Synthesis and biological evaluation of sialylmimetics as rotavirus inhibitors

Rotaviruses cause severe gastroenteritis in infants and are estimated to be responsible for over 600 000 deaths annually, primarily in developing countries. The development of potential inhibitors of this virus is therefore of great interest, particularly since the safety and efficacy of rotaviral vaccines has recently been questioned. This study describes the synthesis of a variety of compounds that can be considered as mimetics of N-acetylneuraminic acid thioglycosides and the subsequent in vitro biological evaluation of these sialylmimetics as inhibitors of rotaviral infection. Our results show that readily accessible carbohydrate-based compounds have the potential to act as inhibitors of rotaviral replication in vitro, presumably through inhibition of the rotaviral adhesion process.     

Assessment of the stroke-specific quality-of-life scale in KFHU,Khobar: A prospective cross-sectional study

Objectives:To assess the overall and domain-specific quality of life (QOL) in post-stroke patients using the stroke-specific quality of life (SS-QOL) scale and to identify variables that may affect the QOL after stroke.Methods:A prospective cross-sectional study, included 80 stroke patients, was conducted in the Neurology department at King Fahad Hospital of the University (KFHU), Khobar, Saudi Arabia, from December 2019 to February 2020. Stroke patients were interviewed using the Arabic version of the SS-QOL questionnaire and modified Rankin scale (mRS).Results:The overall quality of life in the surveyed participants was at the level of 3.72 points, which is above the average recognized in the middle of the scale that ranges from 1 to 5. The overall quality of life was not significantly correlated with sex, age, type of stroke, recurrence of stroke, and time since stroke (p>0.05). Hypertension and atrial fibrillation were the only comorbidities that were determined to be significantly associated with the overall quality of life at the level of (3.53), and (2.97) respectively (p<0.05). There was a statistically significant correlation between the mRS score and the overall quality of life (p<0.05).Conclusion:Performing a comprehensive assessment of the overall QOL in post-stroke patients will result in better health outcomes, particularly in terms of quality of functioning in psycho-social aspects.

Stroke is a disease that is known by its focal neurologic deficit.¹ It occurs when there is a disruption of the blood flow to the brain either by a clot, causing ischemic stroke or by a rupture of the blood vessels, causing hemorrhagic stroke.² It is experienced by approximately 15 million people worldwide and it is considered to be the second cause of mortality. Among these people, 5 million die and another 5 million live with lifelong disability, which creates a major economic and social burden. The number of cases of stroke in Saudi Arabia is increasing and becoming a debilitating reason for death and disability. Research on the incidence and prevalence of stroke in Saudi Arabia is still lacking. There is only one study conducted in Saudi Arabia in the last 10 years, which states that stroke’s prevalence is 29 per 100,000 each year.^2,3Stroke affects the quality of life (QOL) of patients owing to its related cognitive, physical and functional consequences, such as restrictions in mobility, language impairment and depression.^4,5 Although stroke causes extensive functional impairment, the objective methods of evaluation usually fail to assess the subjective impact of these impairments.⁶ The Health-related QOL (HR-QOL) is a term used to evaluate a person’s wellbeing including physical, psychological, functional, and social aspects.⁷ There are various instruments to assess HR-QOL, most of which are based on subjective self-administered questionnaires. Among these instruments is the stroke-specific QOL (SS-QOL) scale, which was established as a multi-dimensional tool for various effects in post-stroke patients.⁸Up to date, there have been 4 studies conducted in Saudi Arabia on the assessment of QOL in post-stroke patients.^9-12 Two of them were conducted in Jeddah; in these studies, the researchers studied QOL among stroke patients using the HR-QOL scale.^9,10 The other 2 studies were conducted in Al Khobar; the first study studied the psychometric properties of an Arabic version of the fatigue severity scale (FSS),¹¹ while the second study measured QOL using SS-QOL and compared its variables such as socio-demographic factors, type of stroke, time passed since the stroke, affected body side, and the living status of stroke patients.¹² However, QOL in post-stroke patients evaluated using SS-QOL has not been studied yet in terms of other variables such as recurrence of stroke, degree of physical disability, comorbidities, and risk factors. Therefore, the aim of this study is to assess the overall and domain-specific QOL in post-stroke patients using the SS-QOL scale and to identify variables that may affect the quality of life after stroke. The quality of life in post-stroke patients has a statistically significant relationship with the type of stroke, duration since the last event, patient demographics, comorbidities, and degree of physical disability.     

Alginate and alginate composites for biomedical applications

Alginate is an edible heteropolysaccharide that abundantly available in the brown seaweed and the capsule of bacteria such as Azotobacter sp. and Pseudomonas sp. Owing to alginate gel forming capability, it is widely used in food, textile and paper industries; and to a lesser extent in biomedical applications as biomaterial to promote wound healing and tissue regeneration. This is evident from the rising use of alginate-based dressing for heavily exuding wound and their mass availability in the market nowadays. However, alginate also has limitation. When in contact with physiological environment, alginate could gelate into softer structure, consequently limits its potential in the soft tissue regeneration and becomes inappropriate for the usage related to load bearing body parts. To cater this problem, wide range of materials have been added to alginate structure, producing sturdy composite materials. For instance, the incorporation of adhesive peptide and natural polymer or synthetic polymer to alginate moieties creates an improved composite material, which not only possesses better mechanical properties compared to native alginate, but also grants additional healing capability and promote better tissue regeneration. In addition, drug release kinetic and cell viability can be further improved when alginate composite is used as encapsulating agent. In this review, preparation of alginate and alginate composite in various forms (fibre, bead, hydrogel, and 3D-printed matrices) used for biomedical application is described first, followed by the discussion of latest trend related to alginate composite utilization in wound dressing, drug delivery, and tissue engineering applications.     

