bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Versatile PDA(DOX) Nanoplatform for Chemo-Photothermal Synergistic Therapy against Breast Cancer and Attenuated Doxorubicin-Induced Cardiotoxicity
Authors: Geng Siqi , Feng Qiang , Wang Chujie , Li Ying , Qin Jiaying , Hou Mingsheng , Zhou Jiedong , Pan Xiaoyu , Xu Fei , Fang Baoru , Wang Ke , Yu Zhangsen 
Published: September 2023

AbstractPhotothermal therapy (PTT) is a highly clinical application promising cancer treatment strategy with safe, convenient surgical procedures and excellent therapeutic efficacy on superficial tumors. However, a single PTT is difficult to eliminate tumor cells completely, and tumor recurrence and metastasis are prone to occur in the later stage. Chemo-photothermal synergistic therapy can conquer the shortcomings by further killing residual tumor cells after PTT through systemic chemotherapy. Nevertheless, chemotherapy drugs' extreme toxicity is also a problematic issue to be solved, such as anthracycline-induced cardiotoxicity. Herein, we selected polydopamine nanoparticles (PDA) as the carrier of the chemotherapeutic drug doxorubicin (DOX) to construct a versatile PDA(DOX) nanoplatform for chemo-photothermal synergistic therapy against breast cancer and simultaneously attenuated DOX-induced cardiotoxicity (DIC). The excellent photothermal properties of PDA were used to achieve the thermal ablation of tumors. DOX carried out chemotherapy to kill residual and occult distant tumors. Furthermore, the PDA(DOX) nanoparticles significantly alleviate DIC, which benefits from PDA's excellent antioxidant enzyme activity. The experimental data of the chemotherapy groups showed that the results of the PDA(DOX) group were much better than the DOX group. This study not only effectively inhibits cancer but tactfully attenuates DIC, bringing a new perspective into synergistic therapy against breast cancer.
Graphical Abstract
Nestin and Notch3 collaboratively regulate angiogenesis, collagen production, and endothelial–mesenchymal transition in lung endothelial cells
Authors: Daido Wakako , Nakashima Taku , Masuda Takeshi , Sakamoto Shinjiro , Yamaguchi Kakuhiro , Horimasu Yasushi , Miyamoto Shintaro , Iwamoto Hiroshi , Fujitaka Kazunori , Hamada Hironobu , Hattori Noboru 
Published: September 2023

Abstract
Background
Nestin, an intermediate filament protein, participates in various pathophysiological processes, including wound healing, angiogenesis, endothelial–mesenchymal transition (EndoMT), and fibrosis. However, the pathophysiological roles of lung nestin-expressing cells remain unclear due to conflicting reports. The objective of this study is to elucidate the characteristics and functions of lung nestin-expressing cells.

Methods
We conducted a series of in vitro and in vivo experiments using endothelial cell line MS1 and nestin-GFP mice. This animal model allows for nestin-expressing cell detection without the use of anti-nestin antibodies.

Results
Lung nestin-expressing cells occurred in approximately 0.2% of CD45− cells and was co-expressed with epithelial, endothelial, and mesenchymal cell-surface markers. Importantly, virtually all nestin-expressing cells co-expressed CD31. When compared to lung nestin-nonexpressing endothelial cells, nestin-expressing endothelial cells showed robust angiogenesis with frequent co-expression of PDGFRβ and VEGFR2. During TGFβ-mediated EndoMT, the elevation of Nes mRNA expression preceded that of Col1a1 mRNA, and nestin gene silencing using nestin siRNA resulted in further upregulation of Col1a1 mRNA expression. Furthermore, Notch3 expression was regulated by nestin in vitro and in vivo; nestin siRNA resulted in reduced Notch3 expression accompanied with enhanced EndoMT. Contrary to previous reports, neither Nes mRNA expression nor nestin-expressing cells were increased during pulmonary fibrosis.

Conclusions
Our study showed that (1) lung nestin-expressing cells are an endothelial lineage but are distinct from nestin-nonexpressing endothelial cells; (2) nestin regulates Notch3 and they act collaboratively to regulate angiogenesis, collagen production, and EndoMT; and (3) nestin plays novel roles in lung angiogenesis and fibrosis.
Sirtuin1, not NAMPT, possesses anti-inflammatory effects in epicardial, pericardial and subcutaneous adipose tissue in patients with CHD
Authors: Opstad Trine Baur , Papotti Bianca , Åkra Sissel , Hansen Charlotte Holst , Braathen Bjørn , Tønnessen Theis , Solheim Svein , Seljeflot Ingebjørg 
Published: September 2023

Abstract
Background
Inflammation in cardiac adipose tissue (AT) is associated with atherosclerosis. We investigated whether the epicardial-, pericardial and pre-sternal subcutaneous AT (EAT, PAT and SAT) expression of Sirtuin1 (SIRT1) and nicotinamide phosphoribosyl transferase (NAMPT) are involved in the inflammatory process in coronary heart disease (CHD), and potentially associated to nod-like receptor family pyrin domain containing 3 (NLRP3) inflammasome-related markers, macrophage polarization markers, cell markers and the cardiometabolic profile.

