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We report a case of infant botulism admitted to the Children’s Hospital “Giovanni XXIII”, Bari, Italy. After a week of constipation, hypotonia, lethargy, ptosis, reduction of suction and cry, a 2-month-old infant male, the first kid of unrelated parents was taken to the closest hospital, after being born normotrophic, at term, without a prenatal, perinatal, or postnatal medical history or neurodevelopmental delay. The patient was referred to the pediatric center for an undiagnosed progressive worsening of awareness and he was intubated for bradypnea and desaturation. The toxicologic panel, cerebrospinal fluid exam, radiological imaging, and laboratory results were negative. Only after neurological instrumental analysis, we found a normal EEG but a positive EMG that is associated with the history of raw honey intake (revealed only later by his mother). We were allowed to define the hypothesis of infant botulism earlier than the confirmation of the standard mouse bioassay. So, as a result, Botulism Immune Globulin-Intravenous IgG over 3 hours in a single recommended dose of 0.1 mL/kg/min was injected. The infant showed a gradual improvement and after 10 days he was extubated. The Preterm Oral Feeding Readiness Scale showed an improvement through the rehabilitation program with physiotherapy and parents’ stimuli. After one month he was discharged. Frequently, infant botulism is not the first hypothesis but it is the result of a strict differentiation from other diseases characterized by hypotonia such as sepsis, infectious, genetic, autoimmune, or metabolic diseases through the use of history, and laboratory tests and radiological imaging. At first, toxin detection can be useful for early diagnosis. In the later stages, the neurological instrumental support can help the clinician to elucidate the cause of muscle weakness. In fact, the EEG and the EMG could be positive when toxins are unlikely to be detectable in the serum and other data are negative. A minimum of one arm and one leg should be examined for motor and sensory nerve conduction velocity along with two distal muscles for 2-Hz nerve stimulation and a needle EMG with an adequate sample. We suggest that the neurological instrumental support can help the clinician to elucidate the cause of muscle weakness, in particular in the later stages. Honey shouldn’t be provided to infants under one-year-old children because the majority of instances still have a good history of exposure to it.

BACKGROUND INFORMATION: Up-regulated Gene clone 7 (URG7) is an ER resident protein, whose expression is upregulated in the presence of hepatitis B virus X antigen (HBxAg) during HBV infection. In virus-infected hepatocytes, URG7 shows an anti-apoptotic activity due to the PI3K/AKT signaling activation, does not seem to have tumorigenic properties, but it appears to promote the development and progression of fibrosis. However, the molecular mechanisms underlying URG7 activity remain largely unknown. RESULTS: To shed light on URG7 activity, we first analyzed its interactome in HepG2 transfected cells: this analysis suggests that URG7 could have a role in affecting protein synthesis, folding and promoting proteins degradation. Moreover, keeping into account its subcellular localization in the ER and that several viral infections give rise to ER stress, a panel of experiments was performed to evaluate a putative role of URG7 in ER stress. Our main results demonstrate that in ER stressed cells URG7 is able to modulate the expression of Unfolded Protein Response (UPR) markers toward survival outcomes, upregulating GRP78 protein and downregulating the pro-apoptotic protein CHOP. Furthermore, URG7 reduces the ER stress by decreasing the amount of unfolded proteins, by increasing both the total protein ubiquitination and the AKT activation and reducing caspase 3 activation. CONCLUSIONS: All together these data suggest that URG7 plays a pivotal role as a reliever of ER stress-induced apoptosis. SIGNIFICANCE: This is the first characterization of URG7 activity under ER stress conditions. The results presented here will help to hypothesize new strategies to counteract the antiapoptotic activity of URG7 in the context of the viral infection. This article is protected by copyright. All rights reserved.

