Silver nanoparticles (AgNPs) have emerged as a promising therapeutic tool for managing glioblastoma (GB), particularly in radiosensitisation. However, their mechanisms of action are not yet fully understood. Since ion channel activity is implicated in various aspects of radioresistance, we investigated the electrophysiological effects of AgNPs on GB cells. In the U251 human GB cell line, the acute application of AgNPs induced the activation of a cationic nonselective current in a dose-dependent manner, which was not affected by ACA (TRPM2 blocker). In addition, AgNPs increased intracellular calcium concentration, caused depolarisation of the mitochondrial inner membrane, and promoted membrane blebbing. The investigation revealed that calcium influx is a critical step in the AgNPs-induced effects. Thiol reagents such as cysteine are known silver chelating agents and their application prevented the activation of cationic currents, intracellular calcium increases, and membrane blebbing formation induced by AgNPs. This finding suggested Ag+ are the active species responsible for these effects, acting through IAg current previously characterized in our laboratory. Intracellular calcium influx induced by AgNPs activated intermediate-conductance calcium-activated potassium currents. This activation was accordingly blocked by TRAM-34, a selective inhibitor of KCa3.1 channels. Finally, AgNPs were found to reduce U251-GB cell viability in a dose-dependent manner and to increase G2/M phase accumulation following sublethal irradiation. In the presence of TRAM-34 the G2/M phase accumulation induced by the combined treatment with AgNPs and irradiation was reduced, suggesting the involvement of radioresistance-associated KCa3.1 currents. These results provide new insights into optimizing the use of AgNPs as radiosensitizing agents in GB therapy.

Synthetic biology has evolved from a set of engineering aspirations to an operationally sophisticated discipline, and artificial intelligence (AI) is its fastest-growing accelerant. This review traces that convergence across six interlocking domains: systems-level biological modeling, de novo protein engineering, metabolic and microbial programming, multi-omics data integration, regulatory element design, and clinical translation. For each domain, we survey established results, integrate findings from 2010–2026 literature, and articulate the trajectories that will define the next decade. Emerging themes include physics-informed neural networks for mechanistically constrained biological modeling, drug design, and federated learning architectures that allow global omics collaboration without centralizing sensitive data, self-driving laboratories that close the Design-Build-Test-Learn loop with minimal human intervention, and large language models that accelerate hypothesis generation from scientific literature. Alongside these opportunities, the review gives equal weight to the governance challenges they create: dual-use risks amplified by generative sequence design, the reproducibility crisis in AI-driven biodesign, and the equitable distribution of autonomous experimentation capacity. The overarching argument is that the promise of synthetic biology, making biological design as deliberate and reliable as any mature engineering discipline, is closer than ever, but will only be realized if technical ambition is matched by scientific rigor, transparent governance, and inclusive access.

Skeletal muscle differentiation is tightly regulated by membrane potential dynamics and voltage-dependent ion channel activity. Potassium (K+) and calcium (Ca2+) currents cooperate to orchestrate the transition of myoblasts into fusion-competent myotubes, and alterations in this process are associated with dystrophic phenotypes. Here, we investigated the electrophysiological remodeling accompanying C2C12 myogenesis and the modulatory effects of the polyphenol resveratrol (RES) on calcium voltage-gated channel subunit alpha 1 S (CACNA1S, Cav1.1, L-type) currents. Whole-cell patch-clamp recordings were performed in proliferating and differentiating C2C12 cells to characterize the temporal expression of K+ currents and voltage-dependent Ca2+ channels (VDCCs). During differentiation, three electrophysiological subpopulations were identified according to K+ current profiles: SK4+/EAG−/Kir−, SK4−/EAG+/Kir−, and SK4−/EAG+/Kir+. This sequence paralleled a progressive membrane hyperpolarization from −20 mV to −70 mV, consistent with the physiological maturation of myogenic cells. In C2C12 myocytes, nimodipine-sensitive L-type currents were the only Ca2+ conductance observed. Their activation threshold (~−30 mV) and half-activation voltage (V/2 ≈ −12 mV) indicated the co-expression of embryonic and adult Cav1.1 isoforms. Exposure to RES (30 µM, 48 h) produced a depolarizing shift in activation (ΔV/2 ≈ +9 mV) and a reduction in current amplitude across all voltages, consistent with a transition toward the adult splice variant of Cav1.1. These findings suggest that RES promotes electrophysiological maturation of skeletal muscle cells by modulating calcium channel expression and gating behavior. Given its known ability to correct splicing abnormalities in CACNA1S and related genes, resveratrol emerges as a promising pharmacological agent for restoring calcium homeostasis in neuromuscular disorders such as myotonic dystrophy type 1 (DM1).

