplasms , Humans , Female , Young Adult , Adult , Retrospective Studies , Carcinoma, Ovarian Epithelial/surgery , Carcinoma, Ovarian Epithelial/pathology , Ovarian Neoplasms/epidemiology , Ovarian Neoplasms/surgery , Ovarian Neoplasms/drug therapy , Neoplasm Staging
6.
Viruses ; 16(4)2024 03 28.
Article En | MEDLINE | ID: mdl-38675866

Gu-Sui-Bu, the dried rhizome of Davallia mariesii, is a traditional Chinese herbal remedy with a significant history of treating osteoporosis and inflammatory conditions. However, its potential as an anti-influenza agent and its underlying mechanisms of action remain unexplored. To obtain a more potent extract from D. mariesii and gain insights into its mechanism of action against influenza A virus (IAV), we utilized a partitioning process involving organic solvents and water, resulting in the isolation of butanolic subfractions of the D. mariesii extract (DMBE). DMBE exhibited a broad anti-viral spectrum, effectively inhibiting IAV, with an EC50 of 24.32 ± 6.19 µg/mL and a selectivity index of 6.05. We subsequently conducted a series of in vitro assays to evaluate the antiviral effects of DMBE and to uncover its mechanisms of action. DMBE was found to inhibit IAV during the early stages of infection by hindering the attachment of the virus onto and its penetration into host cells. Importantly, DMBE was observed to hinder IAV-mediated cell-cell fusion. It also inhibited neuraminidase activity, plaque size, and the expression levels of phospho-AKT. In summary, this study provides evidence for the effectiveness of D. mariesii as a complementary and alternative herbal remedy against IAV. Specifically, our data highlight DMBE's capabilities in inhibiting viral entry and the release of virions.


Antiviral Agents , Influenza A virus , Plant Extracts , Antiviral Agents/pharmacology , Antiviral Agents/chemistry , Influenza A virus/drug effects , Influenza A virus/physiology , Humans , Plant Extracts/pharmacology , Plant Extracts/chemistry , Animals , Madin Darby Canine Kidney Cells , Dogs , Virus Internalization/drug effects , Sapindaceae/chemistry , Virus Replication/drug effects , Virus Attachment/drug effects , Influenza, Human/drug therapy , Influenza, Human/virology , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/chemistry , Neuraminidase/metabolism , A549 Cells , Cell Line
7.
J Adv Res ; 2024 Mar 27.
Article En | MEDLINE | ID: mdl-38548264

INTRODUCTION: Overwhelming neutrophil activation and oxidative stress significantly contribute to acute respiratory distress syndrome (ARDS) pathogenesis. However, the potential of repurposing ribociclib, a cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor used clinically in cancer treatment, for treating neutrophilic ARDS remains uncertain. This study illustrated the ability and underlying mechanism of ribociclib for treating ARDS and neutrophilic inflammation. METHODS: Primary human neutrophils were used to determine the therapeutic effects of ribociclib on respiratory bursts, chemotactic responses, and inflammatory signaling. In vitro and silico analyses were performed to determine the underlying molecular mechanisms. The potential of ribociclib repurposing was evaluated using an in vivo ARDS model in lipopolysaccharide (LPS)-primed mice. RESULTS: We found that treatment using ribociclib markedly limited overabundant oxidative stress (reactive oxygen species [ROS]) production and chemotactic responses (integrin levels and adhesion) in activated human neutrophils. Ribociclib was also shown to act as a selective inhibitor of phosphodiesterase 4 (PDE4), thereby promoting the cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) pathway, leading to the inhibition of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) phosphorylation, and calcium influx. Notably, prophylactic administration and post-treatment with ribociclib ameliorated neutrophil infiltration, lung inflammation, accumulation of oxidative stress, pulmonary destruction, and mortality in mice with LPS-induced ARDS. CONCLUSION: We demonstrated for the first time that ribociclib serves as a novel PDE4 inhibitor for treating neutrophilic inflammation and ARDS. The repurposing ribociclib and targeting neutrophilic PDE4 offer a potential off-label alternative for treating lung lesions and other inflammatory conditions.

