Asprosin—A Fasting-Induced,Glucogenic, and Orexigenic Adipokine as a New Promising Player. Will It Be a New Factor in the Treatment of Obesity,Diabetes, or Infertility? A Review of the Literature

Asprosin is a recently discovered protein released during fasting conditions mainly by adipocytes from white adipose tissue. As a glucogenic peptide, it stimulates the release of glucose from hepatic cells by binding to the OLFR734 receptor and leading to the activation of the G protein-cAMP-PKA pathway. As it crosses the blood–brain barrier, it also acts as an orexigenic peptide that stimulates food intake through activation of AgRP neurons in the hypothalamus; thus, asprosin participates in maintaining the body’s energy homeostasis. Moreover, studies have shown that asprosin levels are pathologically elevated in obesity and related diseases. However, the administration of anti-asprosin antibodies can both normalize its concentration and reduce food intake in obese mice, which makes it an interesting factor to combat obesity and related diseases. Current research also draws attention to the relationship between asprosin and fertility, especially in men. Asprosin improves age- and obesity-related decrease in fertility potential by improving sperm motility. It should also be mentioned that plasma asprosin levels can be differentially modulated by physical activity; intense anaerobic exercise increases asprosin level, while aerobic exercise decreases it. However, further research is necessary to confirm the exact mechanisms of asprosin activity and its potential as a therapeutic target.     

Potential Immunomodulatory Effects from Consumption of Nutrients in Whole Foods and Supplements on the Frequency and Course of Infection: Preliminary Results

A diet rich in nutrients should be implemented in order to boost the immune system and prevent infections. To investigate which nutrients are commonly consumed, an anonymous survey was given to 120 individuals and their responses were collected. The respondents answered questions relating to their health status, and their consumption of nutrients and supplements that produce immunomodulating effects. The participants were also asked about any prior viral, bacterial or fungal infections experienced, and in particular, infection frequency, course, and duration. The data collected were subjected to a statistical analyses to assess the relationship between the reported frequency of infections and nutrients consumed including vitamins D3, A, C, E, selenium, zinc, iron, β-carotene, omega-3 fatty acids as well as live active probiotic bacteria. The findings show that vitamin and mineral supplementation did not positively affect the duration, frequency, or course of infections in the surveyed sample. An exception was vitamin D3 supplementation that was correlated to sporadic incidence of viral infections. Conversely, immunity was positively affected by consumption of natural nutrients contained in whole food (vitamin C, iron, selenium, omega-3 fatty acids), evidenced by lower incidences and milder courses of infection.     

Milk and Dairy Products: Good or Bad for Human Bone? Practical Dietary Recommendations for the Prevention and Management of Osteoporosis

Osteoporosis affects women twice as often as men. Additionally, it is estimated that 0.3 million and 1.7 million people have hip fractures in the USA and Europe, respectively. Having a proper peak bone mass and keeping it as long as possible is especially important for osteoporosis prevention. One of the most important calcium sources is milk and dairy products. Breast milk is the best infant food, but milk should not be avoided later in life to prevent losing bone mass. On the other hand, more and more people limit their milk consumption and consume other dairy or non-dairy products. For example, they are usually replaced with plant beverages, which should be consumed carefully in several age groups. Additionally, an important element of milk and dairy products, as well as plant beverages, are probiotics and prebiotics, which may modulate bone turnover. Dietary recommendations focused on milk, and dairy products are an important element for the prevention of osteoporosis.     

Histamine Intolerance in Children: A Narrative Review

Histamine intolerance is defined as a disequilibrium of accumulated histamine and the capacity for histamine degradation. This clinical term addresses a non-immunologically mediated pathology when histamine ingested with food is not particularly high, however its degradation is decreased. This paper aims to provide a narrative review on etiopathology, epidemiology, possible diagnostic algorithms and diagnostic challenges of histamine intolerance in children. The clinical picture of histamine intolerance in children is similar to that observed in adults apart from male predominance found in paediatric patients. Both in children and adults, a histamine-reduced diet is typically the treatment of choice. Diamine oxidase supplementation offers another treatment option. There is no symptom or test pathognomonic for histamine intolerance. Nevertheless, manifestations of chronic gastrointestinal symptoms, measurements of diamine oxidase deficits, positive results of histamine provocation tests and improvement in symptoms with histamine-reduced diet considerably increase the probability of histamine intolerance diagnosis. These factors have been included in the proposed diagnostic algorithm for histamine intolerance. In children histamine intolerance most likely co-occurs with allergies and bowel diseases, which creates an additional diagnostic challenge. As the evidence for children is poor further research is needed the determine epidemiology, validate diagnostic algorithms and establish possible treatment options regarding histamine intolerance.     

