"Anxiety is not cute" analysis of twitter users' discourses on romanticizing mental illness.

BACKGROUND: The proliferation of social media platforms has provided a unique space for discourse on mental health, originally intended to destigmatize mental illness. However, recent discourses on these platforms have shown a concerning shift towards the romanticization of mental health issues. This research focuses on Twitter (now called X) users' authentic discussions on the phenomenon of romanticizing mental health, aiming to uncover unique perspectives, themes, and language used by users when engaging with this complex topic. METHODS: A comprehensive content analysis was conducted on 600 relevant tweets, with the application of topic modeling techniques. This methodology allowed for the identification and exploration of six primary themes that emerged from Twitter users' discussions. Statistical tests were not applied in this qualitative analysis. RESULTS: The study identified six primary themes resulting from Twitter users' discussions on the romanticization of mental health. These themes include rejecting/critiquing the glamorization of mental health, monetization of mental health by corporate organizations, societal misconceptions of mental health, the role of traditional media and social media, unfiltered realities of depression, and the emphasis on not romanticizing mental health. CONCLUSIONS: This study provides valuable insights into the multifaceted discourses surrounding the romanticization of mental health on Twitter. It highlights users' critiques, concerns, and calls for change, emphasizing the potential harm caused by romanticizing mental illness. The findings underscore the importance of fostering responsible and empathetic discussions about mental health on social media platforms. By examining how Twitter users interact with and respond to the romanticization of mental health, this research advances our understanding of emerging perspectives on mental health issues among social media users, particularly young adolescents. The study also underscores the effects of this phenomenon on individuals, society, and the mental health community. Overall, this research emphasizes the need for more responsible and knowledgeable discussions around mental health in the digital age.

Correlations between serum kidney injury molecule-1, cystatin C and immunosuppressants: A cross-sectional study of renal transplant patients in Bahrain.

Renal transplant patients receive several immunosuppressive drug regimens that are potentially nephrotoxic for treatment. Serum creatinine is the standard for monitoring kidney function; however, cystatin C (Cys C) and kidney injury molecule-1 (KIM-1) have been found to indicate kidney injury earlier than serum creatinine and provide a better reflection of kidney function. Here, we assessed Cys C and KIM-1 serum levels in renal transplant patients receiving mycophenolate mofetil, tacrolimus, sirolimus, everolimus, or cyclosporine to evaluate kidney function. We used both the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2021 equation, which is based on creatinine and combined creatinine with Cys C, and the CKD-EPI 2012 equation, which is based on Cys C alone, to estimate glomerular filtration rate (GFR). Then, we assessed the association between serum KIM-1 and GFR < 90 mL per minute per 1.73 m 2. We observed significantly higher serum Cys C levels in patients with the elevated serum creatinine, compared with those with normal serum creatinine. The estimated GFRs based on creatinine were significantly higher than those based on the other equations, while a significant positive correlation was observed among all equations. Serum KIM-1 levels were negatively correlated with the estimated GFRs by the CKD-EPI Cys C and the combined creatinine with Cys C equations. A serum KIM-1 level above 0.71 ng/mL is likely to indicate GFR < 90 mL per minute per 1.73 m 2. We observed a significant correlation between serum creatinine and Cys C in our renal transplant patients. Therefore, serum KIM-1 may be used to monitor renal function when using potentially nephrotoxic drugs in renal transplants.

Effect of dexamethasone administration on gonadal-fertility functions in female albino rats.

