Amino acid profiles: exploring their diagnostic and pathophysiological significance in hypertension.

Hypertension, a major contributor to cardiovascular morbidity, is closely linked to amino acid metabolism. Amino acids, particularly branched-chain amino acids (BCAAs) and aromatic amino acids (AAAs), may play pivotal roles in the pathogenesis and potential management of hypertension. This review investigated the relationships between amino acid profiles, specifically BCAAs and AAAs, and hypertension, and examined their potential as diagnostic and therapeutic targets. An in-depth analysis was conducted on studies highlighting the associations of specific amino acids such as arginine, glycine, proline, glutamine, and the BCAAs and AAAs with hypertension. BCAAs and AAAs, alongside other amino acids like arginine, glycine, and proline, showed significant correlations with hypertension. These amino acids influence multiple pathways including nitric oxide synthesis, vascular remodeling, and neurotransmitter production, among others. Distinct amino acid profiles were discerned between hypertensive and non-hypertensive individuals. Amino acid profiling, particularly the levels of BCAAs and AAAs, offers promising avenues in the diagnostic and therapeutic strategies for hypertension. Future studies are crucial to confirm these findings and to delineate amino acid-based interventions for hypertension treatment.

A placenta-on-a-chip model to determine the regulation of FKBPL and galectin-3 in preeclampsia.

Preeclampsia is a pregnancy-specific cardiovascular disorder, involving significant maternal endothelial dysfunction. Although inappropriate placentation due to aberrant angiogenesis, inflammation and shallow trophoblast invasion are the root causes of preeclampsia, pathogenic mechanisms are poorly understood, particularly in early pregnancy. Here, we first confirm the abnormal expression of important vascular and inflammatory proteins, FK506-binding protein-like (FKBPL) and galectin-3 (Gal-3), in human plasma and placental tissues from women with preeclampsia and normotensive controls. We then employ a three-dimensional microfluidic placental model incorporating human umbilical vein endothelial cells (HUVECs) and a first trimester trophoblast cell line (ACH-3P) to investigate FKBPL and Gal-3 signaling in inflammatory conditions. In human samples, both circulating (n = 17 controls; n = 30 preeclampsia) and placental (n ≥ 6) FKBPL and Gal-3 levels were increased in preeclampsia compared to controls (plasma: FKBPL, p < 0.0001; Gal-3, p < 0.01; placenta: FKBPL, p < 0.05; Gal-3, p < 0.01), indicative of vascular dysfunction in preeclampsia. In our placenta-on-a-chip model, we show that endothelial cells are critical for trophoblast-mediated migration and that trophoblasts effectively remodel endothelial vascular networks. Inflammatory cytokine tumour necrosis factor-α (10 ng/mL) modulates both FKBPL and Gal-3 signaling in conjunction with trophoblast migration and impairs vascular network formation (p < 0.005). Our placenta-on-a-chip recapitulates aspects of inappropriate placental development and vascular dysfunction in preeclampsia.

Severe depressive symptoms in patients with hypertension: Are antihypertensive medications implicated?

OBJECTIVE: This study examined whether antihypertensive medications and other patient characteristics are associated with severe depressive symptoms in patients with hypertension. METHODS: Patients with a diagnosis of hypertension were recruited from the internal medicine outpatient clinics of a hospital in Amman, Jordan, into this cross-sectional study. Depression severity was assessed using the Patient Health Questionnaire-9 (PHQ-9); anxiety by the General Anxiety Disorder-7; sleep quality by the Insomnia Severity Index; and psychological stress by the Perceived Stress Scale. Multivariable binary logistic regression was used to examine the association between the different classes of antihypertensive medication and depressive symptoms. RESULTS: Of the 431 participants, 282 (65.4%) were men; 240 (55.7%) reported having type 2 diabetes; 359 (83.3%) had dyslipidemia; 142 (32.9%) were on beta-blockers; 197 (45.2%) were on ACE inhibitors or angiotensin receptor blockers; 203 (47.1%) were on metformin; and 133 (30.9%) were taking sulfonylurea. Severe depressive symptoms, indicated by scoring above the cut-off of 14 on the PHQ-9, were present in 165 (38.3%) patients. Severe depression was associated with younger age (<55 years) (OR = 3.15, 95% CI = 1.83-5.41, P < 0.001), unemployment (OR = 2.15, 95% CI = 1.15-4.00, P = 0.01), diabetes (OR = 1.81, 95% CI = 1.09-3.02, P = 0.02), severe anxiety (OR = 6.40, 95% CI = 3.64-11.28, P < 0.001), and severe insomnia (OR = 4.73, 95% CI = 2.85-7.82, P < 0.001). CONCLUSION: Severe depressive symptoms were not associated with antihypertensive medications or other drugs used by hypertensive patients. Younger age, diabetes, anxiety, and insomnia were the primary correlates of depression.

