Plasma-based proteomic profiling identifies the distinct regulation of proteins in hyperplasia and endometrial cancer.

BACKGROUND: Among gynaecological malignancies, endometrial cancer (EC) is the most prevalent type of uterine cancer affecting women. This study explored the proteomic profiles of plasma samples obtained from EC patients, those with hyperplasia (Hy), and a control group (CO). A combination of techniques, such as 2D-DIGE, mass spectrometry, and bioinformatics, including pathway analysis, was used to identify proteins with modified expression levels, biomarkers and their associated metabolic pathways in these groups. METHODS: Thirty-four patients, categorized into three groups-10 with EC, 12 with Hy, and 12 CO-between the ages of 46 and 75 years old were included in the study. Untargeted proteomic analysis was carried out using two-dimensional difference in gel electrophoresis (2D-DIGE) coupled with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). RESULTS: In all three groups, 114 proteins that were significantly (p ≤ 0.05 and fold change ≥ 1.5) altered were successfully identified using peptide mass fingerprints (PMFs). Compared with those in the control group (CO), the EC samples had 85 differentially expressed proteins (39 upregulated and 46 downregulated), and in the Hy group, 81 proteins were dysregulated (40 upregulated and 41 downregulated) compared to those in the CO group, while 33 proteins exhibited differential regulation (12 upregulated and 21 downregulated) in the EC plasma samples compared to those in the Hy group. Vitamin D binding protein and complement C3 distinguished Hy and EC from CO with the greatest changes in expression. Among the differentially expressed proteins identified, enzymes with catalytic activity represented the largest group (42.9%). In terms of biological processes, most of the proteins were involved in cellular processes (28.8%), followed by metabolic processes (16.7%). STRING analysis for protein interactions revealed that the significantly differentially abundant proteins in the three groups are involved in three main biological processes: signalling of complement and coagulation cascades, regulation of insulin-like growth factor (IGF) transport and uptake by insulin-like growth factor binding proteins (IGFBPs), and plasma lipoprotein assembly, remodelling, and clearance. CONCLUSION: The identified plasma protein markers have the potential to serve as biomarkers for differentiating between EC and Hy, as well as for early diagnosis and monitoring of cancer progression.

Cervical Cancer and Human Papillomavirus Awareness among Women in Saudi Arabia.

Background and Objectives: Cervical cancer (CC) is the eighth most common cancer among Saudi women of all ages. With limited national data, we aimed to evaluate the public awareness of cervical cancer, CC risk factors, HPV infection, and HPV vaccines in different regions of Saudi Arabia. Materials and Methods: This was a survey-based cross-sectional study that encompassed 564 Saudi women over a period of a month. A self-administrated questionnaire was distributed through different social media platforms. Results: The collected data included sociodemographic variables and questions assessing awareness of CC, and the attitudes toward CC screening and human papillomavirus (HPV) vaccination. Most respondents were aware of CC (84.0%), although their primary source of information was the internet. However, only 45 females (8.0%) had a history of cervical screening. Furthermore, most females did not know that HPV was transmitted sexually (78.9%), or that it caused genital warts (81.7%) and CC (81.9%). Regarding the HPV vaccine, 100 females (17.7%) had heard about it, but only 11 (2.0%) took the vaccine, although more than half of the respondents (54.1%) were willing to take the vaccine after being informed about it. Conclusions: We noticed a remarkable lack of awareness among the respondents regarding HPV's clinical implications; and the HPV vaccine, and its importance and availability. The main source of information for most of the Saudi women in this study was the internet, which may be an unreliable source, or provide misleading information that may delay screening or discourage vaccination. Thus, organized campaigns by the Ministry of Health or other health-advocating agencies, in addition to screening and vaccination programs, are strongly encouraged.

Plasma Proteomic Signature of Endometrial Cancer in Patients with Diabetes.