Introduction: dexamethasone is misused for skin whitening with broad effects on steroidogenesis and ovarian functions. Here in we investigated the impact of dexamethasone administration on gonadotropin Luteinizing Hormone (LH) and Follicle Stimulating Hormone (FSH), prolactin, and ovarian tissues in albino rats. Methods: in the experimental study, 36 female albino rats weighting (140-162 g) were divided into three groups: control, normal dose received dexamethasone (8.3 µg/kg/day) and high dose (24.9 µg/kg/day), for 30 and 60 days. follicle stimulating hormone, luteinizing hormone, and prolactin (PRL) were measured. Histological ovarian sections were examined. Results: luteinizing hormone, follicle stimulating hormone and prolactin significantly increased (p-value < 0.05) following dexamethasone treatment compared to control. The ovary sections showed degenerative tissue with necrosis of the Graafian follicles, stromal fibrosis, and vacuolation of the interstitial cells. Conclusion: the study concludes that dexamethasone administration has a potentially adverse effect on gonadotropin, prolactin, and ovarian follicle cells in female albino rats.

Assessment of early functional outcome of lumbar discectomy in Soba and Future hospitals, Khartoum, Sudan 2021.

Background: Herniated lumbar disc is one of the common causes of back pain. Discectomy provides rapid relief of back pain and radicular pain. Few studies have been done in our setting to look for the outcome of discectomy. The purpose of this study was to assess the outcome of discectomy. Methods: This prospective cross-sectional hospital-based study was carried out on Soba Teaching Hospital and Future hospitals in Khartoum, Sudan. Sixty-one patients with lumbar discectomy were included in this study, collected data through a direct interviewing questionnaire and took some information from patients' files. Then collected data were analyzed using the statistical package for social science (SPSS) 24. Results: In sixty-one patients with lumbar discectomy of them, 24(39.3%) were within the age group 31-45 years old, 21(34.4%) were within the age group 46-50 years old, and 10(16.4%) were within age group 51-65years old. Results showed a male-to-female ratio of 1.5:1. The most common presenting symptoms were right Leg pain or numbness in 14(23%) patients. In the majority, 33(54.1%) of patients, the duration of symptoms was 6-12 months, 46(75.4%) underwent discectomy only, and 15(24.6%) underwent discectomy with fusion. Preoperatively, the majority of 30(49.1%) patients had a complete disability, 26(42.6%) had a severe disability, and 5(8.2%) had a moderate disability. In contrast, postoperatively, the majority, 35(57.4%) of patients, had mild disability, 24(39.3%) had no disability, and only 2(3.3%) had moderate disability (P value < .001). Moreover, there was a statistically significant association between the presence of co-morbidity and postoperative outcome (P value = .021). Conclusion: Discectomy is a gold stander procedure in the management of LDH. Patients showed excellent functional outcomes. The most common presenting symptoms were right leg pain or numbness. Patients postoperatively showed significant clinical improvement according to the mODI score.

A bilateral asymmetrical hip dislocation: A rare case report.

A 17-year-old male was ejected from the motorcycle and brought to the Emergency Department with bilateral hip dislocation and absence of pelvic or femur fractures or sciatic nerve injury. Closed reduction and postreduction examination were performed with a bilateral stable full range of motion in all directions.

Crimean-Congo haemorrhagic fever during the COVID-19 pandemic in Africa: Efforts, recommendations and challenges at hand.

Since the beginning of the COVID-19 pandemic, millions have suffered globally and as a result, attention and resources for other diseases, such as Crimean-Congo Haemorrhagic Fever (CCHF), has declined. Despite a significantly lower incidence rate compared to COVID-19, CCHF has a considerably higher mortality rate at approximately 30%. Both diseases share symptoms such as headache, fever, nausea and vomiting, fatigue, sore throat, however they have different modes of transmission, mortality rates, and incubation periods. Public health professionals have faced several challenges when attempting to prevent and control the spread of both diseases and despite their differences, many of the prevention methods remain the same. These include increasing public awareness regarding avoiding contact with infected individuals and animals, training healthcare professionals in emergency and preparedness for disease outbreaks and increasing the investment in medical supplies and treatment to control the spread of both diseases.

Government policies and firm performance in the COVID-19 pandemic era: a sectoral analysis.

