Treatment of malignant airway obstruction with Y-shape sigma stent loaded with I125 seeds installed via rigid bronchoscopy.

PURPOSE: To summarize and analyze the safety and efficacy of a Y-shape Sigma stent loaded with I125 in patients with inoperable malignant main airway obstruction. METHODS: This study was approved by the Institutional Ethics Committee, and a written informed consent was obtained from each participant. A Y-shape Sigma stent loaded with I125 was placed under vision from rigid bronchoscopy. The primary endpoint was alleviation of symptoms and improvement of Karnofsky Performance Status (KPS) score, and the secondary endpoint was complications and technical success. RESULTS: From November 2018 through June 2023, total 33 patients with malignant airway obstruction were palliatively treated by installing Y-shape Sigma stents loaded with I125. The airway lumen was immediately restored and the average airway opening significantly increased to 70 ± 9.4% after the procedure from baseline 30.2 ± 10.5% (p < 0.05). Average KPS score was improved from baseline 30.0 ± 10.0 to 70.0 ± 10.0 (p < 0.05) as well as PaO2 from baseline 50.1 ± 15.4 mmHg to 89.3 ± 8.6 mmHg (p < 0.05). The technical success rate of placing the stent in this study was 73%, and adverse events or complications including bleeding, I125 loss, and airway infection occurred during or after the procedure. CONCLUSION: Placement of Y-shape Sigma stents under vision from rigid bronchoscopy in the patients with malignant airway obstruction is feasible and it immediately alleviates dyspnea and significantly improves quality of life.

Nitric oxide/paclitaxel micelles enhance anti-liver cancer effects and paclitaxel sensitivity by inducing ferroptosis, endoplasmic reticulum stress and pyroptosis.

The objective of this study was to investigate the anticancer activities of biodegradable polymeric micelles composed of monomethoxy poly(ethylene glycol), polylactic acid, and nitric oxide (mPEG-PLA-NO) loaded with paclitaxel (PTX) as a nanomedicine delivery system. We aimed to compare the anticancer effects of these NO/PTX micelles with PTX alone and elucidate their mechanism of action. We evaluated the impact of NO/PTX and PTX on cell viability using Cell Counting Kit-8 (CCK8) assays conducted on the Bel-7402 liver cancer cell line. Additionally, we employed H22 xenografted mice to assess the in vivo tumor growth inhibitory activity of NO/PTX. To examine the cytotoxicity of NO/PTX, the intracellular levels of reactive oxygen species (ROS), and the expression of ferroptosis-related proteins, we conducted experiments in the presence of the ferroptosis inhibitor ferrostatin-1 (Fer-1) or the ROS inhibitor N-acetyl cysteine (NAC). Furthermore, we investigated the expression of endoplasmic reticulum stress (ERS) and apoptosis-associated proteins. Our results demonstrated that NO/PTX exhibited enhanced anticancer effects compared to PTX alone in both Bel-7402 cells and H22 xenografted mice. The addition of Fer-1 or NAC reduced the anticancer activity of NO/PTX, indicating the involvement of ferroptosis and ROS in its mechanism of action. Furthermore, NO/PTX modulated the expression of proteins related to ERS and apoptosis, indicating the activation of these cellular pathways. The anticancer effects of NO/PTX in liver cancer cells were mediated through the induction of ferroptosis, pyroptosis, ERS, and apoptosis-associated networks. Ferroptosis and pyroptosis were activated by treatment of NO/PTX at low concentration, whereas ERS was induced to trigger apoptosis at high concentration. The superior anti-tumor effect of NO/PTX may be attributed to the downregulation of a multidrug resistance transporter and the sensitization of cells to PTX chemotherapy. In summary, our study highlights the potential of mPEG-PLA-NO micelles loaded with PTX as a nanomedicine delivery system for liver cancer treatment. The observed enhancement in anticancer activity, combined with the modulation of key cellular pathways, provides valuable insights into the therapeutic potential of NO/PTX in overcoming resistance and improving treatment outcomes in liver cancer patients.

Correction: Nitric oxide/paclitaxel micelles enhance anti-liver cancer effects and paclitaxel sensitivity by inducing ferroptosis, endoplasmic reticulum stress and pyroptosis.

[This corrects the article DOI: 10.1039/D3RA04861F.].

