Does Extraesophageal Reflux Support the Development of Lung Adenocarcinoma? Analysis of Pepsin in Bronchoalveolar Lavage in Non-Smoker Patients.

The significance of extraesophageal reflux as a risk factor in lung adenocarcinoma has been understudied. In this study, we investigated whether extraesophageal reflux leads to higher pepsin concentrations in bronchoalveolar lavage (BAL) in patients with lung adenocarcinoma compared to controls. Subjects were recruited from non-smoker patients (lifelong non-smokers and ex-smokers with more than 5 years of non-smoking history) who had undergone bronchoscopy due to pulmonary abnormalities on a CT scan and met the inclusion criteria.

Changes in the fatty acid profiles and health indexes of bovine colostrum during the first days of lactation and their impact on human health.

Our objective was to analyze the changes in fatty acid (FA) profiles of bovine colostrum and immature milk during the first four days of lactation and assess their potential impact on human health. Colostrum and immature milk samples were collected from Czech Fleckvieh cows during their first to third lactation and the FA profiles were analyzed using multidimensional gas chromatography with a vacuum ultraviolet detector (GC×GC-VUV). The colostrum of primiparous cows contained lower levels of medium-chain and saturated fatty acids, and higher levels of mono- and unsaturated fatty acids compared to that of multiparous cows.

Immunophenotyping of peripheral blood in NSCLC patients discriminates responders to immune checkpoint inhibitors.

Purpose: Immune checkpoint inhibitors (ICIs) dramatically changed the prognosis of patients with NSCLC. Unfortunately, a reliable predictive biomarker is still missing. Commonly used biomarkers, such as PD-L1, MSI, or TMB, are not quite accurate in predicting ICI efficacy.

Radiation-Induced Lymphopoenia and Treatment Outcome in Hereditary Breast Cancer Patients.

Many breast cancer (BC) predisposition genes encode proteins involved in DNA damage repair (DDR). Identification of germline pathogenic va-riants (PV) in DDR genes raises the question whether their presence can influence the treatment outcomes and potential radiation-induced toxicity in their carriers treated by adjuvant radiotherapy, which has not yet been answered conclusively. We retrospectively examined records of 213 BC patients treated by adjuvant radiotherapy, including 39 (18.

Mitochondrially targeted tamoxifen as anticancer therapy: case series of patients with renal cell carcinoma treated in a phase I/Ib clinical trial.

Mitochondrially targeted anticancer drugs (mitocans) that disrupt the energy-producing systems of cancer are emerging as new potential therapeutics. Mitochondrially targeted tamoxifen (MitoTam), an inhibitor of mitochondrial respiration respiratory complex I, is a first-in-class mitocan that was tested in the phase I/Ib MitoTam-01 trial of patients with metastatic cancer. MitoTam exhibited a manageable safety profile and efficacy; among 37% (14/38) of responders, the efficacy was greatest in patients with metastatic renal cell carcinoma (RCC) with a clinical benefit rate of 83% (5/6) of patients.

Microbiota as the unifying factor behind the hallmarks of cancer.

The human microbiota is a complex ecosystem that colonizes body surfaces and interacts with host organ systems, especially the immune system. Since the composition of this ecosystem depends on a variety of internal and external factors, each individual harbors a unique set of microbes. These differences in microbiota composition make individuals either more or less susceptible to various diseases, including cancer.

Mitochondrially targeted tamoxifen in patients with metastatic solid tumours: an open-label, phase I/Ib single-centre trial.

Background: Mitochondria present an emerging target for cancer treatment. We have investigated the effect of mitochondrially targeted tamoxifen (MitoTam), a first-in-class anti-cancer agent, in patients with solid metastatic tumours.

Methods: MitoTam was tested in an open-label, single-centre (Department of Oncology, General Faculty Hospital, Charles University, Czech Republic), phase I/Ib trial in metastatic patients with various malignancies and terminated oncological therapies.

Fecal microbiota transplantation - new possibility to influence the results of therapy of cancer patients.

Background: The intestinal microbio-me is essential for the function of the human body, it affects not only metabolism and digestion, but also the immune and neurobehavioral systems. The composition of the human intestinal microbio-me has been of interest to many scientific teams around the world in recent years, aided by the rapid development of molecular genetics methods. Intestinal microbio-me imbalance (so-called dysbio-sis) can help develop several pathological conditions such as autoimmune diseases or can be involved in the process of carcinogenesis.

