bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interactions of melatonin with various signaling pathways: implications for cancer therapy
Authors: Mihanfar Ainaz , Yousefi Bahman , Azizzadeh Bita , Majidinia Maryam 
Published: December 2022

AbstractMelatonin is a neuro-hormone with conserved roles in evolution. Initially synthetized as an antioxidant molecule, it has gained prominence as a key molecule in the regulation of the circadian rhythm. Melatonin exerts its effect by binding to cytoplasmic and intra-nuclear receptors, and is able to regulate the expression of key mediators of different signaling pathways. This ability has led scholars to investigate the role of melatonin in reversing the process of carcinogenesis, a process in which many signaling pathways are involved, and regulating these pathways may be of clinical significance. In this review, the role of melatonin in regulating multiple signaling pathways with important roles in cancer progression is discussed, and evidence regarding the beneficence of targeting malignancies with this approach is presented.
Targeting SOST using a small-molecule compound retards breast cancer bone metastasis
Authors: Sun Lisha , Zhang Yixiao , Chen Guanglei , Ji Yaoting , Ma Qingtian , Qiao Xinbo , Wu Sijin , Zhou Lin , Bu Jiawen , Zhu Xudong , Zhang Xiaoying , Jiang Xiaofan , Liu Chao , Li Xinnan , Liu Yang , Yang Yongliang , Liu Caigang 
Published: December 2022

Abstract
Background
Breast cancer metastasis to the bone can be exacerbated by osteoporosis, is associated with poor long-term survival, and has limited therapeutic options. Sclerostin (SOST) is an endogenous inhibitor of bone formation, and an attractive target for treatment of osteoporosis. However, it is unclear whether SOST can be used as a therapeutic target for bone metastases of breast cancer, and whether small molecule compounds that target SOST in breast cancer cells can inhibit breast cancer bone metastasis.

Methods
SOST expression in 442 breast cancer tissues was characterized by immunohistochemistry and statistically analyzed for the association with breast cancer bone metastases. Bone metastatic breast cancer SCP2 cells were induced for SOST silencing or overexpression and their bone metastatic behaviors were tested in vitro and in vivo. To identify potential therapeutics, we screened inhibitors of the interaction of SOST with STAT3 from a small chemical molecule library and tested the inhibitory effects of one inhibitor on breast cancer growth and bone metastasis in vitro and in vivo.

Results
We found that up-regulated SOST expression was associated with breast cancer bone metastases and worse survival of breast cancer patients. SOST silencing significantly reduced the bone metastatic capacity of SCP2 cells. SOST interacted with STAT3 to enhance the TGF-β/KRAS signaling, increasing both tumor growth and bone metastasis. Treatment with one lead candidate, S6, significantly inhibited the growth of breast-cancer organoids and bone metastasis in mice.

Conclusions
Our findings highlight a new class of potential therapeutics for treatment of bone metastasis in breast cancer.
Progranulin from different gliocytes in the nucleus accumbens exerts distinct roles in FTD- and neuroinflammation-induced depression-like behaviors
Authors: Wang Jing , Lai Simin , Zhou Ting , Xia Zhihao , Li Weina , Sha Wenqi , Liu Jingjie , Chen Yanjiong 
Published: December 2022

Abstract
Background
Neuroinflammation in the nucleus accumbens (NAc) is well known to influence the progression of depression. However, the molecular mechanisms triggering NAc neuroinflammation in depression have not been fully elucidated. Progranulin (PGRN) is a multifunctional growth factor that is linked to the innate immune response and inflammation, and PGRN plays a key role in neurodegenerative diseases such as frontotemporal dementia (FTD). Here, the purpose of this study was to validate whether PGRN was involved in the NAc neuroinflammation-promoted depressive-like phenotype.

Methods
A NAc neuroinflammation-relevant depression-like model was established using wild-type (WT) and PGRN-knockout (KO) mice after NAc injection with lipopolysaccharide (LPS), and various behavioral tests related to cognition, social recognition, depression and anxiety were performed with WT and PGRNKO mice with or without NAc immune challenge. RT‒PCR, ELISA, western blotting and immunofluorescence staining were used to determine the expression and function of PGRN in the neuroinflammatory reaction in the NAc after LPS challenge. The morphology of neurons in the NAc from WT and PGRNKO mice under conditions of NAc neuroinflammation was analyzed using Golgi–Cox staining, followed by Sholl analyses. The potential signaling pathways involved in NAc neuroinflammation in PGRNKO mice were investigated by western blotting.