The effect of the COVID-19 pandemic has been severely detrimental to most firms. Preliminary estimates from Italy, which experienced the worst devastation from the virus during the early days of the pandemic, predicted that the country could lose at least $8.3 bn in the service and manufacturing sectors due to the coronavirus pandemic. Although there has been a series of ongoing government policies to mitigate the economic effect of the pandemic, we do not know to what extent these policies have been effective. Using two-period panel data (before and during the pandemic) on 419 Italian firms, this study examines the impact of government policies on firms using first difference estimation. The results show that firms that received a government grant in relation to the COVID-19 pandemic saw on average an 11% increase in sales revenue by the end of June 2020 compared to those yet to receive grants. A sectoral decomposition of the analysis indicates government policy to be effective in the services sector if performance is measured by sales revenue. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s43546-021-00170-6.

Factors associated with acceptance of COVID-19 vaccine among University health sciences students in Northwest Nigeria.

Students of the health sciences are the future frontliners to fight pandemics. The students' participation in COVID-19 response varies across countries and are mostly for educational purposes. Understanding the determinants of COVID-19 vaccine acceptability is necessary for a successful vaccination program. This study aimed to investigate the factors associated with COVID-19 vaccine acceptance among health sciences students in Northwest Nigeria. The study was an online self-administered cross-sectional study involving a survey among students of health sciences in some selected universities in Northwest Nigeria. The survey collected pertinent data from the students, including socio-demographic characteristics, risk perception for COVID-19, and willingness to accept the COVID-19 vaccine. Multiple logistic regression was used to determine the predictors of COVID-19 vaccine acceptance. A total of 440 responses with a median (interquartile range) age of 23 (4.0) years were included in the study. The prevalence of COVID-19 vaccine acceptance was 40.0%. Factors that independently predict acceptance of the vaccine were age of 25 years and above (adjusted odds ratio, aOR, 2.72; 95% confidence interval, CI, 1.44-5.16; p = 0.002), instructions from heads of institutions (aOR, 11.71; 95% CI, 5.91-23.20; p<0.001), trust in the government (aOR, 20.52; 95% CI, 8.18-51.51; p<0.001) and willingness to pay for the vaccine (aOR, 7.92; 95% CI, 2.63-23.85; p<0.001). The prevalence of COVID-19 vaccine acceptance among students of health sciences was low. Older age, mandate by heads of the institution, trust in the government and readiness to pay for the vaccine were associated with acceptance of the vaccine. Therefore, stakeholders should prioritize strategies that would maximize the vaccination uptake.

Organization factors influencing nurse ability to prevent and detect adverse drug events in public hospitals using a patient safety model.

The objective of this study was to measure organization factors that can influence the ability of nursing staff to prevent and detect ADEs in public hospitals using Systems Engineering Initiative for Patient Safety (SEIPS) model. METHODS: This was a multi-center cross-sectional study. The study included a self-administered paper-based survey which was distributed and collected between October through December 2019. The study participants were nurses from 11 public hospitals located in two Iraqi provinces. Binary logistic regression was used to measure the relationship between the independent SEIPS factors (persons, organizations, tools, tasks, and environments) and the incidence of ADEs (outcome variable). RESULTS: The study recruited 603 nurses (68.3% men) from 11 public hospitals across two provinces. Less than half (48.8%) of the nurses received enough training to detect ADEs, 43.1% had adequate experience to detect ADEs, and 69.8% had to report ADEs in a special record. More than three-quarters (78.4%) believed that their jobs need fast work. Two of the five SEIPS model domains had significant negative association with the incidence of ADEs including organization (nurse-physician collaboration) and nurse experience in ADE detection. CONCLUSIONS: Nursing staff face several challenges to prevent and minimize ADEs including shortages in nurses, inadequate nurse experience in ADE detection, no training for ADE detection was received, fear of reporting ADEs, and a lack in monitoring equipment. Increasing nurse/patient ratio and providing more monitoring equipment and training courses can minimize ADEs and enhance their detection.