New methodology of TMB assessment from tissue and liquid biopsy in NSCLC.

Immunotherapy has dramatically influenced and changed therapeutical approach in non-small cell lung cancer (NSCLC) in recent five years. Even though we can reach long-term response to this treatment in approximately 20% of patients with NSCLC, we are still not able to identify this cohort of patients based on predictive biomarkers. In our study we have focused on tumor mutation burden (TMB), one of the potential biomarkers which could predict effectiveness of check-point inhibitors, but has several limitations, especially in multiple approaches to TMB quantification and ununiform threshold.

Alternative and Unconventional Feeds in Dairy Diets and Their Effect on Fatty Acid Profile and Health Properties of Milk Fat.

Milk fat is an important nutritional compound in the human diet. From the health point of view, some fatty acids (FAs), particularly long-chain PUFAs such as EPA and DHA, have been at the forefront of interest due to their antibacterial, antiviral, anti-inflammatory, and anti-tumor properties, which play a positive role in the prevention of cardiovascular diseases (CVD), as well as linoleic and γ-linolenic acids, which play an important role in CVD treatment as essential components of phospholipids in the mitochondria of cell membranes. Thus, the modification of the FA profile-especially an increase in the concentration of polyunsaturated FAs and n-3 FAs in bovine milk fat-is desirable.

Future of lung cancer treatment.

The evolution of lung cancer treatment is an example of new perspectives in clinical oncology. Genomically determined targeted therapy of non-small cell lung cancer (NSCLC) is developing very rapidly with the gradual identification of new target structures and the concomitant development of innovative drugs are a great promise for the future. The historical development of systemic treatment of NSCLC is a model example of the path to accurate (precise) treatment.

Production of Bovine Equol-Enriched Milk: A Review.

Milk and dairy products are important sources of nutrients in the human diet because they contain a number of essential substances and other biologically active components. Many of these substances can be modified, and thus offer opportunities to use milk and dairy products as functional food. Isoflavones are particularly important in human nutrition due to their diverse pharmacological and antioxidant properties.

Pembrolizumab as a first-line therapy in spinocellular esophageal cancer.

Background: The treatment options in advanced stage of esophageal cancer are very limited. In recent years, a number of clinical trials have evaluated the effect of checkpoint inhibitors in this dia-gnosis.

Case: In our case report, we will demonstrate the administration of pembrolizumab in first-line therapy in generalized squamous cell carcinoma of the esophagus with PD-L1 expression > 70%.

In sacco evaluation of ruminal degradability of isoflavones from full-fat soybean and extracted soybean meal-A pilot study.

The aim of the study was to determine the ruminal degradability of dry matter (DM), daidzein, genistein, glycitein and total isoflavones in ground full-fat soybean (GFFS) and solvent-extracted soybean meal (SSBM) using the in sacco method. The experiment was carried out in three replications on ruminally cannulated sheep that were fed twice a day with a diet consisted of hay and supplemental mixture (6:4, DM basis). The nylon bags with 2 g feed samples ground to 2 mm were incubated in the rumen for 0, 2, 4, 8, 16 and 24 h.

Feedborne Mycotoxins Beauvericin and Enniatins and Livestock Animals.

Mycotoxins are secondary metabolites produced by several species of fungi, including the , , and species. Currently, more than 300 structurally diverse mycotoxins are known, including a group called minor mycotoxins, namely enniatins, beauvericin, and fusaproliferin. Beauvericin and enniatins possess a variety of biological activities.

In vitro metabolism of red clover isoflavones in rumen fluid.

The degradation of red clover isoflavones was studied in vitro using a rumen fluid buffer system. Various amounts of red clover extract (5-75 mg) together with hay or concentrate-rich diet were added to 40 ml of rumen fluid obtained from non-lactating and lactating dairy cows, respectively, and incubated for 0, 3, 6, 12 or 24 hr. Following incubation, concentrations of daidzein, genistein, formononetin, biochanin A and equol were determined in the samples.

Expression of molecules of the Wnt pathway and of E-cadherin in the etiopathogenesis of human thymomas.

The molecular pathogenesis of thymoma remains largely unknown. It has been recently demonstrated, that activation of Wnt signaling pathway leads to increased incidence of thymoma in murine models. The present study investigated the activation of molecules of the Wnt signaling pathway in human thymoma.

