Castanea sativa Mill. By-Products: Investigation of Potential Anti-Inflammatory Effects in Human Intestinal Epithelial Cells.

Castanea sativa Mill. (C. sativa) processing and pruning generate several by-products, including leaves, burs, and shells (inner and outer teguments), which are considered an important source of high-value phytochemicals. Ellagitannins from C. sativa leaf extracts have been described to impair H. pylori viability and inflammation in gastric cells. Furthermore, chestnut shells showed an important anti-inflammatory effect in gastric epithelial cells. Dietary polyphenols, including tannins, have been reported to interfere with targets of inflammation, including the nuclear factor κB (NF-κB). A promising role as a further therapeutical target for gut disorders has been recently proposed for the regulatory subunit of hypoxia-inducible factor (HIF-1α), as a potential stabilizer of intestinal barrier integrity. Therefore, the main objective of this work is the chemical characterization of several chestnut by-products (bud, spiny bur, wood, pericarp and episperm), together with the exploitation of their anti-inflammatory properties in intestinal cells, scavenging capacity, and stability following gastrointestinal digestion. The chemical characterization confirmed the presence of bioactive polyphenols in the extracts, including ellagitannins. In CaCo-2 cells stimulated by an IL-1ß-IFN-γ cocktail, nearly all chestnut by-products (50 µg/mL) inhibited the release of proinflammatory mediators (CXCL-10, IL-8, MCP-1, ICAM), along with the NF-κB-driven transcription, and induced the HRE-driven transcription. The stability of the most promising extracts, identified through PCA and cluster analysis, was addressed by in vitro gastrointestinal digestion. Despite the significant reduction in total polyphenol index of chestnut bud and wood after gastric and intestinal digestion, the activity of these extracts on both scavenging and anti-inflammatory parameters remained promising. These data contribute to exploit the potential of chestnut by-products as sources of dietary polyphenols with anti-inflammatory properties at the intestinal level. Moreover, this study could represent an important step to encourage the recycling and valorization of chestnut by-products, promoting the circular economy and reducing the environmental impact related to the management of agriculture waste.

A high-throughput screening identifies MCM chromatin loading inhibitors targeting cells with increased replication origins.

Replication origin assembly is a pivotal step in chromosomal DNA replication. In this process, the ORC complex binds DNA and, together with the CDC6 and CDT1, promotes the loading of the MCM helicase. Chemicals targeting origin assembly might be useful to sensitize highly proliferative cancer cells. However, identifying such compounds is challenging due to the multistage nature of this process. Here, using Xenopus laevis egg extract we set up a high-throughput screening to isolate MCM chromatin loading inhibitors, which led to the identification of NSC-95397 as a powerful inhibitor of replication origin assembly that targets CDC6 protein and promotes its degradation. Using systems developed to test selective drug-induced lethality we show that NSC-95397 triggers cell death both in human cells and Xenopus embryos that have higher proliferative ability. These findings demonstrate the effectiveness of molecules disrupting DNA replication processes in targeting hyperproliferating cells, highlighting their potential as anti-cancer molecules.

Investigation into the Anti-Acne Effects of Castanea sativa Mill Leaf and Its Pure Ellagitannin Castalagin in HaCaT Cells Infected with Cutibacterium acnes.

Acne vulgaris is a prevalent skin disorder affecting many young individuals, marked by keratinization, inflammation, seborrhea, and colonization by Cutibacterium acnes (C. acnes). Ellagitannins, known for their antibacterial and anti-inflammatory properties, have not been widely studied for their anti-acne effects. Chestnut (Castanea sativa Mill., C. sativa), a rich ellagitannin source, including castalagin whose acne-related bioactivity was previously unexplored, was investigated in this study. The research assessed the effect of C. sativa leaf extract and castalagin on human keratinocytes (HaCaT) infected with C. acnes, finding that both inhibited IL-8 and IL-6 release at concentrations below 25 µg/mL. The action mechanism was linked to NF-κB inhibition, without AP-1 involvement. Furthermore, the extract displayed anti-biofilm properties and reduced CK-10 expression, indicating a potential role in mitigating inflammation, bacterial colonization, and keratosis. Castalagin's bioactivity mirrored the extract's effects, notably in IL-8 inhibition, NF-κB inhibition, and biofilm formation at low µM levels. Other polyphenols, such as flavonol glycosides identified via LC-MS, might also contribute to the extract's biological activities. This study is the first to explore ellagitannins' potential in treating acne, offering insights for developing chestnut-based anti-acne treatments pending future in vivo studies.