Inhibition of aquaporins as a potential adjunct to breast cancer cryotherapy.

Cryoablation is an emerging type of treatment for cancer. The sensitization of tumors using cryosensitizing agents prior to treatment enhances ablation efficiency and may improve clinical outcomes. Water efflux, which is regulated by aquaporin channels, contributes to cancer cell damage achieved through cryoablation. An increase in aquaporin (AQP) 3 is cryoprotective, whereas its inhibition augments cryodamage. The present study aimed to investigate aquaporin (AQP1, AQP3 and AQP5) gene expression and cellular localization in response to cryoinjury. Cultured breast cancer cells (MDA-MB-231 and MCF-7) were exposed to freezing to induce cryoinjury. RNA and protein extracts were then analyzed using reverse transcription-quantitative PCR and western blotting, respectively. Localization of aquaporins was studied using immunocytochemistry. Additionally, cells were transfected with small interfering RNA to silence aquaporin gene expression and cell viability was assessed using the Sulforhodamine B assay. Cryoinjury did not influence gene expression of AQPs, except for a 4-fold increase of AQP1 expression in MDA-MD-231 cells. There were no clear differences in AQP protein expression for either cell lines upon exposure to frozen and non-frozen temperatures, with the exception of fainter AQP5 bands for non-frozen MCF-7 cells. The exposure of cancer cells to freezing temperatures altered the localization of AQP1 and AQP3 proteins in both MCF-7 and MDA-MD-231 cells. The silencing of AQP1, AQP3 and AQP5 exacerbated MDA-MD-231 cell damage associated with freezing compared with control siRNA. This was also observed with AQP3 and AQP5 silencing in MCF-7 cells. Inhibition of aquaporins may potentially enhance cryoinjury. This cryosensitizing process may be used as an adjunct to breast cancer cryotherapy, especially in the border area targeted by cryoablation where freezing temperatures are not cold enough to induce cellular damage.

Mental Health Consequences of Lockdown During the COVID-19 Pandemic: A Cross-Sectional Study.

OBJECTIVE: We aimed to provide an overview of the psychological status and behavioral consequences of the lockdown during the COVID-19 pandemic in Libya. METHODS: A cross-sectional study was conducted among the Libyan population through May and June 2020 in more than 20 cities. The survey comprised basic demographic data of the participants and anxiety symptoms measured using the seven-item Generalized Anxiety Disorder scale (GAD-7) with ≥15 as the cut-off score for clinically significant anxiety symptoms. Additionally, a survey regarding the lockdown effect was administered, which consisted of several parts, to measure the lockdown status. RESULTS: A total of 8084 responses were recorded, of which, 5090 (63%) were women and 2994 (37%) were men. The mean age (SD) for study participants was 27.2 (8.9) years. Among the participants, 1145 (14.2%) reached the cut-off score to detect anxiety symptoms; however, of the study variables, only five were predictors of clinically significant anxiety: age, gender, marital status, work status, being a financial supporter for the family, and being infected with COVID-19. Women had 1.19 times higher odds to exhibit anxiety symptoms than men. Increasing age was significantly associated with reduced likelihood of exhibiting anxiety symptoms, whereas being married was significantly associated with higher likelihood of anxiety symptoms, compared to not being married. Being suspended from work was associated with an increase in the likelihood of anxiety symptoms. However, we found that being infected with COVID-19 was associated with a 9.59 times higher risk of exhibiting severe anxiety symptoms. Among the study participants, 1451 (17.9%) reported a physical and/or verbal abuse episode from family members, 958 (11.9%) reported abuse outside the family, and 641 (7.9%) reported abuse from enforcers, during the lockdown. CONCLUSION: Our study provided an overview of the psychological and behavioral status, among those who resided in Libya during the civil war and COVID-19 pandemic. The study demonstrates a concerningly high level of clinically significant anxiety during lockdown among the Libyan population during Libya's lockdown period.