BackgroundAlthough Merkel cells (MCs) are well-established mechanoreceptors in human skin, their function within the vaginal epithelium remains undefined. The aim of the present histological study was to investigate whether MCs located in the stratified epithelium of the anterior wall of the human vagina exhibit similar mechanosensory functions to those observed in the skin.MethodsImmunohistochemical analysis was performed on vaginal wall samples from eight women undergoing transabdominal or laparoscopic surgery. Immunohistochemical markers including cytokeratin 20 (CK20), neuron-specific enolase (NSE), synaptophysin (SYN), chromogranin A (CHRA), vasoactive intestinal peptide (VIP), calcitonin gene-related peptide (CGRP), PIEZO2 and protein gene product 9.5 (PGP9.5) were used to identify MCs and assess their distribution and phenotype. To better demonstrate the connection of MCs with nerve fibres, we used sequential double immune-enzymatic technique with different markers for MCs and for nerve fibres (primary antibodies against CK20 and PGP 9.5) and confirmed that none of examined MCs was in contact with the nerve fibre.ResultsMCs were identified as CK20-positive in all specimens (100%), NSE-positive in 88%, SYN-positive in 25%, CHRA-positive in 100%, and VIP-positive in 25%. No samples demonstrated positivity for CGRP and PIEZO2. MCs were localized predominantly in the basal epithelial layers as solitary cells, with CK20 the most effective detection method. Sequential double immune-enzymatic technique confirmed non- innervated Merkel cells with dendritic morphology.ConclusionsThis is the first study to address the possible function of MCs in the vaginal epithelium. The absence of PIEZO2 and CGRP expression, and low expression of VIP and SYN, suggests a non-mechanosensory and non-nociceptive role for MCs in the vaginal epithelium. The immunophenotypic profile supports a potential endocrine (paracrine or autocrine) function distinct from their role in human skin. Vaginal MCs probably form part of the neuroendocrine system of the vagina and maintain vaginal epithelial homeostasis and regeneration.

Cumulus cells (CCs), derived from granulosa cells, play a key role in supporting oocyte maturation and development through bidirectional communication. However, their electrophysiological properties in humans are poorly defined. Here, we characterized ionic currents and their modulation in primary human CCs obtained from patients undergoing in vitro fertilization. Whole cell patch-clamp recordings identified three electrophysiological sub-populations: CC-type 1, expressing voltage-dependent K+ currents supported mainly by potassium voltage-gated channel subfamily A member 5 (KV1.5, KCNA5); CC-type 2, predominantly showing a barium-sensitive cationic current attributable to transient receptor potential cation channel subfamily M member 5 (TRPM5); and CC-type 3, displaying mainly a noisy and voltage-dependent K+ current typical of potassium calcium-activated channel subfamily M alpha 1 (BKCa, KCNMA1). Pharmacological experiments, immunocytochemistry and rt-PCR confirmed the molecular expression of KCNA5, TRPM5 and KCNMA1. Mild extracellular acidification (pH = 6.2) rapidly and reversibly blocked TRPM5-like current, both inward and outward. Furthermore, 100 μM ATP induced metabotropic responses, evoking coupled intracellular Ca2+ release and activating TRPM5-mediated currents, as demonstrated by experiments with patch-clamp and FURA-2 calcium imaging. These findings reveal that human CCs integrate extracellular acidity and purinergic signals via distinct ion channels, suggesting a role as electrochemical sensors of the follicular microenvironment.

