bluuebunny/crossref_metadata_2025 huggingface dataset:
Biological, phytochemical and molecular docking characteristics of Laurus nobilis L. fresh leaves essential oil from Palestine
Authors: Jaradat Nidal , Hawash Mohammed , Qaoud Mohammed T. , Al-Maharik Nawaf , Qadi Mohammad , Hussein Fatimah , Issa Linda , Saleh Ahmad , Saleh Laith , Jadallah Ahmad
Published: June 2024

Background

The historical use of Laurus nobilis L., the plant is native to the Mediterranean region and has been cultivated for its aromatic leaves, which are used as a flavoring agent in cooking and for their potential therapeutic properties.

Methods

The purpose of the current investigation was to characterize the essential oil composition of the fresh L. nobilis leaves from Palestine by using the gas chromatography-mass spectrometry (GC-MS) technique. DPPH (2,2-diphenyl-1-picrylhydrazyl), p-nitrophenyl butyrate, and 3,5-dinitro salicylic acid (DNSA) methods were employed to estimate the antioxidant, antiobesity, and antidiabetic effects of the essential oil. While MTS assay were used to evaluate their antiproliferative activities on panels of cell lines. Moreover, the docking studies were aided by the Prime MM GBSA method for estimating binding affinities.

Results

The GC-MS investigation demonstrated that the fresh L. nobilis leaves essential oil has a variety of chemicals, about 31 different biochemicals were identified, and the major compounds were 1,8-cineole (48.54 ± 0.91%), terpinyl acetate (13.46 ± 0.34%), and α-terpinyl (3.84 ± 0.35%). Furthermore, the investigated oil demonstrated broad-spectrum antimicrobial activity against all tested bacterial and candidal strains and significantly inhibited the growth of MCF-7 cancerous cells more than the chemotherapeutic drug Doxorubicin. Furthermore, it contains robust DPPH free radicals, as well as porcine pancreatic α-amylase and lipase enzymes. Using the 1,8-cineole compound as the predominant biomolecule found in the L. nobilis essential oil, molecular docking studies were performed to confirm these observed fabulous results. The molecular docking simulations proposed that these recorded biological activities almost emanated from its high ability to form strong and effective hydrophobic interactions, this led to the getting of optimal fitting and interaction patterns within the binding sites of the applied crystallographic protein targets.

Conclusion

The results of these experiments showed that the fresh L. nobilis leaves essential oil has outstanding pharmacological capabilities, making this oil a potential source of natural medications.
Exploring dental and oral hygiene students’ interprofessional readiness: a cross-sectional study in joint paediatric outreach training
Authors: Mussalo Fanny , Karaharju-Suvanto Terhi , Pyörälä Eeva
Published: June 2024

Background

Interprofessional education is vital in oral healthcare education and should be integrated into both theoretical and work-based education. Little research addresses interprofessional education in dental hands-on training in authentic oral healthcare settings. The aim of the study was to examine the readiness and attitudes of dental and oral hygiene students towards interprofessional education during joint paediatric outreach training.

Methods

In the spring of 2022, a cross-sectional study was done involving dental and oral hygiene students using the Readiness for Interprofessional Learning Scale (RIPLS) during joint paediatric outreach training. The 19-item tool was answered on a five-point Likert scale (1 = strongly disagree, 2 = disagree, 3 = neutral, 4 = agree, and 5 = strongly agree). Means, standard deviations, minimums, maximums, and medians were calculated for each subscale and overall score. Students grouped according to their categorical variables were compared for statistically significant differences. The Mann-Whitney U-test was used for groups of two and the Kruskal-Wallis one-way analysis for groups of three or more. The internal consistency of the scale was measured with Cronbach’s alpha. Statistical level was set at 0.05.

Results

The survey included 111 participants, consisting of 51 oral hygiene students and 60 dental students, with a response rate of 93%. The questionnaire yielded a high overall mean score of 4.2. Both oral hygiene (4.3) and dental students (4.2) displayed strong readiness for interprofessional education measured by the RIPLS. The subscale of teamwork and collaboration achieved the highest score of 4.5. Students lacking prior healthcare education or work experience obtained higher RIPLS scores. Oral hygiene students rated overall items (p = 0.019) and the subscales of positive professional identity (p = < 0.001) and roles and responsibilities (p = 0.038) higher than dental students. The Cronbach’s alpha represented high internal consistency for overall RIPLS scores on the scale (0.812).

Conclusions

Both oral hygiene and dental students perceived shared learning as beneficial and showcased high readiness for interprofessional education, as evident in their RIPLS scores. Integrating interprofessional learning into oral hygiene and dental curricula is important. Studying together can form a good basis for future working life collaboration.
Total intravenous anesthesia with Ketofol in rabbits: a comparison of the effects of constant rate infusion of midazolam, fentanyl or dexmedetomidine
Authors: Mofidi Arghavan , Vesal Nasser
Published: June 2024

Background

When inhalant anesthetic equipment is not available or during upper airway surgery, intravenous infusion of one or more drugs are commonly used to induce and/or maintain general anesthesia. Total intravenous anesthesia (TIVA) does not require endotracheal intubation, which may be more difficult to achieve in rabbits. A range of different injectable drug combinations have been used as continuous infusion rate in animals. Recently, a combination of ketamine and propofol (ketofol) has been used for TIVA in both human patients and animals. The purpose of this prospective, blinded, randomized, crossover study was to evaluate anesthetic and cardiopulmonary effects of ketofol total intravenous anesthesia (TIVA) in combination with constant rate infusion (CRI) of midazolam, fentanyl or dexmedetomidine in eight New Zealand White rabbits. Following IV induction with ketofol and endotracheal intubation, anesthesia was maintained with ketofol infusion in combination with CRIs of midazolam (loading dose [LD]: 0.3 mg/kg; CRI: 0.3 mg/kg/hr; KPM), fentanyl (LD: 6 µg/kg; CRI: 6 µg/kg/hr; KPF) or dexmedetomidine (LD: 3 µg/kg; CRI: 3 µg/kg/hr; KPD). Rabbits in the control treatment (KPS) were administered the same volume of saline for LD and CRI. Ketofol infusion rate (initially 0.6 mg kg− 1 minute− 1 [0.3 mg kg− 1 minute− 1 of each drug]) was adjusted to suppress the pedal withdrawal reflex. Ketofol dose and physiologic variables were recorded every 5 min.