Risk Factors Associated with Mortality Among Patients with Novel Coronavirus Disease (COVID-19) in Africa.

BACKGROUND: The novel coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in China and later spread rapidly to other parts of the world, including Africa. Africa was projected to be devastated by COVID-19. There is currently limited data regarding regional predictors of mortality among patients with COVID-19. This study aimed to evaluate the independent risk factors associated with mortality among patients with COVID-19 in Africa. METHODS: A total of 1028 confirmed cases of COVID-19 from Africa with definite survival outcomes were identified retrospectively from an open-access individual-level worldwide COVID-19 database. The live version of the dataset is available at https://github.com/beoutbreakprepared/nCoV2019 . Multivariable logistic regression was conducted to determine the risk factors that independently predict mortality among patients with COVID-19 in Africa. RESULTS: Of the 1028 cases included in study, 432 (42.0%) were females with a median (interquartile range, IQR) age of 50 (24) years. Older age (adjusted odds ratio {aOR} 1.06; [95% confidence intervals {95% CI}, 1.04-1.08]), presence of chronic disease (aOR 9.63; [95% CI, 3.84-24.15]), travel history (aOR 2.44; [95% CI, 1.26-4.72]), as well as locations of Central Africa (aOR 0.14; [95% CI, 0.03-0.72]) and West Africa (aOR 0.12; [95% CI, 0.04-0.32]) were identified as the independent risk factors significantly associated with increased mortality among the patients with COVID-19. CONCLUSIONS: The COVID-19 pandemic is evolving gradually in Africa. Among patients with COVID-19 in Africa, older age, presence of chronic disease, travel history, and the locations of Central Africa and West Africa were associated with increased mortality. A regional response should prioritize strategies that will protect these populations. Also, conducting a further in-depth study could provide more insights into additional factors predictive of mortality in COVID-19 patients.

Effects of curcumin complexes on MDA­MB­231 breast cancer cell proliferation.

Curcumin displays anticancer properties; however, some issues with the drug delivery mode limit its therapeutic use. Although reformulation and derivatization of curcumin have improved its bioavailability, curcumin derivatives may not retain the same anticancer properties as the parent compound. The present study investigated the anticancer properties of two curcumin complexes, the iron­curcumin [Fe(Cur)3] and boron­curcumin [B(Cur)2] complexes, in the MDA­MB­231 breast cancer cell line. The cellular localization of curcumin, B(Cur)2 and Fe(Cur)3 was determined by fluorescence microscopy. Cell proliferation, migration and invasion were also analysed. Furthermore, apoptosis­associated proteins were detected by using a proteome profiler array, and ion channel gene expression was analysed by reverse transcription­quantitative PCR. The results demonstrated that the three compounds were localized in the perinuclear and cytoplasmic regions of the cell, and displayed cytotoxicity with IC50 values of 25, 35 and 8 µM for curcumin, B(Cur)2 and Fe(Cur)3, respectively. In addition, the three compounds inhibited cell invasion, whereas only curcumin and B(Cur)2 inhibited cell migration. Furthermore, cell exposure to curcumin resulted in an increase in the relative expression of the two key proapoptotic proteins, cytochrome c and cleaved caspase­3, as well as the antiapoptotic protein haem oxygenase­1. In addition, curcumin increased the expression levels of the voltage­gated potassium channels Kv2.1 and Kv3.2. Similarly, the expression levels of the chloride channel bestrophin­1 and the calcium channel coding gene calcium voltage­gated channel auxiliary subunit γ4 were increased following exposure to curcumin. Taken together, these results indicated that Fe(Cur)3 and B(Cur)2 may display similar anticancer properties as curcumin, suggesting that chemical complexation may be considered as a strategy for improving the potency of curcumin in the treatment of breast cancer.

Unwanted Horse Population in Illinois: Perceptions of Horse Owners, Non-Horse Owners, and Equine Industry Stakeholders.

