Short-term effects of a new resistance exercise approach on physical function during chemotherapy after radical breast cancer surgery: a randomized controlled trial.

BACKGROUND: Approximately 30% of post-operative breast cancer patients develop shoulder joint movement disorders affecting routine upper limb movement. This study discusses the impact of a neuromuscular joint facilitation (NJF) method on the physical function of breast cancer patients experiencing shoulder dysfunction during chemotherapy after radical surgery. METHODS: This study included 162 female patients who have unilateral breast cancer in a cancer hospital in China. They developed shoulder joint mobility disorders during chemotherapy within 1-3 months postoperatively. These patients were divided into three groups: NJF, conventional rehabilitation (conventional group), and control groups. The clinical examination included the maximum passive and active range of motion (ROM) of the shoulder (flexion, extension, abduction, adduction, and external and internal rotation). Other evaluations included a pain score using a visual analog scale (VAS), grip strength, and supraspinatus muscle thickness. All tests were evaluated pre-and post-intervention. RESULTS: The NJF group showed a significant increase in all shoulder ROM angles post-intervention. In the conventional group, all other ROM values increased significantly, except passive external rotation ROM. In the control group, all other ROM values increased significantly, except passive and active external rotation ROM. All three groups had decreased VAS scores, increased grip strength, and supraspinatus muscle thickness post-intervention during active abduction. In the control group, the supraspinatus contraction rate decreased significantly at 60° and 90° abduction post-intervention compared to that at pre-intervention. CONCLUSION: This study revealed that NJF during chemotherapy had positive clinical intervention effects, improving shoulder joint mobility disorders, pain, grip strength, and external rotation following radical breast cancer surgery. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry; https://www.chictr.org.cn/ (ChiCTR2300073170), registered (03/07/2023).

Human RNA-binding protein HNRNPD interacts with and regulates the repair of deoxyribouridine in DNA.

Deoxyribouridine (dU) is an abnormal nucleoside in DNA and plays vital roles in multiple biological and physiological processes. Here, we conducted a mass spectrometry-based screen for dU-binding proteins and found that the heterogeneous nuclear ribonucleoprotein D (HNRNPD) could preferentially bind to dU-containing DNA. We also discovered that HNRNPD engages in the 5-Fluorouracil (5FU)-induced DNA damage response and can modulate the repair of dU in DNA in vitro and in human cells. Moreover, using a shuttle vector- and next-generation sequencing-based method, we unveiled the crucial role of HNRNPD in promoting the replicative bypass of dU in human cells. Taken together, these findings suggested that HNRNPD is a novel dU-bearing DNA-binding protein capable of regulating the removal of dU in DNA, and provided new insights into the molecular mechanisms of dU-associated diseases.

Albumin-encapsulated HSP90-PROTAC BP3 nanoparticles not only retain protein degradation ability but also enhance the antitumour activity of BP3 in vivo.

Proteolysis-targeting chimaera (PROTAC) has received extensive attention in industry. However, there are still some limitations that hinder its further development. In a previous study, our group first demonstrated that the HSP90 degrader BP3 synthesised by the principle of PROTACs showed therapeutic potential for cancer. However, its application was hindered by its high molecular weight and water insolubility. Herein, we aimed to improve these properties of HSP90-PROTAC BP3 by encapsulating it into human serum albumin nanoparticles (BP3@HSA NPs). The results demonstrated that BP3@HSA NPs showed a uniform spherical shape with a size of 141.01 ± 1.07 nm and polydispersity index < 0.2; moreover, BP3@HSA NPs were more readily taken up by breast cancer cells and had a stronger inhibitory effect in vitro than free BP3. BP3@HSA NPs also demonstrated the ability to degrade HSP90. Mechanistically, the improved inhibitory effect of BP3@HSA NPs on breast cancer cells was related to its stronger ability to induce cell cycle arrest and apoptosis. Furthermore, BP3@HSA NPs improved PK properties and showed stronger tumour suppression in mice. Taken together, this study demonstrated that hydrophobic HSP90-PROTAC BP3 nanoparticles encapsulated by human serum albumin could improve the safety and antitumour efficacy of BP3.