Trabajo presentado al 17th European Meeting on Supercritical Fluids (EMSF) y al 7th European Meeting on High Pressure Technology, celebrados en Ciudad Real (España) del 8 al 11 de abril de 2019., This work was supported by the project AGL2017-89417-R (MINECO, Spain). G.A.-R. would like to acknowledge the Ministry of Economy and Competitiveness for a Juan de la Cierva-Formación postdoctoral grant. Z.S.M. would like to acknowledge the University of Nariño (Colombia) for financial support

Resumen del trabajo presentado a las III Jornadas Científicas CIAL Fórum, celebradas del 22 al 23 de noviembre de 2018 en el Instituto de Investigación en Ciencias de la Alimentación (CIAL)., Nowadays, valorization of biological wastes from agricultural activity and processing industry has become a challenge. The olive oil industry has a great economic, commercial and industrial relevance in Spain, being olive leaves one of the main by-products and a promising source of bioactive compounds. Several authors have reported the presence and biological activity of different terpenoids in olive leaves; among them, the most abundant triterpenoids in olive leaves (derived from oleanane and ursane) have been described as possessing pharmacological activity against neurodegenerative disorders. Alzheimer’s disease (AD) is the most common neurodegenerative disorder, accounting for approximately two thirds of all cases of dementia and affecting up to 20% of individuals older than 80 years. At present, there is not effective treatment for this disease. Since AD is a multifactorial neurological pathology, a current strategy is to target different factors, being one of them related to the high activity of the enzyme acetylcholinesterase (AChE) in the brain. This work was oriented towards the valorization of olive leaf residues through the systematic and selective supercritical fluid extraction (SFE) of different families of bioactive terpenoids with potential anticholinergic (anti-AChE) activity. Thus, a sequential SFE procedure was applied for the isolation of low, medium and high molecular weight terpenoids (C10-C15, C15-C20, C20-C30), using CO2 as pure solvent and different working pressures (from 80-120 bar) at 40°C. Extracts obtained at different SFE conditions were characterized by GC-MS and its anti-AChE activity evaluated. Good anti-AChE activity was obtained for some of the terpene-rich SFE extracts from olive leaves, demonstrating the interest of this strategy to help to discover promising therapeutic approaches and natural compounds that can delay the detrimental effects of AD., This work was supported by the project AGL2017-89417-R (MINECO, Spain). G.A.-R. would like to acknowledge the Ministry of Economy and Competitiveness for a Juan de la Cierva-Formación postdoctoral grant. Z.S.M. would like to acknowledge the University of Nariño (Colombia) for financial support

BACKGROUND: Pseudoxanthoma elasticum (PXE) is characterized by progressive ectopic mineralization of elastic fibers in dermal, ocular and vascular tissues. No effective treatment exists. It is caused by inactivating mutations in the gene encoding for the ATP-binding cassette, sub-family C member 6 transporter (ABCC6), which is mainly expressed in the liver. The ABCC6 substrate (s) and the PXE pathomechanism remain unknown. Recent studies have shown that overexpression of ABCC6 in HEK293 cells results in efflux of ATP, which is rapidly converted into nucleoside monophosphates and pyrophosphate (PPi). Since the latter inhibits mineralization, it was proposed that the absence of circulating PPi in PXE patients results in the characteristic ectopic mineralization. These studies also demonstrated that the presence of ABCC6 modifies cell secretory activity and suggested that ABCC6 can change the cell phenotype. METHODS: Stable ABCC6 knockdown HepG2 clones were generated using small hairpin RNA (shRNA) technology. The intracellular glutathione and ROS levels were determined. Experiments using cell cycle analysis, real-time PCR and western blot were performed on genes involved in the senescence phenotype. RESULTS: To shed light on the physiological role of ABCC6, we focused on the phenotype of HepG2 cells that lack ABCC6 activity. Interestingly, we found that ABCC6 knockdown HepG2 cells show: 1) intracellular reductive stress; 2) cell cycle arrest in G1 phase; 3) upregulation of p21Cip p53 independent; and 4) downregulation of lamin A/C. CONCLUSIONS: These findings show that the absence of ABCC6 profoundly changes the HepG2 phenotype, suggesting that the PXE syndrome is a complex metabolic disease that is not exclusively related to the absence of pyrophosphate in the bloodstream.

The phytochemical study of Cissampelos tropaeolifolia aerial parts led to the isolation and structural characterization by spectroscopic and spectrometric methods of two morfinan-7-one alkaolid named 2 O-methylflavinantine and Fissistigine D. The following known compounds were also identified: caffeic acid, caffeic acid methyl ester, caffeic acid ethyl ester, and p-coumaric acid. The structures of isolated compounds were elucidated by 1D- and 2D-NMR Spectroscopy (1H, 13C, 13C DEPT, DQF-COSY, HSQC, HMBC, ROESY ) and confirmed by mass spectrometry studies.