Assessing the potential fasting and postprandial mechanisms involved in the acute hypoglycemic and anti-hyperglycemic effects of four selected plants from Iran used in traditional Persian medicine.

ETHNOPHARMACOLOGICAL RELEVANCE: In traditional Persian medicine (TPM), people often use herbal infusions as a dosage form to treat diseases related to hyperglycemia, known as 'dam-kardeh'. Traditionally, herbal preparations of Eryngium bungei Boiss. (E. b), Tragopogon buphthalmoides (DC.) Boiss. (T. b), Salvia hydrangea DC. ex Benth. (S. h), and Juniperus polycarpos K. Koch. (J. p) are used to manage diabetes in Iran. However, there is no evidence of their effectiveness in controlling glucose levels and their mechanisms remain unclear. AIM OF THE STUDY: This study aimed to investigate whether traditional doses of plant infusions can have hypoglycemic and/or anti-hyperglycemic effects during fasting and/or postprandial states and establish the basis for future research on their potential mechanisms of action. MATERIALS AND METHODS: The effects of traditional doses of herbal extracts on blood glucose levels in STZ-NA-induced hyperglycemic rats were investigated in 2-h acute tests during fasting and postprandial states (with a glucose load). In addition, the potential inhibitory effect in vitro of enzymes involved in relevant pathways, such as gluconeogenesis (fructose-1,6-bisphosphatase, FBPase and glucose-6-phosphatase, G6Pase), carbohydrate breakdown (intestinal α-glucosidases), and insulin sensitivity (protein tyrosine phosphatase 1B, PTP-1B) was evaluated. Acute toxicity tests were carried out and HPLC-SQ-TOF was used to analyze the chemical profiles of the plant extracts. RESULTS: In the fasting state, T. b, S. h, and E. b were as effective as glibenclamide in lowering blood glucose levels in hyperglycemic rats. Moreover, all three suppressed G6Pase and FBPase enzymatic activity by 90-97% and 80-91%, respectively. On the other hand, significant postprandial hypoglycemic efficacy was observed for E. b, S. h, and T. b. Based on the AUC values, T. b caused a reduction comparable to the therapeutic efficacy of repaglinide. When investigating the possible mechanisms of action involved in this activity, E. b, S. h, and T. b showed significant inhibition of PTP-1B in vitro (>70%). Finally, all plant extracts showed no signs of acute toxicity. Several compounds that may contribute to biological activities were identified, including phenolic acids and flavonoid glycosides. CONCLUSIONS: The present study supports the traditional use of T. b, E. b and S. h for the control of diabetes in the fasting and postprandial state. Moreover, these plants were found to be rich in bioactive compounds with hypoglycemic and antihyperglycemic activities. On the other hand, J. p, showed a modest effect only in the fasting state and after 90 min. Further studies are needed to expand these results by analyzing the chemical composition and using complementary experimental models.

Evaluation of the Chetomin effect on histopathological features in a murine acute spinal cord injury model.

Background: Several research studies have been focused on improving the treatment and prognosis of acute spinal cord injury, as part of this initiative we investigated the use of Chetomin to reduce the inflammatory response in this pathology. Methods: An experimental, prospective, cross-sectional study was performed using 42 Wistar rats where we analyzed the effect of Chetomin compared to methylprednisolone administered 1 and 8 h after the spinal cord injury in a murine model. Results: Chetomin administration 8h post-injury decreased IL-6 and VEGF expression; and, and its administration 1h post-injury decreased NF-kB expression. Conclusions: Chetomin has anti-inflammatory effects in acute spinal cord injury, whether these effects are observable with other proinflammatory markers should be investigated.

Purines and purinergic receptors in primary tumors of the central nervous system.