Results

Ketofol induction doses were 14.9 ± 1.8 (KPM), 15.0 ± 1.9 (KPF), 15.5 ± 2.4 (KPD) and 14.7 ± 3.4 (KPS) mg kg− 1 and did not differ among treatments (p > 0.05). Ketofol infusion rate decreased significantly in rabbits in treatments KPM and KPD as compared with saline. Ketofol maintenance dose in rabbits in treatments KPM (1.0 ± 0.1 mg/kg/min) and KPD (1.0 ± 0.1 mg/kg/min) was significantly lower as compared to KPS (1.3 ± 0.1 mg/kg/min) treatment (p < 0.05). Ketofol maintenance dose did not differ significantly between treatments KPF (1.1 ± 0.3 mg/kg/min) and KPS (1.3 ± 0.1 mg/kg/min). Cardiovascular variables remained at clinically acceptable values but ketofol infusion in combination with fentanyl CRI was associated with severe respiratory depression.

Conclusions

At the studied doses, CRIs of midazolam and dexmedetomidine, but not fentanyl, produced ketofol-sparing effect in rabbits. Mechanical ventilation should be considered during ketofol anesthesia, particularly when fentanyl CRI is used.
Correlation between remnant cholesterol and hyperuricemia in American adults
Authors: Zhou Xiaohai , Weng Xiaolu , Xu Jing , Wang Wenxing
Published: June 2024

Background

Remnant cholesterol (RC) is an important marker for assessing the risk of metabolic syndrome. However, the correlation between RC and hyperuricemia (HUA) remains unclear. This study aimed to explore the correlation between RC and HUA in American adults.

Methods

A total of 9089 participants from the 2013–2020 National Health and Nutrition Examination Survey were investigated. The correlation between RC and the odds of HUA was evaluated using multivariate logistic regression analysis. The nonlinear correlation was described using fitted smoothed curves. The correlation in subgroups was analyzed based on race, gender, alcohol consumption, age, body mass index, waist circumference, diabetes and moderate physical activities.

Results

RC was correlated with uric acid (Spearman’s correlation coefficient = 0.208 in males and 0.215 in females; all P < 0.001). Multiple logistic regression analysis indicated a positive correlation between RC and the risk of HUA (odds ratio = 1.022 in males and 1.031 in females; all P < 0.001). Subgroup analysis revealed that the correlation was stronger in females, participants aged < 50 years, and those without diabetes. Furthermore, the generalized smooth curve fitting demonstrated a linear correlation between RC and HUA, without threshold or saturation effects.

Conclusion

Elevated RC significantly and positively correlated with HUA in American adults. This correlation was stronger among females, participants aged < 50 years, and those without diabetes.
The anti-inflammatory properties of vinpocetine mediates its therapeutic potential in management of atherosclerosis
Authors: Alshehri Abdullah A. , Al-kuraishy Hayder M. , Al-Gareeb Ali I. , Jawad Sabrean F. , Khawagi Wael Y. , Alexiou Athanasios , Papadakis Marios , Assiri Abdullah A , Elhadad Heba , El-Saber Batiha Gaber
Published: June 2024

Atherosclerosis (AS) formation is enhanced by different mechanisms including cytokine generation, vascular smooth muscle cell proliferation, and migration. One of the recent treatments towards endothelial dysfunction and AS is Vinpocetine (VPN). VPN is a potent inhibitor of phosphodiesterase enzyme 1 (PDE-1) and has anti-inflammatory and antioxidant effects through inhibition the expression of nuclear factor kappa B (NF-κB). VPN has been shown to be effective against the development and progression of AS. However, the underlying molecular mechanism was not fully clarified. Consequently, objective of the present review was to discuss the mechanistic role of VPN in the pathogenesis AS. Most of pro-inflammatory cytokines that released from macrophages are inhibited by action of VPN through NF-κB-dependent mechanism. VPN blocks monocyte adhesion and migration by constraining the expression and action of pro-inflammatory cytokines. As well, VPN is effective in reducing of oxidative stress a cornerstone in the pathogenesis of AS through inhibition of NF-κB and PDE1. VPN promotes plaque stability and prevents the erosion and rupture of atherosclerotic plaque. In conclusion, VPN through mitigation of inflammatory and oxidative stress, and improvement of plaque stability effects could be effective agent in the management of AS.
Liposome-lentivirus for miRNA therapy with molecular mechanism study
Authors: Sun Fen , Chen Huaqing , Dai Xiaoyong , Hou Yibo , Li Jing , Zhang Yinghe , Huang Laiqiang , Guo Bing , Yang Dongye
Published: June 2024

Background

Cancer stem cells (CSCs) play a vital role in the occurrence, maintenance, and recurrence of solid tumors. Although, miR-145-5p can inhibit CSCs survival, poor understanding of the underlying mechanisms hamperes further therapeutic optimization for patients. Lentivirus with remarkable transduction efficiency is the most commonly used RNA carrier in research, but has shown limited tumor-targeting capability.