Following dental extraction, alveolar bone loss, driven by the osteoclast (OC) bone-eroding cells, is a relevant concern in dental practice since it could compromise the possibility of installing dental implants. This study aimed to develop a drug delivery system releasing the antiosteoclastogenic molecule gallic acid (GA) at the alveolar bone level to control the dysregulated balance between OCs and bone-building osteoblasts and thus delay bone erosion. We functionalized small blocks of the hydroxyapatite- and β-tricalcium phosphate-based RIGENERA BTK BCP biomaterial with layered double hydroxide (LDH) and GA (RIG_LDH-GA). By the in vitro model of Receptor Activator of Nuclear factor Kappa-Β Ligand (RANKL)-induced osteoclastogenesis in RAW 264.7 macrophages, we demonstrated that the conditioned medium (CM) obtained after 1-day incubation with RIG_LDH-GA contrasts the OC formation in a dose-dependent manner until a complete inhibition at the highest tested dose, while the unfunctionalized control (RIG) is ineffective. TRAP enzyme activity, OC marker gene expression, and bone resorption activity confirmed the antiosteoclastogenic effect of RIG_LDH-GA CM. Moreover, the expression of RANK (the RANKL’s receptor), otherwise induced by RANKL treatment, was reduced to the untreated control extent, consistent with the decreased expression of the transcription factors c-Fos and NFATc1, activated downstream in the RANK signaling pathway and inducing RANK itself. Thus, since GA released by the RIG_LDH-GA system effectively exerted an antiosteoclastogenic effect, RIGENERA BTK BCP functionalization with LDH and GA likely appears to be an osteoprotective upgrade of this biomaterial, already possessing bone regenerative properties, and might find successful clinical application in preventing osteoclast-mediated alveolar bone loss.

Background: Nanomedicine has shown significant promise in advancing cancer diagnostics and therapeutics. In particular, nanoparticles (NPs) offer potential for overcoming limitations associated with conventional therapies, such as off-target toxicity and side effects. Among the various NPs, silver nanoparticles (AgNPs) have garnered attention due to their cytotoxic and genotoxic properties in cancer cells. However, despite their potential, the optimization of AgNPs efficacy often necessitates combination strategies with other therapeutic agents. This study explores the potential of AgNPs integrated with Zr-based metal-organic frameworks (MOFs) UiO-66 for drug delivery, to enhance cancer therapy. Methods: We decorated amino-terephthalic based UiO-66-NH2 with AgNPs and loaded it with the chemotherapeutic agent cisplatin (Cis-Pt) to make the UiO-66-NH2@AgNPs@Cis-Pt. A preliminary MTT assay was conducted to evaluate the cytotoxic effects of the nanocomposite on several glioblastoma and other tumour cell lines, including U251, U87, GL261, HeLa, RKO, and HepG2. Results: Our results demonstrate that UiO-66-NH2@AgNPs@Cis-Pt and its combinations exhibit enhanced cytotoxicity compared to individual components such as AgNPs and Cis-Pt. Conclusions: This work offers preliminary insights into the potential of AgNP-functionalized MOFs as effective drug and delivery platforms, particularly in the context of combination therapy for cancer treatment.

The final trigger of oocyte maturation is a pivotal step in assisted reproductive technology (ART). Different molecules and protocols-including human chorionic gonadotropin (hCG), gonadotropin-releasing hormone agonists (GnRHa), the dual trigger, the double trigger, and emerging agents such as kisspeptin-have been investigated to optimize oocyte competence, embryo development, and pregnancy outcomes while minimizing the risk of ovarian hyperstimulation syndrome (OHSS). HCG remains the most widely used trigger, but its pharmacological profile is associated with a significant risk of OHSS. GnRHa has emerged as an alternative in antagonist cycles, abolishing the risk of severe OHSS but often requiring tailored luteal phase support. Several strategies, including hCG, GnRHa, and combined approaches, have shown improvements in specific outcomes such as the oocyte maturity (MII) rate, fertilization rate, embryo development parameters, and, in selected contexts, a reduction in OHSS risk. Kisspeptin represents a promising option; however, its use remains predominantly within the research setting, with clinical application still limited to early-phase or highly selected studies. Beyond the choice of molecule, the timing of trigger administration-adjusted to follicle size, estradiol concentrations, and progesterone levels-also influences oocyte competence and subsequent clinical outcomes. Triggering final oocyte maturation remains a multifaceted decision that should be individualized according to patient characteristics, ovarian response, and risk of OHSS. Although hCG remains the historical reference standard, accumulating but heterogeneous evidence suggests that GnRHa-based strategies, including dual-trigger protocols, may improve specific outcomes in selected patient subgroups. However, results across trials are inconsistent, particularly in poor responders, and any exposure to hCG maintains a residual risk of OHSS. Kisspeptin represents a promising but still experimental option, with current data largely limited to early-phase clinical studies in highly selected high-risk populations. Well-designed randomized trials are required to clarify the true impact of these strategies on live birth, to refine timing and dosing, and to better define which patients are most likely to benefit.

