PeerJ:Women's Healthhttps://peerj.com/articles/index.atom?journal=peerj&subject=7300Women's Health articles published in PeerJThe relationship between cancer associated fibroblasts biomarkers and prognosis of breast cancer: a systematic review and meta-analysishttps://peerj.com/articles/169582024-02-232024-02-23Meimei CuiHao DongWanli DuanXuejie WangYongping LiuLihong ShiBaogang Zhang
Background
To elucidate the relationship between cancer-associated fibroblast (CAFs) biomarkers and the prognosis of breast cancer patients for individualized CAFs-targeting treatment.
Methodology
PubMed, Web of Science, Cochrane, and Embase databases were searched for CAFs-related studies of breast cancer patients from their inception to September, 2023. Meta-analysis was performed using R 4.2.2 software. Sensitivity analyses were performed to explore the sources of heterogeneity. Funnel plot and Egger’s test were used to assess the publication bias.
Results
Twenty-seven studies including 6,830 patients were selected. Univariate analysis showed that high expression of platelet-derived growth factor receptor-β (PDGFR-β) (P = 0.0055), tissue inhibitor of metalloproteinase-2 (TIMP-2) (P < 0.0001), matrix metalloproteinase (MMP) 9 (P < 0.0001), MMP 11 (P < 0.0001) and MMP 13 (P = 0.0009) in CAFs were correlated with reduced recurrence-free survival (RFS)/disease-free survival (DFS)/metastasis-free survival (MFS)/event-free survival (EFS) respectively. Multivariate analysis showed that high expression of α-smooth muscle actin (α-SMA) (P = 0.0002), podoplanin (PDPN) (P = 0.0008), and PDGFR-β (P = 0.0470) in CAFs was associated with reduced RFS/DFS/MFS/EFS respectively. Furthermore, PDPN and PDGFR-β expression in CAFs of poorly differentiated breast cancer patients were higher than that of patients with relatively better differentiated breast cancer. In addition, there is a positive correlation between the expression of PDPN and human epidermal growth factor receptor-2 (HER-2).
Conclusions
The high expression of α-SMA, PDPN, PDGFR-β in CAFs leads to worse clinical outcomes in breast cancer, indicating their roles as prognostic biomarkers and potential therapeutic targets.
Background
To elucidate the relationship between cancer-associated fibroblast (CAFs) biomarkers and the prognosis of breast cancer patients for individualized CAFs-targeting treatment.
Methodology
PubMed, Web of Science, Cochrane, and Embase databases were searched for CAFs-related studies of breast cancer patients from their inception to September, 2023. Meta-analysis was performed using R 4.2.2 software. Sensitivity analyses were performed to explore the sources of heterogeneity. Funnel plot and Egger’s test were used to assess the publication bias.
Results
Twenty-seven studies including 6,830 patients were selected. Univariate analysis showed that high expression of platelet-derived growth factor receptor-β (PDGFR-β) (P = 0.0055), tissue inhibitor of metalloproteinase-2 (TIMP-2) (P < 0.0001), matrix metalloproteinase (MMP) 9 (P < 0.0001), MMP 11 (P < 0.0001) and MMP 13 (P = 0.0009) in CAFs were correlated with reduced recurrence-free survival (RFS)/disease-free survival (DFS)/metastasis-free survival (MFS)/event-free survival (EFS) respectively. Multivariate analysis showed that high expression of α-smooth muscle actin (α-SMA) (P = 0.0002), podoplanin (PDPN) (P = 0.0008), and PDGFR-β (P = 0.0470) in CAFs was associated with reduced RFS/DFS/MFS/EFS respectively. Furthermore, PDPN and PDGFR-β expression in CAFs of poorly differentiated breast cancer patients were higher than that of patients with relatively better differentiated breast cancer. In addition, there is a positive correlation between the expression of PDPN and human epidermal growth factor receptor-2 (HER-2).
Conclusions
The high expression of α-SMA, PDPN, PDGFR-β in CAFs leads to worse clinical outcomes in breast cancer, indicating their roles as prognostic biomarkers and potential therapeutic targets.Effects of BRD4 inhibitor JQ1 on the expression profile of super-enhancer related lncRNAs and mRNAs in cervical cancer HeLa cellshttps://peerj.com/articles/170352024-02-232024-02-23Jianqing ZhengBifen HuangLihua XiaoMin Wu
Objective
To investigate the effects of bromine domain protein 4 (BRD4) inhibitor JQ1 on the expression profile of super-enhancer-related lncRNAs (SE-lncRNAs) and mRNAs in cervical cancer (CC) HeLa-cells.