Results
Under normal conditions, PGRN deficiency induced FTD-like behaviors in mice and astrocyte activation in the NAc, promoted the release of the inflammatory cytokines interleukin (IL)-6 and IL-10 and increased dendritic complexity and synaptic protein BDNF levels in the NAc. However, NAc neuroinflammation enhanced PGRN expression, which was located in astrocytes and microglia within the NAc, and PGRN deficiency in mice alleviated NAc neuroinflammation-elicited depression-like behaviors, seemingly inhibiting astrocyte- and microglia-related inflammatory reactions and neuroplasticity complexity in the NAc via the p38 and nuclear factor of kappa (NF-κB) signaling pathways present in the NAc after neuroinflammation.

Conclusions
Our results suggest that PGRN exerts distinct function on different behaviors, showing protective roles in the FTD-like behavior and detrimental effects on the neuroinflammation-related depression-like behavior, resulting from mediating astrocyte and microglial functions from the NAc in different status.
Effectiveness of mindfulness-based stress reduction on depression, anxiety, and stress of women with the early loss of pregnancy in southeast Iran: a randomized control trial
Authors: Nasrollahi Masumeh , Ghazanfar Pour Masumeh , Ahmadi Atefeh , Mirzaee Mogaddameh , Alidousti Katayoun 
Published: December 2022

Abstract
Background
The loss of the fetus may cause mental health problems in women. The present study aimed to determine the effect of mindfulness-based stress reduction (MBSR) on anxiety, depression, and stress in women with early pregnancy loss.

Methods
This study was performed on 106 women with early pregnancy loss in Shiraz, Iran. The intervention group underwent eight counselling sessions. Pre-test and post-test were performed in both groups with the Depression, Anxiety, and Stress Scale (DASS) 21 questionnaire. Data were analyzed by SPSS 23.

Results
There was a statistically significant difference between the mean scores in the intervention group vs. the control group in terms of anxiety (7.9 ± 1.07 vs. 13.79 ± 5.36, respectively), stress (9.26 ± 1.25 vs.18.13 ± 7.66, respectively), and depression (7.83 ± 1.05 vs.16.26 ± 11.06, respectively) (P < 0.0001).

Conclusions
MBSR can be suggested to promote women's mental health.
Health system to response to economic sanctions: global evidence and lesson learned from Iran
Authors: Sajadi Haniye Sadat , Majdzadeh Reza 
Published: December 2022

Abstract
Background
Sanctions have direct and indirect impacts on people’s lives. Therefore, the health systems of countries targeted by sanctions must respond effectively. This study proposes a set of mitigating measures and response strategies to improve the health systems of countries under sanctions.

Methods
This three-stage study was conducted in Iran within the 2020–2021 period, in which a rapid review of evidence was carried out to identify the measures implemented or proposed to make the health system resilient in confronting sanctions. A qualitative approach was then adopted to determine how the health system could be improved to response to sanctions from the perspectives of 10 key experts. Semi-structured interviews and document analysis were conducted for data collection. Finally, a two-round Delphi technique was employed to help eleven experts reach a consensus on a set of mitigating measures, which were then prioritized.

Results
In this research, 62 proposed or implemented mitigating measures were extracted from 13 eligible studies to improve the health system performance in confronting sanctions. Moreover, 18 measures were identified in interviews for a better health system response to sanctions. They were then classified as five categories: sustained financing, good governance, integrated and updated health information systems, qualified workforce, and efficient and equitable service delivery. In the first Delphi round, 28 mitigating measures were discovered. Nine measures were identified as more effective and feasible in both short and long runs. They were introduced as below: conducting proactive inventory control, developing the nationally essential list of medicines, providing additional clarification that oil revenues can be freely used for medicines procurement, defining tailored health service packages for vulnerable populations, establishing and enhancing an efficient surveillance system, reducing prices of imported medicines, developing dual policies of equity and priority for vulnerable groups, institutionalizing fair and effective resource allocations, and providing clinical guidelines.