8.
Immunology ; 172(3): 362-374, 2024 Jul.
Article En | MEDLINE | ID: mdl-38469682

Small cell lung cancer (SCLC), recognized as the most aggressive subtype of lung cancer, presents an extremely poor prognosis. Currently, patients with small cell lung cancer face a significant dearth of effective alternative treatment options once they experience recurrence and progression after first-line therapy. Despite the promising efficacy of immunotherapy, particularly immune checkpoint inhibitors in non-small cell lung cancer (NSCLC) and various other tumours, its impact on significantly enhancing the prognosis of SCLC patients remains elusive. DLL3 has emerged as a compelling target for targeted therapy in SCLC due to its high expression on the membranes of SCLC and other neuroendocrine carcinoma cells, with minimal to no expression in normal cells. Our previous work led to the development of a novel multiple chain chimeric antigen receptor (CAR) leveraging the TREM1 receptor and DAP12, which efficiently activated T cells and conferred potent cell cytotoxicity. In this study, we have developed a DLL3-TREM1/DAP12 CAR-T (DLL3-DT CAR-T) therapy, demonstrating comparable anti-tumour efficacy against SCLC cells in vitro. In murine xenograft and patient-derived xenograft models, DLL3-DT CAR-T cells exhibited a more robust tumour eradication efficiency than second-generation DLL3-BBZ CAR-T cells. Furthermore, we observed elevated memory phenotypes, induced durable responses, and activation under antigen-presenting cells in DLL3-DT CAR-T cells. Collectively, these findings suggest that DLL3-DT CAR-T cells may offer a novel and potentially effective therapeutic strategy for treating DLL3-expressing SCLC and other solid tumours.


Adaptor Proteins, Signal Transducing , Immunotherapy, Adoptive , Lung Neoplasms , Membrane Proteins , Receptors, Chimeric Antigen , Small Cell Lung Carcinoma , Triggering Receptor Expressed on Myeloid Cells-1 , Xenograft Model Antitumor Assays , Small Cell Lung Carcinoma/immunology , Small Cell Lung Carcinoma/therapy , Humans , Animals , Lung Neoplasms/immunology , Lung Neoplasms/therapy , Receptors, Chimeric Antigen/genetics , Receptors, Chimeric Antigen/immunology , Receptors, Chimeric Antigen/metabolism , Immunotherapy, Adoptive/methods , Mice , Adaptor Proteins, Signal Transducing/metabolism , Adaptor Proteins, Signal Transducing/genetics , Adaptor Proteins, Signal Transducing/immunology , Membrane Proteins/metabolism , Membrane Proteins/genetics , Cell Line, Tumor , Triggering Receptor Expressed on Myeloid Cells-1/metabolism , Triggering Receptor Expressed on Myeloid Cells-1/genetics , Intracellular Signaling Peptides and Proteins/metabolism , Intracellular Signaling Peptides and Proteins/genetics , T-Lymphocytes/immunology , T-Lymphocytes/metabolism , Mice, SCID , Female
9.
Antimicrob Agents Chemother ; 68(4): e0095623, 2024 Apr 03.
Article En | MEDLINE | ID: mdl-38446062

Viral RNA-dependent RNA polymerase (RdRp), a highly conserved molecule in RNA viruses, has recently emerged as a promising drug target for broad-acting inhibitors. Through a Vero E6-based anti-cytopathic effect assay, we found that BPR3P0128, which incorporates a quinoline core similar to hydroxychloroquine, outperformed the adenosine analog remdesivir in inhibiting RdRp activity (EC50 = 0.66 µM and 3 µM, respectively). BPR3P0128 demonstrated broad-spectrum activity against various severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern. When introduced after viral adsorption, BPR3P0128 significantly decreased SARS-CoV-2 replication; however, it did not affect the early entry stage, as evidenced by a time-of-drug-addition assay. This suggests that BPR3P0128's primary action takes place during viral replication. We also found that BPR3P0128 effectively reduced the expression of proinflammatory cytokines in human lung epithelial Calu-3 cells infected with SARS-CoV-2. Molecular docking analysis showed that BPR3P0128 targets the RdRp channel, inhibiting substrate entry, which implies it operates differently-but complementary-with remdesivir. Utilizing an optimized cell-based minigenome RdRp reporter assay, we confirmed that BPR3P0128 exhibited potent inhibitory activity. However, an enzyme-based RdRp assay employing purified recombinant nsp12/nsp7/nsp8 failed to corroborate this inhibitory activity. This suggests that BPR3P0128 may inhibit activity by targeting host-related RdRp-associated factors. Moreover, we discovered that a combination of BPR3P0128 and remdesivir had a synergistic effect-a result likely due to both drugs interacting with separate domains of the RdRp. This novel synergy between the two drugs reinforces the potential clinical value of the BPR3P0128-remdesivir combination in combating various SARS-CoV-2 variants of concern.


Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , COVID-19 , Pyrazoles , Quinolines , Humans , SARS-CoV-2/metabolism , RNA-Dependent RNA Polymerase/metabolism , Molecular Docking Simulation , COVID-19 Drug Treatment , Antiviral Agents/chemistry
10.
J Environ Sci (China) ; 140: 331-340, 2024 Jun.
Article En | MEDLINE | ID: mdl-38331512

Bi2O3 catalyst with Bi-O bond crystal structure has more active sites, which shows better CO2 catalytic performance than pure Bi catalysts in many catalytic reactions. How to strengthen the Bi-O bond in Bi2O3 to obtain higher selectivity and catalytic activity is a problem worthy of consideration. Here, we develop a N2 pre-reduced spherical Bi2O3/ATO catalyst that has a high formate Faradaic efficiency of 92.7%, which is superior to the existing tin oxide catalyst. Detailed electrocatalytic analysis shows that N2 pre-reduction and spherical structure are helpful for Sn to stabilize the oxidation state of Bi, thus retaining part of the Bi-O structure. The existence of the Bi-O structure can reduce the energy barrier of the CO2 production *OCHO reaction and promote the reaction rate of the CO2-*OCHO-HCOOH path, thus promoting the formation of formate.


Carbon Dioxide , Formates , Catalysis
11.
J Formos Med Assoc ; 123(2): 228-237, 2024 Feb.
Article En | MEDLINE | ID: mdl-37596109

BACKGROUND/PURPOSE: Efforts were made to explore the influence of diagnostic timing for cancer-associated thromboembolic events on survival of ovarian cancer patients. METHODS: We reviewed the medical records of 75 ovarian cancer patients with thromboembolism and evaluated the prognostic factors affecting disease-free survival and overall survival. RESULTS: These 75 patients were classified into two categories by the diagnostic timing of the thromboembolism, during (33 cases) and after (42 cases) initial diagnosis of ovarian cancer groups. The diagnostic timing of thromboembolism was not related to disease-free survival or overall survival of the studied population. Advanced disease stage, clear cell histology, interval debulking surgery, no recurrence/persistence of ovarian cancer, and patients treated with anticoagulant(s) treatment >3 months were associated with the disease-free survival. Advanced disease stage, clear cell histology, body mass index (BMI) ≥24 kg/m2 at the diagnosis of ovarian cancer, and no recurrence/persistence of ovarian cancer influenced the overall survival. In the subgroup analysis, compared to the after initial ovarian cancer diagnosis group, patients with stage I/II disease, BMI <24 kg/m2 at the diagnosis of ovarian cancer, or primary debulking surgery in the during cancer diagnosis group had longer disease-free survival, and overall survival benefit was observed in cases with stage I/II disease, or primary debulking surgery. CONCLUSION: The diagnostic timing of thromboembolism was not related to disease-free or overall survival of ovarian cancer patients, but associated with that of specific patient subgroups.


Ovarian Neoplasms , Thromboembolism , Humans , Female , Ovarian Neoplasms/complications , Ovarian Neoplasms/diagnosis , Disease-Free Survival , Progression-Free Survival , Anticoagulants/therapeutic use , Thromboembolism/etiology
12.
J Gynecol Oncol ; 35(3): e33, 2024 May.
Article En | MEDLINE | ID: mdl-38130137