Identification of DEK as a potential therapeutic target for neuroendocrine prostate cancer

Neuroendocrine prostate cancer (NEPC) is an aggressive subtype of prostate cancer which does not respond to hormone therapy. Research of NEPC has been hampered by a lack of clinically relevant in vivo models. Recently, we developed a first-in-field patient tissue-derived xenograft model of complete neuroendocrine transdifferentiation of prostate adenocarcinoma. By comparing gene expression profiles of a transplantable adenocarcinoma line (LTL331) and its NEPC subline (LTL331R), we identified DEK as a potential biomarker and therapeutic target for NEPC. In the present study, elevated DEK protein expression was observed in all NEPC xenograft models and clinical NEPC cases, as opposed to their benign counterparts (0%), hormonal naïve prostate cancer (2.45%) and castration-resistant prostate cancer (29.55%). Elevated DEK expression was found to be an independent clinical risk factor, associated with shorter disease-free survival of hormonal naïve prostate cancer patients. DEK silencing in PC-3 cells led to a marked reduction in cell proliferation, cell migration and invasion. The results suggest that DEK plays an important role in the progression of prostate cancer, especially to NEPC, and provides a potential biomarker to aid risk stratification of prostate cancer and a novel target for therapy of NEPC.     

Tumor protein 53-induced nuclear protein 1 expression is repressed by miR-155, and its restoration inhibits pancreatic tumor development

Pancreatic cancer is a disease with an extremely poor prognosis. Tumor protein 53-induced nuclear protein 1 (TP53INP1) is a proapoptotic stress-induced p53 target gene. In this article, we show by immunohistochemical analysis that TP53INP1 expression is dramatically reduced in pancreatic ductal adenocarcinoma (PDAC) and this decrease occurs early during pancreatic cancer development. TP53INP1 reexpression in the pancreatic cancer-derived cell line MiaPaCa2 strongly reduced its capacity to form s.c., i.p., and intrapancreatic tumors in nude mice. This anti-tumoral capacity is, at least in part, due to the induction of caspase 3-mediated apoptosis. In addition, TP53INP1(-/-) mouse embryonic fibroblasts (MEFs) transformed with a retrovirus expressing E1A/ras(V12) oncoproteins developed bigger tumors than TP53INP1(+/+) transformed MEFs or TP53INP1(-/-) transformed MEFs with restored TP53INP1 expression. Finally, TP53INP1 expression is repressed by the oncogenic micro RNA miR-155, which is overexpressed in PDAC cells. TP53INP1 is a previously unknown miR-155 target presenting anti-tumoral activity.     

Garlock's operation in cancer of the esophagus

Experience in 88 Garlock-type operations carried out in carcinoma of the esophagus allows a certain opinion to be formed on the advantages and shortcomings of this surgical intervention. In esophageal carcinoma with its proximal boundary within the range of the retropericardial segment of the esophagus, a left abdominothoracic approach (Garlock's operation) is adequate in resection of the esophagus in conformity with the oncological principles and allows the formation of the esophagogastric anastomosis at the level of the arch of the aorta without particular technical difficulties. Reduction of the time needed for the operation, determination of the resectability of the esophageal tumor before mobilization of the stomach are obvious advantages of the abdominothoracic approach.     

Increased insulin-like growth factor I receptor expression and signaling are components of androgen-independent progression in a lineage-derived prostate cancer progression model

Apoptosis and inhibition of mitosis are primary mechanisms mediating androgen ablation therapy-induced regression of prostate cancer (PCa). However, PCa readily becomes androgen independent, leading to fatal disease. Up-regulated growth and survival signaling is implicated in development of resistance to androgen ablation therapy. We are testing the hypothesis that insulin-like growth factor (IGF) responsiveness is required for androgen-independent (AI) progression. Using the LNCaP human PCa progression model, we have determined that IGF-I-mediated protection from apoptotic stress and enhanced mitotic activity is androgen dependent in LNCaP cells but is androgen independent in lineage-derived C4-2 cells. Both cell lines exhibit androgen-responsive patterns of IGF-I receptor (IGF-IR) expression, activation, and signaling to insulin receptor substrate-2 and AKT. However, C4-2 cells express higher levels of IGF-IR mRNA and protein and exhibit enhanced IGF-I-mediated phosphorylation and downstream signaling under androgen-deprived conditions. In comparisons of naive and AI metastatic human PCa specimens, we have confirmed that IGF-IR levels are elevated in advanced disease. Together with our LNCaP/C4-2 AI progression model data, these results indicate that increased IGF-IR expression is associated with AI antiapoptotic and promitotic IGF signaling in PCa disease progression.     

Corneal topographic changes in premenopausal and postmenopausal women

Background  

To asses the effect of menopause on the corneal curvature changes using corneal computerized videokeratography (CVK) in premenopausal and postmenopausal healthy women.