Identification of a new familial case of 3q29 deletion syndrome associated with cleft lip and palate via whole-exome sequencing

Many unbalanced large copy number variants reviewed in the paper are associated with syndromic orofacial clefts, including a 1.6 Mb deletion on chromosome 3q29. The current report presents a new family with this recurrent deletion identified via whole-exome sequencing and confirmed by array comparative genomic hybridization. The proband exhibited a more severe clinical phenotype than his affected mother, comprising right-sided cleft lip/alveolus and cleft palate, advanced dental caries, heart defect, hypospadias, psychomotor, and speech delay, and an intellectual disability. Data analysis from the 3q29 registry revealed that the 3q29 deletion increases the risk of clefting by nearly 30-fold. No additional rare and pathogenic nucleotide variants were identified that could explain the clefting phenotype and observed intrafamilial phenotypic heterogeneity. These data suggest that the 3q29 deletion may be the primary risk factor for clefting, with additional genomic variants located outside the coding sequences, methylation changes, or environmental exposure serving as modifiers of this risk. Additional studies, including whole-genome sequencing or methylation analyses, should be performed to identify genetic factors underlying the phenotypic variation associated with the recurrent 3q29 deletion.     

New Organic-Inorganic Hybrid Compounds Based on Sodium Peroxidomolybdates (VI) and Derivatives of Pyridine Acids: Structure Determination and Catalytic Properties

Two organic-inorganic hybrids based on sodium peroxidomolybdates(VI) and 3,5-dicarboxylic pyridine acid (Na-35dcpa) or N-oxide isonicotinic acid (Na-isoO) have been synthesized and characterized. All compounds contain inorganic parts: a pentagonal bipyramid with molybdenum center, and an organic part containing 3,5-dicarboxylic pyridine acid or N-oxide isonicotinic acid moieties. The type of organic part used in the synthesis influences the crystal structure of obtained compounds. This aspect can be interesting for crystal engineering. Crystal structures were determined using powder X-ray diffraction or single crystal diffraction for compounds Na-35dcpa and Na-isoO, respectively. Elemental analysis was used to check the purity of the obtained compounds, while X-ray Powder Diffraction (XRPD) vs. temp. was applied to verify their stability. Moreover, all the compounds were examined by Infrared (IR) spectroscopy. Their catalytic activity was tested in the Baeyer–Villiger (BV) oxidation of cyclohexanone to ε-caprolactone in the oxygen-aldehyde system. The highest catalytic activity in the BV oxidation was observed for Na-35dcpa. The compounds were also tested for biological activity on human normal cells (fibroblasts) and colon cancer cell lines (HT-29, LoVo, SW 620, HCT 116). All compounds were cytotoxic against tumor cells with metastatic characteristics, which makes them interesting and promising candidates for further investigations of specific anticancer mechanisms.     

Assessment of the Effect of Selenium Supplementation on Production of Selected Cytokines in Women with Hashimoto’s Thyroiditis

The impact of selenium on the course of Hashimoto’s thyroiditis (HT) was mainly assessed by monitoring the titer of antithyroid autoantibodies in most of the studies conducted hitherto. On the other hand, the imbalance in activity of T cells such as Th1, Th2, Th17, and Treg may be relevant in the pathogenesis of this disease. Hence, the assessment of changes in the secretion of cytokines by these cells during selenium supplementation in patients with HT seems to be an important issue and was the main goal of this study. A further aim was to search for correlations among these cytokines, as well as markers of thyroid function, selenium/iodine status in the body, and other biochemical parameters. The group of 29 women with newly diagnosed Hashimoto’s thyroiditis was supplemented with selenium in a dose of 100 µg/day for 6 months. Immunological parameters: interferon γ, tumor necrosis factor α, chemokine CXCL10, interleukin 4, interleukin 1β, interleukin 17, transforming growth factor β, and C-reactive protein, as well as selenium status parameters were determined in serum twice, i.e., before and after supplementation. Selenium supplementation was associated with a change in the production of two cytokines: interferon γ and interleukin 1β, for which a decrease and an increase in concentration were observed, respectively. The partial least squares (PLS) model revealed the presence of many relevant correlations among analyzed parameters. The stage of HT development, degree of thyroid dysfunction, and selenium supplementation of diet are interdependent factors which shape the profile of some cytokines secreted by cells participating in the autoimmunity process.     

Vibrational spectroscopy – are we close to finding a solution for early pancreatic cancer diagnosis?