Conclusions
According to the findings, the most critical areas for the resilience of a health system in confronting sanctions include strengthening particular components of governance, improving efficiency, and caring for vulnerable populations. The experts collectively emphasized investment in domestic capacities, public participation, and health diplomacy. Despite the proposed measures, it is unclear how effective these are and, especially whether they can significantly affect the harsh impacts of sanctions on health. Moreover, intensive and long-term sanctions have significant irreversible outcomes that cannot be reversed easily or quickly.
Proliferative epithelial changes in tumour adjacent tissue in Sri Lankan women with breast carcinoma: do morphological changes support molecular models of breast carcinogenesis?
Authors: Jinadasa Indumini Maheshika , Wijesinghe Harshima Disvini , Jayawickrama Modini Manohari Abeydera , Lokuhetty Menaka Dilani Samarawickrama 
Published: December 2022

Abstract
Background
The multistep molecular model of breast carcinogenesis is based on the oestrogen receptor(ER) status of the tumour. Its two main arms comprise ER-positive and ER-negative breast carcinomas(BCa), which are associated with Nottingham grade(NG) of the tumour and different proliferative epithelial changes. According to the model, columnar cell lesions(CCL), lobular carcinoma in-situ(LCIS) and atypical ductal hyperplasia(ADH), low-grade ductal carcinoma in-situ (LG-DCIS) are associated with low grade ER-positive tumours and microglandular adenosis (MGA), pleomorphic LCIS(PLCIS), high-grade DCIS(HG-DCIS) are associated with ER-negative high grade tumours. This study aims to describe the association between proliferative epithelial changes in breast tissue adjacent to tumour, in relation to the ER status and NG of the tumour.

Methods
This descriptive cross-sectional study included 420, wide local excision and mastectomy specimens of BCa from National Hospital of Sri Lanka, between 2017–2019. The histopathological features of the tumour and proliferative epithelial changes in tumour adjacent tissue within 10 mm distance from the tumour-host interface were evaluated independently by two pathologists. The ER, PR(Progesterone receptor) and HER2 status assessed by immunohistochemistry(IHC) was reviewed. The associations between above epithelial lesions and ER status and NG{categorised as low grade (NG1 and NG2) and high grade (NG3)} of the tumour were analyzed.

Results
ER positive BCa showed significant associations with CCH (p = 0.04), FEA (p = 0.035) and LGDCIS (p < 0.001). Although PLCIS was more frequent in ER positive tumours, the association did not attain statistical significance. ER negative BCa showed a significant association with HGDCIS (p = 0.016). CCLs as a whole (p = 0.005) and also CCC (p = 0.006) and FEA (p = 0.048) and LGDCIS (p < 0.001) showed significant associations with low NG tumours. High NG tumours showed a significant association with HGDCIS (p < 0.001). Microglandular adenosis was not identified in our study population.

Conclusion
These morphological findings support the multistep molecular based pathogenetic pathways of breast carcinoma in the studied setting in South Asia. Identification of these proliferative epithelial components in a core biopsy that is negative for BCa, should prompt for close clinicoradiological correlation, and if necessary re-biopsy of women suspected of harbouring a BCa.
RNF31 represses cell progression and immune evasion via YAP/PD-L1 suppression in triple negative breast Cancer
Authors: Yang Huijie , Xue Min , Su Peng , Zhou Yan , Li Xin , Li Zhongbo , Xia Yan , Zhang Chenmiao , Fu Mingxi , Zheng Xiuxia , Luo Guosheng , Wei Tian , Wang Xinxing , Ding Yinlu , Zhu Jian , Zhuang Ting 
Published: December 2022

Abstract
Background
Recently genome-based studies revealed that the abnormality of Hippo signaling is pervasive in TNBC and played important role in cancer progression. RING finger protein 31 (RNF31) comes to RING family E3 ubiquitin ligase. Our previously published studies have revealed RNF31 is elevated in ER positive breast cancer via activating estrogen signaling and suppressing P53 pathway.

Methods
We used several TNBC cell lines and xenograft models and performed immuno-blots, QPCR, in vivo studies to investigate the function of RNF31 in TNBC progression.