Methods

We have applied liposome to decorate lentivirus surface thereby yielding liposome-lentivirus hybrid-based carriers, termed miR-145-5p-lentivirus nanoliposome (MRL145), and systematically analyzed their potential therapeutic effects on liver CSCs (LCSCs).

Results

MRL145 exhibited high delivery efficiency and potent anti-tumor efficacy under in vitro and in vivo. Mechanistically, the overexpressed miR-145-5p can significantly suppress the self-renewal, migration, and invasion abilities of LCSCs by targeting Collagen Type IV Alpha 3 Chain (COL4A3). Importantly, COL4A3 can promote phosphorylating GSK-3β at ser 9 (p-GSK-3β S9) to inactivate GSK3β, and facilitate translocation of β-catenin into the nucleus to activate the Wnt/β-catenin pathway, thereby promoting self-renewal, migration, and invasion of LCSCs. Interestingly, COL4A3 could attenuate the cellular autophagy through modulating GSK3β/Gli3/VMP1 axis to promote self-renewal, migration, and invasion of LCSCs.

Conclusions

These findings provide new insights in mode of action of miR-145-5p in LCSCs therapy and indicates that liposome-virus hybrid carriers hold great promise in miRNA delivery.

Graphical abstract
NIR triggered polydopamine coated cerium dioxide nanozyme for ameliorating acute lung injury via enhanced ROS scavenging
Authors: Yin Mingjing , Lei Doudou , Liu Yalan , Qin Tao , Gao Huyang , Lv Wenquan , Liu Qianyue , Qin Lian , Jin Weiqian , Chen Yin , Liang Hao , Wang Bailei , Gao Ming , Zhang Jianfeng , Lu Junyu
Published: June 2024

Acute lung injury (ALI) is a life threatening disease in critically ill patients, and characterized by excessive reactive oxygen species (ROS) and inflammatory factors levels in the lung. Multiple evidences suggest that nanozyme with diversified catalytic capabilities plays a vital role in this fatal lung injury. At present, we developed a novel class of polydopamine (PDA) coated cerium dioxide (CeO2) nanozyme (Ce@P) that acts as the potent ROS scavenger for scavenging intracellular ROS and suppressing inflammatory responses against ALI. Herein, we aimed to identify that Ce@P combining with NIR irradiation could further strengthen its ROS scavenging capacity. Specifically, NIR triggered Ce@P exhibited the most potent antioxidant and anti-inflammatory behaviors in lipopolysaccharide (LPS) induced macrophages through decreasing the intracellular ROS levels, down-regulating the levels of TNF-α, IL-1β and IL-6, up-regulating the level of antioxidant cytokine (SOD-2), inducing M2 directional polarization (CD206 up-regulation), and increasing the expression level of HSP70. Besides, we performed intravenous (IV) injection of Ce@P in LPS induced ALI rat model, and found that it significantly accumulated in the lung tissue for 6 h after injection. It was also observed that Ce@P + NIR presented the superior behaviors of decreasing lung inflammation, alleviating diffuse alveolar damage, as well as promoting lung tissue repair. All in all, it has developed the strategy of using Ce@P combining with NIR irradiation for the synergistic enhanced treatment of ALI, which can serve as a promising therapeutic strategy for the clinical treatment of ROS derived diseases as well.
3D nanofiber scaffolds from 2D electrospun membranes boost cell penetration and positive host response for regenerative medicine
Authors: Xiao Lingfei , Liu Huifan , Huang Huayi , Wu Shujuan , Xue Longjian , Geng Zhen , Cai Lin , Yan Feifei
Published: June 2024

The ideal tissue engineering scaffold should facilitate rapid cell infiltration and provide an optimal immune microenvironment during interactions with the host. Electrospinning can produce two-dimensional (2D) membranes mimicking the extracellular matrix. However, their dense structure hinders cell penetration, and their thin form restricts scaffold utility. In this study, latticed hydrogels were three-dimensional (3D) printed onto electrospun membranes. This technique allowed for layer-by-layer assembly of the membranes into 3D scaffolds, which maintained their resilience impressively under both dry and wet conditions. We assessed the cellular and host responses of these 3D nanofiber scaffolds by comparing random membranes and mesh-like membranes with three different mesh sizes (250, 500, and 750 μm). It was found that scaffolds with a mesh size of 500 μm were superior for M2 macrophage phenotype polarization, vascularization, and matrix deposition. Furthermore, it was confirmed by subsequent experiments such as RNA sequencing that the mesh-like topology may promote polarization to the M2 phenotype by affecting the PI3K/AKT pathway. In conclusion, our work offers a novel method for transforming 2D nanofiber membranes into 3D scaffolds. This method boasts flexibility, allowing for the use of varied electrospun membranes and hydrogels in terms of structure and composition. It has vast potential in tissue repair and regeneration.
Strategic disruption of cancer’s powerhouse: precise nanomedicine targeting of mitochondrial metabolism
Authors: Lin Pei , Lu Ye , Zheng Jiarong , Lin Yunfan , Zhao Xinyuan , Cui Li
Published: June 2024