Methods
In this cohort study performed between 2016 and 2018, EAT, PAT and SAT biopsies were retrieved from 52 CHD patients (77% men, median age 67) undergoing open-chest coronary artery bypass grafting (CABG), and 22 patients (50% men, median age 69) undergoing aortic valve replacement serving as controls. AT samples were snap-frozen at – 80 °C until RNA extraction and AT expression of actual markers, relatively quantified by PCR. Circulating SIRT1 and NAMPT were measured with Enzyme-linked immunosorbent assays (ELISAs). Non-parametric statistical tests were mainly used, including Friedman’s test coupled to Wilcoxon signed-rank test and Spearman Correlation.

Results
SIRT1 and NAMPT levels were similar in CHD and controls. In CHD, SIRT1 and NAMPT were inter-correlated in all AT compartments (r = 0.37–0.56, p < 0.01, all), and differently expressed between compartments, with the highest expression in SAT, significantly different from EAT (p < 0.01, both). Circulating SIRT1 and NAMPT levels were inversely associated (r = − 0.32, p = 0.024). In EAT and SAT, SIRT1 expression was inversely associated with IL-18 (r = − 0.43 and r = − 0.38, p < 0.01, both), whereas NAMPT expression was positively associated with the NLRP3 inflammasome-related markers in all compartments (r = 0.37–0.55, p < 0.01, all). While SIRT1 and NAMPT correlated to nitric oxide synthase 2 (NOS2), especially in SAT (r = 0.50–0.52, p ≤ 0.01, both), SIRT1 expression was related to endothelial cells, and NAMPT to macrophages. SIRT1 levels were correlated to weight and waist (r = 0.32 and r = 0.38, p < 0.03, both) and inversely to triglycerides and glycated haemoglobin (HbA1c) (r = − 0.33–− 0.37, p < 0.03, all), the latter positively correlated to NAMPT concentration (r = 0.39, p = 0.010).

Conclusion
The study indicates that targeting SIRT1, with its anti-inflammatory properties, may be a novel anti-inflammatory strategy in preventing atherosclerosis and CHD progression. NAMPT may be an early player in AT inflammation, mediating/reflecting a pro-inflammatory state.
Trial Registration: Registration: Clinicaltrials.gov ID: NCT02760914, registered the 5th of February 2016, http://clinicaltrials.gov/NCT02760914

Graphical Abstract
Screw fixation after tripe pelvic osteotomy is reliable: changes of acetabular correction are rare and do not correlate with risk factors
Authors: Dornacher Daniel , Kelsch Maximilian , Sgroi Mirco , Reichel Heiko , Lutz Bernd 
Published: September 2023

Abstract
Purpose
The aim of this examination was to assess whether there is a change of acetabular correction after triple pelvic osteotomy (TPO) and if so, whether there is a correlation with patient-specific risk factors or with certain periods in the postoperative course.

Methods
A consecutive series of 241 TPO was reviewed retrospectively. The close-meshed radiographic follow-up of the first 12 weeks comprised pelvic radiographs performed immediately after the procedure, 5 days, 6 and 12 weeks after TPO. Three observers measured the lateral center edge angle, acetabular index and the craniocaudal offset of the pubic osteotomy. Patient-specific risk factors (e. g. age, gender, body mass index, nicotine abuse) and certain periods in the postoperative course were correlated with a change of acetabular correction.

Results
After application of the exclusion criteria, 225 hips were available for further examination. Intraclass correlation coefficient resulted in predominantly excellent agreement between the measurements of the three observers (0.74–0.91). In 27 cases (12%), the three observers agreed on a change of acetabular correction. In 18 cases (8%), there was a slight change, in 9 cases (4%), a relevant change. The latter entailed consequences in the postoperative aftercare. General equation estimation did not show any correlation between a change of acetabular correction and patient-specific risk factors or certain periods in the postoperative course (p = 0.79–0.99).