Methods
The CCK8 method was implemented to detect the inhibitory effect of JQ1 on HeLa cells and explore the best inhibitory concentration. Whole transcriptome sequencing was performed to detect the changes of lncRNAs and mRNAs expression profiles in cells of the JQ1 treatment group and control group, respectively. The differentially expressed SE-lncRNAs were obtained by matching, while the co-expressed mRNAs were obtained by Pearson correlation analysis.
Results
The inhibitory effect of JQ1 on HeLa cell proliferation increased significantly with increasing concentration and treatment time (P < 0.05). Under the experimental conditions of three concentrations of 0.01, 0.1 and 1 μmol/L of JQ1 on HeLa cells at 24, 48, 72 and 120 h, 1 μmol/L of JQ1 at 72 and 120 h had the same cell viability and the strongest cell proliferation inhibition. In order to understand the inhibitory mechanism of JQ1 on HeLa cells, this study analyzed the expression profile differences from the perspective of SE-lncRNAs and mRNAs. A total of 162 SE-lncRNAs were identified, of which 8 SE-lncRNAs were down-regulated and seven SE-lncRNAs were up-regulated. A total of 418 differentially expressed mRNAs related to SE-lncRNAs were identified, of which 395 mRNAs had positive correlation with 12 SE-lncRNAs and 408 mRNAs had negative correlation with 15 SE-lncRNAs.
Conclusion
JQ1 can significantly inhibit the proliferation of HeLa cells and affect the expression profile of SE-lncRNAs and mRNAs.
Objective
To investigate the effects of bromine domain protein 4 (BRD4) inhibitor JQ1 on the expression profile of super-enhancer-related lncRNAs (SE-lncRNAs) and mRNAs in cervical cancer (CC) HeLa-cells.
Methods
The CCK8 method was implemented to detect the inhibitory effect of JQ1 on HeLa cells and explore the best inhibitory concentration. Whole transcriptome sequencing was performed to detect the changes of lncRNAs and mRNAs expression profiles in cells of the JQ1 treatment group and control group, respectively. The differentially expressed SE-lncRNAs were obtained by matching, while the co-expressed mRNAs were obtained by Pearson correlation analysis.
Results
The inhibitory effect of JQ1 on HeLa cell proliferation increased significantly with increasing concentration and treatment time (P < 0.05). Under the experimental conditions of three concentrations of 0.01, 0.1 and 1 μmol/L of JQ1 on HeLa cells at 24, 48, 72 and 120 h, 1 μmol/L of JQ1 at 72 and 120 h had the same cell viability and the strongest cell proliferation inhibition. In order to understand the inhibitory mechanism of JQ1 on HeLa cells, this study analyzed the expression profile differences from the perspective of SE-lncRNAs and mRNAs. A total of 162 SE-lncRNAs were identified, of which 8 SE-lncRNAs were down-regulated and seven SE-lncRNAs were up-regulated. A total of 418 differentially expressed mRNAs related to SE-lncRNAs were identified, of which 395 mRNAs had positive correlation with 12 SE-lncRNAs and 408 mRNAs had negative correlation with 15 SE-lncRNAs.
Conclusion
JQ1 can significantly inhibit the proliferation of HeLa cells and affect the expression profile of SE-lncRNAs and mRNAs.Hypoxic bone marrow mesenchymal stem cell exosomes promote angiogenesis and enhance endometrial injury repair through the miR-424-5p-mediated DLL4/Notch signaling pathwayhttps://peerj.com/articles/169532024-02-222024-02-22Zhenghua XiongYong HuMin JiangBeibei LiuWenjiao JinHuiqin ChenLinjuan YangXuesong Han
Background
Currently, bone marrow mesenchymal stem cells (BMSCs) have been reported to promote endometrial regeneration in rat models of mechanically injury-induced uterine adhesions (IUAs), but the therapeutic effects and mechanisms of hypoxic BMSC-derived exosomes on IUAs have not been elucidated.
Objective
To investigate the potential mechanism by which the BMSCS-derived exosomal miR-424-5p regulates IUA angiogenesis through the DLL4/Notch signaling pathway under hypoxic conditions and promotes endometrial injury repair.
Methods
The morphology of the exosomes was observed via transmission electron microscopy, and the expression of exosome markers (CD9, CD63, CD81, and HSP70) was detected via flow cytometry and Western blotting. The expression of angiogenesis-related genes (Ang1, Flk1, Vash1, and TSP1) was detected via RT‒qPCR, and the expression of DLL4/Notch signaling pathway-related proteins (DLL4, Notch1, and Notch2) was detected via Western blotting. Cell proliferation was detected by a CCK-8 assay, and angiogenesis was assessed via an angiogenesis assay. The expression of CD3 was detected by immunofluorescence. The endometrial lesions of IUA rats were observed via HE staining, and the expression of CD3 and VEGFA was detected via immunohistochemistry.