Quantification of 3-bromopyruvate in rat plasma by HPLC-MS/MS employing precolumn derivatization and the application to a pharmacokinetics study.

A simple high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method has been developed for the determination of 3-bromopyruvate (3-BrPA) in rat plasma for the first time. The analytes were separated on a C18 column (100 × 2.1 mm, 1.7 µm) and a triple-quadrupole mass spectrometry equipped with an electrospray ionization source was applied for detection. 3-BrPA was extracted from rat plasma with protein precipitation, and then derivatized with 4-nitro-1,2-phenylenediamine to obtain the mass signal because 3-BrPA could not be detected in mass spectrometry. The method was fully validated according to the US Food and Drug Administration guidance. The method was linear over the concentration range 0.5-1,000.0 ng/ml for 3-BrPA. The precision and accuracy, extraction recovery, and matrix effect were within acceptable limits. The method was then applied to support a pharmacokinetic study after 3-BrPA and 3-BrPA-l-Val-l-Ile (a dipeptide prodrug of 3-BrPA, 3-BrPA-l-Valine-l-isoleucine) had been administered to the Sprague-Dawley rats, respectively.

circ-PTTG1IP/miR-671-5p/TLR4 axis regulates proliferation, migration, invasion and inflammatory response of fibroblast-like synoviocytes in rheumatoid arthritis.

Circular RNAs (circRNAs) are related to rheumatoid arthritis (RA) development. However, the function and mechanism of circRNA pituitary tumor-transforming 1 interacting protein (circ- PTTG1IP) in RA are unknown. The expression of circ-PTTG1IP in synovial tissues of RA patients and fibroblast-like synoviocytes from RA patients (RA-FLSs) were detected by RT-qPCR. The results uncovered that circ-PTTG1IP was overexpressed in RA patients and RA-FLSs, and circ-PTTG1IP knockdown suppressed cell proliferation, migration, invasion and inflammatory response in RA-FLSs. Besides, we found that circ-PTTG1IP could directly bind to miR-671-5p, and toll-like receptor 4 (TLR4) was a target of miR-671-5p, which was confirmed by dual-luciferase reporter assay. miR-671-5p inhibitor attenuated the effects of circ-PTTG1IP knockdown on RA-FLSs, while the effects of miR-671-5p mimic on RA-FLSs were partly reversed by TLR4 overexpression. Furthermore, circ-PTTG1IP could upregulate TLR4 expression by miR-671-5p. Thus, circ-PTTG1IP knockdown repressed cell proliferation, migration, invasion and inflammatory response in RA-FLSs by regulating the miR-671-5p/TLR4 axis.

[Effect of moxibustion on clinical symptoms, peripheral inflammatory indexes and T lymphocyte subsets in COVID-19 patients].

OBJECTIVE: To explore the therapeutic effect and the mechanism of the adjuvant treatment with moxibustion on coronavirus disease 2019 (COVID-19). METHODS: A total of 95 patients with COVID-19 were randomly divided into a moxibustion group (45 cases) and a basic treatment group (50 cases). The routine treatment of western medicine was applied in the patients of both groups. In the moxibustion group, on the base of the treatment of western medicine, moxibustion was applied to Dazhui (GV 14), Feishu (BL 13), Qihai (CV 6) and Zusanli (ST 36), once daily and consecutively for 14 days. At the end of treatment courses, clinical symptom scores for cough, asthmatic breathing, chest oppression and short breath, as well as their remission rates were compared between the two groups before and after treatment. Before and after treatment, the white blood cell (WBC) count, the levels of c-reactive protein (CRP) and interleukin-6 (IL-6) and the absolute number of T lymphocyte subsets, i.e. , and of the peripheral blood were compared in the patients between the two groups. The principal component analysis was adopted to analyze the common data extracted from the above 10 clinical indexes variables and comprehensively evaluate the differences in the therapeutic effect of two regimens. RESULTS: The clinical symptom scores were all decreased after treatment in both of the moxibustion group and the basic treatment group as compared with those before treatment (P<0.05). After treatment, the clinical symptom scores of cough, chest oppression and asthmatic breathing in the moxibustion group were lower significantly than those in the basic treatment group (P<0.05) and the remission rates of cough, chest oppression and asthmatic breathing were higher than the basic treatment group (P<0.05). After treatment, WBC count was increased as compared with that before treatment in either group (P<0.05) and the levels of CRP and IL-6 in the moxibustion group were reduced as compared with those before treatment (P<0.05). The reducing range of IL-6 level in the moxibustion group was larger than the basic treatment group (P<0.05). After treatment, the absolute number of , and T lymphocytes was increased as compared with that before treatment in the moxibustion group (P<0.05), and its increase range was larger than the basic treatment group (P<0.05). The difference value was 33.38 for the score of comprehensive evaluation before and after treatment in the moxbustion group, higher obviously than 8.91 in the basic treatment group. CONCLUSION: On the base of the routine treatment with western medicine, moxibustion therapy supplemented relieves the clinical symptoms, reduces the levels of inflammatory indexes, i.e. IL-6 and CRP as well as improves the absolute number of peripheral T lymphocyte subsets. The clinical therapeutic effect of such regimen with moxibustion supplemented is significantly better than the simple routine treatment of western medicine.

