Photoreceptor therapy: generation of neurosphere-like cells from human mesenchymal stem cells expressing erythropoietin

The loss of photoreceptors is a major concern implicated in age-macular degeneration (AMD), a type of neurodegenerative disorder. Failure to prescribe a suitable treatment due to the lack of understanding of the molecular pathogenesis, and limited capacity to compensate irreparably damaged photoreceptors in the retina have greatly contributed to the progression of visual dysfunction. Our previous study has shown that Mesenchymal Stem Cells (MSCs) expressing erythropoietin (EPO) could commit into photoreceptor cell lineage. However, the efficiency of cell differentiation is limited. The present study aims to explore the capacity of these MSCs to form neurospheres. The cells were transduced with lentiviral particles encoding for human EPO and green fluorescent protein (GFP) genes, culture-expanded and sorted before subjected for differentiation induction into neural precursor cells. Our results showed that MSC-EPO developed into larger neurosphere and expressed relatively higher expression of nestin compared with MSCs alone when cultured under neural induction medium. These preliminary findings suggested that MSC-EPO have greater neurogenic potential than MSCs alone. Further study is needed to evaluate the possibilities of neurosphere to delete differentiate into functional photoreceptor cells. We believe that the success of neurosphere expansion may potentially be useful in scaling up the manufacturing of photoreceptors in a shorter time and at an efficient cost for retinal cell replacement therapy

The role of AdipoR1 and AdipoR2 in liver fibrosis

Activation of the adiponectin (APN) signaling axis retards liver fibrosis. However, understanding of the role of AdipoR1 and AdipoR2 in mediating this response is still rudimentary. Here, we sought to elucidate the APN receptor responsible for limiting liver fibrosis by employing AdipoR1 and AdipoR2 knock-out mice in the carbon tetrachloride (CCl4) model of liver fibrosis. In addition, we knocked down receptor function in primary hepatic stellate cells (HSCs) in vitro. Following the development of fibrosis, AdipoR1 and AdipoR2 KO mice had no quantitative difference in fibrosis by Sirius red staining. However, AdipoR2 KO mice had an enhanced fibrotic signature with increased Col1-α1, TGFß-1, TIMP-1, IL-10, MMP-2 and MMP-9. Knockdown of AdipoR1 or AdipoR2 in HSCs followed by APN treatment demonstrated that AdipoR1 and AdipoR2 did not affect proliferation or TIMP-1 gene expression, while AdipoR2 modulated Col1-α1 and α-SMA gene expression, HSC migration, and AMPK activity. These finding suggest that AdipoR2 is the major APN receptor on HSCs responsible for mediating its anti-fibrotic effects

Rutin ameliorates carbon tetrachloride (CCl4)-induced hepatorenal toxicity and hypogonadism in male rats

Rutin, a food derived-polyphenolic bioflavonoid, has been acknowledged for several health benefits. This study aims to explore the ameliorative effects of rutin against carbon tetrachloride (CCl4) toxicity in male rats. Adult male rats were given either CCl4 (30% in olive oil, 3 ml/kg b.w. intraperitoneally) alone or in combination with rutin (70 mg/kg intragastrically) twice a week for 4 weeks. Our data showed that rutin mitigated CCl4 hepatorenal damage, as indicated by diagnostic markers (i.e., transaminases, alkaline phosphatase, total bilirubin, total protein, albumin, urea, uric acid and creatinine), and histopathological findings. In addition, CCl4 induced profound elevation of free radical generation and oxidative stress, as evidenced by increasing lipid peroxidation and reducing catalase, superoxide dismutase and glutathione peroxidase activities in liver, kidney and testicular tissues; these effects were suppressed by coexposure with rutin. Moreover, the increase in the levels of serum triglycerides, cholesterol, low-density lipoprotein cholesterol, and very-low-density lipoprotein cholesterol induced by CCl4 was effectively counteracted by rutin. The decrease in the level of high-density lipoprotein cholesterol in the CCl4 group was also counteracted by rutin treatment. Interestingly, the decreased levels of hormonal mediators associated with sperm production, including serum testosterone, luteinizing hormone and follicle-stimulating hormone, and the impaired sperm quality induced by CCl4 were reversed by rutin. Data from the current study clearly demonstrated that rutin supplementation could at least partly overcome CCl4-induced hepatotoxicity, nephrotoxicity and reproductive toxicity by antioxidant and antidyslipidemic effects

