Cancer research is linked to modern life-sciences, encompassing achievements in virology, yeast-biology, molecular-biology, genetics, systems-biology, bioinformatics, and so on. With these fascinating developments, it's easy to overlook that the fundamental theories and treatment strategies were established in the early 20th century and have remained valid ever since. Therefore, tribute must be paid to the founders of the field. The main hypotheses on carcinogenesis, the genetic model and the metabolic model, and the concept of cancer-treatment with cytotoxic, targeted or metabolic drugs were proposed more than 100 years ago by great minds such as T. Boveri, O. Warburg, and P. Ehrlich. Hence nothing about these cancer concepts is really new. Through development of powerful new technologies, we have been able to decipher the mechanisms of malignant transformation, thus significantly advancing the field. Our own studies have been focused on the cross-talk between cell-growth-signaling and lipid-metabolism in ovarian cancer to find crossover-points for co-targeting in order to achieve synergistic treatment effects. Notably, a side-effect of the application of current methods of molecular-cell-biology is a deeper knowledge of the laws of normal cell-biology and cell-life. Thus we anticipate the field will advance rapidly in the near future.

Olfactory dysfunction (OD) is a common symptom associated with Covid-19. During the Covid-19 pandemic, the importance of psychophysical olfactory tests and electrophysiological olfactory assessment increased. The purpose of the study was to analyze the psychophysical olfactory tests and the post-covid curves of olfactory event-related potentials (OERPs) and trigeminal event-related potentials (TERPs).

Cell senescence is intensively related to aging and neurodegenerative diseases. This study aimed to explore the effect and targets of Astragaloside IV against amyloid-beta-induced astrocyte senescence. Oligomerized amyloid-beta was prepared to culture with human astrocytes. The effects of Astragaloside IV were assessed based on SA-β-gal staining analysis, senescence markers (p53, p16INK4, and p21WAF1), neurotrophic growth factor levels (qRT-PCR), and cell proliferation (CCK-8 kit). The targets for Astragaloside IV were predicted, and hsp90aa1 protein was verified using molecular docking. After hsp90aa1 overexpression, the effects of Astragaloside IV on amyloid-beta-induced astrocytes were assessed. Treatment of human amyloid-beta-induced astrocytes with Astragaloside IV can decrease the percentage of SA-β-gal positive cells, downregulate the p53, p16INK4, and p21WAF1 levels, and increase the levels of neurotrophic growth factors (IGF-1 and NGF mRNA) and cell proliferation. Based on target prediction, hsp90aa1 was found to be a potential target of Astragaloside IV. Moreover, cellular experiments demonstrated that exogenously enhanced expression of hsp90aa1 overexpression suppressed the protective effect of Astragaloside IV on amyloid-beta-induced human astrocytes. The results presented here demonstrate that Astragaloside IV could confront amyloid-beta-induced astrocyte senescence via hsp90aa1, possibly opening new therapeutic avenues.

Anti-N-methyl D-aspartate receptor (anti-NMDAR) encephalitis is an autoimmune disorder characterized by IgG antibodies targeting NMDAR. The prevalence is remarkably higher in women and some develop the condition during pregnancy. While immunotherapies have shown good outcomes for pregnant mothers and their infants, the impact on early neurodevelopment remains elusive. This study investigates the effects of anti-NMDAR antibody on the development of primary cortical cultures. Anti-NMDAR antibody was administered to the cultures at day in vitro 5 for the following 5 days to assess dendritic branching and arbor complexity, and at day in vitro 14 for measuring the expression of brain-derived neurotrophic factor (BDNF) and synaptic proteins. Immature cultured neurons treated with anti-NMDAR antibody exhibited impaired dendritic branching and arbor complexity. Interestingly, BDNF expression was unaffected in mature neurons. Additionally, GluN1 expression, a mandatory NMDAR subunit, was significantly reduced, while no significant alterations were observed in PSD-95, gephyrin and synaptophysin expression. These findings shed light on the structural and synaptic impacts of anti-NMDAR antibody on immature neurons, providing evidence for their consequences in early neuronal development.

The role of Helicobacter pylori (Hp) in the pathological processes of the gastric mucosa is well understood. Decreasing trend in successful eradication of HP from the stomach was observed in last years. This lack of succes is mainly caused by increasing ATB resistance. Nevertheless other possible causes of this phenomenon are being explored. Thus, many studies have focused on the search for extragastric reservoirs as potential sources of persistence or reinfection after successful Hp eradication. The pathological potential of Hp at these localities has also been studied.