Numerical and experimental study of pyrophoric activated metal Mg surface combustion characteristics.

The combustion of multi-hole pyrophoric activated metal is solid combustion and the combustion mechanism is quite complex, which is a difficult problem to be solved. Once the pyrophoric activated metal is exposed to air, the oxygen diffuses to the interior of the activated metal within plenty of holes and reacts with it, which enlarges the contact area with oxygen. Consequently, the whole combustion is vigorous and the temperature rises rapidly. To study the combustion mechanism of the chaff, the surface heat balance equation is established in this work by taking Mg as the activated metal. To solve this equation, the chaff adiabatic wall temperature distribution is computed by computational fluid dynamics in the presence of high-speed airflow. Then, the chaff surface temperature distribution is obtained by solving the heat balance equations. Finally, numerical and experimental results obtained via an infrared thermal imager are compared to demonstrate the effectiveness of the established equation.

Colorimetric discrimination for Stokes polarimetric imaging.

Traditional methods of discrimination for Stokes polarimetric imaging use grayscale images, in which the difference of the polarimetric properties is only reflected by the difference of grayscale. In this paper, we propose a method of colorimetric discrimination and classification for Stokes polarimetric imaging by the composed color polarimetric image, in which the objects with different polarization properties can appear in different colors. We show with real-world experiment that compared with the traditional method for the grayscale Stokes scalar image, the method proposed in this paper has a better performance for distinguishing objects with different polarization properties.

Nitric oxide-donating derivatives of hederacolchiside A1: Synthesis and biological evaluation in vitro and in vivo as potential anticancer agents.

A series of nitric oxide (NO) donating derivatives of hederacolchiside A1 bearing triterpenoid saponin motif were designed, synthesized and evaluated for their anticancer activity. All of the tested furoxan-based NO releasing compounds showed significant proliferation inhibitory activities. Especially compound 6a exhibited strong cytotoxicity (IC50=1.6-6.5µM) against four human tumor cell lines (SMMC-7721, NCI-H460, U251, HCT-116) in vitro and the highest level of NO releasing. Furthermore, compound 6a was revealed low acute toxicity to mice and weak haemolytic activity with potent tumor growth inhibition against mice H22 hepatocellular cells in vivo (51.5%).

Synthesis and biological evaluation of Hederacolchiside A1 derivatives as anticancer agents.

Modification of Hederacolchiside A1 (HA1) on 28-COOH gave a series of novel triterpenoid saponin compounds containing ester or amide group. Comparing with natural product HA1, several derivatives showed decreased toxicity in the mice acute toxicity trial and increased the anticancer activity in vitro. Especially compound 1 exhibited the strongest antiproliferative activities against human cancer cell lines tested (IC50=1.1-4.6µM) and potent tumor inhibition rate in vivo (46.8%).

Rutin, A Natural Flavonoid Protects PC12 Cells Against Sodium Nitroprusside-Induced Neurotoxicity Through Activating PI3K/Akt/mTOR and ERK1/2 Pathway.