Conclusion
Every once treated hip should be followed-up with the same attention, irrespective of the apparent risk profile. There is no rationale to skip a radiographic follow-up in the first 12 weeks after TPO.
Z-ligustilide preferentially caused mitochondrial dysfunction in AML HL-60 cells by activating nuclear receptors NUR77 and NOR1
Authors: Liu Gen , Chen Zhi-gang , Yang Li-rong , Rong Yu-xia , Wang Qin , Li Li , Lu Qian-wei , Jiang Ming-dong , Qi Hong-yi 
Published: September 2023

Abstract
Background
Nuclear receptors NUR77 and NOR1 were identified as critical targets in acute myeloid leukemia (AML) therapy. Previously, we showed that Z-ligustilide (Z-LIG) selectively targeted AML by restoring NUR77 and NOR1. However, its downstream mechanisms are yet to be elucidated.

Methods
SRB staining assay was used to measure cell viability. Cell apoptosis, mitochondrial membrane potential and mitochondrial reactive oxygen species were analyzed using flow cytometry. The potential targets of Z-LIG in AML HL-60 cells were evaluated by RNA sequencing. Changes in RNA levels were measured using quantitative RT-qPCR and western blot analysis was used to detect the expression of proteins.

Results
Z-LIG preferentially induced mitochondrial dysfunction in HL-60 cells compared with 293T cells. Furthermore, RNA sequencing revealed that mitochondrial transcription and translation might be potential Z-LIG targets inhibiting HL-60 cells. NUR77/NOR1 overexpression significantly reduced the mitochondrial ATP and mitochondrial membrane potential and increased mitochondrial reactive oxygen species in HL-60 cells but not in 293T cells. Moreover, Z-LIG induced mitochondrial dysfunction by restoring NUR77 and NOR1 in HL-60 cells. Compared with HL-60 cells, the apoptosis-inducing activities of NUR77/NOR1 and Z-LIG were significantly reduced in HL-60 ρ0 cells depleted in mitochondrial DNA (mt-DNA). Moreover, NUR77/NOR1 and Z-LIG downregulated mitochondrial transcription and translation related proteins in HL-60 cells. Notably, Z-LIG remarkably reduced mitochondrial ATP in primary AML cells and showed anti-AML activity in mouse models of human AML.

Conclusions
Collectively, our findings suggested that Z-LIG selectively induces mitochondrial dysfunction in AML HL-60 cells by restoring NUR77 and NOR1, a process associated with interference in mtDNA transcription.
Curdione induces ferroptosis mediated by m6A methylation via METTL14 and YTHDF2 in colorectal cancer
Authors: Wang Fang , Sun Zheng , Zhang Qunyao , Yang Hao , Yang Gang , Yang Qi , Zhu Yimiao , Wu Wenya , Xu Wenwen , Wu Xiaoyu 
Published: September 2023

Abstract
Background
Curdione is a sesquiterpene isolated from Curcumae Rhizoma that possesses high biological activity and extensive pharmacological effects. As a traditional Chinese medicine, Curcumae Rhizoma can inhibit the development of many types of cancer, especially colorectal cancer. However, the anti-colorectal mechanism of its monomer curdione remains unclear.

Methods
Colorectal cancer (CRC) cells were treated with curdione at doses of 12.5 μM, 25 μM, and 50 μM, and then the cells’ activity was measured with methyl thiazolyl tetrazolium (MTT). Nude mice were administered different doses of curdione subcutaneously and oxaliplatin by tail vein injection, and then hematoxylin–eosin (HE) staining was adopted to examine tumor histology. Moreover, flow cytometry was applied to detect reactive oxygen species in cells and tissues. Kits were employed to detect the levels of iron ions, malondialdehyde, lipid hydroperoxide, and glutathione. Polymerase chain reaction (PCR) and Western blotting were adopted to detect ferroptosis and m6A modification-related factors. A methylation spot hybridization assay was performed to measure changes in overall methylation. SLC7A11 and HOXA13 were measured by MeRIP-qPCR. The shRNA-METTL14 plasmid was constructed to verify the inhibitory effect of curdione on CRC.

Results
A dose-dependent decrease in activity was observed in curdione-treated cells. Curdione increased the accumulation of reactive oxygen species in CRC cells and tumor tissues, greatly enhanced the levels of malondialdehyde, lipid hydroperoxide and Fe2+, and lowered the activity of glutathione. According to the qPCR and Western blot results, curdione promoted the expression of METTL14 and YTHDF2 in CRC cells and tissues, respectively, and decreased the expression of SLC7A11, SLC3A2, HOXA13, and glutathione peroxidase 4. Additionally, in animal experiments, the curdione-treated group showed severe necrosis of tumor cells, as displayed by HE staining. Furthermore, compared with the control group, levels of m6A modifying factors (namely, SLC7A11 and HOXA13) were increased in the tissues after drug intervention. METTL14 knockdown was followed by an increase in CRC cell activity and glutathione levels. However, the levels of reactive oxygen species, malondialdehyde, and iron ions decreased. The expression levels of SLC7A11, SLC3A2, HOXA13, and GPX4 were all increased after METTL14 knockdown.