Mitochondria occupy a central role in the biology of most eukaryotic cells, functioning as the hub of oxidative metabolism where sugars, fats, and amino acids are ultimately oxidized to release energy. This crucial function fuels a variety of cellular activities. Disruption in mitochondrial metabolism is a common feature in many diseases, including cancer, neurodegenerative conditions and cardiovascular diseases. Targeting tumor cell mitochondrial metabolism with multifunctional nanosystems emerges as a promising strategy for enhancing therapeutic efficacy against cancer. This review comprehensively outlines the pathways of mitochondrial metabolism, emphasizing their critical roles in cellular energy production and metabolic regulation. The associations between aberrant mitochondrial metabolism and the initiation and progression of cancer are highlighted, illustrating how these metabolic disruptions contribute to oncogenesis and tumor sustainability. More importantly, innovative strategies employing nanomedicines to precisely target mitochondrial metabolic pathways in cancer therapy are fully explored. Furthermore, key challenges and future directions in this field are identified and discussed. Collectively, this review provides a comprehensive understanding of the current state and future potential of nanomedicine in targeting mitochondrial metabolism, offering insights for developing more effective cancer therapies.
pH/GSH dual-responsive nanoparticle for auto-amplified tumor therapy of breast cancer
Authors: Huang Shengnan , Xu Zhiling , Zhi Weiwei , Li Yijing , Hu Yurong , Zhao Fengqin , Zhu Xiali , Miao Mingsan , Jia Yongyan
Published: June 2024

Breast cancer remains a malignancy that poses a serious threat to human health worldwide. Chemotherapy is one of the most widely effective cancer treatments in clinical practice, but it has some drawbacks such as poor targeting, high toxicity, numerous side effects, and susceptibility to drug resistance. For auto-amplified tumor therapy, a nanoparticle designated GDTF is prepared by wrapping gambogic acid (GA)-loaded dendritic porous silica nanoparticles (DPSNs) with a tannic acid (TA)-Fe(III) coating layer. GDTF possesses the properties of near-infrared (NIR)-enhanced and pH/glutathione (GSH) dual-responsive drug release, photothermal conversion, GSH depletion and hydroxyl radical (·OH) production. When GDTF is exposed to NIR laser irradiation, it can effectively inhibit cell proliferation and tumor growth both in vitro and in vivo with limited toxicity. This may be due to the synergistic effect of enhanced tumor accumulation, and elevated reactive oxygen species (ROS) production, GSH depletion, and TrxR activity reduction. This study highlights the enormous potential of auto-amplified tumor therapy.
Boosting the sonodynamic performance of CoBiMn-layered double hydroxide nanoparticles via tumor microenvironment regulation for ultrasound imaging-guided sonodynamic therapy
Authors: Yang Shuqing , Hu Tingting , Williams Gareth R. , Yang Yu , Zhang Susu , Shen Jiayi , Chen Minjiang , Liang Ruizheng , Lyu Lingchun
Published: June 2024

Sonodynamic therapy (SDT), a promising strategy for cancer treatment with the ability for deep tissue penetration, has received widespread attention in recent years. Sonosensitizers with intrinsic characteristics for tumor-specific curative effects, tumor microenvironment (TME) regulation and tumor diagnosis are in high demand. Herein, amorphous CoBiMn-layered double hydroxide (a-CoBiMn-LDH) nanoparticles are presented as multifunctional sonosensitizers to trigger reactive oxygen species (ROS) generation for ultrasound (US) imaging-guided SDT. Hydrothermal-synthesized CoBiMn-LDH nanoparticles are etched via a simple acid treatment to obtain a-CoBiMn-LDH nanoparticles with abundant defects. The a-CoBiMn-LDH nanoparticles give greater ROS generation upon US irradiation, reaching levels ~ 3.3 times and ~ 8.2 times those of the crystalline CoBiMn-LDH nanoparticles and commercial TiO2 sonosensitizer, respectively. This excellent US-triggered ROS generation performance can be attributed to the defect-induced narrow band gap and promoted electrons and holes (e−/h+) separation. More importantly, the presence of Mn4+ enables the a-CoBiMn-LDH nanoparticles to regulate the TME by decomposing H2O2 into O2 for hypoxia relief and US imaging, and consuming glutathione (GSH) for protection against ROS clearance. Biological mechanism analysis shows that a-CoBiMn-LDH nanoparticles modified with polyethylene glycol can serve as a multifunctional sonosensitizer to effectively kill cancer cells in vitro and eliminate tumors in vivo under US irradiation by activating p53, apoptosis, and oxidative phosphorylation-related signaling pathways.
Dual depletion of myeloid-derived suppressor cells and tumor cells with self-assembled gemcitabine-celecoxib nano-twin drug for cancer chemoimmunotherapy
Authors: Zhang Xiaojie , Liang Qiangwei , Cao Yongjin , Yang Ting , An Min , Liu Zihan , Yang Jiayu , Liu Yanhua
Published: June 2024

Myeloid-derived suppressor cells (MDSCs) have played a significant role in facilitating tumor immune escape and inducing an immunosuppressive tumor microenvironment. Eliminating MDSCs and tumor cells remains a major challenge in cancer immunotherapy. A novel approach has been developed using gemcitabine-celecoxib twin drug-based nano-assembled carrier-free nanoparticles (GEM-CXB NPs) for dual depletion of MDSCs and tumor cells in breast cancer chemoimmunotherapy. The GEM-CXB NPs exhibit prolonged blood circulation, leading to the preferential accumulation and co-release of GEM and CXB in tumors. This promotes synergistic chemotherapeutic activity by the proliferation inhibition and apoptosis induction against 4T1 tumor cells. In addition, it enhances tumor immunogenicity by immunogenic cell death induction and MDSC-induced immunosuppression alleviation through the depletion of MDSCs. These mechanisms synergistically activate the antitumor immune function of cytotoxic T cells and natural killer cells, inhibit the proliferation of regulatory T cells, and promote the M2 to M1 phenotype repolarization of tumor-associated macrophages, considerably enhancing the overall antitumor and anti-metastasis efficacy in BALB/c mice bearing 4T1 tumors. The simplified engineering of GEM-CXB NPs, with their dual depletion strategy targeting immunosuppressive cells and tumor cells, represents an advanced concept in cancer chemoimmunotherapy.