Estrogen Receptor Status Oppositely Modifies Breast Cancer Prognosis in Mutation Carriers Versus Non-Carriers.

Breast cancer (BC) prognosis in BRCA1 and BRCA2 mutation carriers has been reported contradictorily, and the significance of variables influencing prognosis in sporadic BC is not established in BC patients with hereditary BRCA1/BRCA2 mutations. In this retrospective cohort study, we analyzed the effect of clinicopathological characteristics on BC prognosis (disease-free survival [DFS] and disease-specific survival [DSS]) in hereditary BRCA1/BRCA2 mutation carriers. We enrolled 234 BRCA1/BRCA2 mutation carriers and 899 non-carriers, of whom 191 carriers and 680 non-carriers, with complete data, were available for survival analyses.

Isoflavones.

Phytoestrogens are naturally occurring nonsteroidal phenolic plant compounds that, due to their molecular structure and size, resemble vertebrate steroids estrogens. This review is focused on plant flavonoids isoflavones, which are ranked among the most estrogenic compounds. The main dietary sources of isoflavones for humans are soybean and soybean products, which contain mainly daidzein and genistein.

Role of Fatty Acids in Milk Fat and the Influence of Selected Factors on Their Variability-A Review.

Fatty acids (FAs) of milk fat are considered to be important nutritional components of the diets of a significant portion of the human population and substantially affect human health. With regard to dairy farming, the FA profile is also seen as an important factor in the technological quality of raw milk. In this sense, making targeted modifications to the FA profile has the potential to significantly contribute to the production of dairy products with higher added value.

p19-Targeting ILP Protein Blockers of IL-23/Th-17 Pro-Inflammatory Axis Displayed on Engineered Bacteria of Food Origin.

IL-23-mediated Th-17 cell activation and stimulation of IL-17-driven pro-inflammatory axis has been associated with autoimmunity disorders such as Inflammatory Bowel Disease (IBD) or Crohn’s Disease (CD). Recently we developed a unique class of IL-23-specific protein blockers, called ILP binding proteins that inhibit binding of IL-23 to its cognate cell-surface receptor (IL-23R) and exhibit immunosuppressive effect on human primary blood leukocytes ex vivo. In this study, we aimed to generate a recombinant strain which could serve as in vivo producer/secretor of IL-23 protein blockers into the gut.

Determination of in vitro isoflavone degradation in rumen fluid.

The aim of this study was to determine the degradation of dietary isoflavones in rumen fluid under 2 feeding regimens. The experiments were performed in vitro using a rumen fluid buffer system. The rumen fluid was taken from cows fed either a hay diet or a concentrate-rich diet (the diet consisted of 34.

p19-targeted ABD-derived protein variants inhibit IL-23 binding and exert suppressive control over IL-23-stimulated expansion of primary human IL-17+ T-cells.

Interleukin-23 (IL-23), a heterodimeric cytokine of covalently bound p19 and p40 proteins, has recently been closely associated with development of several chronic autoimmune diseases such as psoriasis, psoriatic arthritis or inflammatory bowel disease. Released by activated dendritic cells, IL-23 interacts with IL-23 receptor (IL-23R) on Th17 cells, thus promoting intracellular signaling, a pivotal step in Th17-driven pro-inflammatory axis. Here, we aimed to block the binding of IL-23 cytokine to its cell-surface receptor by novel inhibitory protein binders targeted to the p19 subunit of human IL-23.

Changes in equol and major soybean isoflavone contents during processing and storage of yogurts made from control or isoflavone-enriched bovine milk determined using LC-MS (TOF) analysis.

The effect of supplementing a basal diet for dairy cows with "Soybean extract 40" (Biomedica, Prague, Czech Republic), containing 40% soybean isoflavones, on the contents of daidzein, glycitein, genistein, and equol in milk as well as fresh and mature yogurts was estimated. To determine the contents of these isoflavonoids, an efficient analytical LC-MS (TOF) technique was used. The "Soybean extract 40" used in our study contained an especially high proportion of daidzein (307gkg).

Bacterial community dynamics in a rumen fluid bioreactor during in-vitro cultivation.

To study the various processes in the rumen the in vitro techniques are widely used to realize more controlled and reproducible conditions compared to in vivo experiments. Mostly, only the parameters like pH changes, volatile fatty acids content or metabolite production are monitored. In this study we examine the bacterial community dynamics of rumen fluid in course of ten day cultivation realize under standard conditions described in the literature.