OBJECTIVE: In early-stage endometrial cancer, aggressive histologic types (grade 3 endometrioid, serous, clear cell, carcinosarcomas, undifferentiated, mixed, and other unusual types) are associated with an increased risk of distant metastases and worse survival. However, the optimal adjuvant treatment for these patients remains controversial. The present study investigated the outcomes of different adjuvant treatments in patients with 2023 FIGO stage IIC endometrial cancer. METHODS: We retrospectively identified patients with 2023 FIGO stage IIC endometrial cancer who underwent surgery followed by either adjuvant treatment or observation from 2000 to 2020 at two tertiary centers in Korea and Taiwan. Recurrence-free survival (RFS) and overall survival (OS) were evaluated using Kaplan-Meier estimates and Cox proportional-hazards models. We also analyzed recurrence patterns after different adjuvant treatments. RESULTS: A total of 272 patients were identified; 204 received adjuvant treatment postoperatively, whereas 68 only underwent observation. Adjuvant treatment was not associated with improved RFS or OS. Non-endometrioid histologic types (p=0.003) and presence of lymphovascular space invasion (LVSI, p=0.002) were associated with worse RFS, whereas only non-endometrioid histologic types impacted OS (p=0.004). In subgroup analyses, adjuvant treatment improved OS in patients with LVSI (p=0.020) and in patients with both LVSI and grade 3 endometrioid histologic type (p=0.007). We found no difference in locoregional and distant recurrence between patients undergoing adjuvant treatment or observation. CONCLUSION: In this study, the addition of adjuvant treatment was associated with an OS benefit for patients with LVSI, especially those with grade 3 endometrioid tumors.


Endometrial Neoplasms , Neoplasm Staging , Humans , Female , Endometrial Neoplasms/pathology , Endometrial Neoplasms/mortality , Endometrial Neoplasms/therapy , Retrospective Studies , Middle Aged , Taiwan/epidemiology , Aged , Chemotherapy, Adjuvant , Republic of Korea , Tertiary Care Centers , Radiotherapy, Adjuvant , Neoplasm Recurrence, Local/pathology , Adult , Carcinoma, Endometrioid/pathology , Carcinoma, Endometrioid/mortality , Carcinoma, Endometrioid/therapy , Disease-Free Survival , Kaplan-Meier Estimate , Hysterectomy
13.
Front Pharmacol ; 14: 1218315, 2023.
Article En | MEDLINE | ID: mdl-38074126

The Eucalyptus tree, belonging to the myrtle family, grows all over the world for its pharmaceutical and industrial benefits. In this article, we present a comparative analysis of the chemical composition of the hydrodistilled oils obtained from three different Eucalyptus species growing in Egypt viz. E. citriodora, E. camaldulensis, and E. ficifolia. Gas Chromatography-Mass Spectrometric guided analysis resulted in the identification of a total of 20 metabolites in E. citriodora oil with citronellal (54.9%) and citronellol (25.4%) being the most dominant components. ß-cymene (12.7%) and 1,8-cineole (11.7%) were the major volatile constituents identified in E. camaldulensis oil, while trans-ß-ocimene (22.4%), 1,8-cineole (13.5%), and L-trans-pinocarveol (12.5%) were the dominating components in the oil of E. ficifolia. The essential oils of the studied species were evaluated for their in vitro anti-inflammatory, antiviral including anti-SARS-CoV-2 (severe acute respiratory syndrome corona virus 2), antibacterial, and antifungal activities. E. citriodora oil displayed the highest inhibitory activity on the release of the superoxide radical (32%) and elastase enzyme (31%) in human neutrophils, while E. ficifolia oil had enhancing effects on elastase. The latter showed significant antiviral effects against hepatitis A, herpes simplex, and coxsackie viruses with IC50 values at 2.1, 2.5, and 5.6 µg/mL, respectively. Moderate antibacterial and antifungal activities were observed for Eucalyptus oils with Staphylococcus aureus being the most susceptible bacterial strain. E. ficifolia oil, similarly, displayed the best antibacterial activity with minimum inhibitory concentration (MIC) value at ca. 25 µg/mL (for S. aureus). On the contrary, E. camaldulensis oil was the most active against Candida albicans with an MIC value at 45 µg/mL. In silico studies were performed with a number of macromolecular drug targets for confirming the biological activities of the identified compounds and for interpreting their ADME (absorption-distribution-metabolism-elimination) parameters.

14.
Cell Rep Med ; 4(11): 101247, 2023 11 21.
Article En | MEDLINE | ID: mdl-37863059

Homologous recombination (HR)-mediated DNA repair is a prerequisite for maintaining genome stability. Cancer cells displaying HR deficiency (HRD) are selectively eliminated by poly(ADP-ribose) polymerase inhibitors (PARPis). To date, sequencing of HR-associated genes and analyzing genome instability have been used as clinical predictions for PARPi therapy. However, these genetic tests cannot reflect dynamic changes in the HR status. Here, we have developed a virus- and activity-based functional assay to quantify real-time HR activity directly. Instead of focusing on a few HR-associated genes, our functional assay detects endpoint HR activity and establishes an activity threshold for identifying HRD across cancer types, validated by PARPi sensitivity and BRCA status. Notably, this fluorescence-based assay can be applied to primary ovarian cancer cells from patients to reflect their level of HRD, which is associated with survival benefits. Thus, our work provides a functional test to predict the response of primary cancer cells to PARPis.