This study aimed to investigate the phenolic composition, antioxidant capacity, and toxicity of aqueous extracts of Calamintha nepeta L. leaves and their potential vasorelaxant effects.

Myo-inositol (MI), present in a variety of foods, is essential in several important processes of cell physiology. In this study, we explored the protective effects of MI against hyperglycemia and dyslipidemia in db/db mice, a typical animal model of type 2 diabetes mellitus (T2DM). MI supplement effectively suppressed the high plasma glucose and insulin levels and markedly relieved the insulin resistance (IR) in the db/db mice, comparable to metformin's effects. In MIN6 pancreatic β cells, MI also restrained the upsurge of insulin secretion stimulated by high-concentration glucose but had no impact on the promoted cell proliferation. Moreover, MI abated the enhanced plasma triglyceride and total cholesterol levels in the db/db mice. Notably, the lipid droplet formation of mesenchymal stem cells (MSCs) from db/db mice was significantly diminished after the treatment of MI, indicating that MI could effectively inhibit the differentiation of db/db mouse MSCs into adipocytes. However, MI regretfully failed to control obesity in db/db mice. This work proved that MI significantly helped db/db mice's metabolic disorders, indicating that MI has potential as an effective adjunctive treatment for hyperglycemia and dyslipidemia in T2DM patients.

This study investigates the potential relationship between exposure to polycyclic aromatic hydrocarbons (PAHs), specifically monohydroxylated metabolites (OH-PAHs), in urine, and the prevalence of respiratory diseases in 2-year-old children residing in two locations within the Czech Republic - České Budějovice (control location) and the historically contaminated mining district of Most. Despite current air quality and lifestyle similarities between the two cities, our research aims to uncover potential long-term health effects, building upon previous data indicating distinctive patterns in the Most population. A total of 248 urine samples were analysed for the presence of 11 OH-PAHs. Employing liquid-liquid extraction with ethyl acetate and clean-up through dispersive solid-phase extraction, instrumental analysis was conducted using ultra-high performance liquid chromatography coupled with tandem mass spectrometry. The incidence of respiratory diseases was assessed through questionnaires administered by paediatricians. The concentrations of OH-PAHs were elevated in urine samples from 2-year-olds in Most compared to those from České Budějovice. The incidence of respiratory diseases showed statistically significant higher levels of OH-PAHs in children from Most, together with a higher incidence of influenza. This association underlines the impact of environmental PAH exposure on children's respiratory health. It suggests that elevated urinary OH-PAH levels indicate an increased risk of developing respiratory diseases in the affected population. Further studies are needed to clarify the possible long-term health effects and to contribute to sound public health strategies.

Resveratrol (RSV) is a polyphenol antioxidant that has been shown to have neuroprotective effects. We sought molecular mechanisms that emphasize the anti-inflammatory activity of RSV in traumatic brain injury (TBI) in mice associated with endoplasmic reticulum stress (ERS). After establishing three experimental groups (sham, TBI, and TBI+RSV), we explored the results of RSV after TBI on ERS and caspase-12 apoptotic pathways. The expression levels of C/EBP homologous protein (CHOP), glucose regulated protein 78kD (GRP78), caspase-3, and caspase-12 in cortical brain tissues were assessed by western blotting. The qPCR analysis was also performed on mRNA expression of tumor necrosis factor (TNF)-α and interleukin (IL)-1β in cortical brain tissue. In addition, the expression of GRP78 in microglia (ionized calcium binding adaptor molecule 1; Iba-1) and neurons (neuronal nuclei; NeuN) was identified by immunofluorescence staining. The neurological function of mice was assessed by modified neurological severity scores (mNSS). After drug treatment, the expression of CHOP, GRP78, caspase-3 and caspase-12 decreased, and qPCR results showed that TNF-α and IL-1β were down-regulated. Immunofluorescence staining showed down-regulation of Iba-1+/GRP78+ and NeuN+/GRP78+ cells after RSV treatment. The mNSS analysis confirmed improvement after RSV treatment. RSV improved apoptosis by downregulating the ERS signaling pathway and improved neurological prognosis in mice with TBI.