This paper presents the results of an investigation to determine perceptions, awareness, and knowledge of the unwanted horse population in Illinois from the viewpoint of horse owners, non-horse owners, and equine industry stakeholders. A questionnaire included items that pertained to knowledge of current legislation, equine background, current methods of controlling the unwanted horse population, and methods that respondents believe would reduce the unwanted horse population in Illinois. Results indicated that 58% of horse owners viewed horses as companion animals. Respondents perceived financial hardship to be the major reason why horses become unwanted. Current methods of managing unwanted horse populations were found to be ineffective. Reducing the costs of euthanasia and carcass disposal, allowing processing facilities to reopen in Illinois, and increasing the availability of gelding programs emerged as the most effective ways to manage the unwanted horse population. Results of this survey may lead to greater awareness of the unwanted horse population in Illinois. Furthermore, these results may lead to discussions about future legislation in the State designed to support and manage unwanted horses.

Curcumin⁻Copper Complex Nanoparticles for the Management of Triple-Negative Breast Cancer.

Breast cancer is the most common cancer diagnosed among females worldwide. Although breast cancer survival has largely improved in the past 30 years, it remains highly heterogeneous in its response to treatment. Triple-negative breast cancer (TNBC) is a subtype of breast cancer that lacks the expression of the estrogen receptor (ER), progesterone receptor (PR) and epidermal growth factor receptor-2 (Her2). While TNBC may initially be responsive to chemotherapy, recurrence and subsequent high mortality rates are frequently reported. Studies have shown curcumin and its derivatives to be effective against TNBC cell lines in vitro. To improve its anti-cancer effects, we have synthesized Fe3+⁻curcumin (Fe⁻Cur3) and Cu2+⁻curcumin (CD) complexes and investigated them experimentally. Further, CD was encapsulated into a poly(styrene)-co-maleic acid (SMA) micelle to enhance its stability. We assessed the cytotoxicity of these formulations both in vitro and in vivo. SMA⁻CD demonstrated dose-dependent cytotoxicity and abolished TNBC tumor growth in vivo. The encapsulation of the curcumin⁻copper complex improved its anti-cancer activity without overt adverse effects in a murine model of TNBC. These results provide evidence and insights into the value of nanoformulations in enhancing drug-delivery and increasing the potential therapeutic efficacy of curcumin derivatives.

Acute lower gastrointestinal bleeding in Sudanese patients: a study on 301 patients in a specialized centre.

BACKGROUND AND STUDY AIMS: Lower gastrointestinal bleeding originates from a site distal to the ligament of Treitz. It can present as an acute life-threatening or chronicbleeding. It is common among older patients and those with comorbidity. The common causes are diverticular disease, angiodysplasias, neoplasms, colitis, ischaemia and anorectal disorders. The aim of this study is to determine the prevalence and causes of acute lower gastrointestinal bleeding among Sudanese patients. PATIENTS AND METHODS: In a period of 2 years we studied 301 patients with fresh rectal bleeding out of 5625 patients with gastrointestinal bleeding in Ibn Sina Specialized Hospital, Khartoum, Sudan, This is a cross sectional observational hospital based study. All patients with fresh rectal bleeding within 24 h were included and consented. RESULT: Lower gastrointestinal bleeding constituted 5.37% of total cases of gastrointestinal bleeding. The mean age of patients was 55.43 ±â€¯17.779, male: female ratio was 2:1. The most common cause (if upper gastrointestinal bleeding is excluded) was diverticular disease 39.6% (n = 61) followed by piles 24.1% (n = 35), colonic tumours 12.34% (n = 19), ulcerative colitis 5.19% (n = 8), Crohn's 5.19% (n = 8), colonic polyps 3,89% (n = 6), angiodysplesia 4.5% (n = 7), colonic ulcer 2.59% (n = 4), ischaemic colitis 1.3%, nonspecific colitis 1.3% (n = 2), and small bowel source in 1.3% (n = 2). The majority of those patients with diverticular disease were male and with first presentation. The commonest cause in those patients younger than 20 years was polyps, and in those between 21 and 40 was piles followed by inflammatory bowel disease, and in those between 41 and 60 years old was piles followed by diverticular disease and tumours, and in those above 60 years was diverticular disease followed by piles and tumours. The correlation between positive colonoscopy finding and diabetes and the use of nonsteroidal anti-inflammatory drugs were statistically significant. The one-month mortality rate was 2.3% CONCLUSION: Acute lower gastrointestinal bleeding is common among elderly patients and the commonest cause is diverticular disease. Colonoscopy plays an important role in the diagnosis. Most patients respond to conservative therapy.