Graphical Abstract
Bacterial outer membrane vesicle-cancer cell hybrid membrane-coated nanoparticles for sonodynamic therapy in the treatment of breast cancer bone metastasis
Authors: Wang Jiahao , Liang Shuailong , Chen Sijie , Ma Tianliang , Chen Mingyu , Niu Chengcheng , Leng Yi , Wang Long
Published: June 2024

Breast cancer bone metastasis is a terminal-stage disease and is typically treated with radiotherapy and chemotherapy, which causes severe side effects and limited effectiveness. To improve this, Sonodynamic therapy may be a more safe and effective approach in the future. Bacterial outer membrane vesicles (OMV) have excellent immune-regulating properties, including modulating macrophage polarization, promoting DC cell maturation, and enhancing anti-tumor effects. Combining OMV with Sonodynamic therapy can result in synergetic anti-tumor effects. Therefore, we constructed multifunctional nanoparticles for treating breast cancer bone metastasis. We fused breast cancer cell membranes and bacterial outer membrane vesicles to form a hybrid membrane (HM) and then encapsulated IR780-loaded PLGA with HM to produce the nanoparticles, IR780@PLGA@HM, which had tumor targeting, immune regulating, and Sonodynamic abilities. Experiments showed that the IR780@PLGA@HM nanoparticles had good biocompatibility, effectively targeted to 4T1 tumors, promoted macrophage type I polarization and DC cells activation, strengthened anti-tumor inflammatory factors expression, and presented the ability to effectively kill tumors both in vitro and in vivo, which showed a promising therapeutic effect on breast cancer bone metastasis. Therefore, the nanoparticles we constructed provided a new strategy for effectively treating breast cancer bone metastasis.

Graphical Abstract
The IL-33-ST2 axis plays a vital role in endometriosis via promoting epithelial–mesenchymal transition by phosphorylating β-catenin
Authors: Ruan Jingyao , Tian Qi , Li Siting , Zhou Xiaoyu , Sun Qianzhi , Wang Yuning , Xiao Yinping , Li Mingqing , Chang Kaikai , Yi Xiaofang
Published: June 2024

Objectives

Interleukin 33 (IL-33) is a crucial inflammatory factor that functions as an alarm signal in endometriosis (EMs). Epithelial-mesenchymal transition (EMT), a process related to inflammatory signals, intracellular reactive oxygen species (ROS) production, and lipid peroxidation, have been proposed as potential mechanisms that contribute to the development and progression of EMs. IL-33 is highly upregulated in the ectopic milieu. Moreover, ectopic endometrial cells constitutively express interleukin-33 receptor ST2 (IL-33R). However, the role of IL-33/ST2 in the EMT of EMs remains largely unknown. In this study, we aimed to mechanistically determine the role of IL-33/ST2 in EMs-associated fibrosis.

Materials and methods

We established a non-lethal oxidative stress model to explore the conditions that trigger IL-33 induction. We performed α-smooth muscle actin (α-SMA) protein detection, cell counting kit-8 (CCK-8) assays, and scratch assays to analyze the impact of IL-33 on primary endometrial stromal cells (ESCs) proliferation and invasion. Clinical samples from patients with or without EMs were subjected to immunohistochemical (IHC) and and immunofluorescence(IF) staining to assess the clinical relevance of IL-33 receptor ST2 and EMT-related proteins. Furthermore, we used the ectopic human endometrial epithelial cell line 12Z and normal human epithelial cell line EEC to evaluate the effects of IL-33 on Wnt/β-catenin signaling. The effect of IL-33 on EMT-associated fibrosis was validated in vivo by intraperitoneal injections of IL-33 and antiST2.

Results

We observed that ectopic milieu, characterized by ROS, TGF-β1, and high level of estrogen, triggers the secretion of IL-33 from ectopic ESCs. Ectopic endometrial lesions exhibited higher level of fibrotic characteristics and ST2 expression than that in the normal endometrium. Exogenous recombinant human (rhIL-33) enhanced ESC migration and survival. Similarly, 12Z cells displayed a higher degree of EMT characteristics with elevated expression of CCN4 and Fra-1, downstream target genes of the WNT/β-catenin pathway, than that observed in EECs. Conversely, blocking IL-33 with neutralizing antibodies, knocking down ST2 or β-catenin with siRNA, and β-catenin dephosphorylation abolished its effects on EMT promotion. In vivo validation demonstrated that IL-33 significantly promotes EMs-related fibrosis through the activation of Wnt/β-catenin signaling.

Conclusion

Our data strongly support the vital role of the IL-33/ST2 pathway in EMs-associated fibrosis and emphasize the importance of the EMT in the pathophysiology of fibrosis. Targeting the IL-33/ST2/Wnt/β-catenin axis may hold promise as a feasible therapeutic approach for controlling fibrosis in EMs.
Genome-wide DNA methylation in relation to ARID1A deficiency in ovarian clear cell carcinoma
Authors: Li Shang , Meersma Gert Jan , Kupryjanczyk Jolanta , de Jong Steven , Wisman G. Bea A.
Published: June 2024

Background

The poor chemo-response and high DNA methylation of ovarian clear cell carcinoma (OCCC) have attracted extensive attentions. Recently, we revealed the mutational landscape of the human kinome and additional cancer-related genes and found deleterious mutations in ARID1A, a component of the SWI/SNF chromatin-remodeling complex, in 46% of OCCC patients. The present study aims to comprehensively investigate whether ARID1A loss and genome-wide DNA methylation are co-regulated in OCCC and identify putative therapeutic targets epigenetically regulated by ARID1A.