Exploring the Roles of Vitamins C and D and Etifoxine in Combination with Citalopram in Depression/Anxiety Model: A Focus on ICAM-1, SIRT1 and Nitric Oxide.

The study of intercellular adhesion molecule-1 (ICAM-1) and SIRT1, a member of the sirtuin family with nitric oxide (NO), is emerging in depression and anxiety. As with all antidepressants, the efficacy is delayed and inconsistent. Ascorbic acid (AA) and vitamin D (D) showed antidepressant properties, while etifoxine (Etx), a GABAA agonist, alleviates anxiety symptoms. The present study aimed to investigate the potential augmentation of citalopram using AA, D and Etx and related the antidepressant effect to brain and serum ICAM-1, SIRT1 and NO in an animal model. BALB/c mice were divided into naive, control, citalopram, citalopram + etx, citalopram + AA, citalopram + D and citalopram + etx + AA + D for 7 days. On the 8th day, the mice were restrained for 8 h, followed by a forced swim test and marble burying test before scarification. Whole-brain and serum expression of ICAM-1, Sirt1 and NO were determined. Citalopram's antidepressant and sedative effects were potentiated by ascorbic acid, vitamin D and etifoxine alone and in combination (p < 0.05), as shown by the decreased floating time and rearing frequency. Brain NO increased significantly (p < 0.05) in depression and anxiety and was associated with an ICAM-1 increase versus naive (p < 0.05) and a Sirt1 decrease (p < 0.05) versus naive. Both ICAM-1 and Sirt1 were modulated by antidepressants through a non-NO-dependent pathway. Serum NO expression was unrelated to serum ICAM-1 and Sirt1. Brain ICAM-1, Sirt1 and NO are implicated in depression and are modulated by antidepressants.

Exploring the therapeutic potential of Anastatica hierochuntica essential oil in DSS-induced colitis.

The aim of this investigation was to explore the protective impacts and mechanisms of Anastatica hierochuntica essential oil (EOAH) against dextran sulfate sodium (DSS)-induced experimental colitis in mice. EOAH demonstrated a reduction in DSS-induced body weight decline, disease activity index (DAI), colon length reduction, colonic tissue damage, and myeloperoxidase (MPO) activity. The essential oil significantly mitigated the production of pro-inflammatory agents including TNF-α, IL-1ß, and IL-12. Further analysis revealed that EOAH's anti-inflammatory effects involved the regulation of NF-κB and PPARγ pathways, as well as the inhibition of NLRP3 activation in colitis mice. Notably, EOAH treatment elevated the levels of beneficial commensal bacteria such as Lactobacillus and Bifidobacteria, while reducing Escherichia coli levels in the mice's feces. In addition, EOAH restored the expression of occludin and ZO-1 proteins in colonic tissues affected by ulcerative colitis (UC). These findings indicate that supplementing with EOAH might offer a novel therapeutic approach for UC prevention.

Unraveling the potential of vitamins C and D as adjuvants in depression treatment with escitalopram in an LPS animal model.