Purine nucleotides and nucleosides play critical roles in various pathological conditions, including tumor cell growth. Adenosine triphosphate (ATP) activates pro-tumor receptors, while adenosine (ADO) is a potent immunosuppressant and modulator of cell growth. This study aims to analyze the purinergic actions of ATP and its metabolites, associated enzymes, and P1 or P2 class receptors in primary central nervous system tumors. Additionally, we sought to correlate the levels of nucleosides and the density of P1, P2X, and P2Y receptors in cells with tumor progression. The results indicate that purinergic signaling depends on the receptor concentration and signaling molecules specific to each cell type, tissue, and tumor histology. The purinergic system may function as either a tumor-promoting agent or an antitumor factor, depending on the microenvironmental conditions and the concentrations of receptors and their respective activators. Notably, ATP emerges as the most significant extracellular signal, capable of being converted into other cellular stimulators pertinent to neoplasms, such as adenosine diphosphate, adenosine monophosphate, adenosine, and inosine. Consequently, a cascade of responses to these stimuli promotes tumor development, cell division, and metastasis. Purine nucleotides in central nervous system tumors are pivotal in cellular responses in glioblastoma multiforme, vestibular schwannoma, medulloblastoma, adenomas, gliomas, meningiomas, and pineal tumors. These findings hold the potential for developing novel therapeutic strategies and aiding in therapeutic management.

Volatilome of the maize phytopathogenic fungus Fusarium verticillioides: potential applications in diagnosis and biocontrol.

BACKGROUND: Fusarium verticillioides is a maize fungal phytopathogen and a producer of volatile organic compounds (VOCs) and fumonisin B1 (FB1). Our aim was to study the volatilome, conidial production, ergosterol and FB1 biosynthesis in maize cultures over a 30-day incubation period (5, 10, 15, 20, 25, 30 days post inoculation [DPI]). The effect of pure VOCs on the same parameters was then evaluated to study their potential role as biocontrol agents. RESULTS: In total, 91 VOCs were detected, with volatile profiles being more similar between 5 and 10 DPI compared with 15, 20, 25 and 30 DPI. Ergosterol content increased steadily with incubation time, and three growth stages were identified: a lag phase (0 to 15 DPI), an exponential phase (15 to 20 DPI) and a stationary phase (20 to 30 DPI). The maximum concentration of FB1 was detected at 25 (0.030 µg FB1/µg ergosterol) and 30 DPI (0.037 µg FB1/µg ergosterol), whereas conidial production showed a maximum value at 15 DPI (4.3 ± 0.2 × 105 conidia/µg ergosterol). Regarding pure VOCs, minimal inhibitory concentration values ranged from 0.3 mm for 4-hexen-3-one to 7.4 mm for 2-undecanone. Pure VOCs reduced radial growth, conidial production and ergosterol and FB1 biosynthesis. CONCLUSIONS: The marked resemblance between VOC profiles at 5 and 10 DPI suggests that they could act as early indicators of fungal contamination, particularly 4-ethylguaiacol, 4-ethyl-2-methoxyanisole, heptanol and heptyl acetate. On the other hand, their role as inhibitors of fungal growth and FB1 biosynthesis prove their great potential as safer alternatives to control phytopathogenic fungi. © 2024 Society of Chemical Industry.

Analysis of the relationship between resistin with prognosis, cell migration, and p38 and ERK1/2 activation in breast cancer.

Obesity increases the risk and mortality of breast cancer through dysregulated secretion of proinflammatory cytokines and tumor adipokines that induce an inflammatory breast microenvironment. Resistin is an adipokine secreted by adipocytes, immune cells, and predominantly macrophages, which contributes to cancer progression, but its molecular mechanism in cancer is not completely described. In this study, we analyzed the relationship of resistin on breast cancer prognosis and tumor progression and the effect in vitro of resistin on p38 and ERK1/2 activation in breast cancer cell lines. By bioinformatic analysis, we found that resistin is overexpressed in the basal subtype triple-negative breast cancer and is related to poor prognosis. In addition, we demonstrated a positive correlation between RETN and MAPK3 expression in basal triple-negative breast cancer. Importantly, we found amplifications of the RETN gene in at least 20 % of metastatic samples from patients with breast cancer. Most samples with RETN amplifications metastasized to bone and showed high expression of IL-8 (CXCL8) and IL-6 (IL6). Finally, resistin could be considered a prognostic marker for basal triple-negative breast cancer, and we also proposed the possibility that resistin-induced cell migration involves the activation of MAPK in breast cancer cells.

Mantle Cell Lymphoma in the Oral Cavity: Exploring the Differential Microscopic Diagnosis of a Rare Case.

Mantle cell lymphoma (MCL) is a rare subtype of B-cell non-Hodgkin's lymphoma (NHL), which generally has an aggressive course. Its pathophysiology seems to be related with the malignant transformation of B-cell mantle zone lymphocytes due to the CCND1 rearrangement. The occurrence of MCL in the oral cavity is especially rare. In this report, we present an exceptional case of oral MCL diagnosed in the palate in a 56-year-old male patient, highlighting its distinct morphological and immunohistochemical features that may assist in the accurate diagnosis.