Ceramide is a critical molecule in both the physiology and pathology of the central nervous system. The most studied aspect is its effect on embryonic/stem cells. A salient question is whether low doses of ceramide induce neuronal differentiation without interfering with sphingolipid metabolism and whether high doses can be used in glioblastoma for their cytotoxic effect. Here, we examined the effect of a high dose of ceramide (13 µM) on HN9.10e cells. Interestingly, 13 µM ceramide induced an immediate increase in cell viability, followed by an increase in the number of mitochondria. Microscopic and morphometric analysis revealed a decrease in the number of differentiated cells with 13 µM compared to 0.1 µM but with longer neurites. Furthermore, the lipidomic study demonstrated an increase in the formation of medium–long-chain ceramide and sphingomyelin species and sphingosine 1 phosphate. Sphingolipid modification correlated with SMPD3, ASAH2, and SPHK2 gene expression coding for neutral sphingomyenase 2, ceramidase 2, and sphingosine kinase 2, respectively. Overall, our data show that the variety of responses to ceramide of the same cell type is dependent on the concentration used. Low doses do not affect sphingolipid metabolism, and high doses do so with a different cellular response.

BACKGROUND:Embryo implantation and early survival in a synchronized, receptive endometrium are critical for establishing a successful pregnancy, but uterine pathologies can present challenges to reproductive success by significantly impacting this complex process. OBJECTIVES:The purpose of this review was to analyze the impact of uterine pathologies on embryo implantation, early embryo survival, and finally on the development of infertility, with references to reproductive outcomes and the main evidence related to therapeutic strategies. METHODS:The relevant publications were identified after queries of the following sources: PubMed, Google Scholar, Web of Science, and publishers' databases, complemented by a cross-check of the reference lists. We used a combination of the search terms "uterine pathology," "infertility," "embryo implantation," and "embryo survival" with terms relevant to the topic of each paragraph, such as "endometrial polyps (EPs)," "leiomyoma," "uterine malformations," "adenomyosis," and "intrauterine adhesions (IUAs)." OUTCOME:All articles describing the influence of each uterine pathology on embryo implantation/early survival were included, with a focus on the role of EPs, leiomyomas, uterine malformations, adenomyosis, and IUAs. CONCLUSIONS AND OUTLOOK:The exact influence of uterine diseases on the uterine-embryo crosstalk is unknown. Nevertheless, numerous molecular mechanisms have been proposed to explain some of the underlying processes. Tailored treatments for each specific disease may improve the endometrial milieu and, thus, reproductive outcomes. Future studies should aim to further understand the underlying molecular phenomena driving the development of these pathologies, how they may disrupt early embryo life stages, and the exact benefit of medical and surgical treatments on embryo survival.