Ovarian Neoplasms , Female , Humans , Ovarian Neoplasms/genetics , Ovarian Neoplasms/drug therapy , Homologous Recombination/genetics , BRCA1 Protein/genetics , BRCA2 Protein/genetics , Poly(ADP-ribose) Polymerase Inhibitors/pharmacology , Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use
15.
Proc Natl Acad Sci U S A ; 120(37): e2305380120, 2023 Sep 12.
Article En | MEDLINE | ID: mdl-37669372

Proactively programming materials toward target nonlinear mechanical behaviors is crucial to realize customizable functions for advanced devices and systems, which arouses persistent explorations for rapid and efficient inverse design strategies. Herein, we propose a "mechanical Fourier transform" strategy to program mechanical behaviors of materials by mimicking the concept of Fourier transform. In this strategy, an arbitrary target force-displacement curve is decomposed into multiple cosine curves and a constant curve, each of which is realized by a rationally designed multistable module in an array-structured metamaterial. Various target curves with distinct shapes can be rapidly programmed and reprogrammed through only amplitude modulation on the modules. Two exemplary metamaterials are demonstrated to validate the strategy with a macroscale prototype based on magnet lattice and a microscale prototype based on an etched silicon wafer. This strategy applies to a variety of scales, constituents, and structures, and paves a way for the property programming of materials.

16.
Heliyon ; 9(8): e18422, 2023 Aug.
Article En | MEDLINE | ID: mdl-37534003

Non-valvular atrial fibrillation (NVAF) is a common form of cardiac arrhythmia that affects 1-1.5% of adults and roughly 10% of elderly adults with dysphagia. Apixaban is an anticoagulant referred to as a factor Xa inhibitor, which has been shown to reduce the risk of stroke and systemic embolism in cases of NVAF. Our objective in the current study was to formulate an orally disintegrating film to facilitate the administration of apixaban to elderly patients who have difficulty swallowing. Researchers have used a wide variety of cellulose-based or non-cellulose-based polymers in a variety of combinations to achieve specific characteristics related to film formation, disintegration performance, drug content, in vitro drug release, and stability. One of the two formulations in this study was specify that bioequivalence criteria met with respect to Cmax of the reference drug (ELIQUIS®) in terms of pharmacokinetic profile. Further research will be required to assess the applicability of orodispersible films created using colloidal polymers of high and low molecular weights to other drugs with poor solubility in water.

17.
J Immunother Cancer ; 11(7)2023 07.
Article En | MEDLINE | ID: mdl-37463789

BACKGROUND: Expression of immune checkpoints in the tumor microenvironment is one mechanism underlying paclitaxel (PTX) chemoresistance. This study aimed to investigate whether the addition of checkpoint blockade to PTX can improve the therapeutic efficacy against apparently disseminated intraperitoneal tumors. METHODS: We analyzed the in vivo expression of various immune checkpoints in CD3+CD8+ cytotoxic T cells from tumor-bearing mice treated with or without PTX and validated the tumor-killing activities of selected checkpoint-expressing T-cell subpopulations ex vivo. The regulation of selected checkpoints was investigated in vitro. The therapeutic effects of inhibition of a targeted checkpoint pathway with antibodies added to PTX therapy were examined. RESULTS: CD3+CD8+ T cells expressed with herpes virus entry mediator (HVEM), programmed cell death 1 (PD-1), and T-cell immunoglobulin domain and mucin domain 3 (TIM-3) in tumor-bearing hosts treated with PTX had effective tumoricidal activities. In addition to PTX and cytokines, B and T lymphocyte attenuator (BTLA) or homologous to lymphotoxin, exhibits inducible expression and competes with herpes simplex virus (HSV) glycoprotein D for binding to HVEM, a receptor expressed on T lymphocytes (LIGHT) interacting with HVEM can regulate the expression of PD-1 on CD3+CD8+ T cells. Interleukin (IL)-15 increased the percentage of HVEMhighgranzyme B (GZMB)+ cells among CD3+CD8+ T cells, which was suppressed by the BTLA/HVEM signal. LIGHT induced the percentage of HVEM+GZMB+ cells but not HVEMhighGZMB+ cells among CD3+CD8+ T cells. Expression of IL-15, BTLA, or LIGHT was detected in CD19+ B cells and regulated by damage-associated molecular patterns/Toll-like receptor interactions. In the tumor-bearing hosts treated with PTX, certain proportions of BTLA+ B or PD-1+ T lymphocytes were still noted. When dual inhibition of BTLA and PD-1 was added to PTX, the antitumor effects on intraperitoneally disseminated tumors can be significantly improved. CONCLUSIONS: Dual blockade of BTLA on B cells and PD-1 on cytotoxic T cells may have clinical potential for enhancing the efficacy of PTX in the treatment of tumors with intraperitoneal spread, including epithelial ovarian carcinomas.