Radiomics for Detection of the EGFR Mutation in Liver Metastatic NSCLC.

RATIONALE AND OBJECTIVES: The research aims to investigate whether MRI radiomics on hepatic metastasis from primary nonsmall cell lung cancer (NSCLC) can be used to differentiate patients with epidermal growth factor receptor (EGFR) mutations from those with EGFR wild-type, and develop a prediction model based on combination of primary tumor and the metastasis. MATERIALS AND METHODS: A total of 130 patients were enrolled between Aug. 2017 and Dec. 2021, all pathologically confirmed harboring hepatic metastasis from primary NSCLC. The pyradiomics was used to extract radiomics features from intra- and peritumoral areas of both primary tumor and metastasis. The least absolute shrinkage and selection operator (LASSO) regression was applied to identify most predictive features and to develop radiomics signatures (RSs) for prediction of the EGFR mutation status. The receiver operating characteristic (ROC) curve analysis was performed to assess the prediction capability of the developed RSs. RESULTS: A RS-Primary and a RS-Metastasis were derived from the primary tumor and metastasis, respectively. The RS-Combine by combination of the primary tumor and metastasis achieved the highest prediction performance in the training (AUCs, RS-Primary vs. RS-Metastasis vs. RS-Combine, 0.826 vs. 0.821 vs. 0.908) and testing (AUCs, RS-Primary vs. RS-Metastasis vs. RS-Combine, 0.760 vs. 0.791 vs. 0.884) set. The smoking status showed significant difference between EGFR mutant and wild-type groups (p < 0.05) in the training set. CONCLUSION: The study indicates that hepatic metastasis-based radiomics can be used to detect the EGFR mutation. The developed multiorgan combined radiomics signature may be helpful to guide individual treatment strategies for patients with metastatic NSCLC.

Evaluation of supraspinatus muscle changes in the shoulder joint of stroke patients with hemiplegic and shoulder subluxation using ultrasonography: comparison between affected and unaffected sides.

[Purpose] The shoulder joint has a very unstable structure yet a significantly wide range of motion. Weakness of the muscles around the shoulder joint may cause shoulder joint subluxation. This study aimed to determine changes in supraspinatus muscle thickness between different shoulder abduction angles using ultrasonography and to compare differences in supraspinatus muscle thickness changes between the affected and unaffected sides depending on shoulder joint subluxation. [Participants and Methods] Forty hemiplegic patients with stroke were recruited (20 patients with and 20 without shoulder subluxation). Using ultrasonography, we measured supraspinatus muscle thickness at three shoulder joint abduction angles and calculated the differences in supraspinatus muscle thickness. Depending on subluxation, we separately analyzed the thickness and variations in the supraspinatus muscle on both the affected and unaffected sides. [Results] In stroke patients with shoulder subluxation, the difference in supraspinatus muscle thickness was significantly less in the affected side than in the unaffected side. [Conclusion] The thickness and rate of supraspinatus muscle thickness change was significantly less in the affected side than in the unaffected side in stroke patients with shoulder subluxation.

Bioactive oleanane-type saponins from Hylomecon Japonica.