Result
Here, we demonstrate that RNF31 plays tumor suppressive function in triple negative breast cancer (TNBC). RNF31 depletion increased TNBC cell proliferation and migration in vitro and in vitro. RNF31 depletion in TNBC coupled with global genomic expression profiling indicated Hippo signaling could be the potential target for RNF31 to exert its function. Further data showed that RNF31 depletion could increase the level of YAP protein, and Hippo signaling target genes expression in several TNBC cell lines, while clinical data illustrated that RNF31 expression correlated with longer relapse-free survival in TNBC patients and reversely correlated with YAP protein level. The molecular biology assays implicated that RNF31 could associate with YAP protein, facilitate YAP poly-ubiquitination and degradation at YAP K76 sites. Interestingly, RNF31 could also repress PDL1 expression and sensitive TNBC immunotherapy via inhibiting Hippo/YAP/PDL1 axis.

Conclusions
Our study revealed the multi-faced function of RNF31 in different subtypes of breast malignancies, while activation RNF31 could be a plausible strategy for TNBC therapeutics.
The effects of neutral argon plasma versus electrocoagulation on tissue in advanced-stage ovarian cancer: a case series
Authors: Nieuwenhuyzen-de Boer Gatske M. , van de Berg Nick J. , Gao Xu Shan , Ewing-Graham Patricia C. , van Beekhuizen Heleen J. 
Published: December 2022

Abstract
Background
The aim of surgery for advanced-stage ovarian cancer is a complete cytoreduction, because this is the most important independent prognostic factor for prolonged survival. Yet this can be difficult to achieve when there are micrometastases on the intestinal mesentery or intestines. The PlasmaJet device is an instrument to remove these micrometastases, but little is known about the depth of damage in human tissue compared to electrocoagulation devices.

Methods
A prospective study was performed for the ex-vivo comparison of the histological depth of thermal damage of neutral argon plasma (PlasmaJet®) and electrocoagulation devices, in a series of 106 histological slides of 17 advanced-stage ovarian cancer patients. Depending on the tissue types resected during complete cytoreductive surgery, samples were collected from reproductive organs (uterus, ovaries), intestines (ileum, colon, rectum) and omentum, intestinal mesentery and peritoneum.

Results
Average thermal damage depth was 0.15 mm (range 0.03–0.60 mm) after use of neutral argon plasma and 0.33 mm (range 0.08–1.80 mm) after use of electrocoagulation (p < 0.001). Greater disruption of the tissue surface was often observed after electrocoagulation.

Conclusion
Our case series suggests that the use of neutral argon plasma during cytoreductive surgery produces significantly less thermal damage than electrocoagulation treatment. It is therefore considered a thermally safe alternative, aiding in the achievement of cytoreductive surgery.
SRC kinase-mediated signaling pathways and targeted therapies in breast cancer
Authors: Luo Juan , Zou Hailin , Guo Yibo , Tong Tongyu , Ye Liping , Zhu Chengming , Deng Liang , Wang Bo , Pan Yihang , Li Peng 
Published: December 2022

AbstractBreast cancer (BC) has been ranked the most common malignant tumor throughout the world and is also a leading cause of cancer-related deaths among women. SRC family kinases (SFKs) belong to the non-receptor tyrosine kinase (nRTK) family, which has eleven members sharing similar structure and function. Among them, SRC is the first identified proto-oncogene in mammalian cells. Oncogenic overexpression or activation of SRC has been revealed to play essential roles in multiple events of BC progression, including tumor initiation, growth, metastasis, drug resistance and stemness regulations. In this review, we will first give an overview of SRC kinase and SRC-relevant functions in various subtypes of BC and then systematically summarize SRC-mediated signaling transductions, with particular emphasis on SRC-mediated substrate phosphorylation in BC. Furthermore, we will discuss the progress of SRC-based targeted therapies in BC and the potential future direction.
Focused Ultrasound and RadioTHERapy for non-invasive palliative pain treatment in patients with bone metastasis: a study protocol for the three armed randomized controlled FURTHER trial
Authors: Slotman Derk J. , Bartels Marcia M. T. J. , Ferrer Cyril J. , Bos Clemens , Bartels Lambertus W. , Boomsma Martijn F. , Phernambucq Erik C. J. , Nijholt Ingrid M. , Morganti Alessio G. , Siepe Giambattista , Buwenge Milly , Grüll Holger , Bratke Grischa , Yeo Sin Yuin , Blanco Sequeiros Roberto , Minn Heikki , Huhtala Mira , Napoli Alessandro , De Felice Francesca , Catalano Carlo , Bazzocchi Alberto , Gasperini Chiara , Campanacci Laura , Simões Corrêa Galendi Julia , Müller Dirk , Braat Manon N. G. J. A. , Moonen Chrit , Verkooijen Helena M. ,   on behalf of the FURTHER consortium
Published: December 2022