Phenotypic Heterogeneity of Patients With Marfan Syndrome in Puerto Rico: A Case Series.

PURPOSE: Previous studies have reported on the cardiovascular, ocular, and musculoskeletal findings in patients with Marfan syndrome (MFS). This study aims to report the ocular and genotypic findings in patients with the syndrome in Puerto Rico. PATIENTS AND METHODS: A chart review of a cohort of patients with the syndrome from Puerto Rico was done. Patients were examined by at least one of the authors (NJI). Fibrillin-1 (FBN1) full gene sequencing was done to all patients (Laboratory for Molecular Medicine, Center for Genetics and Genomics, Cambridge, MA). This study was approved by the Institutional Review Board of the Universidad Central del Caribe (approval number: 2024-07).  Results: Six patients aged 28-79 years were examined. There were seven female and three male patients. The average visual acuity was 0.49 and 0.52 in the right eye (OD) and left eye (OS), respectively. The average refraction (spherical equivalent) was -1.28 sph OD and -1.07 sph OS. The average intraocular pressure was 14 mmHg in both eyes (OU). A patient had a dislocated lens OD; a patient had lens dislocation OU; and a patient had prosthesis OD and aphakia OS. Upon optical coherence tomography (OCT), the retinal nerve fiber layer (RNFL) average was 75.86 µm OD and 81.85 ​​µm OS; the average cup-to-disc (C/D) ratio was 0.41 and 0.35 in the right and left eye, respectively. Upon visual field testing, the average mean deviation (MD) was -6.27 dB OD and -8.55 dB OS. CONCLUSIONS: Our findings underscore the significant phenotypic and genotypic heterogeneity of patients with MFS in Puerto Rico. The identification of several mutations in the FBN1 gene in the Puerto Rican population demonstrates the need for an up-to-date approach to diagnose and co-manage patients with the syndrome. This study contributes to a deeper understanding of the genetic heritage of patients with the syndrome and highlights the potential for personalized therapeutic interventions.

Bio-adsorption of Fe (II) by dry biomass of metal-tolerant haloarchaeon Haloferax alexandrinus GUSF-1.

Mining-associated activities result in iron pollution exceeding the acceptable limit of 0.3 mg L- 1 and are rampant in estuarine soil and water bodies that harbor halophilic microorganisms. Biotechnologies are underway to unveil the concentrations and recover the metals that skip existing physico-chemical methods. Concerning this, the present study describes for the first time the development of a bio-adsorption batch system using dried cells of Haloferax alexandrinus GUSF-1 for Fe (II) from saline water under microaerophilic conditions. A maximum of 99.5% Fe (II) was adsorbed at pH 6.0, 30 ºC in 3 h with 92% efficiency over three adsorption-desorption cycles with saturation and pseudo-second-order kinetics and heterogeneity of Freundlich model having KF of 1.38 mg g- 1 with the n value of 0.96. Adsorbed Fe (II) by the cells was detected by scanning electron microscopy. The involvement of the carboxyl, amino, hydroxyl, and phosphate groups of the cells in interaction with the metal ions was detected by infrared spectroscopy. Conclusively, the study is the first report of whole dried cells mediated metal adsorption by the haloarcheon Haloferax alexandrinus GUSF-1 which acts as promising candidate for metal clean-up strategy and bioremediation in hypersaline ecosystems.

In vitro evidence that the vasorelaxant effects of 2-nitro-1-phenyl-1-propanol on rat coronary arteries involve cyclic nucleotide pathways.