Methods

DNA methylation of ARID1Amt/ko and ARID1Awt OCCC tumors and cell lines were analyzed by Infinium MethylationEPIC BeadChip. The clustering of OCCC tumors in relation to clinical and mutational status of tumors were analyzed by hierarchical clustering analysis of genome-wide methylation. GEO expression profiles were used to identify differentially methylated (DM) genes and their expression level in ARID1Amt/ko vs ARID1Awt OCCCs. Combining three pre-ranked GSEAs, pathways and leading-edge genes epigenetically regulated by ARID1A were revealed. The leading-edge genes that passed the in-silico validation and showed consistent ARID1A-related methylation change in tumors and cell lines were regarded as candidate genes and finally verified by bisulfite sequencing and RT-qPCR.

Results

Hierarchical clustering analysis of genome-wide methylation showed two clusters of OCCC tumors. Tumor stage, ARID1A/PIK3CA mutations and TP53 mutations were significantly different between the two clusters. ARID1A mutations in OCCC did not cause global DNA methylation changes but were related to DM promoter or gene-body CpG islands of 2004 genes. Three pre-ranked GSEAs collectively revealed the significant enrichment of EZH2- and H3K27me3-related gene-sets by the ARID1A-related DM genes. 13 Leading-edge DM genes extracted from the enriched gene-sets passed the expression-based in-silico validation and showed consistent ARID1A-related methylation change in tumors and cell lines. Bisulfite sequencing and RT-qPCR analysis showed promoter hypermethylation and lower expression of IRX1, TMEM101 and TRIP6 in ARID1Amt compared to ARID1Awt OCCC cells, which was reversed by 5-aza-2′-deoxycytidine treatment.

Conclusions

Our study shows that ARID1A loss is related to the differential methylation of a number of genes in OCCC. ARID1A-dependent DM genes have been identified as key genes of many cancer-related pathways that may provide new candidates for OCCC targeted treatment.
Health care providers attitude towards safe abortion care and its associated factors in Northwest, Ethiopia, 2021: a health facility-based cross-sectional study
Authors: Wubetu Abebay Tadie , Munea Alemtsehay Mekonnen , Balcha Wondu Feyisa , Chekole Fentahun Alemnew , Nega Amanuel Tebabal , Getu Alemwork Abie , Asresie Melash Belachew
Published: June 2024

Background

A negative attitude towards abortion among health care providers providing abortion services could be an obstacle even under a law, which permits abortion on request. Healthcare providers are expected to perform and be change agents of abortion services. However, little information is known about the attitude toward safe abortion among healthcare providers in Ethiopia.

Objective

This study aimed to assess health care provider’s attitudes towards safe abortion care and its associated factors at the public health facilities of Bahir Dar City, Northwest Ethiopia.

Methods

A health facility-based cross-sectional study was employed from March 1 to 30/2021 among 416 health-care providers. The data were collected by computer-based generated simple random sampling technique, entered, coded, and cleaned using Epi data version 4.2 and analyzed using Statistical Package of Social Sciences version 25.0. Bivariate and multivariable logistic regression analyses were employed to estimate the crude and adjusted odds ratio with a confidence interval of 95% and a P-value of less than 0.05 considered statistically significant.

Results

The response rate of the study was 99.3%, and 70.2% [95% CI: 65.6–74.6] of health-care providers had a favorable attitude towards safe abortion care. Multivariable analysis indicated that health care providers who are found in the age group of 25–29, 30–34, and ≥ 35 years [AOR = 3.34, 95% CI = 1.03–10.85], [AOR = 4.58, 95% CI = 1.33- 15.83] and [AOR = 5.30, 95% CI = 1.43–19.66] respectively, male health care providers [AOR = 3.20, 95% CI = 1.55–6.60], midwives [AOR = 6.50, 95% CI = 2.40–17.44], working at hospital [AOR = 4.77, 95% CI = 1.53–14.91], ever trained on safe abortion [AOR = 5.09, 95% CI = 2.29–11.32], practicing of an abortion procedure [AOR = 2.52, 95%, CI = 1.13–5.60], knowledge of abortion [AOR = 7.35, 95% CI = 3.23–16.71], awareness on revised abortion law [AOR = 6.44, 95% CI = 3.15–13.17] and need further legalization of abortion law [AOR = 11.78, 95% CI = 5.52–24.26] were associated with a favorable attitude towards safe abortion care.

Conclusions

Healthcare providers who had a favorable attitude toward safe abortion care were relatively high compared to the previous studies. Age, sex, profession, workplace, training, knowledge, and practice-related factors were associated with a favorable attitude toward safe abortion. This study indicated that, a need for intervention to help improve the attitude of healthcare providers toward safe abortion care, especially for those working in the maternity care units.
Alterations in brain fluid physiology during the early stages of development of ischaemic oedema
Authors: Hladky Stephen B. , Barrand Margery A.
Published: June 2024