Abstract
Background

Cancer-induced bone pain (CIBP), caused by bone metastases, is a common complication of cancer and strongly impairs quality of life (QoL). External beam radiotherapy (EBRT) is the current standard of care for treatment of CIBP. However, approximately 45% of patients have no adequate pain response after EBRT. Magnetic resonance image-guided high-intensity focused ultrasound (MR-HIFU) may improve pain palliation in this patient population. The main objective of this trial was to compare MR-HIFU, EBRT, and MR-HIFU + EBRT for the palliative treatment of bone metastases.

Methods/design
The FURTHER trial is an international multicenter, three-armed randomized controlled trial. A total of 216 patients with painful bone metastases will be randomized in a 1:1:1 ratio to receive EBRT only, MR-HIFU only, or combined treatment with EBRT followed by MR-HIFU. During a follow-up period of 6 months, patients will be contacted at eight time points to retrieve information about their level of pain, QoL, and the occurrence of (serious) adverse events. The primary outcome of the trial is pain response at 14 days after start of treatment. Secondary outcomes include pain response at 14 days after trial enrolment, pain scores (daily until the 21st day and at 4, 6, 12 and 24 weeks), toxicity, adverse events, QoL, and survival. Cost-effectiveness and cost-utility analysis will be conducted.

Discussion
The FURTHER trial aims to evaluate the effectiveness and cost-effectiveness of MR-HIFU—alone or in combination with EBRT—compared to EBRT to relieve CIBP. The trial will be performed in six hospitals in four European countries, all of which are partners in the FURTHER consortium.

Trial registration
The FURTHER trial is registered under the Netherlands Trials Register number NL71303.041.19 and ClinicalTrials.gov registration number NCT04307914. Date of trial registration is 13–01-2020.
HTRA1 methylation in peripheral blood as a potential marker for the preclinical detection of stroke: a case–control study and a prospective nested case–control study
Authors: Liu Chunlan , Li Mengxia , Yin Qiming , Fan Yao , Shen Chong , Yang Rongxi 
Published: December 2022

Abstract
Background
Stroke is the leading cause of mortality in China. DNA methylation has essential roles in multiple diseases, but its association with stroke was barely studied. We hereby explored the association between blood-based HTRA serine protease 1 (HTRA1) methylation and the risk of stroke.

Results
The association was discovered in a hospital-based case–control study (cases/controls = 190:190) and further validated in a prospective nested case–control study including 139 cases who developed stroke within 2 years after recruitment and 144 matched stroke-free controls. We observed stroke-related altered HTRA1 methylation and expression in both case–control study and prospective study. This blood-based HTRA1 methylation was associated with stroke independently from the known risk factors and mostly affected the older population. The prospective results further showed that the altered HTRA1 methylation was detectable 2 years before the clinical determination of stroke and became more robust with increased discriminatory power for stroke along with time when combined with other known stroke-related variables [onset time ≤ 1 year: area under the curve (AUC) = 0.76].

Conclusions
In our study, altered HTRA1 methylation was associated with stroke at clinical and preclinical stages and thus may provide a potential biomarker in the blood for the risk evaluation and preclinical detection of stroke.
Neglected case of a huge leiomyoma in an elderly postmenopausal woman: a case report
Authors: Garg Priyanka , Bansal Romi 
Published: December 2022

Abstract
Background
Fibroids are benign tumors of the female reproductive tract originating from the myometrial smooth muscle cells. They are a frequent occurrence in women of childbearing age but their incidence is rare after menopause. In addition, there is a remote possibility of malignant transformation to leiomyosarcoma in less than 1% of cases.

Case presentation
We hereby report a case of large fibroid in a postmenopausal Indian female with rapid growth, raising the suspicion of malignant transformation into leiomyosarcoma. Total abdominal hysterectomy with bilateral salpingo-oophorectomy was performed. Histopathology report confirmed it to be benign leiomyoma without any evidence of neoplasia.

Conclusion
Sudden enlargement of leiomyoma in postmenopausal women should not be ignored due to possible malignant transformation and is to be dealt immediately with hysterectomy followed by histopathology.