The synthetic nitro-alcohol 2-nitro-1-phenyl-1-propanol (NPP) has endothelium-independent relaxing properties in isolated preparations of rat aorta and mesenteric artery. In this study, we investigated whether the vasodilator effects occur in coronary vessels and explored whether hyperpolarization is involved in the underlying mechanism of NPP-induced smooth muscle relaxation. The relaxing responses were studied in isolated preparations of the left anterior descending coronary (ADC) and the septal coronary (SC) arteries, which had been previously maintained under sustained contraction induced by the thromboxane A2 analogue U-46619. Administered cumulatively, NPP elicited concentration-dependent vasorelaxation with similar potency in both vessels. The relaxant effect remained unaffected by the nitric oxide synthase inhibitor L-NAME, the protein kinase C inhibitor bisindolylmaleimide IV and the Rho-associated protein kinase inhibitor Y-27632. However, it was significantly diminished by the adenylyl cyclase inhibitor MDL-12,330A, the guanylyl cyclase inhibitor ODQ, as well as the K+ channel inhibitors tetraethylammonium and CsCl. In ADC preparations impaled with intracellular micropipettes, NPP hyperpolarized the vascular preparation. When the isolated preparation was precontracted by 5-hydroxytryptamine or 80 mM KCl, NPP-induced relaxation with lower pharmacological potency compared to the vessels contracted by U-46619. In conclusion, NPP exhibits vasorelaxant effects on rat coronary arteries, likely involving pathways that include cyclic nucleotide production and membrane hyperpolarization.

Rare primary vasculitis: update on multiple complex diseases and the new kids on the block.

Systemic vasculitis is a group of rare diseases that share an essential characteristic: inflammation of blood vessel walls. This injury occurs during the disease course, but specific features vary for each entity. In this paper, we will address relevant aspects of the newest monogenic mutation vasculitis, such as deficiency of adenosine deaminase 2 (ADA2) and VEXAS syndrome (UBA1), and other relevant vasculitis, such as Cogan syndrome and Susac syndrome that may share some similarities with them.

A double ttrA and pduA knock-out mutant of Salmonella Typhimurium is not attenuated for mice (Mus musculus).

Despite numerous studies on Salmonella enterica subsp. enterica serovar Typhimurium, the underlying mechanisms of several aspects of its virulence are still under investigation, including the role of the pdu and ttrA genes, associated with the metabolism of 1,2-propanediol using tetrathionate as an electron acceptor respectively. Our objective was to contribute to an understanding of the role of these genes inbacterial virulence for mice (Mus musculus) using an S. Typhumirum ΔttrApduA mutant. The experiment was conducted with a group infected by the S. Typhimurium mutant and a control group infected with a wild-type strain. The mutant was not attenuated compared with the parent strain. There were no differences in the bacterial numbers recovered from the mesenteric lymph nodes and Peyer's patches but at 8-day after oral infection higher numbers were recovered from the spleen, liver, and cecum. Unlike the single pduA and ttrA mutants, the double ΔttrApduA mutation did not affect invasion and survival in mice, which highlights the need for further studies to clarify the role of these important metabolism genes under reduced redox conditions linked to Salmonella virulence.

Nitric oxide participates in sucrose-TOR signaling during meristem activation in Arabidopsis thaliana.

MAIN CONCLUSION: This study provides evidence about the relationship between Target of Rapamycin (TOR) kinase and the signal molecule nitric oxide (NO) in plants. We showed that sucrose (SUC)-mediated TOR activation of root apical meristem (RAM) requires NO and that NO, in turn, participates in the regulation of TOR signaling. Nitric oxide (NO) constitutes a signal molecule that regulates important target proteins related to growth and development and also contributes to metabolic reprogramming that occurs under adverse conditions. Taking into account the important role of NO and its relationship with Target of Rapamycin (TOR) signaling in animals, we wondered about the putative link between both pathways in plants. With this aim, we studied a TOR-dependent process which is the reactivation of the root apical meristem (RAM) in Arabidopsis thaliana. We used pharmacological and genetic tools to evaluate the relationship between NO and TOR on the sugar induction of RAM, using SNP as NO donor, cPTIO as NO scavenger and the nitrate reductase (NR) mutant nia2. The results showed that sucrose (SUC)-mediated TOR activation of the RAM requires NO and that NO, in turn, participates in the regulation of TOR signaling. Interestingly, TOR activation induced by sugar increased the NO levels. We also observed that NO could mediate the repression of SnRK1 activity by SUC. By computational prediction we found putative S-nitrosylation sites in the TOR complex proteins and the catalytic subunit of SnRK1, SnRK1.1. The present work demonstrates for the first time a link between NO and TOR revealing the complex interplay between the two pathways in plants.

Captopril inhibits the overproduction of proopiomelanocortin and adrenocorticotropic hormone in the pituitary gland of male diabetic mice in close relationship with an increase in glucocorticoid receptor expression.