The incidence and mortality of endometrial cancer (EC) have increased in recent years. There is mounting evidence that diabetes may play a role in the greater incidence of EC. The molecular mechanisms of the interaction between type 2 diabetes and EC are not yet clearly understood yet. The present study was undertaken to investigate the plasma proteomics of EC patients with diabetes in comparison to those of EC patients without diabetes. Plasma samples were obtained from age-matched patients (EC diabetic and EC nondiabetic). Untargeted proteomic analysis was carried out using a two-dimensional differential gel electrophoresis coupled with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Of the 33 proteins identified, which significantly differed in the plasma abundance between groups, 17 were upregulated and 16 were downregulated. The majority of the altered proteins are involved in the acute phase reaction, cholesterol metabolism, scavenging of heme from plasma, and plasma lipoprotein assembly and mobilization. α-2-macroglobulin, Ras association domain-containing protein 3, apolipoprotein A-I, α-1B-glycoprotein, and zinc-α-2-glycoprotein were significantly upregulated. The significantly downregulated proteins included haptoglobin, apolipoprotein A-IV, hemopexin, and α-1-antichymotrypsin. The differential expression of proteins found in patients who had EC and diabetes indicated severe disease and a poor prognosis. The protein interaction analysis showed dysregulation of cholesterol metabolism and heme scavenging pathways in these patients.

Metabolomic Profiling of Blood Plasma in Females with Hyperplasia and Endometrial Cancer.

Uterine cancer is the most prevalent gynecologic malignancy in women worldwide. Endometrial cancer (EC) has an 81% five-year survival rate, depending on disease stage and time of diagnosis. While endometrial cancer is largely treatable when detected early, no established screening techniques are available in clinical practice. As a result, one of the most significant issues in the medical field is the development of novel ways for early cancer identification, which could boost treatment success rates. Liquid chromatography-high-resolution mass spectrometry (LC-HRMS)-based metabolomics was employed to explore the metabolomic markers and pathways unique to this cancer type and link them to the benign endometrial hyperplasia that may progress to cancer in 5% to 25% of patients. The study involved 59 postmenopausal participants, 20 with EC type 1, 20 with benign hyperplasia, and 19 healthy participants. Metabolite distribution changes were analyzed, and 338 of these features were dysregulated and significant. The first two main components, PC1 and PC2, were responsible for 11.5% and 12.2% of the total metabolites, respectively. Compared with the control group (CO), EC samples had 203 differentially expressed metabolites (180 upregulated and 23 downregulated); in hyperplasia (HP), 157 metabolites were dysregulated (127 upregulated and 30 downregulated) compared to the CO group while 21 metabolites exhibited differential regulation (16 upregulated and 5 downregulated) in EC plasma samples compared to the HP group. Hyperplasia samples exhibited similar metabolic changes to those reported in cancer, except for alterations in triglyceride levels, 7a,12 b-dihydroxy-5b-Cholan-24-oic acid, and Hept-2-enedioyl carnitine levels. The metabolites N-heptanoyl glycine and -(Methylthio)-2,3-isopentyl phosphate and formimino glutamic acid can be specific markers for hyperplasia conditions and dimethyl phosphatidyl ethanolamine and 8-isoprostaglandin E2 can be specific markers for EC conditions. Metabolic activities rely on mitochondrial oxidative phosphorylation for energy generation. The changes in metabolites identified in our study indicate that endometrial cancer cells adopt alternative strategies to increase energy production to meet the energy demand, thereby supporting proliferation.

Knowledge, Attitude, and Practice Regarding Periodontal and Dental Diseases During Pregnancy Among Obstetricians and Dentists in King Saud University Medical City.

BACKGROUND: Providing effective dental treatment during pregnancy is related to controlling oral diseases and helps maintain a healthy oral cavity. One of the possible treatment options for endodontic disease is to treat the odontogenic infection, maintain a healthy oral environment, and minimize the expected complications that can occur later in pregnancy or during the postpartum period. Sufficient awareness among obstetricians and dentists is essential to delivering appropriate preventive and curative care to pregnant patients. OBJECTIVE: The aim of this cross-sectional study is to assess knowledge, attitudes, and behaviors regarding oral health care and providing dental treatment among King Saud University Medical City obstetricians and dentists during pregnancy and the association of dental and periodontal disease with adverse pregnancy outcomes. METHODS: This study was conducted in Saudi Arabia, Riyadh, from December 2022 to June 2023 (six months). The data were collected from 381 participants in Riyadh, Saudi Arabia, from January 2023 to June 2023. The study targeted male and female general dentists and obstetricians living in Riyadh, Saudi Arabia, and excluded those who are not dentists and obstetricians or not living in Riyadh, Saudi Arabia. RESULT: Out of a total of 381 completed responses, 281 (73.8%) of the participants were dentists, while 100 (26.2%) were obstetricians. It was observed that the majority of the participants agreed that oral health is a part of prenatal care, while the minority did not agree (0.3%). Of the 281 (73.8%) respondents, most of them reported periodontal disease can cause preterm birth, low birth weight, and gestational diabetes (73.2%), while only 0.5% answered no. Two hundred and seventy-eight of the participants answered that it is essential to consult with an obstetrician before treating pregnant patients. CONCLUSION: The overall knowledge of dentists and obstetricians was adequate regarding dental disease during pregnancy. However, more education should be assessed and continuously improved regarding the treatment options, as well as future recommendations regarding the medications used in dental clinics and awareness programs promoting dental health care in pregnant patients.