A comparative study of the spectral, fluorometric properties and photostability of natural curcumin, iron- and boron- complexed curcumin.

Curcumin is a yellow phenolic compound with a wide range of reported biological effects. However, two main obstacles hinder the use of curcumin therapeutically, namely its poor bioavailability and photostability. We have synthesized two curcumin complexes, the first a boron curcumin complex (B-Cur2) and the second an iron (Fe-Cur3) complex of curcumin. Both derivatives showed high fluorescence efficiency (quantum yield) and greater photostability in solution. The improved photostability could be attributed to the coordination structures and the removal of ß-diketone group from curcumin. The fluorescence and ultra violet/visible absorption spectra of curcumin, B-Cur2 and Fe-Cur3 all have a similar spectral pattern when dissolved in the same organic solvent. However, a shift towards a lower wavelength was observed when moving from polar to non-polar solvents, possibly due to differences in solvent polarity. A plot of Stokes' shift vs the orientation polarity parameter (Δf) or vs the solvent polarity parameter (ET 30) showed an improved correlation between the solvent polarity parameter than with the orientation polarity parameter and indicating that the red shift observed could be due to hydrogen-bonding between the solvent molecules. A similar association was obtained when Stokes' shift was replaced by maximum synchronous fluorescence. Both B-Cur2 and Fe-Cur3 had larger quantum yields than curcumin, suggesting they may be good candidates for medical imaging and in vitro studies.

Blockade of voltage-gated sodium channels inhibits invasion of endocrine-resistant breast cancer cells.

Voltage-gated Na+ channels (VGSCs) are membrane proteins which are normally expressed in excitable cells but have also been detected in cancer cells, where they are thought to be involved in malignancy progression. In this study we examined the ion current and expression profile of VGSC (Nav1.5) in estrogen receptor (ER)-positive (MCF-7) and silenced (pII) breast cancer cells and its possible influence on their proliferation, motility and invasion. VGSC currents were analysed by whole cell patch clamp recording. Nav1.5 expression and localization, in response to EGF stimulation, was examined by western blotting and immunofluorescence respectively. Cell invasion (under-agarose and Matrigel assays), motility (wound healing assay) and proliferation (MTT assay) were assessed in pII cells in response to VGSC blockers, phenytoin (PHT) and tetrodotoxin (TTX), or by siRNA knockdown of Nav1.5. The effect of PHT and TTX on modulating EGF-induced phosphorylation of Akt and ERK1/2 was determined by western blotting. Total matrix metalloproteinase (MMP) was determined using a fluorometric-based activity assay. The level of various human proteases was detected by using proteome profiler array kit. VGSC currents were detected in pII cells, but were absent in MCF-7. Nav1.5 showed cytoplasmic and perinuclear expression in both MCF-7 and pII cells, with enhanced expression upon EGF stimulation. Treatment of pII cells with PHT, TTX or siRNA significantly reduced invasion towards serum components and EGF, in part through reduction of P-ERK1/2 and proteases such as cathepsin E, kallikrein-10 and MMP-7, as well as total MMP activity. At high concentrations, PHT inhibited motility while TTX reduced cell proliferation. Pharmacological or genetic blockade of Nav1.5 may serve as a potential anti-metastatic therapy for breast cancer.