Methylation and Expression of FTO and PLAG1 Genes in Childhood Obesity: Insight into Anthropometric Parameters and Glucose–Lipid Metabolism

The occurrence of childhood obesity is influenced by both genetic and epigenetic factors. FTO (FTO alpha-ketoglutarate dependent dioxygenase) is a gene of well-established connection with adiposity, while a protooncogene PLAG1 (PLAG1 zinc finger) has been only recently linked to this condition. We performed a cross-sectional study on a cohort of 16 obese (aged 6.6–17.7) and 10 healthy (aged 11.4–16.9) children. The aim was to evaluate the relationship between methylation and expression of the aforementioned genes and the presence of obesity as well as alterations in anthropometric measurements (including waist circumference (WC), body fat (BF_kg) and body fat percent (BF_%)), metabolic parameters (lipid profile, blood glucose and insulin levels, presence of insulin resistance) and blood pressure. Expression and methylation were measured in peripheral blood mononuclear cells using a microarray technique and a method based on restriction enzymes, respectively. Multiple regression models were constructed to adjust for the possible influence of age and sex on the investigated associations. We showed significantly increased expression of the FTO gene in obese children and in patients with documented insulin resistance. Higher FTO expression was also associated with an increase in WC, BF_kg, and BF_% as well as higher fasting concentration of free fatty acids (FFA). FTO methylation correlated positively with WC and BF_kg. Increase in PLAG1 expression was associated with higher BF%. Our results indicate that the FTO gene is likely to play an important role in the development of childhood adiposity together with coexisting impairment of glucose-lipid metabolism.     

Synthesis, and antiprotozoal and antibacterial activities of S-substituted 4,6-dibromo- and 4,6-dichloro-2-mercaptobenzimidazoles.

The synthesis and some germicidal activities in vitro of two congener series of S-substituted 4,6-dihalogeno-2-mercapto-1H-benzimidazoles are reported. There was no substantial difference between antibacterial activities of corresponding 4,6-dichloro- and 4,6-dibromo-derivatives. The present results confirm lower susceptibility to substituted benzimidazoles of Gram-negative compared to Gram-positive bacteria. Minimum inhibitory concentrations (MICs) of a majority of the novel derivatives ranged between 25 and 100microg/ml for Gram-positive bacteria. The most active compounds (MICs for Gram-positive bacteria: 0.78-50microg/ml) were 4,6-dichloro-2-(4-nitrobenzylthio)-1H-benzimidazole and 4,6-dibromo-2-(4-nitrobenzylthio)-1H-benzimidazole that were 4-32 times more potent than nitrofurantoin against all Gram-positive bacteria utilized but Escherichia faecalis, against which they were, respectively, 2 and 4 times less potent than nitrofurantoin. Among Gram-negative bacteria used, Stenotrophomonas maltophilia and Bordetella bronchiseptica were most sensitive (as evidenced by a number of MICs 400microg/ml). All the new compounds were at least several times more active against Giardia intestinalis (IC(50): 0.006-0.053microg/ml), and a half of them were at least several times more active against Trichomonas vaginalis (IC(50): 0.0015-0.182microg/ml) than metronidazole (IC(50): 0.210 and 0.037microg/ml, respectively), the drug of choice in the treatment of G. intestinalis and T. vaginalis infections.     

Clear-cell Renal Cell Carcinoma: Molecular Characterization of IMDC Risk Groups and Sarcomatoid Tumors