Amniotic fluid is a complex and dynamic biological matrix that surrounds the fetus during the pregnancy. From this fluid, is possible to isolate various cell types with particular interest directed towards stem cells (AF-SCs). These cells are highly appealing due to their numerous potential applications in the field of regenerative medicine for tissues and organs as well as for treating conditions such as traumatic or ischemic injuries to the nervous system, myocardial infarction, or cancer. AF-SCs, when subcultured in the presence of basic Fibroblast Growth Factor (bFGF), have been shown to survive and migrate when transplanted into the striatum of the rat brain, exhibiting behavior characteristics of neuronal/glial progenitor cells. In this work, we performed an electrophysiological characterization to ascertain the propensity of AF-SCs to differentiate into glial and neuronal cells by bFGF. By using patch clamp technique we characterized a fibroblast-like morphology that display a barium-sensitive inward-rectifying potassium current (Kir) and calcium-activated potassium currents (KCa). The electrophysiological and calcium dynamics of histamine, a marker of undifferentiated neural progenitors, was further studied. Histamine promoted intracellular calcium increase by Fura-2 recording and calcium-activated potassium current activation with a similar temporal profile in AF-SC. The data presented in this paper ultimately confirm the expression in AF-SCs of the Kir and KCa currents, also showing regulation by endogenous stimuli such as histamine for the latter.

Thermo-oxidative stability testing plays a critical role in accurately predicting shelf life. These tests are performed in real time and under stress conditions, where degradation processes are accelerated by increasing storage conditions. In this study, high-performance liquid chromatography (HPLC) analyses were performed to evaluate the degradation of resveratrol in nutraceutical tablets as a function of time under different storage conditions in terms of temperature and relative humidity (RH), namely 25 °C/60% RH, 30 °C/65% RH, and 40 °C/75% RH. The latter is an accelerated test and is used to estimate shelf life for long-term storage. Resveratrol is present in both pure form and as a solid dispersion on magnesium dihydroxide microparticles (Resv@MDH). Degradation kinetic constants were determined at 25 °C, 30 °C, and 40 °C, and the Arrhenius behavior of the kinetic constants as a function of temperature was verified. The main results of this work are as follows: (i) the stability of resveratrol in nutraceutical tablets is affected by temperature; (ii) the dependence of the kinetic constants on temperature does not follow the Arrhenius equation, determining an overestimation of the degradation rate at 25 °C; in this regard a modified version of the Arrhenius equation that takes into account the deviation from linearity has been used to estimate the dependence of the kinetic constant on the temperature. These results suggest that accelerated testing does not provide a general model for predicting the shelf life of foods and dietary supplements. The reason may be due to possible matrix effects that result in different degradation mechanisms depending on the temperature. In this regard, symmetry relationships in the kinetics of chemical reactions resulting from microscopic reversibility and their relationship to the deviation from the Arrhenius equation are discussed. However, further research is needed to characterize the degradation mechanisms at different temperatures. The results of these studies would allow accurate prediction of food degradation to improve food safety and risk management and reduce food waste. In addition, knowledge of stability processes is necessary to ensure the maintenance of physiological processes by dietary supplements.

Background Resveratrol is a natural polyphenolic compound present in plants and red wine with many potential health benefits. This compound has various anti-inflammatory and anti-tumor properties and can improve cellular mitochondrial activity. This trial was designed to evaluate the effect on the outcome of IVF of Resveratrol supplementation in women > 35 years with good ovarian reserve (AMH > 1.2 ng/ml). Women were randomized to receive or placebo or Resveratrol (150 mg per day) for three months preceding the ovarian stimulation (OS). All patients were stimulated with a starting dose of recombinant FSH ranging between 150 and 300 IU according to age and ovarian reserve. GnRH antagonist flexible protocol was adopted for pituitary suppression. Triggering was performed with urinary hCG (10.000 IU). Results The study was conducted between January 2019 and December 2022 with aa total of 37 cases and 33 controls were recruited. No statistically significant differences in the number of oocytes retrieved, biochemical pregnancy, clinical pregnancy and live birth rates were observed between women treated with resveratrol and control group. A statistically significant increase in the follicle output rate (FORT) and follicle-to oocyte index (FOI) was observed in women treated with resveratrol-based nutraceutical (0.92 versus 0.77 [p = 0.02], and 0.77 versus 0.64 [p = 0.006], respectively). Conclusions Preliminary results from this study indicate that pre-treatment with resveratrol may improve ovarian sensitivity to exogenous FSH, which in turn may decrease the risk of hypo-response to OS in advanced reproductive age women.