Free radicals induced neural damage is implicated in CNS diseases and rutin isolated form Lonicera japonica are reported to have neuroprotective activity. Previously, we confirmed that rutin exerted neuroprotective effect against sodium nitroprusside (SNP)-induced cell death in PC12 cells. However, the neuroprotective mechanism of rutin is still not fully uncovered. Here, we found that rutin significantly decreased SNP-induced reactive oxygen species in PC12 cells. Rutin reversed the declined GSH/GSSG ratio and mitochondrial membrane potential induced by SNP. Moreover, rutin activated both the protein Akt/mTOR and the extracellular signal-regulated kinase (ERK1/2) signaling pathways and the neuroprotective effects of rutin were blocked by either the specific PI3K inhibitor LY294002 or the MAPK pathway inhibitor PD98059. In summary, these results demonstrated that the neuroprotective effects of rutin might be through activating both the PI3K/Akt/mTOR and ERK1/2 signaling pathways. Our findings support that rutin may have therapeutic potential for the treatment of CNS diseases related to NO neurotoxicity.

Metabolites profiling of Pulsatilla saponin D in rat by ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF-MS/MS).

Pulsatilla saponin D, an antitumor substance isolated from traditional Chinese herbal medicine Pulsatilla chinensis (Bge.) Regel, is a promising candidate for new drug development. The purpose of the present study is to establish a simple and practical strategy for the metabolite profiling of Pulsatilla saponin D in vivo. A total of 18 metabolites were identified in rat plasma, urine and feces samples based on MS and MS/MS data by using ESI-Q-TOF-MS/MS, and eight of them (M11-M18) were reported for the first time. The results indicated that deglycosylation, dehydrogenation, hydroxylation and sulfation were the major metabolic transformations of Pulsatilla saponin D in vivo. This study has improved our understanding of the metabolic fate of Pulsatilla saponin D in vivo, and the information gained from the current study is relevant to the pharmacological activity of Pulsatilla saponin D.

High-performance liquid chromatography/tandem mass spectrometry for simultaneous determination of four dicaffeoylquinic acids in rat plasma.

A specific and reliable HPLC-MS/MS method was developed and validated for the simultaneous determination of four dicaffeoylquinic acids (DCQA): 3,4-DCQA, 1,5-DCQA, 3,5-DCQA and 4,5-DCQA. The analytes were separated on a C18 column (150 mm × 2.1 mm, 1.8 µm) and a triple-quadrupole mass spectrometry equipped with an electrospray ionization (ESI) source was applied for detection. The plasma sample was prepared by a liquid-liquid extraction method and the recovery for the four analytes was around 80%. The calibration curves were linear over a concentration range of 10.6-1060.0 ng/mL for 3,4-DCQA, 19.2-1920.0 ng/mL for 1,5-DCQA, 14.0-2900.0 ng/mL for 3,5-DCQA, 9.7-970.0 ng/mL for 4,5-DCQA. The intra-day and inter-day precision was less than 15% and the relative error (RE) were all within ±15%. The validated method was successfully applied to a pharmacokinetics study in rats after oral administration of the extracts of Ainsliaea fragrans cham (a traditional Chinese herb).

[Association of intercellular adhesion molecule-1 gene K469E polymorphism with chronic obstructive pulmonary disease].

OBJECTIVE: To test the association of K469E, the common intercellular adhesion molecule-1 (ICAM-1) polymorphism with chronic obstructive pulmonary disease (COPD) and expression of ICAM-1 in Han people of Central and South Region in China. METHODS: A case-control study was done on 91 patients with COPD and 80 matched controls of Han people from central and south region in China, mainly from Hunan Province. Genomic DNA was extracted from white blood cells. ICAM-1 sequences were amplified by PCRand analyzed by agarose gel electrophoresis. Genotypes were defined by base sequencing. In addition, soluable intercellular adhesion molecule-1 (sICAM-1) serum levels were measured in 86 people picked out randomly from the COPD group and the control group. RESULTS: There was no difference in the frequency of the genotype and allele between the COPD group and the controls, but compared with those who were not very severe, the frequency of KE/ EE genotypes and E allele in COPD patients at very severe stage was significantly higher (10/16 vs 26/75, 12/30 vs 20/150, P<0.05). The level of sICAM-1 increased in the COPD patients, with negative correlation to forced expiratory volume in one second for the percentage of predicted value (FEV1%). But in both COPD patients and controls, the level of sICAM-1 did not differ significantly in different genotypes(P>0.05). CONCLUSION: K469E polymorphism of ICAM-1 may not affect the susceptibility of COPD and the expression of ICAM-1 in Han people from central and south of China in this study, but carriers of E allele are at high risk of developing severe stage of COPD.