Optimized D-α-tocopherol polyethylene glycol succinate/phospholipid self-assembled mixed micelles: A promising lipid-based nanoplatform for augmenting the antifungal activity of fluconazole

Fluconazole (FLZ) is the most widely used antifungal agent for treating cutaneous candidiasis. Although oral FLZ has been proved to be effective, the incidence of side effects necessitates the development of an effective formulation that could surpass the pitfalls associated with systemic availability. Accordingly, this research aimed at developing a self-assembled mixed micelles topical delivery system to enhance the topical delivery of the drug. Self-assembled mixed micelles were developed using D-α-tocopheryl polyethylene glycol 1000 succinate and phospholipids and optimized using Box-Behnken design. The optimized formulation with minimized size was then tested in vivo for the antifungal activity against C. albicans in immunocompromised mice. Treatment with the optimized formulation led to decreased peripheral erythema as well as lesions due to fungal infection in comparison to raw FLZ loaded gel. Therefore, the developed formulation was found to be a promising vehicle for the treatment of cutaneous candidiasis

Biallelic RIPK1 mutations in humans cause severe immunodeficiency, arthritis, and intestinal inflammation.

RIPK1 (receptor-interacting serine/threonine kinase 1) is a master regulator of signaling pathways leading to inflammation and cell death and is of medical interest as a drug target. We report four patients from three unrelated families with complete RIPK1 deficiency caused by rare homozygous mutations. The patients suffered from recurrent infections, early-onset inflammatory bowel disease, and progressive polyarthritis. They had immunodeficiency with lymphopenia and altered production of various cytokines revealed by whole-blood assays. In vitro, RIPK1-deficient cells showed impaired mitogen-activated protein kinase activation and cytokine secretion and were prone to necroptosis. Hematopoietic stem cell transplantation reversed cytokine production defects and resolved clinical symptoms in one patient. Thus, RIPK1 plays a critical role in the human immune system

A population-based study of 15,000 people on Knowledge and awareness of lung cancer symptoms and risk factors in Saudi Arabia

Background: Lung cancer is currently the most fatal form of cancer worldwide, ranking as the fourth most prevalent type in Saudi Arabia, particularly among males. This trend is expected to increase with growing population, lifestyle changes, and aging population. Understanding the awareness of the Saudi population regarding the risk factors and symptoms of lung cancer is necessary to attenuate the predicted increase in cases. Method: A cross-sectional, population-based survey was performed using a previously validated questionnaire (Lung CAM). Multiple linear regression analysis was used to assess variables associated with deficiency in knowledge and awareness of risk factors and symptoms of lung cancer. Results: Majority of the 15,099 respondents were male (65%), aged between 18 and 30 years (53%), 50% of which were educated up to a bachelor’s degree level. Overall awareness of lung cancer signs and symptoms was 53%, with painful cough and coughing up blood being the best-known symptoms. Conversely, persistent shoulder pain (44%) and clubbing fingers (47%) were the least known lung cancer symptoms. Also, 60% of the respondents showed low confidence in identifying the signs and symptoms of lung cancer. The overall awareness of the risk factors for lung cancer development was 74%, with first-hand (74%) and second-hand (68%) smoking being the most known risk factors. However, only ≤ 62% know the other non-smoking risk factors. Awareness of the risk factors and symptoms of lung cancer depended on age, gender, education, marital and employment status (p < 0.001). Conclusion: Public awareness of the risk factors and symptoms of lung cancer in Saudi Arabia is inadequate and heavily dependent on education and socio-economic status. Awareness can be improved through campaigns to raise awareness about other lesser-known lung cancer risk factors and symptoms

A population-based study of 15,000 people on Knowledge and awareness of lung cancer symptoms and risk factors in Saudi Arabia