Depression is linked with oxidative stress and inflammation, where key players include nitric oxide (NO), nuclear factor erythroid 2-related factor 2 (Nrf2), Brain-Derived Neurotrophic Factor (BDNF), and Heme Oxidase-1 (HO-1). Augmenting the efficacy of antidepressants represents a compelling avenue of exploration. We explored the potential of vitamins C and D as adjuncts to escitalopram (Esc) in a lipopolysaccharide (LPS)-induced depression model focusing on the aforementioned biomarkers. Male Swiss albino mice were stratified into distinct groups: control, LPS, LPS + Esc, LPS + Esc + Vit C, LPS + Esc + Vit D, and LPS + Esc + Vit C + Vit D. After a 7-day treatment period, a single LPS dose (2 mg/kg), was administered, followed by comprehensive assessments of behavior and biochemical parameters. Notably, a statistically significant (p < 0.05) alleviation of depressive symptoms was discerned in the Esc + Vit C + Vit D group versus the LPS group, albeit with concomitant pronounced sedation evident in all LPS-treated groups (p < 0.05). Within the cortex, LPS reduced (p < 0.05) the expression levels of NOx, Nrf2, BDNF, and HO-1, with only HO-1 being reinstated to baseline in the LPS + Esc + Vit D and the LPS + Esc + Vit C + Vit D groups. Conversely, the hippocampal NOx, Nrf2, and HO-1 levels remained unaltered following LPS administration. Notably, the combination of Esc, Vit C, and Vit D effectively restored hippocampal BDNF levels, which had been diminished by Esc alone. In conclusion, vitamins C and D enhance the therapeutic effects of escitalopram through a mechanism independent of Nrf2. These findings underscore the imperative need for in-depth investigations.

Targeting Cancer Hallmarks with Epigallocatechin Gallate (EGCG): Mechanistic Basis and Therapeutic Targets.

Epigallocatechin gallate (EGCG) is a catechin, which is a type of flavonoid found in high concentrations in green tea. EGCG has been studied extensively for its potential health benefits, particularly in cancer. EGCG has been found to exhibit anti-proliferative, anti-angiogenic, and pro-apoptotic effects in numerous cancer cell lines and animal models. EGCG has demonstrated the ability to interrupt various signaling pathways associated with cellular proliferation and division in different cancer types. EGCG anticancer activity is mediated by interfering with various cancer hallmarks. This article summarize and highlight the effects of EGCG on cancer hallmarks and focused on the impacts of EGCG on these cancer-related hallmarks. The studies discussed in this review enrich the understanding of EGCG's potential as a therapeutic tool against cancer, offering a substantial foundation for scientists and medical experts to advance scientific and clinical investigations regarding EGCG's possibility as a potential anticancer treatment.

Knowledge, Attitudes, and Practices (KAP) of community pharmacists regarding antibiotic use and resistance: a cross-sectional study from the United Arab Emirates.

One of the main contributing factors of antibiotic resistance is the dispensing of antibiotics without prescription. This study investigated community pharmacists' knowledge, attitudes, and practices in relation to antibiotic dispensing and resistance in United Arab Emirates (UAE). A cross-sectional survey was conducted using validated questionnaire. (40.1%) had an overall positive KAP score. A total of (88%) respondents were aware of the illegality of dispensing antibiotics without a prescription. Only (31%) had good knowledge regarding amoxicillin dosage for upper respiratory tract infection. The primary misconduct found numerous pharmacists prescribing antibiotics without a prescription, even though they were aware that this should never be done. Pharmacists who attended events focused on antibiotic use and resistance were more likely to have good knowledge about antibiotics (Adjusted Odd Ratio (AOR): 1.673; 95%CI: 1.029-2.719; p = 0.038), more likely to have positive attitude (AOR: 1.889; 95%CI: 1.133-3.149; p = 0.015), and more likely to have good practice (AOR: 3.182; 95%CI: 1.541-6.572; p = 0.002).

Unraveling the Potential of Isorhamnetin as an Adjuvant in Depression Treatment with Escitalopram.