Diffuse large B-cell lymphoma (DLBCL) stands out as the most common type of malignant cancer, representing the majority of cases of non-Hodgkin's lymphoma. Ethyl pyruvate (EP) is a derivative of pyruvic acid and found to have potent anti-tumor properties. Despite its potential benefits, the impact of EP on DLBCL remains ambiguous. Our objective is to elucidate the role of EP in modulating the development of DLBCL. Analysis of cholecystokinin-8 (CCK-8) revealed that treatment with EP significantly diminished the viability of DLBCL cells. Furthermore, EP administration suppressed colony formation and hindered cell adhesion and invasion in DLBCL cells. Examination of cell cycle progression showed that EP treatment induced arrest at the G1 phase and subsequently reduced the S phase population in DLBCL cells. EP treatment consistently exhibited apoptosis-inducing properties in Annexin-V assays, and notably downregulated the expression of Bcl-2 while increasing levels of proapoptotic cleaved caspase 3 and BAX in DLBCL cells. Additionally, EP treatment decreased the overexpression of c-Jun in c-Jun-transfected DLBCL cells. Further, EP demonstrated DNA-damaging effects in TUNEL assays. In vivo, xenograft animal models revealed that EP treatment significantly mitigated DLBCL tumor growth and suppressed DLBCL cell adhesion to bone marrow stromal cells. In summary, these findings suggest that EP mitigates DLBCL progression by inducing apoptosis, inducing cell cycle arrest, and promoting DNA damage.

In 2020, there were numerous cases in Kazakhstan with clinical symptoms of COVID-19 but negative PCR results in nasopharyngeal and oropharyngeal swabs. The diagnosis was confirmed clinically and by CT scans (computed tomography). The problem with such negative PCR results for SARS-CoV-2 infection confirmation still exists and indicates the need to confirm the diagnosis in the bronchoalveolar lavage in such cases. There is also a lack of information about confirmation of SARS-CoV-2 infection in deceased patients. In this study, various tissue materials, including lungs, bronchi, and trachea, were examined from eight patients who died, presumably from SARS-CoV-2 infection, between 2020 and 2022. Naso/oropharyngeal swabs taken from these patients in hospitals tested PCR negative for SARS-CoV-2. This study presents a modified RNA isolation method based on a comparison of the most used methods for RNA isolation in laboratories: QIAamp Viral RNA Mini Kit and TRIzol-based method. This modified nucleic acid extraction protocol can be used to confirm SARS-CoV-2 infection by RT-qPCR in the tissues of deceased patients in disputed cases. RT-qPCR with RNA of SARS-CoV-2 re-extracted with such method from post-mortem tissues that were stored at -80 °C for more than 32 months still demonstrated high-yielding positive results.

We aimed to determine the effects of vanillic acid (VA) on fracture healing radiologically, histologically, immunohistochemically, and biomechanically using a rat femur open fracture injury model.

The current obstructive sleep apnea (OSA) diagnostic uses polysomnography or limited polygraphy and requires specialized personnel and technical equipment. Glycoprotein biomarkers and microRNAs are being explored as a possible new method for screening. We aimed to evaluate whether certain biomarkers and microRNA, previously identified as related to OSA, could be influenced by factors such as gender, age, and obesity level in patients with OSA.

It has long been known that airborne polycyclic aromatic hydrocarbons (PAHs) can negatively affect pregnancy and birth outcomes, such as birth weight, fetal development, and placental growth factors. However, similar studies yield divergent results. Our goal was to estimate the amount of monohydroxylated PAH (OH-PAH) metabolites in the urine of pregnant women/mothers and their newborns in relation to birth outcomes, such as placenta weight, Apgar 5', and the growth parameters of children up to the age of two.

Cholesterol-lowering drugs, antidiabetics, antiarrhythmics, antidepressants, and antibiotics belong to the most prescribed drugs worldwide. Because of the manufacture, excretion, and improper disposal of leftover drugs, the drugs enter waste waters and, subsequently, surface waters. They have been detected in surface waters all over the world, from concentrations of ng/l to concentrations several orders of magnitude higher. Since pharmaceuticals are designed to be both biologically and chemically stable, photochemical degradation by sun radiation represents a way of transformation in the natural environment. This review provides a survey of how selected drugs of the above-mentioned classes affect aquatic organisms of different trophic level. The emphasis is on the harmful effects of phototransformation products, an area of scientific investigation that has only attracted attention in the past few years, revealing the surprising fact that products of photochemical degradation might be even more toxic to aquatic organisms than the parent drugs.