Results
Compared with those in exosomes from normoxic conditions, miR-424-5p was more highly expressed in the exosomes from hypoxic BMSCs. Compared with those in normoxic BMSC-derived exosomes, the proliferation and angiogenesis of HUVECs were significantly enhanced after treatment with hypoxic BMSC-derived exosomes, and these effects were weakened after inhibition of miR-424-5p. miR-424-5p can target and negatively regulate the expression of DLL4, promote the expression of the proangiogenic genes Ang1 and Flk1, and inhibit the expression of the antiangiogenic genes Vash1 and TSP1. The effect of miR-424-5p can be reversed by overexpression of DLL4. In IUA rats, treatment with hypoxic BMSC exosomes and the miR-424-5p mimic promoted angiogenesis and improved endometrial damage.
Conclusion
The hypoxic BMSC-derived exosomal miR-424-5p promoted angiogenesis and improved endometrial injury repair by regulating the DLL4/Notch signaling pathway, which provides a new idea for the treatment of IUAs.
Background
Currently, bone marrow mesenchymal stem cells (BMSCs) have been reported to promote endometrial regeneration in rat models of mechanically injury-induced uterine adhesions (IUAs), but the therapeutic effects and mechanisms of hypoxic BMSC-derived exosomes on IUAs have not been elucidated.
Objective
To investigate the potential mechanism by which the BMSCS-derived exosomal miR-424-5p regulates IUA angiogenesis through the DLL4/Notch signaling pathway under hypoxic conditions and promotes endometrial injury repair.
Methods
The morphology of the exosomes was observed via transmission electron microscopy, and the expression of exosome markers (CD9, CD63, CD81, and HSP70) was detected via flow cytometry and Western blotting. The expression of angiogenesis-related genes (Ang1, Flk1, Vash1, and TSP1) was detected via RT‒qPCR, and the expression of DLL4/Notch signaling pathway-related proteins (DLL4, Notch1, and Notch2) was detected via Western blotting. Cell proliferation was detected by a CCK-8 assay, and angiogenesis was assessed via an angiogenesis assay. The expression of CD3 was detected by immunofluorescence. The endometrial lesions of IUA rats were observed via HE staining, and the expression of CD3 and VEGFA was detected via immunohistochemistry.
Results
Compared with those in exosomes from normoxic conditions, miR-424-5p was more highly expressed in the exosomes from hypoxic BMSCs. Compared with those in normoxic BMSC-derived exosomes, the proliferation and angiogenesis of HUVECs were significantly enhanced after treatment with hypoxic BMSC-derived exosomes, and these effects were weakened after inhibition of miR-424-5p. miR-424-5p can target and negatively regulate the expression of DLL4, promote the expression of the proangiogenic genes Ang1 and Flk1, and inhibit the expression of the antiangiogenic genes Vash1 and TSP1. The effect of miR-424-5p can be reversed by overexpression of DLL4. In IUA rats, treatment with hypoxic BMSC exosomes and the miR-424-5p mimic promoted angiogenesis and improved endometrial damage.
Conclusion
The hypoxic BMSC-derived exosomal miR-424-5p promoted angiogenesis and improved endometrial injury repair by regulating the DLL4/Notch signaling pathway, which provides a new idea for the treatment of IUAs.Sleep duration has a limited impact on the prevalence of menstrual irregularities in athletes: a cross-sectional studyhttps://peerj.com/articles/169762024-02-162024-02-16Mana MiyamotoKenichi Shibuya
Background
This study aimed to investigate the relationship between the prevalence of menstrual irregularities, energy intake, and sleep deprivation among female athletes.
Methods
A total of 128 female athletes, with an average age of 19.2 ± 1.2 years, participated in the study and tracked their food intake over a three-day period. Menstrual status and sleep duration were assessed using a questionnaire, and psychological anxiety was evaluated using the State and Trait Anxiety Inventory (STAI). These were measured once during the investigation. The impact of sleep status on state anxiety and daily energy intake was examined using the T-test. A generalized linear model (GLM) with a log link function was employed to investigate the effects of sleep deprivation on the presence of menstrual irregularities.
Results
As the results of the present study, sleep deprivation significant increased both state and trait anxiety (p < 0.05), as well as affecting energy intake (p < 0.05), particularly protein and carbohydrate intakes (p < 0.05). However, GLM analysis indicated that while sleep deprivation did not directly influence the prevalence of menstrual irregularities (p > 0.05), state anxiety emerged as a significant factor impacting the prevalence of menstrual irregularities (p < 0.05).