Oxidative stress and inflammation are implicated in depression. While selective serotonin reuptake inhibitors (SSRIs) like escitalopram are commonly prescribed as first-line treatments, their inconsistent efficacy and delayed onset of action necessitates the exploration of adjunctive therapies. Isorhamnetin, a flavonol, has shown antioxidant and anti-inflammatory properties that makes exploring its antidepressant effect attractive. This study aims to investigate the adjuvant potential of isorhamnetin in combination with escitalopram to enhance its antidepressant efficacy in a lipopolysaccharide (LPS)-induced depression model using Swiss albino mice. Behavioral paradigms, such as the forced swim test and open field test, were employed to assess depressive symptoms, locomotion, and sedation. Additionally, enzyme-linked immunosorbent assays were utilized to measure Nrf2, BDNF, HO-1, NO, and IL-6 levels in the prefrontal cortex and hippocampus. The results demonstrate that isorhamnetin significantly improves the antidepressant response of escitalopram, as evidenced by reduced floating time in the forced swim test. Moreover, isorhamnetin enhanced antidepressant effects of escitalopram and effectively restored depleted levels of Nrf2, BDNF, and HO-1 in the cortex caused by LPS-induced depression. Isorhamnetin shows promise in enhancing the efficacy of conventional antidepressant therapy through antioxidant and anti-inflammatory effects.

The emerging importance of immunophilins in fibrosis development.

Immunophilins are a family of proteins encompassing FK506-binding proteins (FKBPs) and cyclophilins (Cyps). FKBPs and Cyps exert peptidyl-prolyl cis-trans isomerase (PPIase) activity, which facilitates diverse protein folding assembly, or disassembly. In addition, they bind to immunosuppressant medications where FKBPs bind to tacrolimus (FK506) and rapamycin, whereas cyclophilins bind to cyclosporin. Some large immunophilins have domains other than PPIase referred to as tetratricopeptide (TPR) domain, which is involved in heat shock protein 90 (Hsp90) and heat shock protein 70 (Hsp 70) chaperone interaction. The TPR domain confers immunophilins' pleotropic actions to mediate various physiological and biochemical processes. So far, immunophilins have been implicated to play an important role in pathophysiology of inflammation, cancer and neurodegenerative disorders. However, their importance in the development of fibrosis has not yet been elucidated. In this review we focus on the pivotal functional and mechanistic roles of different immunophilins in fibrosis establishment affecting various organs. The vast majority of the studies reported that cyclophilin A, FKBP12 and FKBP10 likely induce organ fibrosis through the calcineurin or TGF-ß pathways. FKBP51 demonstrated a role in myelofibrosis development through calcineurin-dependant pathway, STAT5 or NF-κB pathways. Inhibition of these specific immunophilins has been shown to decrease the extent of fibrosis suggesting that immunophilins could be a novel promising therapeutic target to prevent or reverse fibrosis.

The Emerging Importance of Cirsimaritin in Type 2 Diabetes Treatment.

Cirsimaritin is a dimethoxy flavon that has different biological activities such as antiproliferative, antimicrobial, and antioxidant activities. This study aims to investigate the anti-diabetic effects of cirsimaritin in a high-fat diet and streptozotocin-(HFD/STZ)-induced rat model of type 2 diabetes mellitus (T2D). Rats were fed HFD, followed by a single low dose of STZ (40 mg/kg). HFD/STZ diabetic rats were treated orally with cirsimaritin (50 mg/kg) or metformin (200 mg/kg) for 10 days before terminating the experiment and collecting plasma, soleus muscle, adipose tissue, and liver for further downstream analysis. Cirsimaritin reduced the elevated levels of serum glucose in diabetic rats compared to the vehicle control group (p < 0.001). Cirsimaritin abrogated the increase in serum insulin in the treated diabetic group compared to the vehicle control rats (p < 0.01). The homeostasis model assessment of insulin resistance (HOMA-IR) was decreased in the diabetic rats treated with cirsimaritin compared to the vehicle controls. The skeletal muscle and adipose tissue protein contents of GLUT4 (p < 0.01 and p < 0.05, respectively) and pAMPK-α1 (p < 0.05) were upregulated following treatment with cirsimaritin. Cirsimaritin was able to upregulate GLUT2 and AMPK protein expression in the liver (p < 0.01, <0.05, respectively). LDL, triglyceride, and cholesterol were reduced in diabetic rats treated with cirsimaritin compared to the vehicle controls (p < 0.001). Cirsimaritin reduced MDA, and IL-6 levels (p < 0.001), increased GSH levels (p < 0.001), and reduced GSSG levels (p < 0.001) in diabetic rats compared to the vehicle control. Cirsimaritin could represent a promising therapeutic agent to treat T2D.