Intimate Partner Violence and Its Associations with Adverse Pregnancy Outcomes in Saudi Arabia: A Cross-Sectional Study.

Intimate partner violence (IPV) during pregnancy is a significant issue. Nevertheless, the prevalence of IPV and its adverse outcomes in pregnant women in Saudi Arabia are not well documented. This study examines the prevalence of IPV, its relationship with women's background characteristics, and its effect on adverse pregnancy outcomes. A cross-sectional study was conducted using a convenience sample of 684 women who were either pregnant or in the first six weeks postpartum in Riyadh, Saudi Arabia. IPV severity was measured using the Composite Abuse Scale. The results showed that 28.9% of the women included in this study experienced IPV. Smoking habit, income, polygamous marriage, presence of chronic diseases and sexual dysfunction, and number of children were significantly associated with IPV severity. In each one-unit increase in total IPV severity, the possibility of the occurrence of preterm labor, vaginal bleeding, dehydration, gestational diabetes, urinary tract infection, spontaneous abortion, and intrauterine growth retardation significantly increases. Furthermore, regarding the types of abuse, we found that for each one-unit increase in verbal abuse, the possibility of the occurrence of preterm labor, dehydration, urinary tract infection, and intrauterine growth retardation significantly increases. Moreover, for each one-unit increase in physical abuse and one-unit increase in controlling behavior, the possibility of the occurrence of intrauterine growth retardation significantly increases. The current results highlight the importance of paying substantial attention to IPV and its types as a health issue that increases the risk of adverse pregnancy outcomes in women. A clinical assessment during pregnancy is needed to identify and manage cases of IPV survivors and ultimately reduce their risk of IPV.

Proteomic Analysis of Endometrial Cancer Tissues from Patients with Type 2 Diabetes Mellitus.

Endometrial cancer (EC) is the most common form of gynecological cancer. Type 2 diabetes mellitus is associated with an increased risk of EC. Currently, no proteomic studies have investigated the role of diabetes in endometrial cancers from clinical samples. The present study aims to elucidate the molecular link between diabetes and EC using a proteomic approach. Endometrial tissue samples were obtained from age-matched patients (EC Diabetic and EC Non-Diabetic) during surgery. Untargeted proteomic analysis of the endometrial tissues was carried out using a two-dimensional difference in gel electrophoresis (2D-DIGE) coupled with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI TOF). A total of 53 proteins were identified, with a significant difference in abundance (analysis of variance (ANOVA) test, p ≤ 0.05; fold-change ≥ 1.5) between the two groups, among which 30 were upregulated and 23 downregulated in the EC Diabetic group compared to EC Non-Diabetic. The significantly upregulated proteins included peroxiredoxin-1, vinculin, endoplasmin, annexin A5, calreticulin, and serotransferrin. The significantly downregulated proteins were myosin regulatory light polypeptide 9, Retinol dehydrogenase 12, protein WWC3, intraflagellar transport protein 88 homolog, superoxide dismutase [Cu-Zn], and retinal dehydrogenase 1. The network pathway was related to connective tissue disorder, developmental disorder, and hereditary disorder, with the identified proteins centered around dysregulation of ERK1/2 and F Actin signaling pathways. Cancer-associated protein alterations such as upregulation of peroxiredoxin-1, annexin 5, and iNOS, and downregulation of RDH12, retinaldehyde dehydrogenase 1, SOD1, and MYL 9, were found in the EC tissues of the diabetic group. Differential expression of proteins linked to cancer metastasis, such as the upregulation of vinculin and endoplasmin and downregulation of WWC3 and IFT88, was seen in the patients with diabetes. Calreticulin and alpha-enolase, which might have a role in the interplay between diabetes and EC, need further investigation.

Tissue-Based Proteomic Profiling in Patients with Hyperplasia and Endometrial Cancer.