Conclusions
The results of the present study suggest a potential pathway wherein sleep deprivation might elevate state anxiety levels, consequently indirectly contributing to an increase the probability of menstrual irregularities. In conclusion, the results of the presents study provide novels insights suggesting that sleep deprivation might directly increase state anxiety and indirectly affect the prevalence of menstrual irregularities. Hence, decreased sleep duration might be related to mental health issues and the prevalence of menstrual irregularities both significant concerns among female athletes. Future studies will play a crucial role in further elucidating how sleep patterns impact the health and well-being of female athletes.
Background
This study aimed to investigate the relationship between the prevalence of menstrual irregularities, energy intake, and sleep deprivation among female athletes.
Methods
A total of 128 female athletes, with an average age of 19.2 ± 1.2 years, participated in the study and tracked their food intake over a three-day period. Menstrual status and sleep duration were assessed using a questionnaire, and psychological anxiety was evaluated using the State and Trait Anxiety Inventory (STAI). These were measured once during the investigation. The impact of sleep status on state anxiety and daily energy intake was examined using the T-test. A generalized linear model (GLM) with a log link function was employed to investigate the effects of sleep deprivation on the presence of menstrual irregularities.
Results
As the results of the present study, sleep deprivation significant increased both state and trait anxiety (p < 0.05), as well as affecting energy intake (p < 0.05), particularly protein and carbohydrate intakes (p < 0.05). However, GLM analysis indicated that while sleep deprivation did not directly influence the prevalence of menstrual irregularities (p > 0.05), state anxiety emerged as a significant factor impacting the prevalence of menstrual irregularities (p < 0.05).
Conclusions
The results of the present study suggest a potential pathway wherein sleep deprivation might elevate state anxiety levels, consequently indirectly contributing to an increase the probability of menstrual irregularities. In conclusion, the results of the presents study provide novels insights suggesting that sleep deprivation might directly increase state anxiety and indirectly affect the prevalence of menstrual irregularities. Hence, decreased sleep duration might be related to mental health issues and the prevalence of menstrual irregularities both significant concerns among female athletes. Future studies will play a crucial role in further elucidating how sleep patterns impact the health and well-being of female athletes.Fine-scale mapping of chromosome 9q22.33 identifies candidate causal variant in ovarian cancerhttps://peerj.com/articles/169182024-02-142024-02-14Tongyu XingYanrui ZhaoLili WangWei GengWei LiuJingjing ZhouCaiyun HuangWei WangXinlei ChuBen LiuKexin ChenHong ZhengLian Li
Ovarian cancer is a complex polygenic disease in which genetic factors play a significant role in disease etiology. A genome-wide association study (GWAS) identified a novel variant on chromosome 9q22.33 as a susceptibility locus for epithelial ovarian cancer (EOC) in the Han Chinese population. However, the underlying mechanism of this genomic region remained unknown. In this study, we conducted a fine-mapping analysis of 130 kb regions, including 1,039 variants in 200 healthy women. Ten variants were selected to evaluate the association with EOC risk in 1,099 EOC cases and 1,591 controls. We identified two variants that were significantly associated with ovarian cancer risk (rs7027650, P = 1.91 × 10−7; rs1889268, P = 3.71 × 10−2). Expression quantitative trait locus (eQTL) analysis found that rs7027650 was significantly correlated with COL15A1 gene expression (P = 0.009). The Luciferase reporter gene assay confirmed that rs7027650 could interact with the promoter region of COL15A1, reducing its activity. An electrophoretic mobility shift assay (EMSA) showed the allele-specific binding capacity of rs7027650. These findings revealed that rs7027650 could be a potential causal variant at 9q22.33 region and may regulate the expression level of COL15A1. This study offered insight into the molecular mechanism behind a potential causal variant that affects the risk of ovarian cancer.
Ovarian cancer is a complex polygenic disease in which genetic factors play a significant role in disease etiology. A genome-wide association study (GWAS) identified a novel variant on chromosome 9q22.33 as a susceptibility locus for epithelial ovarian cancer (EOC) in the Han Chinese population. However, the underlying mechanism of this genomic region remained unknown. In this study, we conducted a fine-mapping analysis of 130 kb regions, including 1,039 variants in 200 healthy women. Ten variants were selected to evaluate the association with EOC risk in 1,099 EOC cases and 1,591 controls. We identified two variants that were significantly associated with ovarian cancer risk (rs7027650, P = 1.91 × 10−7; rs1889268, P = 3.71 × 10−2). Expression quantitative trait locus (eQTL) analysis found that rs7027650 was significantly correlated with COL15A1 gene expression (P = 0.009). The Luciferase reporter gene assay confirmed that rs7027650 could interact with the promoter region of COL15A1, reducing its activity. An electrophoretic mobility shift assay (EMSA) showed the allele-specific binding capacity of rs7027650. These findings revealed that rs7027650 could be a potential causal variant at 9q22.33 region and may regulate the expression level of COL15A1. This study offered insight into the molecular mechanism behind a potential causal variant that affects the risk of ovarian cancer.Galectin-3 promotes fibrosis in ovarian endometriosishttps://peerj.com/articles/169222024-02-142024-02-14Guimin YangYupeng DengGuangming CaoChongdong Liu
Objective
This study aimed to investigate the potential role of galectin-3 (Gal-3) in the pathogenesis of fibrotic alterations in ovarian endometriosis (OVE).