Isorhamnetin Reduces Glucose Level, Inflammation, and Oxidative Stress in High-Fat Diet/Streptozotocin Diabetic Mice Model.

Background: Isorhamnetin is a flavonoid that is found in medical plants. Several studies showed that isorhamnetin has anti-inflammatory and anti-obesity effects. This study aims to investigate the anti-diabetic effects of isorhamnetin in a high-fat diet and Streptozotocin-(HFD/STZ)-induced mice model of type 2 diabetes. Materials and Methods: Mice were fed with HFD followed by two consecutive low doses of STZ (40 mg/kg). HFD/STZ diabetic mice were treated orally with isorhamnetin (10 mg/kg) or (200 mg/kg) metformin for 10 days before sacrificing the mice and collecting plasma and soleus muscle for further analysis. Results: Isorhamnetin reduced the elevated levels of serum glucose compared to the vehicle control group (p < 0.001). Isorhamnetin abrogated the increase in serum insulin in the treated diabetic group compared to the vehicle control mice (p < 0.001). The homeostasis model assessment of insulin resistance (HOMA-IR) was decreased in diabetic mice treated with isorhamnetin compared to the vehicle controls. Fasting glucose level was significantly lower in diabetic mice treated with isorhamnetin during the intraperitoneal glucose tolerance test (IPGTT) (p < 0.001). The skeletal muscle protein contents of GLUT4 and p-AMPK-α were upregulated following treatment with isorhamnetin (p > 0.01). LDL, triglyceride, and cholesterol were reduced in diabetic mice treated with isorhamnetin compared to vehicle control (p < 0.001). Isorhamnetin reduced MDA, and IL-6 levels (p < 0.001), increased GSH levels (p < 0.001), and reduced GSSG levels (p < 0.05) in diabetic mice compared to vehicle control. Conclusions: Isorhamnetin ameliorates insulin resistance, oxidative stress, and inflammation. Isorhamnetin could represent a promising therapeutic agent to treat T2D.

Factors Associated with Psychotropic Medications Literacy among Community Pharmacists.

Background and objectives: Community pharmacists play an important role in ensuring the patient's adherence to medications, thus achieving therapeutic outcomes. The present study had two aims: to measure the extent of knowledge that community pharmacists had about psychotropic medications and to determine the factors associated with higher knowledge scores. Methods: A cross-sectional design was employed, using a structured online questionnaire. The study instrument assessed demographics, general practice characteristics related to psychotropics and a battery of factual questions that assessed the knowledge of pharmacists about psychotropic medications using closed-ended responses. A total knowledge score consisting of the sum of correct responses was calculated; the passing score was 75%. A total of 676 pharmacists completed the survey. Results: Only 20% passed the threshold score (75%) for the factual knowledge questions, and only (11.0%) were very comfortable with their knowledge of psychotropic agents. A total of 49.0% of the respondents felt that they had been adequately trained to counsel patients on psychotropic agents. According to the regression model, pharmacists who reported higher knowledge were more experienced (0.63, (0.26-1.0), p < 0.001), reported studying the topic in the pharmacy school (0.77 (0.27-1.26), p = 0.002) holding a Doctor of Pharmacy (Pharm D) degree (0.24 (0.05-0.43), p = 0.01), and reported a higher perceived knowledge (0.29 (0.01-0.38), p = 0.038). Conclusion: Community pharmacists reported poor knowledge of psychotropic medications, and continuous medical and professional education programs are mandatory.

