This review summarizes the current understanding of the role of transient receptor potential melastatin-subfamily member 7 (TRPM7) channels in the pathophysiology of neoplastic diseases. The TRPM family represents the largest and most diverse group in the TRP superfamily. Its subtypes are expressed in virtually all human organs playing a central role in (patho)physiological events. The TRPM7 protein (along with TRPM2 and TRPM6) is unique in that it has kinase activity in addition to the channel function. Numerous studies demonstrate the role of TRPM7 chanzyme in tumorigenesis and in other tumor hallmarks such as proliferation, migration, invasion and metastasis. Here we provide an up-to-date overview about the possible role of TRMP7 in a broad range of malignancies such as tumors of the nervous system, head and neck cancers, malignant neoplasms of the upper gastrointestinal tract, colorectal carcinoma, lung cancer, neoplasms of the urinary system, breast cancer, malignant tumors of the female reproductive organs, prostate cancer and other neoplastic pathologies. Experimental data show that the increased expression and/or function of TRPM7 are observed in most malignant tumor types. Thus, TRPM7 chanzyme may be a promising target in tumor therapy.

NMDA receptors in the prefrontal cortex (PFC) play a crucial role in cognitive functions. Previous research has indicated that angiotensin II (Ang II) affects learning and memory. This study aimed to examine how Ang II impacts NMDA receptor activity in layer V pyramidal cells of the rat PFC. Whole-cell patch-clamp experiments were performed in pyramidal cells in brain slices of 9–12-day-old rats. NMDA (30 μM) induced inward currents. Ang II (0.001–1 µM) significantly enhanced NMDA currents in about 40% of pyramidal cells. This enhancement was reversed by the AT1 antagonist eprosartan (1 µM), but not by the AT2 receptor antagonist PD 123319 (5 μM). When pyramidal neurons were synaptically isolated, the increase in NMDA currents due to Ang II was eliminated. Additionally, the dopamine D1 receptor antagonist SCH 23390 (10 μM) reversed the Ang II-induced enhancement, whereas the D2 receptor antagonist sulpiride (20 μM) had no effect. The potentiation of NMDA currents in a subpopulation of layer V pyramidal neurons by Ang II, involving AT1 receptor activation and dopaminergic signaling, may serve as an underlying mechanism for the effects of the renin–angiotensin system (RAS) elements on neuronal functions.

Background/Objectives: In preclinical research of airway inflammation, the endotoxin (lipopolysaccharide: LPS)–induced acute interstitial pneumonitis is the most commonly used mechanism model. However, studies apply different LPS serotypes, doses, administration routes, and reference compounds, making result interpretation challenging and drawing conclusions difficult. Therefore, here we aimed to optimize, characterize, and validate this model with dexamethasone in mice. Methods: Pneumonitis was induced by intratracheal LPS (0.25, 1, 2.5, 5 mg/kg; E. coli O111:B4) in C57BL/6J and NMRI mice; controls received phosphate-buffered saline (PBS). Dexamethasone (5 mg/kg i.p.) was used as a positive control. Respiratory functions were measured by restrained plethysmography 24 h after induction, and core body temperature was monitored. Lungs were excised and weighed, and then myeloperoxidase (MPO) activity and histopathological analysis were performed to assess pulmonary inflammation. Results: LPS-induced significant body weight loss, perivascular pulmonary edema, MPO activity increase, neutrophil infiltration, and respiratory function impairment in a dose-independent manner. However, LPS-induced hypothermia dynamics and duration were dose-dependent. The inhibitory effects of the reference compound dexamethasone were only detectable in the case of the 0.25 mg/kg LPS dose on most inflammatory parameters. These results did not differ substantially between C57BL/6J and NMRI mouse strains. Conclusions: Very low doses of LPS induce characteristic functional and morphological inflammatory alterations in the lung, which do not worsen in response to even 20 times higher doses. Since the effect of pharmacological interventions is likely to be detectable in the case of the 0.25 mg/kg LPS dose, we suggest this protocol for testing novel anti-inflammatory agents.

Background: N-methyl-D-aspartate type glutamate receptors (NMDARs) are fundamental to neuronal physiology and pathophysiology. The prefrontal cortex (PFC), a key region for cognitive function, is heavily implicated in neuropsychiatric disorders, positioning the modulation of its glutamatergic neurotransmission as a promising therapeutic target. Our recently published findings indicate that AT₁ receptor activation enhances NMDAR activity in layer V pyramidal neurons of the rat PFC. At the same time, it suggests that alternative angiotensin pathways, presumably involving AT₄ receptors (AT4Rs), might exert inhibitory effects. Angiotensin IV (Ang IV) and its analogs have demonstrated cognitive benefits in animal models of learning and memory deficits. Methods: Immunohistochemistry and whole-cell patch-clamp techniques were used to map the cell-type-specific localization of AT4R, identical to insulin-regulated aminopeptidase (IRAP), and to investigate the modulatory effects of Ang IV on NMDAR function in layer V pyramidal cells of the rat PFC. Results: AT4R/IRAP expression was detected in pyramidal cells and GABAergic interneurons, but not in microglia or astrocytes, in layer V of the PFC in 9–12-day-old and 6-month-old rats. NMDA (30 μM) induced stable inward cation currents, significantly inhibited by Ang IV (1 nM–1 µM) in a subset of pyramidal neurons. This inhibition was reproduced by the IRAP inhibitor LVVYP-H7 (10–100 nM). Synaptic isolation of pyramidal neurons did not affect the Ang IV-mediated inhibition of NMDA currents. Conclusions: Ang IV/IRAP-mediated inhibition of NMDA currents in layer V pyramidal neurons of the PFC may represent a way of regulating cognitive functions and thus a potential pharmacological target for cognitive impairments and related neuropsychiatric disorders.

Colorectal cancer (CRC) is the third most common cancer worldwide and the second leading cause of cancer-related deaths. Early detection through non-invasive methods is critical for improving patient outcomes. This study investigates the association between the presence and relative abundance of Fusobacterium nucleatum (Fn) in saliva and CRC, evaluating its potential as a non-invasive biomarker. A systematic search was performed in MEDLINE, Embase, CENTRAL, and Scopus databases on November 25, 2023. Studies analyzing Fn in salivary samples from adults with CRC, colorectal polyps (CRP), or healthy individuals were included. Statistical analyses were performed using random-effects models to calculate pooled odds ratios (OR) and mean differences (MD) with 95% confidence intervals (CI). The risk of bias was assessed using the Quality in Prognosis Studies (QUIPS) tool. Of the 14,200 studies identified, twelve were included in our systematic review. Of these, eight were analyzed by meta-analysis. The results indicated no significant difference in the presence (OR 1.40; 95% CI [0.77; 2.54]; I ² = 0% [0; 71%], p = 0.215) or relative abundance (MD -0.01; 95% CI [-0.13; 0.11]; I ² = 25% [0; 69%], p = 0.851) of salivary Fn among CRC patients, compared to a combined group of CRP and healthy controls. Our findings suggest that the presence and relative abundance of salivary Fn are not associated with CRC.