Background: Lung cancer is currently the most fatal form of cancer worldwide, ranking as the fourth most prevalent type in Saudi Arabia, particularly among males. This trend is expected to increase with growing population, lifestyle changes, and aging population. Understanding the awareness of the Saudi population regarding the risk factors and symptoms of lung cancer is necessary to attenuate the predicted increase in cases. Method: A cross-sectional, population-based survey was performed using a previously validated questionnaire (Lung CAM). Multiple linear regression analysis was used to assess variables associated with deficiency in knowledge and awareness of risk factors and symptoms of lung cancer. Results: Majority of the 15,099 respondents were male (65%), aged between 18 and 30 years (53%), 50% of which were educated up to a bachelor’s degree level. Overall awareness of lung cancer signs and symptoms was 53%, with painful cough and coughing up blood being the best-known symptoms. Conversely, persistent shoulder pain (44%) and clubbing fingers (47%) were the least known lung cancer symptoms. Also, 60% of the respondents showed low confidence in identifying the signs and symptoms of lung cancer. The overall awareness of the risk factors for lung cancer development was 74%, with first-hand (74%) and second-hand (68%) smoking being the most known risk factors. However, only ≤ 62% know the other non-smoking risk factors. Awareness of the risk factors and symptoms of lung cancer depended on age, gender, education, marital and employment status (p < 0.001). Conclusion: Public awareness of the risk factors and symptoms of lung cancer in Saudi Arabia is inadequate and heavily dependent on education and socio-economic status. Awareness can be improved through campaigns to raise awareness about other lesser-known lung cancer risk factors and symptoms

Prevalence of Bipolar Disorder and Associated Risk Factors Among Population in Western Region Of Saudi Arabia: A Cross-Sectional Study

Objective: To determine the prevalence of bipolar disorder and associated risk factors among the population in the Western Region, KSA. Methods:This research will employ a cross-sectional study design. Cross-sectional studies are well-suited for assessing the prevalence and risk factors of a particular condition in a specific population at a single point in time. This design will allow us to gather data on the prevalence of bipolar disorder and identify associated risk factors among the population in the Western region of Saudi Arabia. Results: The study included 407 participants. The most frequent weight among them was 51-65 kg (n= 109, 26.8%), followed by 66-75 kg (n= 93, 22.9%). The most frequent height among study participants was 1.61-1.70 m (n= 137, 33.7%) followed by 1.51-1.60 m (n= 128, 31.4%). The most frequent body mass index value was 18.5-24.9 kg/m2 (n= 161, 39.6%), followed by 25-29.9 kg/m2 (n= 142, 34.9%). The gender of study participants is almost equal with male (n= 204, 50.1%) and female (n= 203, 49.9%). The most frequent age among them was 62 years and above (n= 157, 38.6%), followed by 40-50 years (n= 92, 22.6%). Participants were asked the participants about what is the duration of their mental illness(bipolar). The most frequent answer was nothing (n=277,68.1%), followed by one year (n=96, 23.6%), and the least of them were six years (n=1,0.2%). Conclusion: The results showed that most of the study participants are married and intermediate owners and most of them have a university education. Most participants are not overweight according to their body's bodies. Most of the study participants had a good social link

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Left Main Coronary Artery Revascularization in Patients with Impaired Renal Function: Percutaneous Coronary Intervention versus Coronary Artery Bypass Grafting

Introduction: The evidence about the optimal revascularization strategy in patients with left main coronary artery (LMCA) disease and impaired renal function is limited. Thus, we aimed to compare the outcomes of LMCA disease revascularization (percutaneous coronary intervention [PCI] vs. coronary artery bypass grafting [CABG]) in patients with and without impaired renal function. Methods: This retrospective cohort study included 2,138 patients recruited from 14 centers between 2015 and 2,019. We compared patients with impaired renal function who had PCI (n= 316) to those who had CABG (n = 121) and compared patients with normal renal function who had PCI (n = 906) to those who had CABG (n = 795). The study outcomes were in-hospital and follow-up major adverse cardiovascular and cerebrovascular events (MACCE). Results: Multivariable logistic regression analysis showed that the risk of in-hospital MACCE was significantly higher in CABG compared to PCI in patients with impaired renal function (odds ratio [OR]: 8.13 [95% CI: 4.19–15.76], p < 0.001) and normal renal function (OR: 2.59 [95% CI: 1.79–3.73]; p < 0.001). There were no differences in follow-up MACCE between CABG and PCI in patients with impaired renal function (HR: 1.14 [95% CI: 0.71–1.81], p = 0.585) and normal renal function (HR: 1.12 [0.90–1.39], p = 0.312). Conclusions: PCI could have an advantage over CABG in revascularization of LMCA disease in patients with impaired renal function regarding in-hospital MACCE. The follow-up MACCE was comparable between PCI and CABG in patients with impaired and normal renal function