Perspective of biopharmaceutics knowledge and practice of pharmacy personnel toward the effect of medication route and medical procedure on nullifying fasting.

Background: In Ramadan, most of the dosing schedules for the patients are changed, and to ensure patient compliance to medications and to healthy life among patients, appropriate guidelines and educations are needed. This can be achieved by pharmacy personnel in all clinical settings who are recognized as biopharmaceutical experts and integral educators of medications. Aims: This study aimed to identify the perspective knowledge of pharmacy personnel about effect of medication route and medical procedure on nullifying fasting in Ramadan and to determine the predictors of this knowledge. Methods: A cross-sectional study was conducted in Jordan during March-April 2022. An internet-based self-administrated questionnaire on knowledge, and views was distributed using social media groups to the pharmacy personnel among different geographical areas in Jordan. A descriptive and univariate analysis were performed. Binary logistic regression was conducted to determine the predictors of knowledge including all variables with p < 0.20 on univariate analysis. Results: A total of 1003 responses to the study questionnaire were collected and included in the analysis. The most common source that pharmacy personnel used to get information on medication intake and medical procedures during fasting in Ramadan was Fatwa (57.8%) followed by Islamic materials "books and brochures" (47.1%). The majority of respondents were knowledgeable about the effect of administration route of medication and medical procedures on nullifying fasting in Ramadan (greater than70%). The univariate analysis showed that more than half of respondents (56.1%) were considered knowledgeable, and the binary logistic regression analysis identified that both professional degree type and confidence of respondents to modify the patient's medication schedule as predictors for knowledge (OR = 1.791, 95% CI = 1.035-3.098, p = 0.037), (OR = 1.375, 95% CI = 1.04-1.817, p = 0.025), respectively. Conclusions: Most of pharmacy personnel in Jordan are knowledgeable in biopharmaceutics principles and practice toward effect of medication route and medical procedure on nullifying fasting, and the identified predictors for this knowledge, can provide an opportunity to improve safe and effective use of medications and medical procedures during the holy month of Ramadan.

Awareness and Knowledge of Pharmacists toward Biosimilar Medicines: A Survey in Jordan.

Aims: Pharmacists in all clinical settings are recognized drug experts and integral educators of biosimilar medicines. Therefore, the objective of this study was to assess pharmacists' knowledge, predictors of knowledge, and views toward biosimilar medicines in Jordan. Methods: A cross-sectional study was conducted in Jordan during October-December 2020. An Internet-based self-administrated questionnaire on knowledge and views was distributed using social media groups to the pharmacists among different areas in Jordan. A descriptive and univariate analysis was performed. Binary logistic regression was conducted to determine the predictors of knowledge including all variables with p < 0.20 on univariate analysis. Results: A total 536 responses were received, 502 of which were completed (93.7% response rate). A total of 52.6% of the pharmacists were knowledgeable about biosimilar medicines and the mean of knowledge level was 6.47 ± 1.62 (range 2-10). Multivariate analysis identified that respondents who had heard about biosimilars before (OR = 1.942, 95% CI = 1.231-3.063, p < 0.05) was more likely to be knowledgeable. Respondents who had not taken the course or the postgraduating training course about biosimilars that were less likely to be knowledgeable (OR = 0.548, 95% CI = 0.357-0.839, p < 0.05). A positive response was noted in pharmacist's view regarding the implementation of biosimilar medicines in healthcare setting, biosimilar medicine prescription related to decreased costs, self-study about biosimilar medicine, and incorporating biosimilar education program at the pharmacy school curriculum universities level. Conclusions: Pharmacists' views and knowledge vary regarding the particularities and key issues on biosimilar medicines in Jordan. Incorporating biosimilar course in pharmacy school curriculum could improve their acceptance for future pharmacy jobs.

About anxiety levels and anti-anxiety drugs among quarantined undergraduate Jordanian students during COVID-19 pandemic.