Six undescribed oleanane-type saponins, named as Hylomeconosides L-Q, were isolated from the whole herb of Hylomecon Japonica, their structures were determined by analysis of 1D and 2D-NMR (1H-1H COSY, HSQC, and HMBC) spectroscopic data, mass spectrometry (HRESI-MS) and chromatographic data (GC and LC). Their structures were identified as 3-O-ß-D-galactopyranosyl-(1 â†’ 2)-ß-D-glucuronopyranosyl gypsogenin 28-O-ß-D-galactopyranosyl-(1 â†’ 3)-α-L-rhamnopyranosyl-(1 â†’ 2)-ß-L-arabinopyranoside; 3-O-ß-D-galactopyranosyl-(1 â†’ 2)-ß-D-glucuronopyranosyl gypsogenin 28-O-ß-D-xylopyranosyl-(1 â†’ 4)-α-L-rhamnopyranosyl-(1 â†’ 2)-ß-D-quinovopyranoside; 3-O-ß-D-glucuronopyranosyl gypsogenin 28-O-ß-D-xylopyranosyl-(1 â†’ 3)-ß-D-xylopyranosyl-(1 â†’ 4)-α-L-rhamnopyranosyl-(1 â†’ 2)-ß-D-quinovopyranoside; 3-O-ß-D-xylopyranosyl-(1 â†’ 3)-ß-D-glucuronopyranosyl gypsogenin 28-O-ß-D-xylopyranosyl-(1 â†’ 4)-α-L-rhamnopyranosyl-(1 â†’ 2)-ß-D-quinovopyranoside; 3-O-ß-D-galactopyranosyl-(1 â†’ 2)-[α-L-rhamnopyranosyl-(1 â†’ 3)]-ß-D-glucuronopyranosyl quillaic acid 28-O-ß-D-xylopyranosyl-(1 â†’ 3)-ß-D-xylopyranosyl-(1 â†’ 4)-α-L-rhamnopyranosyl-(1 â†’ 2)-ß-D-quinovopyranoside; 3-O-ß-D-galactopyranosyl-(1 â†’ 2)-[α-L-rhamnopyranosyl-(1 â†’ 3)]-ß-D-glucuronopyranosyl quillaic acid 28-O-ß-D-xylopyranosyl-(1 â†’ 3)-ß-D-xylopyranosyl-(1 â†’ 4)-α-L-rhamnopyranosyl-(1 â†’ 2)-ß-D-galactopyranoside. Hylomeconosides L-Q showed selective cytotoxicities against human cancer cell lines A549, AGS, HeLa, Huh 7, HT29 and K562. These results represent a contribution to the chemotaxonomy of the saponins of Hylomecon Japonica and their bioactivities.

Studies on isolation and structural identification of saponins from the herb Hylomecon japonica and their bioactivities.

Three undescribed oleanane type triterpenoid saponins (1-3), along with one known saponin (4) were isolated from the whole herb of Hylomecon japonica. Their structures were elucidated by analysis of 1D and 2D-NMR (1H-1H COSY, HSQC, and HMBC) spectroscopic data, mass spectrometry (HR-ESI-MS) and chromatographic date (GC and LC) as 3-O-ß-d-glucopyranosyl-(1 â†’ 2)-ß-d-glucuronopyranosyl gypsogenin 28-O-ß-d-galactopyranosyl-(1 â†’ 3)-[ß-d-xylopyranosyl-(1 â†’ 4)]-α-l-rhamnopyranosyl-(1 â†’ 2)-ß-l-arabinopyranosyl ester (1), 3-O-ß-d-galactopyranosyl-(1 â†’ 2)-ß-d-glucuronopyranosyl gypsogenin 28-O-α-l-arabinopyranosyl-(1 â†’ 3)-[ß-d-xylopyranosyl-(1 â†’ 4)]-α-l-rhamnopyranosyl-(1 â†’ 2)-ß-l-arabinopyranosyl ester (2), 3-O-ß-d-galactopyranosyl-(1 â†’ 2)-ß-d-glucuronopyranosyl gypsogenin 28-O-ß-d-galactopyranosyl-(1 â†’ 3)-[ß-d-xylopyranosyl-(1 â†’ 4)]-α-l-rhamnopyranosyl-(1 â†’ 2)-ß-d-galactopyranosyl ester (3), 3-O-ß-d-galactopyranosyl-(1 â†’ 2)-[α-l-arabinopyranosyl-(1 â†’ 3)]-ß-d-glucuronopyranosyl gypsogenin 28-O-ß-d-glucopyranosyl-(1 â†’ 3)-[ß-d-xylopyranosyl-(1 â†’ 4)]-α-l-rhamnopyranosyl-(1 â†’ 2)-ß-d-fucopyranosyl ester (4). All saponins possess a partial sequence ß-d-galactopyranosyl-(1 â†’ 2)-ß-d-glucuronopyranosyl at C-3 of the aglycon. Compound 1 has cytotoxic activity against human colon cancer cell lines HT29, 3 against human gastric cancer cell lines AGS, and 4 against human lung cancer cell lines A549, AGS and HT29. Among them, compounds 3 and 4 showed significant inhibitory effect against AGS with IC50 value of 6.01 ± 1.4 µM, 3.66 ± 1.8 µM, respectively. These results represent a contribution to the chemotaxonomy of the saponins of Hylomecon japonica and their bioactivities.