Prior investigation shows that diabetic patients present hypothalamus-pituitary-adrenal (HPA) axis hyperactivity related to impaired negative feedback. This study investigates the effect of Captopril on the overproduction of adrenocorticotropic hormone (ACTH) and its precursor proopiomelanocortin (POMC) in the pituitary gland of male diabetic mice. Diabetes was induced by intravenous injection of alloxan into fasted Swiss-webster mice, and the animals were treated with Captopril for 14 consecutive days, starting 7 days post-diabetes induction. Plasma corticosterone levels were evaluated by ELISA, while pituitary gland expressions of angiotensin-II type 1 receptor (AT1), angiotensin-II type 2 receptor (AT2), ACTH, Bax, Bcl-2, KI-67, POMC, and glucocorticoid receptor (GR) were evaluated using immunohistochemistry or Western blot. Diabetic mice showed pituitary gland overexpression of AT1, without altering AT2 levels, which were sensitive to Captopril treatment. Furthermore, diabetic mice presented hypercortisolism, along with an increase in the number of corticotroph cells, POMC and ACTH expression, and number of proliferative cells, and a decrease of GR expression in the pituitary gland. In addition, treatment with Captopril reduced systemic corticosterone levels, corticotroph and proliferative cell numbers, and Bcl-2, POMC, and ACTH expression in the pituitary gland of diabetic mice, besides increasing the expression of Bax and GR. In conclusion, these findings show that Captopril is a promising therapy for treating complications associated with HPA axis hyperactivity in diabetic patients, in a mechanism probably related to the downregulation of POMC production in the pituitary gland and subsequent reduction of systemic corticosterone levels.

Thyroid Hormone Upregulates Cav1.2 Channels in Cardiac Cells via the Downregulation of the Channels' ß4 Subunit.

Thyroid hormone binds to specific nuclear receptors, regulating the expression of target genes, with major effects on cardiac function. Triiodothyronine (T3) increases the expression of key proteins related to calcium homeostasis, such as the sarcoplasmic reticulum calcium ATPase pump, but the detailed mechanism of gene regulation by T3 in cardiac voltage-gated calcium (Cav1.2) channels remains incompletely explored. Furthermore, the effects of T3 on Cav1.2 auxiliary subunits have not been investigated. We conducted quantitative reverse transcriptase polymerase chain reaction, Western blot, and immunofluorescence experiments in H9c2 cells derived from rat ventricular tissue, examining the effects of T3 on the expression of α1c, the principal subunit of Cav1.2 channels, and Cavß4, an auxiliary Cav1.2 subunit that regulates gene expression. The translocation of phosphorylated cyclic adenosine monophosphate response element-binding protein (pCREB) by T3 was also examined. We found that T3 has opposite effects on these channel proteins, upregulating α1c and downregulating Cavß4, and that it increases the nuclear translocation of pCREB while decreasing the translocation of Cavß4. Finally, we found that overexpression of Cavß4 represses the mRNA expression of α1c, suggesting that T3 upregulates the expression of the α1c subunit in response to a decrease in Cavß4 subunit expression.

Impacts of linseed oil diet on anxiety and memory extinction after early life stress: A sex-specific analysis of mitochondrial dysfunction, astrocytic markers, and inflammation in the amygdala.