OBJECTIVE: This study was conducted to study the anxiety scores among undergraduate university students in Jordan during COVID-19 pandemic and to assess the relationship between quarantine and shifting to distance learning resulted from the governmental strict isolation measures and severity of anxiety among students. METHODS: A cross-sectional design was conducted to meet the study objectives. A convenience sample of 736 undergraduate university students in Jordan was recruited, and anxiety was assessed using the Hamilton Anxiety Scale. RESULTS: The results indicated that anxiety score was 22.76 and 40.6% of the participant experienced moderate to severe anxiety, whereas 23.5% experienced mild to moderate anxiety and 35.9% experienced mild anxiety. Factors like suffering from chronic illnesses, having chronic medications, grade point average, shifting to distance learning, quarantine during the pandemic, study duties, the newly developed evaluation methods and the experience of students towards the use of anti-anxiety drugs and herbs had significantly increased the anxiety scores. CONCLUSION: Our findings indicate that quarantine and shifting to distance learning during COVID-19 pandemic have negatively affected the anxiety scores of the university students which should be taken in consideration by the policymakers in Jordan in order to support this vulnerable group.

FKBPL and its peptide derivatives inhibit endocrine therapy resistant cancer stem cells and breast cancer metastasis by downregulating DLL4 and Notch4.

BACKGROUND: Optimising breast cancer treatment remains a challenge. Resistance to therapy is a major problem in both ER- and ER+ breast cancer. Tumour recurrence after chemotherapy and/or targeted therapy leads to more aggressive tumours with enhanced metastatic ability. Self-renewing cancer stem cells (CSCs) have been implicated in treatment resistance, recurrence and the development of metastatic disease. METHODS: In this study, we utilised in vitro, in vivo and ex vivo breast cancer models using ER+ MCF-7 and ER- MDA-MB-231 cells, as well as solid and metastatic breast cancer patient samples, to interrogate the effects of FKBPL and its peptide therapeutics on metastasis, endocrine therapy resistant CSCs and DLL4 and Notch4 expression. The effects of FKBPL overexpression or peptide treatment were assessed using a t-test or one-way ANOVA with Dunnett's multiple comparison test. RESULTS: We demonstrated that FKBPL overexpression or treatment with FKBPL-based therapeutics (AD-01, pre-clinical peptide /ALM201, clinical peptide) inhibit i) CSCs in both ER+ and ER- breast cancer, ii) cancer metastasis in a triple negative breast cancer metastasis model and iii) endocrine therapy resistant CSCs in ER+ breast cancer, via modulation of the DLL4 and Notch4 protein and/or mRNA expression. AD-01 was effective at reducing triple negative MDA-MB-231 breast cancer cell migration (n ≥ 3, p < 0.05) and invasion (n ≥ 3, p < 0.001) and this was translated in vivo where AD-01 inhibited breast cancer metastasis in MDA-MB-231-lucD3H1 in vivo model (p < 0.05). In ER+ MCF-7 cells and primary breast tumour samples, we demonstrated that ALM201 inhibits endocrine therapy resistant mammospheres, representative of CSC content (n ≥ 3, p < 0.05). Whilst an in vivo limiting dilution assay, using SCID mice, demonstrated that ALM201 alone or in combination with tamoxifen was very effective at delaying tumour recurrence by 12 (p < 0.05) or 21 days (p < 0.001), respectively, by reducing the number of CSCs. The potential mechanism of action, in addition to CD44, involves downregulation of DLL4 and Notch4. CONCLUSION: This study demonstrates, for the first time, the pre-clinical activity of novel systemic anti-cancer therapeutic peptides, ALM201 and AD-01, in the metastatic setting, and highlights their impact on endocrine therapy resistant CSCs; both areas of unmet clinical need.

Service evaluation of diabetes management during pregnancy in a regional maternity hospital: potential scope for increased self-management and remote patient monitoring through mHealth solutions.

