Targeting the unfolded protein response,XBP1, and the NLRP3 inflammasome in fibrosis and cancer

Increasing health care costs in the US are due in a large part to the increasing prevalence of chronic diseases in an aging population. Current therapeutic strategies for treating chronic diseases alleviate symptoms allowing patients to live longer with these diseases, but they do little, however, to alter the underlying disease course. Recent advances in molecular biology are revealing new drug targets that may significantly alter the course of these diseases and, as a result, offer economic relief from burgeoning health care costs. Endoplasmic reticulum (ER) stress has been implicated as an underlying pathology in many chronic diseases, and, therefore, the development of therapies designed to ameliorate ER stress may yield novel, effective treatment strategies. Herein, we report that X-box binding protein 1 (XBP1) may be one of the earliest proteins engaged in response to ER stress. We show that a new signaling peptide derived from the ER-embedded transient receptor potential calcium channel protein 1 (TRPC1) engages XBP1 upstream of NLRP3 inflammasome-mediated maturation and secretion of IL-1β/IL-18. Moreover, we show that a synthetic homolog of this signaling peptide (Naclynamide™) administered intravenously twice weekly over a 4-week treatment course induced suppuration and evoked partial or complete resolution of lesions associated with a fibrotic granuloma, a lymphosarcoma, and a colo-rectal carcinoma in canine patients. The mode of action for Naclynamide™ as a first-in-class anti-cancer drug candidate is discussed.     

Coelioscopy in gynecologic emergencies. About 239 cases

OBJECTIVE: The goal of this study was to determine the efficiency of lapaorscopy as method of diagnosis and treatment of gynecologic emergencie. METHODS: A laparoscopy was performed in two hundred and thirty-nine patients who presented in emergency with signs like acute pelvic pain, uterine bleeding or fever. Diagnoses and treatments are presented in a retrospective study. RESULTS: The median patient age was 30.4 years and median parity was 14 sonography was performed in all patients and bHCG rate was positive in 101 patients. The most suspected diagnosis was ectopic pregnancy (42%) followed by complicated cysts (30%) and ligh genital infections (27%) At laparoscopy 92 cases of ectopic pregnancy, 66 cysts complicated or not and 47 high genital infections were found. Laparoscopy didn't show any evident pathology in 6.6% of patients. We didn't note any anesthesial or surgical complication. CONCLUSION: Laparoscopy for gynecologic emergencies can be satisfactorily performed in the majority of patients, regardingly to low fiability of usual diagnostic methods. II is useful for diagnosis and treatment. The rate of it's overall complications is relatively low.     

Scalable synthesis and antibacterial evaluation of 2‐(3‐(N‐(substituted phenyl)sulfamoyl)ureido)benzothiazoles

A new series of 2‐(3‐(N‐(substituted phenyl)sulfamoyl)ureido)benzothiazoles was synthesized via a one‐pot efficient and scalable method, involving the condensation of 2‐aminobenzothiazoles derivatives, substituted anilines, and chlorosulfonyl isocyanate. The products were obtained in good yield with a simple workup, and their structures were confirmed from their spectral analyses. The synthesized compounds were further screened for their antibacterial activity against Gram‐positive and Gram‐negative pathogenic strains. The molecules show promising activity in the MIC value range of 2–0.25 µg/ml against selected bacterial strains, especially against nonfermentative carbapenem‐resistant bacteria (Pseudo VIM‐2 and Acinetobacter baumanni).     

Soaking and cooking modify the alpha-galacto-oligosaccharide and dietary fibre content in five Mediterranean legumes

The effects of soaking and cooking on soluble sugars, alpha-galacto-oligosaccharides (α-GOS) and soluble dietary fibres (SDF) and insoluble dietary fibres (IDF) were assessed in five legumes (lentil, chickpea, fenugreek, faba bean and Egyptian faba bean). In raw seeds, total α-GOS content ranged from 2500?mg/100?g (chickpea) to over 4000?mg/100?g (fenugreek). Stachyose was predominant in fenugreek, lentil and chickpea, whereas verbascose was the main α-GOS in faba bean and Egyptian faba bean. IDF represented 69–87% of the total dietary fibres in all studied legumes, while SDF content varied noticeably. During soaking, total α-GOS content decreased between 10% (lentil and faba bean) and 40% (chickpea). In fenugreek, soaking reduced IDF and increased SDF concentration, possibly due to partial IDF solubilisation from the cell wall. Cooking further decreased α-GOS and increased total dietary fibre content. The different behaviours of these five legumes during processing illustrate the high biodiversity within legume species.     

Ceratomyxa gouletti n. sp. (Myxosporea: Ceratomyxidae), a parasite of the red scorpionfish Scorpaena scrofa (L.) from Tunisian waters

Parasitology Research - Ceratomyxa gouletti n. sp. is a new parasite described from the gallbladder of the red scorpionfish Scorpaena scrofa (Scorpaeniformes: Scorpaenidae) collected from La...     

Neurotherapeutic applications of nanoparticles in Alzheimer's disease

A rapid increase in incidence of neurodegenerative disorders has been observed with the aging of the population. Alzheimer's disease (AD) is the most common neurodegenerative disorder among the elderly. It is characterized by memory dysfunction, loss of lexical access, spatial and temporal disorientation and impairment of judgement clinically. Unfortunately, clinical development of drugs for the symptomatic and disease-modifying treatment of AD has resulted in both promise and disappointment. Indeed, a large number of drugs with differing targets and mechanisms of action were investigated with only a few of them being clinically available. The targeted drug delivery to the central nervous system (CNS), for the diagnosis and treatment of neurodegenerative disorders such as AD, is restricted due to the limitations posed by the blood-brain barrier (BBB) as well as due to opsonization by plasma proteins in the systemic circulation and peripheral side-effects. Over the last decade, nanoparticle-mediated drug delivery represents one promising strategy to successfully increase the CNS penetration of several therapeutic moieties. Different nanocarriers are being investigated to treat and diagnose AD by delivering at a constant rate a host of therapeutics over times extending up to days, weeks or even months. This review provides a concise incursion on the current pharmacotherapies for AD besides reviewing and discussing the literature on the different drug molecules that have been successfully encapsulated in nanoparticles (NPs). Some of them have been shown to cross the BBB and have been tested either for diagnosis or treatment of AD. Finally, the route of NPs administration and the future prospects will be discussed.