Methods
In this study, we collected the ectopic endometrial tissues and eutopic endometrial tissues from 31 OVE patients treated by laparoscopy, and the eutopic endometrial tissues from 23 non-OVE patients with leiomyoma or other benign diseases were used as control. Hematoxylin and eosin (H&E) and Masson’s trichrome staining were utilized for histopathological assessment. The primary normal endometrial stromal cells (NESC), ectopic endometrial stromal cells (ECSC), and eutopic endometrial stromal cells (EUSC) were isolated. Gal-3 overexpression plasmids (Gal-OE) and short hairpin RNA targeting Gal-3 (Gal-3-shRNA) were transfected into the immortalized human endometriotic cell line 12Z, respectively. RT-qPCR, Western blot analysis, and immunohistochemistry were used to detect the mRNA and protein expression levels of Gal-3, type I collagen (COL-1), connective tissue growth factor (CTGF) and α-smooth muscle actin (α-SMA), respectively.
Results
H&E and Masson staining showed that ovarian ectopic endometrium exhibited glandular hyperplasia, high columnar glandular epithelium, apical plasma secretion, more subnuclear vacuoles, and obvious fibrosis, compared with normal endometrium. The mRNA and protein levels of Gal-3 , CTGF, α-SMA, and COL-1 were all upregulated in the ectopic endometrial tissues of OVE patients compared to the eutopic endometrial tissues from OVE patients and non-OVE patients. Moreover, ECSC expressed higher levels of Gal-3, CTGF, α-SMA, and COL-1 than EUSC and NESC. Follow-up investigations demonstrated that the Gal-3 overexpression substantially increased fibrosis-related markers including CTGF, α-SMA, and COL-1 within the 12Z cell line. Conversely, Gal-3 knockdown showed the opposite effects.
Conclusion
Gal-3 promotes fibrosis in OVE, positioning it as a prospective therapeutic target for mitigating fibrosis in endometriosis.
Objective
This study aimed to investigate the potential role of galectin-3 (Gal-3) in the pathogenesis of fibrotic alterations in ovarian endometriosis (OVE).
Methods
In this study, we collected the ectopic endometrial tissues and eutopic endometrial tissues from 31 OVE patients treated by laparoscopy, and the eutopic endometrial tissues from 23 non-OVE patients with leiomyoma or other benign diseases were used as control. Hematoxylin and eosin (H&E) and Masson’s trichrome staining were utilized for histopathological assessment. The primary normal endometrial stromal cells (NESC), ectopic endometrial stromal cells (ECSC), and eutopic endometrial stromal cells (EUSC) were isolated. Gal-3 overexpression plasmids (Gal-OE) and short hairpin RNA targeting Gal-3 (Gal-3-shRNA) were transfected into the immortalized human endometriotic cell line 12Z, respectively. RT-qPCR, Western blot analysis, and immunohistochemistry were used to detect the mRNA and protein expression levels of Gal-3, type I collagen (COL-1), connective tissue growth factor (CTGF) and α-smooth muscle actin (α-SMA), respectively.
Results
H&E and Masson staining showed that ovarian ectopic endometrium exhibited glandular hyperplasia, high columnar glandular epithelium, apical plasma secretion, more subnuclear vacuoles, and obvious fibrosis, compared with normal endometrium. The mRNA and protein levels of Gal-3 , CTGF, α-SMA, and COL-1 were all upregulated in the ectopic endometrial tissues of OVE patients compared to the eutopic endometrial tissues from OVE patients and non-OVE patients. Moreover, ECSC expressed higher levels of Gal-3, CTGF, α-SMA, and COL-1 than EUSC and NESC. Follow-up investigations demonstrated that the Gal-3 overexpression substantially increased fibrosis-related markers including CTGF, α-SMA, and COL-1 within the 12Z cell line. Conversely, Gal-3 knockdown showed the opposite effects.