The uterus is a highly innervated organ, and during labor, this innervation is at its highest level. Oxytocinergic fibers play an important role in labor and delivery and, in particular, the Lower Uterine Segment, cervix, and fundus are all controlled by motor neurofibers. Oxytocin is a neurohormone that acts on receptors located on the membrane of the smooth cells of the myometrium. During the stages of labor and delivery, its binding causes myofibers to contract, which enables the fundus of the uterus to act as a mediator. The aim of this study was to investigate the presence of oxytocinergic fibers in prolonged and non-prolonged dystocic delivery in a cohort of 90 patients, evaluated during the first and second stages of labor. Myometrial tissue samples were collected and evaluated by electron microscopy, in order to quantify differences in neurofibers concentrations between the investigated and control cohorts of patients. The authors of this experiment showed that the concentration of oxytocinergic fibers differs between non-prolonged and prolonged dystocic delivery. In particular, in prolonged dystocic delivery, compared to non-prolonged dystocic delivery, there is a lower amount of oxytocin fiber. The increase in oxytocin appeared to be ineffective in patients who experienced prolonged dystocic delivery, since the dystocic labor ended as a result of the altered presence of oxytocinergic fibers detected in this group of patients.

Human glioblastoma is probably the most malignant and aggressive among cerebral tumors, of which it represents approximately 80% of the reported cases, with an overall survival rate that is quite low. Current therapies include surgery, chemotherapy, and radiotherapy, with associated consistent side effects and low efficacy. The hardness in reaching the site of action, and overcoming the blood–brain barrier, is a major limitation of pharmacological treatments. In this paper, we report the synthesis and characterization of ZIF-90 (ZIF, Zeolitic Imidazolate Framework) nanoparticles as putative carriers of anticancer drugs to the brain. In particular, we successfully evaluated the biocompatibility of these nanoparticles, their stability in body fluids, and their ability to uptake in U251 human glioblastoma cell lines. Furthermore, we managed to synthesize ZIF-90 particles loaded with berberine, an alkaloid reported as a possible effective adjuvant in the treatment of glioblastoma. These findings could suggest ZIF-90 as a possible new strategy for brain cancer therapy and to study the physiological processes present in the central nervous system.

IntroductionPolycystic ovary syndrome (PCOS) is a common multifactorial and polygenic disorder of the endocrine system, affecting up to 20% of women in reproductive age with a still unknown etiology. Follicular fluid (FF) represents an environment for the normal development of follicles rich in metabolites, hormones and neurotransmitters, but in some instances of PCOS the composition can be different. Vasoactive intestinal peptide (VIP) is an endogenous autonomic neuropeptide involved in follicular atresia, granulosa cell physiology and steroidogenesis.MethodsELISA assays were performed to measure VIP and estradiol levels in human follicular fluids, while AMH, FSH, LH, estradiol and progesterone in the plasma were quantified by chemiluminescence. UHPLC/QTOF was used to perform the untargeted metabolomic analysis.ResultsOur ELISA and metabolomic results show: i) an increased concentration of VIP in follicular fluid of PCOS patients (n=9) of about 30% with respect to control group (n=10) (132 ± 28 pg/ml versus 103 ± 26 pg/ml, p=0,03) in women undergoing in vitro fertilization (IVF), ii) a linear positive correlation (p=0.05, r=0.45) between VIP concentration and serum Anti-Müllerian Hormone (AMH) concentration and iii) a linear negative correlation between VIP and noradrenaline metabolism. No correlation between VIP and estradiol (E2) concentration in follicular fluid was found. A negative correlation was found between VIP and noradrenaline metabolite 3,4-dihydroxyphenylglycolaldehyde (DOPGAL) in follicular fluids.ConclusionVIP concentration in follicular fluids was increased in PCOS patients and a correlation was found with noradrenaline metabolism indicating a possible dysregulation of the sympathetic reflex in the ovarian follicles. The functional role of VIP as noradrenergic modulator in ovarian physiology and PCOS pathophysiology was discussed.

