Hepatocellular carcinoma is the most common primary malignancy of the liver, with hepatocellular differentiation. It is ranked sixth among the most common cancers worldwide and is the third leading cause of cancer-related deaths. The most important etiological factors discussed here are viral infection (HBV, HCV), exposure to aflatoxin B1, metabolic syndrome, and obesity (as an independent factor). Directly or indirectly, they induce chromosomal aberrations, mutations, and epigenetic changes in specific genes involved in intracellular signaling pathways, responsible for synthesis of growth factors, cell proliferation, differentiation, survival, the metastasis process (including the epithelial–mesenchymal transition and the expression of adhesion molecules), and angiogenesis. All these disrupted molecular mechanisms contribute to hepatocarcinogenesis. Furthermore, equally important is the interaction between tumor cells and the components of the tumor microenvironment: inflammatory cells and macrophages—predominantly with a pro-tumoral role—hepatic stellate cells, tumor-associated fibroblasts, cancer stem cells, extracellular vesicles, and the extracellular matrix. In this paper, we reviewed the molecular biology of hepatocellular carcinoma and the intricate mechanisms involved in hepatocarcinogenesis, and we highlighted how certain signaling pathways can be pharmacologically influenced at various levels with specific molecules. Additionally, we mentioned several examples of recent clinical trials and briefly described the current treatment protocol according to the NCCN guidelines.

C-reactive protein (CRP) represents an early clinical biomarker that indicates the presence of inflammatory or infectious conditions in the human body. Today's procedures approved by the Food and Drug Administration (FDA) imply expensive equipment and highly trained personnel to perform the test. Therefore, a new diagnostic method with high detection efficiency and less cost is urgently needed for delivering rapid and timely results in point-of-care (POC) service. Herein, we propose a new, equipment-free, and portable sensing method for the future POC detection of CRP based on the Tyndall effect (TE). In our study, aptamer-conjugated citrate-stabilized gold nanoparticles (apta-AuNPs) are exploited as the sensing platform. The apta-AuNPs' interaction with CRP in a saline environment leads to their aggregation, thus enhancing the scattering of light when the solution is exposed to a 640 nm pointer laser line. Firstly, the enhancement of the scattering light as a function of increasing concentration of CRP in solution is measured spectroscopically using a typical 90-degree angle spectrofluorometer and then the measurements are compared to the classic colorimetric detection using an UV-Vis spectrophotometer. Finally, to achieve high portability and accessibility, we demonstrate that the measurement of CRP concentration can be performed with similar accuracy but in a more direct and inexpensive way by using a laser pointer pen as the excitation source and a camera of a low-budget smartphone as a quantitative reader instead of most expensive spectrofluorometer. The portable TE-based assay exhibits a wide linear dynamic range (1-60 μg/mL) for the detection of CRP with a limit of detection (LOD) of 92 ng/mL The proposed method is capable to integrate both standard and high-sensitivity CRP analysis in a single procedure with increased sensitivity and prompt delivery of analysis results. Moreover, the sensing procedure is significantly faster than the FDA approved ones with a detection time of only 10 min. Finally, as a proof-of-concept, our findings demonstrate excellent recovery for CRP detection in spiked and diluted urine samples, highlighting the strong potential of this sensing method for POC applications.

Diabetic retinopathy (DR) and cataracts (CA) have an early onset in diabetes mellitus (DM) due to the redox imbalance and inflammation triggered by hyperglycaemia. Plant-based therapies are characterised by low tissue bioavailability. The study aimed to investigate the effect of gold nanoparticles phytoreduced with Rutin (AuNPsR), as a possible solution. Insulin, Rutin, and AuNPsR were administered to an early, six-week rat model of DR and CA. Oxidative stress (MDA, CAT, SOD) was assessed in serum and eye homogenates, and inflammatory cytokines (IL-1 beta, IL-6, TNF alpha) were quantified in ocular tissues. Eye fundus of retinal arterioles, transmission electron microscopy (TEM) of lenses, and histopathology of retinas were also performed. DM was linked to constricted retinal arterioles, reduced endogen antioxidants, and eye inflammation. Histologically, retinal wall thickness decreased. TEM showed increased lens opacity and fibre disorganisation. Rutin improved retinal arteriolar diameter, while reducing oxidative stress and inflammation. Retinas were moderately oedematous. Lens structure was preserved on TEM. Insulin restored retinal arteriolar diameter, while increasing MDA, and amplifying TEM lens opacity. The best outcomes were obtained for AuNPsR, as it improved fundus appearance of retinal arterioles, decreased MDA and increased antioxidant capacity. Retinal edema and disorganisation in lens fibres were still present.

Phospholipase A₂ (PLA₂) is a prevalent molecule in the honeybee venom. Its importance is reflected by the number of scientists focused on studying it from various points of view. This review summarises a significant amount of data concerning this fascinating substance. Firstly, the origin and occurrence of PLA₂, with similarities and differences among species or populations of bees are highlighted. Next, its synthesis, post-translational processing and structural features are described, followed by the PLA₂ availability. In a larger section, the multiple effects of honeybee venom PLA₂ are detailed, starting with the main ability as an enzyme to interact with biological membranes and to hydrolyse the sn-2 ester bond in 1,2-diacyl-sn-3-phosphoglycerides; the docking process, the substrate binding and the catalytic steps are analysed too. Then, the pro-/anti-inflammatory effect and allergenic property, the anticoagulant effect and the involvement of PLA₂ in apoptosis are revised. Selected antiviral, antibiotic and antitumoral effects of PLA₂, as well as its use in immunotherapy are mentioned as beneficial applications. Additionally, the mechanisms of toxicity of PLA₂ are presented in detail. Finally, a number of anti-PLA₂ compounds are enumerated. In each section, the features of the honeybee venom molecule are discussed in relation to PLA₂s from other species.

Sleep deprivation (SD) induces significant neurobiological changes, including oxidative stress, neuroinflammation, and behavioural impairments. This study was designed as a proof of concept to assess the potential for modulating the effects of SD through a short-term seven-day administration of Cornus mas (C. mas) in a rapid eye movement (REM) SD rodent paradigm. Adult male Wistar rats were randomised in four groups (n = 7): control, C. mas (CM), sleep deprivation (SD), and sleep deprivation with C. mas (SD + CM). Behaviourally, SD induced hyperactivity and hyperlocomotion. SD determined histological alterations in the prefrontal cortex and corpus callosum myelin coupled with ultrastructural mitochondrial and cellular abnormalities in the prefrontal cortex, hippocampus, and pineal gland. Despite evidence of systemic oxidative stress coupled with decreased serum GABA and BDNF following SD, no significant changes were observed in redox markers or inflammatory cytokine levels (TNF-α, IL-1β) within the prefrontal cortex or hippocampus. C. mas extract has shown an overall modest modulatory action, mainly evidenced on behavioural, histological, and ultrastructural parameters. Taken together, these findings highlight behavioural changes and region-specific molecular and structural abnormalities following prolonged REM SD in rats.