Early exposure to stressors affects how the organism reacts to stimuli, its emotional state throughout life, and how it deals with emotional memories. Consequently, it may affect susceptibility to psychopathology later in life. We used an animal model of early stress by maternal separation to study its potential impact on the extinction of aversive memories and anxiety-like behavior in adulthood, as well as its effects on mitochondrial functionality, inflammatory and astrocytic markers in the amygdala. We also assessed whether a diet enriched with linseed oil, known for its high content in omega-3 fats, could be used to attenuate the behavioral and neurochemical effects of early stress. Litters of Wistar rats were divided into controls (intact) or subjected to maternal separation (MS). They were subdivided into two groups receiving isocaloric diets enriched in soy or linseed oils at weaning. In adulthood, the animals were exposed to the open field and the elevated plus maze, to evaluate exploratory activity and anxiety-like behavior. They were also trained in a context of fear conditioning, and afterward subjected to an extinction session, followed by a test session to evaluate the extinction memory. Amygdalae were evaluated for inflammatory cytokines (interleukin (IL)-1beta, IL-6, and tumor-necrose factor (TNF)-alpha), mitochondrial functionality, and astrocyte markers (glial fibrillary acidic protein - GFAP, S100B, and glutamine synthetase activity). MS induced anxiety-like behavior in the elevated plus-maze, which was reversed by a diet enriched in linseed oil offered from weaning. When testing the memory of an extinction session of fear conditioning, MS animals showed more freezing behavior. MS males receiving a linseed oil-enriched diet had lower functional mitochondria in the amygdala. In addition, MS led to increased inflammatory cytokines, particularly IL-1beta, and the diet enriched in linseed oil further increased these levels in MS animals. MS also increased S100B levels. These results point to a higher emotionality presented by MS animals, with higher levels of inflammatory cytokines and S100B. While a diet enriched in linseed oil attenuated anxiety-like behavior, it further altered amygdala IL-1beta and reduced mitochondria functionality, particularly in males. MS also increased glutamine synthetase activity in the amygdala, and this effect was higher when the animals received a diet enriched in linseed oil, particularly in females. In conclusion, these results point to MS effects on emotional behavior, and neurochemical alterations in the amygdala, with sex-specific effects. Although a diet enriched in linseed oil appears to be able to reverse some of MS behavioral effects, these results must be considered with caution, since biochemical parameters could be worsened in MS animals receiving a linseed oil-enriched diet. This knowledge is important for the understanding of mechanisms of action of strategies aiming to reverse early stress effects, and future studies are warranted to determine possible interventions to promote resilience.

Intrathyroidal neurofibroma, a case report. / Neurofibroma intratiroideo, a propósito de un caso.

Neurofibromatosis type 1 (NF1) is the most common neurocutaneous disease. It is characterized by café-au-lait spots, melanocytic hamartomas of the iris, pseudo-freckles, neurofibromas, and tumor predisposition. The presence of neurofibromas in the thyroid gland is extremely rare. Here we present the case of a 6-year-old male patient with NF1 who consulted at the Department of Endocrinology due to a thyroid tumor and whose ultrasound confirmed a heterogeneous mass at the posterior level of the right lobe. A cervical surgery found the tumor was adhered to the larynx and trachea, with the recurrent laryngeal nerve entering the tumor. Due to the impossibility of dissection, a right hemithyroidectomy was performed and the pathological examination confirmed the presence of plexiform neurofibroma and intrathyroidal neurofibroma. This is the second case reported in childhood and the youngest case to date. Neurofibroma with thyroid involvement should be suspected in patients with cervical mass and NF1, since diagnostic guidance allows avoiding unnecessary studies and guide treatment.

La neurofibromatosis tipo 1 (NF1) es la enfermedad neurocutánea más frecuente, caracterizada por manchas café con leche, hamartomas melanocíticos en iris, pseudoefélides, neurofibromas y predisposición a tumores. La presencia de neurofibromas en la glándula tiroides es extremadamente rara. Se presenta un paciente de sexo masculino de 6 años con NF1 que consultó al Servicio de Endocrinología por tumoración tiroidea, con ecografía que confirmó formación heterogénea a nivel posterior del lóbulo derecho. Se realizó cirugía cervical con tumor adherido a laringe y tráquea, con nervio recurrente que ingresaba al tumor. Por imposibilidad de disección, se realizó hemitiroidectomía derecha, con anatomía patológica confirmatoria de neurofibroma plexiforme y neurofibroma intratiroideo. Este caso es el segundo reportado en la infancia y el de menor edad hasta el momento. Se debe sospechar neurofibroma con compromiso tiroideo en pacientes con masa cervical y NF1, ya que la orientación diagnóstica permite evitar estudios innecesarios y orientar el tratamiento.

Fungiform Papillae and Gustatory Function in Neurofibromatosis Type 1: A Case-Control Study.