Uterine cancers are among the most prevalent gynecological malignancies, and endometrial cancer (EC) is the most common in this group. This study used tissue-based proteomic profiling analysis in patients with endometrial cancer and hyperplasia, and control patients. Conventional 2D gel electrophoresis, followed by a mass spectrometry approach with bioinformatics, including a network pathway analysis pipeline, was used to identify differentially expressed proteins and associated metabolic pathways between the study groups. Thirty-six patients (twelve with endometrial cancer, twelve with hyperplasia, and twelve controls) were enrolled in this study. The mean age of the participants was 46-75 years. Eighty-seven proteins were significantly differentially expressed between the study groups, of which fifty-three were significantly differentially regulated (twenty-eight upregulated and twenty-five downregulated) in the tissue samples of EC patients compared to the control (Ctrl). Furthermore, 26 proteins were significantly dysregulated (8 upregulated and 18 downregulated) in tissue samples of hyperplasia (HY) patients compared to Ctrl. Thirty-two proteins (nineteen upregulated and thirteen downregulated) including desmin, peptidyl prolyl cis-trans isomerase A, and zinc finger protein 844 were downregulated in the EC group compared to the HY group. Additionally, fructose bisphosphate aldolase A, alpha enolase, and keratin type 1 cytoskeletal 10 were upregulated in the EC group compared to those in the HY group. The proteins identified in this study were known to regulate cellular processes (36%), followed by biological regulation (16%). Ingenuity pathway analysis found that proteins that are differentially expressed between EC and HY are linked to AKT, ACTA2, and other signaling pathways. The panels of protein markers identified in this study could be used as potential biomarkers for distinguishing between EC and HY and early diagnosis and progression of EC from hyperplasia and normal patients.

Intimate Partner Violence in Saudi Arabia: A Systematic Review.

Intimate partner violence (IPV) is a serious public health issue at the global level, with cultural differences in its nature and prevalence. Most of the current evidence related to IPV comes from Western countries; however, there is a lack of evidence of IPV in developing countries such as Saudi Arabia. The issue of IPV has been investigated in Saudi Arabia only recently, and data have been inconsistent and inconclusive. Hence, we conducted a systematic review of the extant literature devoted to IPV prevalence, risk factors, and outcomes as well as Saudi women's help-seeking behaviors. Various databases, such as PubMed, CINAHL, Medline, PsycINFO, and reference lists of the reviewed studies, were searched to identify relevant studies by using different keywords. The review included 16 studies that met the inclusion criteria, which revealed several findings. There is no national representative prevalence study of IPV in the Saudi context. Various IPV definitions were used with limited evidence for the reliability and validity of the used IPV measures. IPV is a prevalent issue among Saudi women, but rates are comparable to those of other countries. There are various individual, relational, and sociocultural factors that increase women's vulnerability to IPV victimization. However, limited information is available regarding IPV protective factors. More importantly, IPV experiences negatively affect Saudi women's physical and mental health status. Saudi women rarely seek formal support for IPV. This review also highlights the lack of IPV data and inconsistencies in defining and measuring IPV. More rigorous research regarding IPV is needed to help develop relevant preventive and intervention programs.

A comparative study between a single-dose and 24-hour multiple-dose antibiotic prophylaxis for elective hysterectomy.

INTRODUCTION: Surgical site infections (SSIs) are a major health issue in surgical specialties in terms of health care costs and patients' clinical outcomes. At the level of the patient, prolonged hospital stays or readmissions for SSIs, can affect the patient's quality of life. At the level of the health care system, it exhausts the hospital's resources and increases the burden on the medical staff due to the need for continuous wound care, microbiological cultures, laboratory tests and medications. In this study, we assessed the effectiveness of two antibiotic prophylaxis regimens for the prevention of SSIs in patients undergoing elective hysterectomy surgeries. METHODOLOGY: A retrospective cohort, analyzing 141 patients, was conducted between November 2016 and January 2019 at a university hospital. We compared the efficacy of a single dose vs. 24-hour multiple doses of Cefazolin in patients who underwent elective hysterectomy for benign or malignant indications. The secondary objective was to identify potential risk factors associated with SSIs. RESULTS: There was no statistically significant difference between both groups (p = 0.872). Obesity and a laparotomy surgical approach are risk factors to the development of SSIs (p = 0.001 and 0.014, respectively). Other potential risk factors include the duration of hospital stay, the duration of the surgery and the amount of blood loss. CONCLUSIONS: Although the rate of SSIs is not significantly different between both groups, risk stratification can be done after screening patients and the prophylactic regimen must be tailored for each patient in a cost-effective manner and using a multidisciplinary approach.