Conclusion
Gal-3 promotes fibrosis in OVE, positioning it as a prospective therapeutic target for mitigating fibrosis in endometriosis.Nonpharmacological pain relief for labour pain: knowledge, attitude, and barriers among obstetric care providershttps://peerj.com/articles/168622024-02-022024-02-02Heba Abdel-Fatah IbrahimMajed Said AlshahraniAmlak Jaber Al-QinnahWafaa Taha Elgzar
Background
Labor pain is considered the worst pain in a woman’s life. Hence, pain control should be essential to labor management at any level. There is scarce information, and there are gaps regarding the knowledge, attitude, and barriers to the utilization of nonpharmacological approaches for pain relief in Saudi Arabia. Therefore, the current study aims to evaluate nonpharmacological pain relief (NPPR)-related knowledge, attitudes, and barriers among obstetric care providers in Najran, Saudi Arabia.
Methods
A cross-sectional analytical study was performed at maternity departments in Maternal and Children Hospital (MCH), Najran, Saudi Arabia, from April 1 to May 26 2023. The study involved 186 obstetric care providers (OPCs), physicians (19), nurses (144), and midwives (23). A structured self-reported questionnaire was used to collect data and involves five main sections: demographic data, work-related data, nonpharmacological pain relief-related attitude, perceived barriers, and knowledge quiz. The adjusted odds ratio (AOR) along with 95% CI was estimated to determine the factors associated with nonpharmacological pain relief-related knowledge and attitude using multivariate analysis in the binary logistic regression.
Results
Over three-quarters (79%) of obstetric care providers had adequate knowledge of nonpharmacological pain relief methods. The majority (85.5%) of the participants had a positive attitude toward NPPR in labour pain management, with the mean scores ranging from 3.55–4.23 for all sub-items. Obstetric care providers acknowledged that patient belief, lack of time, and workload were the strongest barriers to offering nonpharmacological pain relief methods for labour pain 67.6%, 64.5%, and 61.3%, respectively. In binary logistic regression analysis, the in-service training related to nonpharmacological pain relief (AOR = 5.871 (2.174–15.857), p = 0.000), (AOR = 3.942 (1.926–11.380), p = 0.013) and years of work experience (AOR = 1.678 (1.080–2.564), p = 0.019), (AOR = 1.740 (1.188–2.548), p = 0.003) were significantly associated with obstetric care providers’ knowledge and attitudes regarding nonpharmacological pain relief (p ≤ 0.05).
Conclusion
Although most OPCs have adequate knowledge and a positive attitude regarding NPPR, they need motivational strategies to enhance their utilization. In addition, an effort should be made to decrease OPCs’ workload to provide more time for NPPR application and patient education. Training courses and in-service training can play an important role in enhancing NPPR knowledge and attitude and, consequently, its application. Also, in each working unit, the policymakers should provide clear guidelines and policies that enhance and control the utilization of NPPR.
Background
Labor pain is considered the worst pain in a woman’s life. Hence, pain control should be essential to labor management at any level. There is scarce information, and there are gaps regarding the knowledge, attitude, and barriers to the utilization of nonpharmacological approaches for pain relief in Saudi Arabia. Therefore, the current study aims to evaluate nonpharmacological pain relief (NPPR)-related knowledge, attitudes, and barriers among obstetric care providers in Najran, Saudi Arabia.
Methods
A cross-sectional analytical study was performed at maternity departments in Maternal and Children Hospital (MCH), Najran, Saudi Arabia, from April 1 to May 26 2023. The study involved 186 obstetric care providers (OPCs), physicians (19), nurses (144), and midwives (23). A structured self-reported questionnaire was used to collect data and involves five main sections: demographic data, work-related data, nonpharmacological pain relief-related attitude, perceived barriers, and knowledge quiz. The adjusted odds ratio (AOR) along with 95% CI was estimated to determine the factors associated with nonpharmacological pain relief-related knowledge and attitude using multivariate analysis in the binary logistic regression.
Results
Over three-quarters (79%) of obstetric care providers had adequate knowledge of nonpharmacological pain relief methods. The majority (85.5%) of the participants had a positive attitude toward NPPR in labour pain management, with the mean scores ranging from 3.55–4.23 for all sub-items. Obstetric care providers acknowledged that patient belief, lack of time, and workload were the strongest barriers to offering nonpharmacological pain relief methods for labour pain 67.6%, 64.5%, and 61.3%, respectively. In binary logistic regression analysis, the in-service training related to nonpharmacological pain relief (AOR = 5.871 (2.174–15.857), p = 0.000), (AOR = 3.942 (1.926–11.380), p = 0.013) and years of work experience (AOR = 1.678 (1.080–2.564), p = 0.019), (AOR = 1.740 (1.188–2.548), p = 0.003) were significantly associated with obstetric care providers’ knowledge and attitudes regarding nonpharmacological pain relief (p ≤ 0.05).