IntroductionRecent trials have suggested predictive biomarkers in advanced clear-cell renal cell carcinoma (accRCC): International Metastatic RCC Database Consortium (IMDC) good risk or angiogenic gene signature for sunitinib and IMDC intermediate/poor risk for ipilimumab-nivolumab and T-effector cell signature or sarcomatoid dedifferentiation for atezolizumab-bevacizumab. We hypothesized that earlier described molecular subtypes, ccrcc1 to ccrcc4, could provide similar information as a single generic biomarker and molecularly characterize the heterogeneous intermediate-risk group.Patients and MethodsPatients with accRCC treated with systemic therapies were included. We assessed associations between the 5 biomarkers and their impact on progression-free survival (PFS) and response rate (RR) on first-line sunitinib or pazopanib. The cutoff percentage of sarcomatoid dedifferentiation with optimal discriminative value was determined.ResultsIn total, 430 patients were included (163 with molecular data). The molecular ccrcc2 subtype identified tumors with higher angiogenic gene expression across IMDC risk groups: prevalence was high in IMDC good risk and low in IMDC poor risk (P < .001). Molecular subtype, IMDC, and angiogenic gene expression had comparable C-indices to predict PFS and RR (range, 60%-66%). The ccrcc2 subtype and angiogenic gene expression were positive predictors of PFS in IMDC intermediate-risk patients (P = .006; P = .04). Immune signature did not differ between IMDC groups, but was strongly correlated with molecular subtype (P = .8 and P = .0007). A cutoff value of 25% sarcomatoid differentiation discriminated tumors with distinct molecular characteristics and therapeutic sensitivity.ConclusionIn accRCC, molecular subtypes can explain differences in IMDC risk group, expression of angiogenesis and immune response genes, and sarcomatoid dedifferentiation. They can identify molecularly different patient populations within the heterogeneous IMDC intermediate group and select patients for systemic therapies.     

Prevalence of Human papillomavirus (HPV) and Epstein-Barr virus (EBV) in oral and oropharyngeal squamous cell carcinoma in south-eastern Poland

Objective

The aim of this study was to analyze the prevalence of HPV and EBV in oral and oropharyngeal squamous cell carcinoma in south-eastern Poland. The correlation between viral infection, OSCC, alcohol use, tobacco smoking, demographic data (gender, age, place of residence), anatomic location, pre-treatment staging, evidence of metastases to lymph nodes, and grading was also investigated.

Methods

The examination samples were collected from paraffin tissue blocks, from 154 patients. Viral DNA was amplified by the nested-PCR method.

Results

HPV DNA was detected in 29.2 % of the tested samples (in 27.4 % of oropharyngeal and in 30.4 % of oral cavity). The HPV type 16 was detected in 15.6 % of all samples, and in 53.3 % of HPV-positive group. In HPV-positive samples from oropharyngeal HPV 16 constitute 76.5 %, and in HPV-positive samples from oral cavity HPV 16 constitute 39.3 %. Mixed infection (more than one type of HPV) was observed in 23.5 and 60.7 %, respectively, and in 46.7 % of all HPV-positive samples, and in 12.3 % of the whole study group. EBV DNA was detected in 27.3 % of the cases and HPV-EBV co-infection in 7.8 % of samples.

Conclusions

In major patients from Southeastern region of Poland with oropharyngeal cancer HPV type 16 was detected but in oral cavity cancer other mixed infections were observed (i.e. 51, 52, 59, 66, 68, 71, 74). HPV 16 was detected more often among patients younger than 50 years of age, whereas the mixed HPV in the group aged 50–59. The pathogenesis of oral squamous cell carcinoma may be connected with EBV infection. Future studies on the mechanisms of HPV/EBV co-infection and/or superinfection and their role in oral squamous cell carcinoma are necessary.

     

Carbonate Lake Sediments in the Plastics Processing-Preliminary Polylactide Composite Case Study: Mechanical and Structural Properties

In this study, the influence of carbonate lake sediments (Polylactide/Carbonate Lake Sediments–PLA/CLS) on the mechanical and structural properties of polylactide matrix composites was investigated. Two fractions of sediments originating from 3–8 and 8–12 m were analysed for differences in particle size by distribution (Dynamic Light Scattering–DLS), phase composition (X-ray Diffraction–XRD), the presence of surface functional groups (Fourier Transform-Infrared–FT-IR), and thermal stability (Thermogravimetric Analysis–TGA). Microscopic observations of the composite fractures were also performed. The effect of the precipitate fraction on the mechanical properties of the composites before and after conditioning in the weathering chamber was verified through peel strength, flexural strength, and impact strength tests. A melt flow rate study was performed to evaluate the effect of sediment on the processing properties of the PLA/CLS composite. Hydrophobic-hydrophilic properties were also investigated, and fracture analysis was performed by optical and electron microscopy. The addition of carbon lake sediments to PLA allows for the obtention of composites resistant to environmental factors such as elevated temperature or humidity. Moreover, PLA/CLS composites show a higher flow rate and higher surface hydrophobicity in comparison with unmodified PLA.