SARS-CoV-2 is the causative agent of the COVID-19 pandemic, the acute respiratory disease which, so far, has led to over 7 million deaths. There are several symptoms associated with SARS-CoV-2 infections which include neurological and psychiatric disorders, at least in the case of pre-Omicron variants. SARS-CoV-2 infection can also promote the onset of glioblastoma in patients without prior malignancies. In this study, we focused on the Envelope protein codified by the virus genome, which acts as viroporin and that is reported to be central for virus propagation. In particular, we characterized the electrophysiological profile of E-protein transfected U251 and HEK293 cells through the patch-clamp technique and FURA-2 measurements. Specifically, we observed an increase in the voltage-dependent (Kv) and calcium-dependent (KCa) potassium currents in HEK293 and U251 cell lines, respectively. Interestingly, in both cellular models, we observed a depolarization of the mitochondrial membrane potential in accordance with an alteration of U251 cell growth. We, therefore, investigated the transcriptional effect of E protein on the signaling pathways and found several gene alterations associated with apoptosis, cytokines and WNT pathways. The electrophysiological and transcriptional changes observed after E protein expression could explain the impact of SARS-CoV-2 infection on gliomagenesis.

In eutocic labor, the autonomic nervous system is dominated by the parasympathetic system, which ensures optimal blood flow to the uterus and placenta. This study is focused on the detection of the quantitative presence of catecholamine (C) neurofibers in the internal uterine orifice (IUO) and in the lower uterine segment (LUS) of the pregnant uterus, which could play a role in labor and delivery. A total of 102 women were enrolled before their submission to a scheduled cesarean section (CS); patients showed a singleton fetus in a cephalic presentation outside labor. During CS, surgeons sampled two serial consecutive full-thickness sections 5 mm in depth (including the myometrial layer) on the LUS and two randomly selected samples of 5 mm depth from the IUO of the cervix. All histological samples were studied to quantify the distribution of A nerve fibers. The authors demonstrated a significant and notably higher concentration of A fibers in the IUO (46 ± 4.8) than in the LUS (21 ± 2.6), showing that the pregnant cervix has a greater concentration of A neurofibers than the at-term LUS. Pregnant women’s mechanosensitive pacemakers can operate normally when the body is in a physiological state, which permits normal uterine contractions and eutocic delivery. The increased frequency of C neurofibers in the cervix may influence the smooth muscle cell bundles’ activation, which could cause an aberrant mechano-sensitive pacemaker activation–deactivation cycle. Stressful circumstances (anxiety, tension, fetal head position) cause the sympathetic nervous system to become more active, working through these nerve fibers in the gravid cervix. They might interfere with the mechano-sensitive pacemakers, slowing down the uterine contractions and cervix ripening, which could result in dystocic labor.

Oocyte–cumulus cell interaction is essential for oocyte maturation and competence. The bidirectional crosstalk network mediated by gap junctions is fundamental for the metabolic cooperation between these cells. As cumulus cells exhibit a more glycolytic phenotype, they can provide metabolic substrates that the oocyte can use to produce ATP via oxidative phosphorylation. The impairment of mitochondrial activity plays a crucial role in ovarian aging and, thus, in fertility, determining the success or failure of assisted reproductive techniques. This review aims to deepen the knowledge about the electro-metabolic coupling of the cumulus–oocyte complex and to hypothesize a putative role of potassium channel modulators in order to improve fertility, promote intracellular Ca2+ influx, and increase the mitochondrial biogenesis and resulting ATP levels in cumulus cells.

Based on low solubility in water and high membrane permeability, resveratrol is collocated in the second class of the Biopharmaceutical Classification System, with limited absorption derived from a low dissolution rate. Solid microdispersion of resveratrol supported by magnesium dihydroxide (Resv@MDH, trademark Revifast®) represents a physical mixture of resveratrol (30% w/w) and magnesium dihydroxide (70% w/w) obtained by traditional techniques, such as mixing and micronization under appropriate conditions. Establishing the wide use of Revifast® in food supplements, in the present work we deepen its physicochemical characterization by using diffractometric and infrared analysis. No novel species are found in the Resv@MDH mixture except magnesium dihydroxide and resveratrol extracted from Polygonum cuspidatum. The results herein reported strengthened the safety of Revifast® ingredients for resveratrol-based food supplements.