OBJECTIVE: Fungiform papillae enlargement is a common oral manifestation of neurofibromatosis type 1 (NF1). This study aimed to objectively evaluate the size, number, and symmetry of fungiform papillae in NF1 individuals and investigate the relationship between these alterations and taste perception, salivary flow, dietary habits, and BMI. MATERIALS AND METHODS: A cross-sectional case-control study was conducted on 80 participants (40 with NF1 and 40 controls), matched by age and sex. Participants underwent quantitative and morphological evaluation of fungiform papillae, gustatory perception tests, sialometry, saliva analysis, xerostomia assessment, dietary assessments, and Body Mass Index calculations. RESULTS: The NF1 group exhibited significantly larger and more asymmetric fungiform papillae and exhibited a higher detection threshold for sweet and sour tastes, as well as hyposalivation and lower preference for healthy foods compared to the controls. No correlation was found between papillae morphology, gustatory perception tests, saliva properties, xerostomia, food preferences, or BMI in the NF1 group. CONCLUSIONS: Enlarged and asymmetric fungiform papillae, hyposalivation, heightened sensitivity to sweet and sour tastes, and reduced healthy eating habits were common in NF1. Although fungiform papillae alterations seem unrelated to taste sensitivity and food preferences, further investigation is needed to better understand the mechanisms underlying these changes.

Modulation of the tumor microenvironment in non-muscle-invasive bladder cancer by OncoTherad® (MRB-CFI-1) nanoimmunotherapy: effects on tumor-associated macrophages, tumor-infiltrating lymphocytes, and monoamine oxidases.

Non-muscle-invasive bladder cancer (NMIBC) presents management challenges due to its high recurrence rate and a complex tumor microenvironment (TME). This study investigated the effects of OncoTherad® (MRB-CFI1) nanoimmunotherapy on the TME of BCG-unresponsive NMIBC, focusing on alterations in monoamine oxidases (MAO-A and MAO-B) and immune markers: CD163, FOXP3, CD8, and CX3CR1. A comparative analysis of immunoreactivities was made before and after OncoTherad® treatment and an immune score (IS) was established to evaluate the correlation between immunological changes and clinical outcomes. Forty bladder biopsies of twenty patients were divided into 2 groups (n = 20/group): 1 (pre-treatment biopsies); and 2 (post-treatment biopsies). Our results showed stable MAO-A levels but a significant (p < 0.05) decrease in MAO-B immunoreactivity after treatment, suggesting OncoTherad®'s efficacy in targeting the tumor-promoting and immunosuppressive functions of MAO-B. Significant (p < 0.05) reductions in CD163 and FOXP3 immunoreactivities were seen in post-treatment biopsies, indicating a decreased presence of M2 macrophages and Tregs. Corroborating with these results, we observed reductions in tumor histological grading, focality and size, factors that collectively enhanced recurrence-free survival (RFS) and pathological complete response (PCR). Moreover, elevated IFN-γ immunoreactivities in treated biopsies correlated with increased counts of CD8+ T cells and higher CX3CR1 expression, underscoring OncoTherad®'s enhancement of cytotoxic T cell functionality and overall antitumor immunity. The IS revealed improvements in immune responses post-treatment, with higher scores associated with better RFS and PCR outcomes. These findings validate OncoTherad®'s capability to modify the bladder cancer microenvironment favorably, promoting effective immune surveillance and response.

Anti-Cancer Potential of Linear ß-(1→6)-D-Glucan from Agaricus bisporus on Estrogen Receptor-Positive (ER+) Breast Cancer Cells.

Mushroom ß-D-glucans can be isolated from several species, including the widely consumed Agaricus bisporus. Besides immunomodulatory responses, some ß-D-glucans may exhibit direct antitumoral effects. It was previously observed that a ß-(1→6)-D-glucan (BDG16) has indirect cytotoxicity on triple-negative breast cancer cells. In this study, the cytotoxicity of this same glucan was observed on estrogen receptor-positive (ER+) breast cancer cells (MCF-7). Cell viability was determined by multiple methods to assess metabolic activity, lysosomal membrane integrity, and adhesion capacity. Assays to evaluate cell respiration, cell cycle, apoptosis, necroptosis, and oxidative stress were performed to determine the action of BDG16 on MCF-7 cells. A gradual and significant cell viability reduction was observed when the cells were treated with BDG16 (10-1000 µg/mL). This result could be associated with the inhibition of the basal state respiration after incubation with the ß-D-glucan. The cells showed a significant arrest in G1 phase population at 1000 µg/mL, with no induction of apoptosis. However, an increase in necrosis and necroptosis at the same concentration was observed. No difference in oxidative stress-related molecules was observed. Altogether, our findings demonstrate that BDG16 directly induces toxicity in MCF-7 cells, primarily by impairing mitochondrial respiration and promoting necroptosis. The specific mechanisms that mediate this action are being investigated.