Chemical proteomic profiling of UTP-binding proteins in human cells.

Nucleotide-binding proteins play important roles in a variety of biological processes. While ATP- and GTP-binding proteins have been well studied, the systematical identification of UTP-interacting proteins remains under investigated. Here, we developed a chemical proteomic strategy using a biotinylated UTP affinity probe coupled with liquid chromatography tandem mass spectrometry (LC-MS/MS) method to enrich, identify and quantify UTP-binding proteins at the entire proteome scale. By performing labeling reactions with high vs low concentrations of UTP probe (100 and 10 µM) or with the UTP probe in the presence of free UTP in stable isotope labeling by amino acids in cell culture (SILAC) experiments, we identified more than 70 potential UTP-binding proteins which are involved in multiple cellular processes, such as translational elongation and protein folding. We also validated the UTP-binding capability of the cytoskeletal protein ACTB by using cellular thermal shift assay (CETSA). Together, we performed a high-throughput chemical proteomics-based analysis to identify, for the first time, UTP-binding proteins in human proteome, which should be applicable for the identification and quantification of UTP-binding proteins in other organisms.

Triterpenoid saponins from the herb Hylomecon japonica.

Six undescribed triterpenoid saponins, named as hylomeconoside C-H, were isolated from the EtOH extract of Hylomecon japonica. On the basis of spectroscopic and chemical evidence, their structures were identified as 3-O-ß-D-galactopyranosyl-(1 â†’ 2)-ß-D-glucuronopyranosyl gypsogenin 28-O-α-L-rhamnopyranosyl-(1 â†’ 2)-ß-L-arabinopyranoside; 3-O-ß-D-galactopyranosyl-(1 â†’ 2)-ß-D-glucuronopyranosyl gypsogenin 28-O-ß-D-xylopyranosyl-(1 â†’ 4)-α-L-rhamnopyranosyl-(1 â†’ 2)-ß-L-arabinopyranoside; 3-O-ß-D-galactopyranosyl-(1 â†’ 2)-[α-L-arabinopyranosyl-(1 â†’ 3)]-ß-D-glucuronopyranosyl gypsogenin 28-O-ß-D-glucopyranosyl-(1 â†’ 3)-[ß-D-xylopyranosyl-(1 â†’ 4)]-α-L-rhamnopyranosyl-(1 â†’ 2)-ß-L-arabinopyranoside; 3-O-ß-D-galactopyranosyl-(1 â†’ 2)-ß-D-glucuronopyranosyl gypsogenin 28-O-ß-D-galactopyranosyl-(1 â†’ 3)-[ß-D-xylopyranosyl-(1 â†’ 4)]-α-L-rhamnopyranosyl-(1 â†’ 2)-ß-D-fucopyranoside; 3-O-α-L-rhamnopyranosyl-(1 â†’ 3)-[ß-D-galactopyranosyl-(1 â†’ 4)]-ß-D-glucuronopyranosyl quillaic acid 28-O-ß-D-galactopyranosyl-(1 â†’ 3)-[ß-D-xylopyranosyl-(1 â†’ 4)]-α-L-rhamnopyranosyl-(1 â†’ 2)-ß-D-fucopyranoside; 3-O-α-L-rhamnopyranosyl-(1 â†’ 3)-[ß-D-galactopyranosyl-(1 â†’ 4)]-ß-D-glucuronopyranosyl quillaic acid 28-O-ß-D-xylopyranosyl-(1 â†’ 3)-ß-D-xylopyranosyl-(1 â†’ 4)-α-L-rhamnopyranosyl-(1 â†’ 2)-ß-D-quinovopyranoside. The 50% EtOH extract showed moderate inhibitory activity on the human cancer cell line HeLa, HepG-2, MCF-7, A549, K562 and TE-1. And these six compounds were tested for cytotoxicity against K562. Among them, hylomeconoside H was found to be the most active on the K562 cell lines (IC50 6.60 µM).