Conclusion
Although most OPCs have adequate knowledge and a positive attitude regarding NPPR, they need motivational strategies to enhance their utilization. In addition, an effort should be made to decrease OPCs’ workload to provide more time for NPPR application and patient education. Training courses and in-service training can play an important role in enhancing NPPR knowledge and attitude and, consequently, its application. Also, in each working unit, the policymakers should provide clear guidelines and policies that enhance and control the utilization of NPPR.Integrin-associated transcriptional characteristics of circulating tumor cells in breast cancer patientshttps://peerj.com/articles/166782024-01-182024-01-18Evgeniya GrigoryevaLiubov TashirevaVladimir AlifanovOlga SavelievaMarina ZavyalovaMaxim MenyailoAnna KhozyainovaEvgeny V. DenisovOlga BraginaNataliya PopovaNadezhda V. CherdyntsevaVladimir Perelmuter
Background
Integrins enable cell communication with the basal membrane and extracellular matrix, activating signaling pathways and facilitating intracellular changes. Integrins in circulating tumor cells (CTCs) play a significant role in apoptosis evasion and anchor-independent survival. However, the link between CTCs expressing different integrin subunits, their transcriptional profile and, therefore, their functional activity with respect to metastatic potential remains unclear.
Methods
Single-cell RNA sequencing of CD45-negative cell fraction of breast cancer patients was performed. All CTCs were divided into nine groups according to their integrin profile.
Results
СTCs without the gene expression of integrins or with the expression of non-complementary α and β subunits that cannot form heterodimers prevailed. Only about 15% of CTCs expressed integrin subunits which can form heterodimers. The transcriptional profile of CTCs appeared to be associated with the spectrum of expressed integrins. The lowest potential activity was observed in CTCs without integrin expression, while the highest frequency of expression of tumor progression-related genes, namely genes of stemness, epithelial-mesenchymal transition (EMT), invasion, proinflammatory chemokines and cytokines as well as laminin subunits, were observed in CTCs co-expressing ITGA6 and ITGB4. Validation on the protein level revealed that the median of integrin β4+ CTCs was higher in patients with more aggressive molecular subtypes as well as in metastatic breast cancer patients. One can expect that CTCs with ITGA6 and ITGB4 expression will have pronounced metastatic potencies manifesting in expression of EMT and stemness-related genes, as well as potential ability to produce chemokine/proinflammatory cytokines and laminins.
Background
Integrins enable cell communication with the basal membrane and extracellular matrix, activating signaling pathways and facilitating intracellular changes. Integrins in circulating tumor cells (CTCs) play a significant role in apoptosis evasion and anchor-independent survival. However, the link between CTCs expressing different integrin subunits, their transcriptional profile and, therefore, their functional activity with respect to metastatic potential remains unclear.
Methods
Single-cell RNA sequencing of CD45-negative cell fraction of breast cancer patients was performed. All CTCs were divided into nine groups according to their integrin profile.
Results
СTCs without the gene expression of integrins or with the expression of non-complementary α and β subunits that cannot form heterodimers prevailed. Only about 15% of CTCs expressed integrin subunits which can form heterodimers. The transcriptional profile of CTCs appeared to be associated with the spectrum of expressed integrins. The lowest potential activity was observed in CTCs without integrin expression, while the highest frequency of expression of tumor progression-related genes, namely genes of stemness, epithelial-mesenchymal transition (EMT), invasion, proinflammatory chemokines and cytokines as well as laminin subunits, were observed in CTCs co-expressing ITGA6 and ITGB4. Validation on the protein level revealed that the median of integrin β4+ CTCs was higher in patients with more aggressive molecular subtypes as well as in metastatic breast cancer patients. One can expect that CTCs with ITGA6 and ITGB4 expression will have pronounced metastatic potencies manifesting in expression of EMT and stemness-related genes, as well as potential ability to produce chemokine/proinflammatory cytokines and laminins.Impact of online learning on physical activity during COVID-19 lockdown period among female undergraduate students in Saudi Arabia: a cross-sectional studyhttps://peerj.com/articles/165792024-01-152024-01-15Rania AlmeheyawiAlaa AlsiniBayadir AljadrawiLayan AlshehriRawan AlgethamiRazan AlthobaitiAhlam AlrubeaiHosam AlzahraniFahad AlshehriYousef Alshehre
Background
During early 2020, because of the COVID-19 pandemic and related lockdown, most education systems—including universities—shifted from face-to-face classes to online learning. In Saudi Arabia, this might have contributed to a decreased level of physical activity (PA) and a concurrent increase in sedentary behaviour among young adults. This study aimed to investigate the impact of online learning on PA during the COVID-19 lockdown period among female undergraduate students in Saudi Arabia.