Conclusion
The results suggest that curdione induces ferroptosis in CRC by virtue of m6A methylation.
Electrophysiological characterization of a Cav3.2 calcium channel missense variant associated with epilepsy and hearing loss
Authors: Stringer Robin N. , Cmarko Leos , Zamponi Gerald W. , De Waard Michel , Weiss Norbert 
Published: September 2023

AbstractT-type calcium channelopathies encompass a group of human disorders either caused or exacerbated by mutations in the genes encoding different T-type calcium channels. Recently, a new heterozygous missense mutation in the CACNA1H gene that encodes the Cav3.2 T-type calcium channel was reported in a patient presenting with epilepsy and hearing loss—apparently the first CACNA1H mutation to be associated with a sensorineural hearing condition. This mutation leads to the substitution of an arginine at position 132 with a histidine (R132H) in the proximal extracellular end of the second transmembrane helix of Cav3.2. In this study, we report the electrophysiological characterization of this new variant using whole-cell patch clamp recordings in tsA-201 cells. Our data reveal minor gating alterations of the channel evidenced by a mild increase of the T-type current density and slower recovery from inactivation, as well as an enhanced sensitivity of the channel to external pH change. To what extend these biophysical changes and pH sensitivity alterations induced by the R132H mutation contribute to the observed pathogenicity remains an open question that will necessitate the analysis of additional CACNA1H variants associated with the same pathologies.
Feasibility of delivering supervised exercise training following surgical resection and during adjuvant chemotherapy for pancreatic ductal adenocarcinoma (PRECISE): a case series
Authors: Brown Malcolm , O’Connor Dominic , Turkington Richard , Eatock Martin , Vince Rebecca , Hulme Claire , Bowdery Roy , Robinson Rebecca , Wadsley Jonathan , Maraveyas Anthony , Prue Gillian 
Published: September 2023

Abstract
Introduction
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive neoplasm, with surgical resection and adjuvant chemotherapy the only curative treatment. Treatment-related toxicities place a considerable burden on patients although exercise training has shown promise is helping to manage such adversities and facilitate rehabilitation. The feasibility and safety of exercise training as a supportive therapy during adjuvant chemotherapy remains unknown.

Methods
Patients with PDAC were screened post-surgical resection and enrolled in a 16-week, progressive, concurrent exercise programme alongside their chemotherapy regimen. Feasibility was the primary objective detailing recruitment, retention and adherence rates throughout as well as the safety and fidelity of the intervention. Secondarily, the impact on functional fitness and patient-reported outcomes was captured at baseline, post-intervention and 3-month follow up.

Results
Eight patients consented to participate in this trial, with five proceeding to enrol in exercise training. Concurrent exercise training is feasible and safe during adjuvant chemotherapy and prevented an expected decline in functional fitness and patient-reported outcomes during this time.

Discussion
This case series provides preliminary evidence that concurrent exercise training during adjuvant therapy is safe, feasible and well tolerated, preventing an expected decline in functional fitness, muscular strength and health-related quality of life (HRQoL). Given the adverse effects of treatment, these findings are promising and provide further evidence for the inclusion of exercise training as a standard of care for surgical rehabilitation and managing treatment-related toxicities. Future research should explore the impact of exercise training during neoadjuvant chemotherapy, with prehabilitation now standard practice for borderline resectable disease.

Trial registration
ClinicalTrials.gov Identifier: NCT04305067, prospectively registered 12/03/2020, https://classic.clinicaltrials.gov/ct2/show/NCT04305067.
A rare presentation of large bowel obstruction post haemorrhoidectomy: a case report
Authors: Comella Assia , Mogridge Emily , Arachchi Asiri 
Published: September 2023

Abstract
Background
Hemorrhoidal disease is a common anorectal pathology. Complications post hemorrhoidectomy are rare. Postoperative complications following hemorrhoidectomy include bleeding (2%), infection (0.4–8%), urinary retention (15%), and constipation (15–30%).