Oedema occurs when higher than normal amounts of solutes and water accumulate in tissues. In brain parenchymal tissue, vasogenic oedema arises from changes in blood–brain barrier permeability, e.g. in peritumoral oedema. Cytotoxic oedema arises from excess accumulation of solutes within cells, e.g. ischaemic oedema following stroke. This type of oedema is initiated when blood flow in the affected core region falls sufficiently to deprive brain cells of the ATP needed to maintain ion gradients. As a consequence, there is: depolarization of neurons; neural uptake of Na+ and Cl− and loss of K+; neuronal swelling; astrocytic uptake of Na+, K+ and anions; swelling of astrocytes; and reduction in ISF volume by fluid uptake into neurons and astrocytes. There is increased parenchymal solute content due to metabolic osmolyte production and solute influx from CSF and blood. The greatly increased [K+]isf triggers spreading depolarizations into the surrounding penumbra increasing metabolic load leading to increased size of the ischaemic core. Water enters the parenchyma primarily from blood, some passing into astrocyte endfeet via AQP4. In the medium term, e.g. after three hours, NaCl permeability and swelling rate increase with partial opening of tight junctions between blood–brain barrier endothelial cells and opening of SUR1-TPRM4 channels. Swelling is then driven by a Donnan-like effect. Longer term, there is gross failure of the blood–brain barrier. Oedema resolution is slower than its formation. Fluids without colloid, e.g. infused mock CSF, can be reabsorbed across the blood–brain barrier by a Starling-like mechanism whereas infused serum with its colloids must be removed by even slower extravascular means. Large scale oedema can increase intracranial pressure (ICP) sufficiently to cause fatal brain herniation. The potentially lethal increase in ICP can be avoided by craniectomy or by aspiration of the osmotically active infarcted region. However, the only satisfactory treatment resulting in retention of function is restoration of blood flow, providing this can be achieved relatively quickly. One important objective of current research is to find treatments that increase the time during which reperfusion is successful. Questions still to be resolved are discussed.
CIC::NUTM1 sarcomas occurred in soft tissues of upper limbs : a rare case report and literature review
Authors: Zhao Lina , He Huihua , Ren Jiacai , Huang Yabing , Yan Honglin , Yuan Jingping
Published: June 2024

Background

CIC-rearranged sarcomas (CRS) represent a new entity of undifferentiated small round cell sarcoma belonging to the Ewing-like sarcomas family. CRS are the most common type. Fusion partners for the CIC gene include DUX4, FOXO4, and the recently recognizedNUTM1. Rare cases of CIC::NUTM1 sarcoma in pediatric patients have recently been reported in brain, kidney, bone, and soft tissues. However, such cases have not been identified in the soft tissues of the limbs.

Case presentation

We reported a case of CIC::NUTM1 sarcoma located in the right upper limb of an 18-year-old man. The tumor displayed morphologic features typical of CIC::DUX4 sarcomas, with small- to medium-sized round cells, a lobular pattern, focal spindling, myxoid stroma, and patchy necrosis. The tumor diffusely expressed NUTM1, was positive for WT1cter at weak to moderate intensity, and was focally positive for CD99, while it was negative for keratins, EMA, P40, MyoD1, myogenin, NKX2.2, BCOR, and pan-TRK. Fluorescence in situ hybridization analyses revealed cleavage of the CIC and NUTM1 genes.

Conclusion

CIC::NUTM1 sarcomas represent a novel molecular variant of CRS with a preference for the central nervous system and younger pediatric persons. Its morphology and phenotype may be mistaken for NUT carcinomas, and the behavior is more progressive than other forms of CRS. For this rare and newly discovered gene fusion variant, it is necessary to integrate molecular and immunohistochemical findings with morphologic features in the diagnosis of undifferentiated neoplasms.
Exploring UAS-lidar as a sampling tool for satellite-based AGB estimations in the Miombo woodland of Zambia
Authors: Shamaoma Hastings , Chirwa Paxie W. , Zekeng Jules C. , Ramoelo Able , Hudak Andrew T. , Handavu Ferdinand , Syampungani Stephen
Published: June 2024

To date, only a limited number of studies have utilized remote sensing imagery to estimate aboveground biomass (AGB) in the Miombo ecoregion using wall-to-wall medium resolution optical satellite imagery (Sentinel-2 and Landsat), localized airborne light detection and ranging (lidar), or localized unmanned aerial systems (UAS) images. On the one hand, the optical satellite imagery is suitable for wall-to-wall coverage, but the AGB estimates based on such imagery lack precision for local or stand-level sustainable forest management and international reporting mechanisms. On the other hand, the AGB estimates based on airborne lidar and UAS imagery have the precision required for sustainable forest management at a local level and international reporting requirements but lack capacity for wall-to-wall coverage. Therefore, the main aim of this study was to investigate the use of UAS-lidar as a sampling tool for satellite-based AGB estimation in the Miombo woodlands of Zambia. In order to bridge the spatial data gap, this study employed a two-phase sampling approach, utilizing Sentinel-2 imagery, partial-coverage UAS-lidar data, and field plot data to estimate AGB in the 8094-hectare Miengwe Forest, Miombo Woodlands, Zambia, where UAS-lidar estimated AGB was used as reference data for estimating AGB using Sentinel-2 image metrics. The findings showed that utilizing UAS-lidar as reference data for predicting AGB using Sentinel-2 image metrics yielded superior results (Adj-R2 = 0.70, RMSE = 27.97) than using direct field estimated AGB and Sentinel-2 image metrics (R2 = 0.55, RMSE = 38.10). The quality of AGB estimates obtained from this approach, coupled with the ongoing advancement and cost-cutting of UAS-lidar technology as well as the continuous availability of wall-to-wall optical imagery such as Sentinel-2, provides much-needed direction for future forest structural attribute estimation for efficient management of the Miombo woodlands.
Hyperspectral imaging for quantifying Magnaporthe oryzae sporulation on rice genotypes
Authors: Maina Angeline Wanjiku , Oerke Erich-Christian
Published: June 2024

Background

Precise evaluation of fungal conidia production may facilitate studies on resistance mechanisms and plant breeding for disease resistance. In this study, hyperspectral imaging (HSI) was used to quantify the sporulation of Magnaporthe oryzae on the leaves of rice cultivars grown under controlled conditions. Three rice genotypes (CO 39, Nipponbare, IR64) differing in susceptibility to blast were inoculated with M. oryzae isolates Guy 11 and Li1497. Spectral information (450–850 nm, 140 wavebands) of typical leaf blast symptoms was recorded before and after induction of sporulation of the pathogen.