CD8-Positive T-Lymphocytes , Neoplasms , Mice , Animals , CD8-Positive T-Lymphocytes/metabolism , Programmed Cell Death 1 Receptor/metabolism , Receptors, Immunologic/metabolism , Cytokines/metabolism , Neoplasms/metabolism , Tumor Microenvironment
18.
Semin Oncol Nurs ; 39(4): 151464, 2023 08.
Article En | MEDLINE | ID: mdl-37400343

OBJECTIVE: The combined impact of disease status and treatment phase on the quality of life (QoL) of women with ovarian cancer has not been fully considered. Therefore, this clinical, epidemiologic study compared the QoL of patients with ovarian cancer between five different treatment phases and identified the factors predicting their QoL through multivariate modeling. DATA SOURCES: This study had a cross-sectional survey design. The participants total of 183 were recruited from the inpatient and outpatient departments of the medical center in northern Taiwan. QoL was measured using the Quality of Life Scales QLQ-C30 and QLQ-OV28 and the Pittsburgh Sleep Quality Index. The patient's clinical characteristics data were obtained from the databank of the Taiwan Gynecologic Cancer Network, a registry of active patients being treated with gynecologic cancer. CONCLUSION: Chemotherapeutic agents were the major predictors of poor global health status in patients with ovarian cancer. However, good sleep was beneficial to patients' QoL. The study results can be used as a reference to adjust oncological treatment regimens for more effective symptom management and to promote patient education to improve patients' QoL. IMPLICATIONS FOR NURSING PRACTICE: The predicting factors can be considered by physicians and nurses to adjust treatment regimens and enhance patient education.


Genital Neoplasms, Female , Ovarian Neoplasms , Female , Humans , Quality of Life , Cross-Sectional Studies , Ovarian Neoplasms/therapy , Health Status
20.
Ann Surg Oncol ; 30(11): 6855-6864, 2023 Oct.
Article En | MEDLINE | ID: mdl-37386310

BACKGROUND: This study compared oncologic outcomes between minimally invasive surgery (MIS) and open surgery for the treatment of endometrial cancer with a high risk of recurrence. METHODS: This study included patients with endometrial cancer who underwent primary surgery at two tertiary centers in Korea and Taiwan. Low-grade advanced-stage endometrial cancer (endometrioid grade 1 or 2) or endometrial cancer with aggressive histology (endometrioid grade 3 or non-endometrioid) at any stage was considered to have a high risk of recurrence. We conducted 1:1 propensity score matching between the MIS and open surgery groups to adjust for the baseline characteristics. RESULTS: Of the total of 582 patients, 284 patients were included in analysis after matching. Compared with open surgery, MIS did not show a difference in disease-free survival [hazard ratio (HR) 1.09; 95% confidence interval (CI) 0.67-1.77, P = 0.717] or overall survival (HR 0.67; 95% CI 0.36-1.24, P = 0.198). In the multivariate analysis, non-endometrioid histology, tumor size, tumor cytology, depth of invasion, and lymphovascular space invasion were risk factors for recurrence. There was no association between the surgical approach and either recurrence or mortality in the subgroup analysis according to stage and histology. CONCLUSIONS: MIS did not compromise survival outcomes for patients with endometrial cancer with a high risk of recurrence when compared with open surgery.


Endometrial Neoplasms , Female , Humans , Retrospective Studies , Taiwan/epidemiology , Propensity Score , Endometrial Neoplasms/pathology , Republic of Korea/epidemiology , Minimally Invasive Surgical Procedures , Neoplasm Staging
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