Pancreatic cancer (PC) is an aggressive and lethal neoplasm, ranking seventh in the world for cancer deaths, with an overall 5-year survival rate of below 10%. The knowledge about PC pathogenesis is rapidly expanding. New aspects of tumor biology, including its molecular and morphological heterogeneity, have been reported to explain the complicated “cross-talk” that occurs between the cancer cells and the tumor stroma or the nature of pancreatic ductal adenocarcinoma-associated neural remodeling. Nevertheless, currently, there are no specific and sensitive diagnosis options for PC. Vibrational spectroscopy (VS) shows a promising role in the development of early diagnosis technology. In this review, we summarize recent reports about improvements in spectroscopic methodologies, briefly explain and highlight the drawbacks of each of them, and discuss available solutions. The important aspects of spectroscopic data evaluation with multivariate analysis and a convolutional neural network methodology are depicted. We conclude by presenting a study design for systemic verification of the VS-based methods in the diagnosis of PC.     

Mucinous cystadenocarcinomas of the pancreas

BACKGROUND/AIMS: The purpose of this study was to evaluate the clinicopathologic characteristics, diagnosis and treatment of mucinous cystadenocarcinomas (MCACs) of the pancreas. METHODOLOGY: This is a retrospective review of 6 patients who underwent curative resection for MCACs of the pancreas in the Department of General Endocrine and Transplantation Surgery, Medical University of Gdańsk from 1994-2004. Clinical presentation, radiological evaluation and surgical procedures were analyzed. RESULTS: There were 4 women and 2 men. Median age was 59 years. Patients complained of abdominal pain, nausea, vomiting and weigh loss, 2 of them had jaundice and 1 gastrointestinal (GI) bleeding. Ultrasonography and computed tomography showed cystic lesions. Solid component was found in 3 cases. Three endoscopic retrograde cholangiopancreatographys (ERCPs) were unhelpful in differentiating between malignant tumor and benign lesion. All patients underwent resection. In 3 cases Whipple resection, in 1 case Traverso - Longmire resection and in 2 cases distal pancreatectomy was performed. Histopathologically, all tumors were mucinous cystadenocarcinomas. CONCLUSIONS: Diagnostic accuracy for cystic pancreatic neoplasm is still limited. Surgical resection is recommended in all cystic tumors that are not clearly defined.     

Kynurenic acid and zaprinast diminished CXCL17-evoked pain-related behaviour and enhanced morphine analgesia in a mouse neuropathic pain model

Background

The G protein-coupled receptor 35 (GPR35), is considered important for nociceptive transmission, as suggested by accumulating evidence. This receptor was discovered in 1998; however, a lack of pharmacological tools prevented a complete understanding of its function and how to exploit it therapeutically. We studied the influence of CXCL17, kynurenic acid and zaprinast on nociceptive transmission in naïve and neuropathic mice. Additionally, we investigated the influence of kynurenic acid and zaprinast on morphine effectiveness in neuropathic pain.

Influence of the Selected Physical Modifier on the Dynamical Behavior of the Polymer Composites Used in the Aviation Industry

In this research, an analysis of polymer composite with the matrix of L285-cured hardener H286 and six reinforcement layers of carbon fabric GG 280 T was provided. It involved a comparison of the dynamical behavior responses for three cases of composite structures in the context of the presence of the mass share modifier. The samples with the addition of a physical modifier with varying mass percentages were investigated by being subjected to dynamic tests with specific parameters, i.e., constant excitation amplitude and vibration frequency in the vicinity of the base resonance zone. The analysis allowed for indicating the relationship between the composition of the prepared composites and their dynamic response via stiffness characteristics. In addition, the investigation resulted in determining the range of harmful dynamical operating conditions, which may contribute to damage to the composite structures.     

Influence of Reaction Parameters on the Gelation of Silanised Linseed Oil

The subject of this work was to characterize the catalytic course of the linseed oil silylation reaction with vinyltrimethoxysilane (VTMOS), carried out under elevated pressure and temperature conditions, and an explanation of the reasons for rapid gelation of the reaction product. To explain and describe the process, analytical methods were used, i.e., ¹H and ¹³C NMR (nuclear magnetic resonance), GC-FID (gas chromatography coupled with flame ionisation detection), and GPC (gel permeation chromatography). Reaction products were monitored after 3, 6 and 12 h. The molar mass of the VTMOS-modified oil in only 3 h was comparable with the molar mass of the product obtained by conventional polymerisation. An increase in the reaction time resulted in further transformations resulting from the hydrolysis and condensation reactions taking place. In contrast to reactivity of soybean oil, the silanisation of linseed oil occurred much faster and without the need for cross-linking catalysts. The reason for the high reactivity of linseed oil to VTMOS and rapid gelation of the resulting product was primarily the amount of double bonds present in linseed oil and their high availability, in particular the double bond in the acid linolenic acid located at the C16 carbon.