Case presentation
A 40-year-old of Asian background female presented to a tertiary colorectal service with large bowel obstruction post hemorrhoidectomy. This is the first case in the surgical literature describing large bowel obstruction secondary to extrinsic compression from urinary retention following hemorrhoidectomy. The patient developed urinary retention and obstructed defecation in setting of inadequate analgesia post hemorrhoidectomy. The patient required indwelling catheter insertion and aggressive constipation management to resolve symptoms. Histopathology from the hemorrhoidectomy did not reveal a malignancy.

Conclusion
Anesthetic choice and postoperative analgesia are important factors to avoid the development of complications. A missed malignancy diagnosis must always be excluded with patients presenting post hemorroidectomy with bowel obstruction.
Extract of the bioconverted fine root of ginseng induces apoptosis and cell cycle arrest in mouse colon cancer cells
Authors: Seo Yeonju , Chae Jongbeom , Nam Ju-Ock 
Published: September 2023

AbstractCancer is the major cause of death worldwide, and the anticancer effect of ginseng and its main root has been studied. However, study of fine root of ginseng (FRG) is still insufficient. The purpose of this study was to discover a new anticancer effect from FRG, which does not show an anticancer effect, through a bioconversion technique. We measured and compared cell viability in FRG- and bioconverted fine root of ginseng (BFRG)-stimulated CT26 cells to investigate differences caused by bioconversion. Cell viability of CT26 was suppressed upon treatment with BFRG, unlike FRG. The effect of BFRG on apoptosis and cell cycle arrest was investigated by flow cytometry. BFRG-stimulated CT26 cells showed an increased apoptotic cells and cell cycle arrest. Additionally, BFRG induced mitochondrial impairment by reducing the expression of anti-apoptosis protein Bcl-2. When confirming the signaling pathway, it was found that the p38 MAPK pathway was activated by BFRG. Collectively, our results reveal anticancer effects against colorectal cancer and represent potential targets for anticancer drug development.
Postoperative ratio of C-reactive protein to albumin is an independent prognostic factor for gastric cancer
Authors: Li Chenxi , Yang Xuhui , Li Hui , Fu Yan , Wang Wenying , Jin Xin , Bian Lihua , Peng Liang 
Published: September 2023

Objective
The role of postoperative of the ratio of c-reactive protein to albumin (CRP/Alb ratio) in the prognosis of gastric cancer is rarely evaluated. Our purpose was to investigate the correlation of the postoperative CRP/Alb ratio and long-term prognosis of gastric cancer.

Methods
We enrolled 430 patients who suffered from radical gastrectomy. The commonly used inflammatory indices, clinical-pathological characteristics and oncologic outcomes were recorded. The median was used to the cut-off value for preoperative and postoperative CRP/Alb ratio, respectively. Kaplan–Meier analysis and Cox proportional hazards regression model were performed to determine its prognostic significance.

Results
In univariate analysis, there were significant differences were observed in overall survival (OS) according to perioperative CRP/Alb ratio, c-reactive protein (CRP), serum albumin (Alb), respectively. According to the multivariate analysis, higher postoperative CRP/Alb ratio (HR 2.03, 95% CI 1.55–2.66, P < 0.001), lower postoperative albumin (Alb), higher preoperative c-reactive protein (CRP) and higher postoperative CRP were indicated a shorter overall survival.

Conclusion
Postoperative inflammatory factors in patients with gastric cancer should be pay attention, especially postoperative CRP/Alb ratio may be an independent predictor of long-term prognosis of gastric cancer.
Tackling barriers to scale up human papillomavirus vaccination in China: progress and the way forward
Authors: Zhao Xue-Lian , Hu Shang-Ying , Hu Jia-Wei , Wang Hong-Hao , Wen Tian-Meng , Feng Yu-Shu , Qiao You-Lin , Zhao Fang-Hui , Zhang Yong 
Published: September 2023

AbstractThe human papillomavirus (HPV) vaccine is the first vaccine developed specifically targeting the prevention of cervical cancer. For more than 15 years, China has expedited a series of efforts on research and development of the domestically manufactured HPV vaccines, producing local population-based evidence, promoting free HPV vaccination from pilots, and launching action plans to tackle barriers in the scale-up of HPV vaccination. To further roll out the HPV vaccination program in China, several challenges should be addressed to support the steps forward. The availability of more locally manufactured HPV vaccines, pricing negotiation and local evidence supporting the efficacy of one-dose schedule would greatly alleviate the continued supply and financial constraints in China. Meanwhile, more attention should be paid to girls living in low-resource areas and males to ensure equal access to the HPV vaccination. Furthermore, linkage to secondary prevention and further real-world monitoring and evaluation are warranted to inform effective cervical cancer prevention strategies in the post-vaccine era.
Graphical Abstract