Dictyophora indusiata, commonly known as bamboo fungus, is a type of edible mushroom that is highly popular worldwide for its rich flavor and nutritional value. It is also recognized for its pharmaceutical efficacy, with medicinal benefits attributed to its consumption. One of the most important components of Dictyophora indusiata is polysaccharide, which has been acknowledged as a promising regulator of biological response due to its immunostimulatory and anti-inflammatory properties. However, the specific roles of polysaccharide in modulating the NOD-like receptor protein 3 (NLRP3) inflammasome activation within macrophages remain relatively under-researched. To investigate this further, the mechanism by which Dictyophora indusiata polysaccharide (DIP) exerts its immunostimulatory activity in RAW 264.7 macrophages was analyzed. Results indicated that DIP has the potential to facilitate the priming of NLRP3 inflammasome activation by enhancing TLR4 expression, phosphorylation of IκB-α, and nuclear translocation of NF-κB p65 subunit. It was noted that DIP was unable to mediate the second step of NLRP3 inflammasome activation. The findings of this study provide compelling evidence that DIP has immunomodulatory effects by modulating the NLRP3 inflammasome in RAW264.7 macrophages.

The aim of this study was to investigate whether luteoloside, a flavonoid, could protect human dental pulp cells (HDPCs) against inflammation and oxidative stress induced by methylglyoxal (MGO), one of the advanced glycated end products (AGE) substances.

Endoplasmic reticulum (ER) stress has been shown to play an important role in osteoarthritis (OA).

We have extracted and characterized Phasa fish (Setipinna phasa) oil for the first time to evaluate the anti-obesity and related anti-inflammatory effects on obese mice. Inbred male albino BALB/c mice were segregated into three categories: control (C), Obese control group (OC), and Phasa fish oil treated group (TX). To establish the potentiality of Setipinna phasa oil for its anti-obesity and anti-inflammatory properties, it was extracted and characterized using GC-MS method. To evaluate the anti-obesity effect, different parameters were considered, such as body weight, lipid composition, obesity, and obesity associated inflammation. The physicochemical characteristics of Phasa fish oil revealed that the oil quality was good because acid value, peroxide value, p-anisidine value, Totox value, refractive index, and saponification value were within the standard value range. The GC-MS study explored the presence of fatty acids beneficial to health such as Hexadec-9-enoic acid; Octadec-11-enoic acid; EPA, DHA, Methyl Linolenate, etc. The application of Setipinna phasa oil on the treated mice group acutely lowered body weight and serum lipid profile compared to the obese group. In connection with this, leptin, FAS, and pro-inflammatory cytokines TNF-α genes expression were downregulated in the treated group compared to the obese group. The Phasa oil treated group had an elevated expression of PPAR-α, adiponectin, LPL gene, and anti-inflammatory markers IL-10 and IL-1Ra compared to the obese group. This study suggests that Phasa fish oil, enriched with essential fatty acid, might be used as an anti-obesity and anti-inflammatory supplement.

COVID-19 is a viral disease notorious for frequent worldwide outbreaks. It is difficult to control, thereby resulting in overload of the healthcare system. A possible solution to prevent overcrowding is rapid triage of patients, which makes it possible to focus care on the high-risk patients and minimize the impact of crowding on patient prognosis.

Spisulosine (1-deoxysphinganine) is a sphingoid amino alcohol isolated from the sea clams that showed potent antiproliferative activity against a broad spectrum of solid tumors but failed in clinical trials due to neurotoxicity. However, its structural similarity to other bioactive sphingoids, interesting mode of action, and appreciable potency against cancer cells make it a suitable lead for future anticancer drug development. The present study was conducted to elucidate mechanisms of the antiproliferative/cytotoxic effects of newly synthesized spisulosine analog homospisulosine (KP7). The evaluation was performed on cervical carcinoma cells, representing an in vitro model of one of the most common cancer types and a significant worldwide cause of women's cancer mortality. Treatment with homospisulosine (2.0 μM) for 24, 48, and 72 h significantly inhibited the growth of HeLa cells in vitro and induced apoptosis detectable by DNA fragmentation, externalization of phosphatidylserine, dissipation of mitochondrial membrane potential, activation of caspase-3 and cleavage of PARP. In addition, treating HeLa cells with spisulosine increased p27 and Bcl-2 on protein levels and phosphorylation of Bcl-2 on Ser70 residue. These results support the potential for spisulosine analogs represented here by homospisulosine for future therapeutic development.