Results

M. oryzae produced more conidia on the highly susceptible genotype than on the moderately susceptible genotype, whereas the resistant genotype resulted in no sporulation. Changes in reflectance spectra recorded before and after induction of sporulation were significantly higher in genotype CO 39 than in Nipponbare. The spectral angle mapper algorithm for supervised classification allowed for the classification of blast symptom subareas and the quantification of lesion areas with M. oryzae sporulation. The correlation between the area under the difference spectrum (viz. spectral difference without and with sporulation) and the number of conidia per lesion and the number of conidia per lesion area was positive and count-based differences in rice - M. oryzae interaction could be reproduced in the spectral data.

Conclusions

HSI provided a precise and objective method of assessing M. oryzae conidia production on infected rice plants, revealing differences that could not be detected visually.
Radiation pneumonitis prediction with dual-radiomics for esophageal cancer underwent radiotherapy
Authors: Li Chenyu , Zhang Ji , Ning Boda , Xu Jiayi , Lin Zhixi , Zhang Jicheng , Tan Ninghang , Yu Xianwen , Su Wanyu , Ni Weihua , Yu Wenliang , Wu Jianping , Cao Guoquan , Cao Zhuo , Xie Congying , Jin Xiance
Published: June 2024

Background

To integrate radiomics and dosiomics features from multiple regions in the radiation pneumonia (RP grade ≥ 2) prediction for esophageal cancer (EC) patients underwent radiotherapy (RT).

Methods

Total of 143 EC patients in the authors’ hospital (training and internal validation: 70%:30%) and 32 EC patients from another hospital (external validation) underwent RT from 2015 to 2022 were retrospectively reviewed and analyzed. Patients were dichotomized as positive (RP+) or negative (RP-) according to CTCAE V5.0. Models with radiomics and dosiomics features extracted from single region of interest (ROI), multiple ROIs and combined models were constructed and evaluated. A nomogram integrating radiomics score (Rad_score), dosiomics score (Dos_score), clinical factors, dose-volume histogram (DVH) factors, and mean lung dose (MLD) was also constructed and validated.

Results

Models with Rad_score_Lung&Overlap and Dos_score_Lung&Overlap achieved a better area under curve (AUC) of 0.818 and 0.844 in the external validation in comparison with radiomics and dosiomics models with features extracted from single ROI. Combining four radiomics and dosiomics models using support vector machine (SVM) improved the AUC to 0.854 in the external validation. Nomogram integrating Rad_score, and Dos_score with clinical factors, DVH factors, and MLD further improved the RP prediction AUC to 0.937 and 0.912 in the internal and external validation, respectively.

Conclusion

CT-based RP prediction model integrating radiomics and dosiomics features from multiple ROIs outperformed those with features from a single ROI with increased reliability for EC patients who underwent RT.
Can zoledronic acid reduce the risk of cage subsidence after oblique lumbar interbody fusion combined with bilateral pedicle screw fixation in the elderly population? A retrospective study
Authors: Jin Cong , Shang JinXiang , Chen Xi , Zheng Jiewen , He Wei , He Lei , Han Weiqi
Published: June 2024

Background

The objective of this study was to evaluate the potential of zoledronic acid for reducing the incidence of cage subsidence and enhancing interbody fusion rates following oblique lumbar interbody fusion (OLIF) surgery, particularly as the first reported evidence of the role of zoledronic acid combined with OLIF.

Methods

A retrospective analysis was conducted on data from 108 elderly patients treated for degenerative lumbar diseases using OLIF combined with bilateral pedicle screw fixation from January 2018 to December 2021. Patients were divided into the zoledronic acid (ZOL) group (43 patients, 67 surgical segments) and the control group (65 patients, 86 surgical segments). A comparative analysis of the radiographic and clinical outcomes between the groups was performed, employing univariate and multivariate regression analyses to explore the relationships between cage subsidence and the independent variables.

Results

Radiographic outcomes, including anterior height, posterior height, disc height, coronal disc angle, foraminal height, and lumbar lordosis, were not significantly different between the two groups. Similarly, no statistically significant differences were noted in the back visual analog scale (VAS) scores and Oswestry Disability Index (ODI) scores between the groups. However, at the 1-year follow-up, the leg VAS score was lower in the ZOL group than in the control group (P = 0.028). The ZOL group demonstrated a notably lower cage subsidence rate (20.9%) than did the control group (43.0%) (P < 0.001). There was no significant difference in the interbody fusion rate between the ZOL group (93.0%) and the control group (90.8%). Non-use of zoledronic acid emerged as an independent risk factor for cage subsidence (OR = 6.047, P = 0.003), along with lower bone mineral density, lower postoperative anterior height, and concave endplate morphology. The model exhibited robust discriminative performance, with an area under the curve (AUC) of 0.872.

Conclusion

The administration of zoledronic acid mitigates the risk of cage subsidence following OLIF combined with bilateral pedicle screw fixation in elderly patients; however, it does not improve the interbody fusion rate.