BACKGROUND: Pre-gestational and gestational diabetes mellitus are common complications in pregnancy affecting one in six pregnancies. The maternity services are under significant strain managing the increasing number of complex pregnancies. This has an impact on patients' experience of antenatal care. Therefore, there is a clear need to address pregnancy care. One possible solution is to use home-based digital technology to reduce clinic visits and improve clinical monitoring. METHODS: The aim of this study was to evaluate the antenatal services provided to pregnant women with diabetes who were monitored at the joint metabolic and obstetric clinic at the Southern Health and Social Care Trust in Northern Ireland. RESULTS: The questionnaires were completed by sixty-three women, most of whom had gestational diabetes mellitus. Most of the participants were between 25 and 35 years of age (69.8%), had one or more children (65.1%) and spent over 2 h attending the clinics (63.9%); 78% of women indicated that their travel time to and from the clinic appointment was over 15 min. Over 70% of women used smartphones for health-related purposes. However, only 8.8% used smartphones to manage their health or diabetes. Less than 25% of the women surveyed expressed concerns about using digital technology from home to monitor various aspects of their health in pregnancy. CONCLUSIONS: Overall, pregnant women who had or developed diabetes in pregnancy experience frequent hospital visits and long waiting times in the maternity clinics. Most of these pregnant women are willing to self-manage their condition from home and to be monitored remotely by the healthcare staff.

Elucidating the Pathogenesis of Pre-eclampsia Using In Vitro Models of Spiral Uterine Artery Remodelling.

PURPOSE OF REVIEW: The aim of the study is to perform a critical assessment of in vitro models of pre-eclampsia using complementary human and cell line-based studies. Molecular mechanisms involved in spiral uterine artery (SUA) remodelling and trophoblast functionality will also be discussed. RECENT FINDINGS: A number of proteins and microRNAs have been implicated as key in SUA remodelling, which could be explored as early biomarkers or therapeutic targets for prevention of pre-eclampsia. Various 2D and 3D in vitro models involving trophoblast cells, endothelial cells, immune cells and placental tissue were discussed to elucidate the pathogenesis of pre-eclampsia. Nevertheless, pre-eclampsia is a multifactorial disease, and the mechanisms involved in its pathogenesis are complex and still largely unknown. Further studies are required to provide better understanding of the key processes leading to inappropriate placental development which is the root cause of pre-eclampsia. This new knowledge could identify novel biomarkers and treatment strategies.

Factors associated with insomnia and fatigue symptoms during the outbreak of Oct.7th war on Gaza: A study from Jordan.

Objective: The Jordanian and the Palestinian communities are tightly related, hence, the current war on Gaza also has social and psychological impacts on Jordanians. Therefore, this study aims to identify the factors associated with severe insomnia and fatigue symptoms in a cohort of Jordanians during the Gaza War outbreak. Methods: This is a cross-sectional web-based questionnaire study. The Insomnia Severity Index-Arabic version (ISI-A), and the Brief Fatigue Inventory-Arabic (BFI-A) were employed, binary logistic and linear regression analyses was performed to identify predictors to severe insomnia and fatigue respectively. Data were collected between December 2023 and January 2024. Results: Data were analyzed from 477 participants, of which 315 (66 %) were females, 107 (22.4 %) reported having a family relative or a friend residing in Gaza, 365 (76.5 %) reported not using any sleep aid, 78 (16.4 %) reported using homeopathy herbal remedies for sleep, and only 52 (10.9 %) reported using over-the-counter sedating antihistamines. Severe insomnia was significantly associated with participants "younger than 30 years old" (OR = 1.81, 95 %CI = 1.22-2.66, p = 0.003), participants "using over-the-counter sedating antihistamines" (OR = 2.78, 95 % CI = 1.27-6.06, p = 0.01). Severe fatigue was significantly associated with "females" (B = 5.87, t = 2.78, p = 0.006), and "smokers" (B = 5.09, t = 2.52, p = 0.01). On the other hand, "not using sleep aids" demonstrated significantly lower odds for severe insomnia (OR = 0.41, 95 % CI = 0.24-0.68, p = 0.001), and fatigue (B = -10.84, t = -4.81, p < 0.001). Conclusions: Addressing modifiable risk factors such as smoking and sleep self-medications is essential to improve insomnia and fatigue symptoms.