Methods
Data were collected through an online survey administered to participants. It consisted of three sections including demographic information, participants’ perception towards online learning and PA, and PA level using the self-reported active-questionnaire survey tool. The association between online learning and PA was measured using linear regression. The statistical significance was set at P < 0.05.
Results
A total of 197 female undergraduate students were included; 95.4% of them were aged 18–24 years old, and 59.9% were in the normal body mass index range (18.5–24.9 kg/m2). In terms of PA level, 55.3% were highly active, 33.5% were moderately active and 10.1% were low-active. In terms of students’ perception of engaging in PA, 53.3% of students reported that engaging in PA definitely affected their psychological status. Moreover, compared with those attending <25 hours/week of online learning, those who attended >30 hours/week had lower PA (r = − 363.24; 95% confidence interval (CI) −593.97, −132.50), followed by those attending 25–30 hours/week (r = − 277.66; 95% CI −484.65, −70.66).
Conclusion
Online learning has negatively affected the PA level of female undergraduate students in Saudi Arabia during the COVID-19 lockdown period, in a dose-dependent manner. Moreover, this might affect their phycological status. Nevertheless, future studies are warranted to further investigate the relationship between PA level and psychological status.
Background
During early 2020, because of the COVID-19 pandemic and related lockdown, most education systems—including universities—shifted from face-to-face classes to online learning. In Saudi Arabia, this might have contributed to a decreased level of physical activity (PA) and a concurrent increase in sedentary behaviour among young adults. This study aimed to investigate the impact of online learning on PA during the COVID-19 lockdown period among female undergraduate students in Saudi Arabia.
Methods
Data were collected through an online survey administered to participants. It consisted of three sections including demographic information, participants’ perception towards online learning and PA, and PA level using the self-reported active-questionnaire survey tool. The association between online learning and PA was measured using linear regression. The statistical significance was set at P < 0.05.
Results
A total of 197 female undergraduate students were included; 95.4% of them were aged 18–24 years old, and 59.9% were in the normal body mass index range (18.5–24.9 kg/m2). In terms of PA level, 55.3% were highly active, 33.5% were moderately active and 10.1% were low-active. In terms of students’ perception of engaging in PA, 53.3% of students reported that engaging in PA definitely affected their psychological status. Moreover, compared with those attending <25 hours/week of online learning, those who attended >30 hours/week had lower PA (r = − 363.24; 95% confidence interval (CI) −593.97, −132.50), followed by those attending 25–30 hours/week (r = − 277.66; 95% CI −484.65, −70.66).
Conclusion
Online learning has negatively affected the PA level of female undergraduate students in Saudi Arabia during the COVID-19 lockdown period, in a dose-dependent manner. Moreover, this might affect their phycological status. Nevertheless, future studies are warranted to further investigate the relationship between PA level and psychological status.Polymethoxylated flavonoids in citrus fruits: absorption, metabolism, and anticancer mechanisms against breast cancerhttps://peerj.com/articles/167112024-01-032024-01-03Yiyu WangYuan MouSenlin LuYuhua XiaBo Cheng
Polymethoxylated flavonoids (PMFs) are a subclass of flavonoids found in citrus fruits that have shown multifunctional biological activities and potential anticancer effects against breast cancer. We studied the absorption, metabolism, species source, toxicity, anti-cancer mechanisms, and molecular targets of PMFs to better utilize their anticancer activity against breast cancer. We discuss the absorption and metabolism of PMFs in the body, including the methylation, demethylation, and hydroxylation processes. The anticancer mechanisms of PMFs against breast cancer were also reviewed, including the estrogen activity, cytochrome P-450 enzyme system, and arylhydrocarbon receptor (AhR) inhibition, along with various molecular targets and potential anticancer effects. Although PMFs may be advantageous in the prevention and treatment for breast cancer, there is a lack of clinical evidence and data to support their efficacy. Despite their promise, there is still a long way to go before PMFs can be applied clinically.
Polymethoxylated flavonoids (PMFs) are a subclass of flavonoids found in citrus fruits that have shown multifunctional biological activities and potential anticancer effects against breast cancer. We studied the absorption, metabolism, species source, toxicity, anti-cancer mechanisms, and molecular targets of PMFs to better utilize their anticancer activity against breast cancer. We discuss the absorption and metabolism of PMFs in the body, including the methylation, demethylation, and hydroxylation processes. The anticancer mechanisms of PMFs against breast cancer were also reviewed, including the estrogen activity, cytochrome P-450 enzyme system, and arylhydrocarbon receptor (AhR) inhibition, along with various molecular targets and potential anticancer effects. Although PMFs may be advantageous in the prevention and treatment for breast cancer, there is a lack of clinical evidence and data to support their efficacy. Despite their promise, there is still a long way to go before PMFs can be applied clinically.