Ellagitannins from Castanea sativa Mill. Leaf Extracts Impair H. pylori Viability and Infection-Induced Inflammation in Human Gastric Epithelial Cells.

Helicobacter pylori (H. pylori) is an etiologic factor of peptic ulcer disease and gastric cancer. Virulent strains of H. pylori are correlated with the severity of gastritis, due to NF-κB activation and IL-8 expression at the epithelial level. Ellagitannins have been documented for antibacterial and anti-inflammatory activities, thus suggesting their potential use in gastritis. Recently, several authors, including our group, demonstrated that tannin-rich extracts from chestnut byproducts, at present considered agricultural waste, display promising biological activities. In this work, we detected high levels of polyphenols in hydroalcoholic extracts from chestnut leaves (Castanea sativa L.). Among polyphenols, the ellagitannin isomers castalagin and vescalagin (about 1% w/w of dry extract) were identified as potential bioactive compounds. In GES-1 cells infected by H. pylori, leaf extract and pure ellagitannins inhibited IL-8 release (IC50 ≈ 28 µg/mL and 11 µM, respectively). Mechanistically, the anti-inflammatory activity was partly due to attenuation of NF-κB signaling. Moreover, the extract and pure ellagitannins reduced bacterial growth and cell adhesion. A simulation of the gastric digestion suggested that the bioactivity might be maintained after oral administration. At the transcriptional level, castalagin downregulated genes involved in inflammatory pathways (NF-κB and AP-1) and cell migration (Rho GTPase). To the best of our knowledge, this is the first investigation in which ellagitannins from plant extracts have demonstrated a potential role in the interaction among H. pylori and human gastric epithelium.

Multidisciplinary Management of Children with Occult Spinal Dysraphism: A Comprehensive Journey from Birth to Adulthood.

Occult spinal dysraphism (OSD) comprises different forms of failure in embryogenic development that can lead to genitourinary, spinal, or lower limb alterations, thus determining progressive neurological deterioration. The correct management of children harboring OSD represents a significant issue during their life up to adulthood. However, patients often have to entertain individual consultations with each specialist. We settled on a multidisciplinary team comprising pediatric neurosurgeons, urologists, neurologists, orthopedists, and other supporting physicians. We present the results of such actions by analyzing a series of 141 children with OSD subjected to neurosurgical procedures, evaluating the impact of multidisciplinary management on outcomes. We also evaluated the specific actions according to the different ages of OSD patients from birth to adulthood to provide a schematic plan that could represent a basis for establishing and disseminating the need for a multidisciplinary approach in OSD management. The multidisciplinary team allows all consultants to see the patient together, covering specific aspects of history and examination pertinent to their management. Offering a one-stop service prevents coordination issues between the different medical teams, avoids delays or cancellations of the various appointments, optimizes cost-effectiveness, and improves efficiency and parents' satisfaction.

A ±0.5dB, 6nW RSSI Circuit with RF Power-to-Digital Conversion Technique for Ultra-low Power IoT Radio Applications.

This paper presents a new technique of radio frequency (RF) signal strength detection with a received signal strength indicator (RSSI) circuit which can be deployed in an internet-of-things (IoT) network. The proposed RSSI circuit is based on a direct conversion of RF to digital code indicating the signal strength. The direct conversion is achieved by the repeated switching of a rectifier's output voltage using an ultra-low power comparator. A 5-bit programmable feedback circuit is used to correct detection inaccuracies. The RSSI circuit is implemented in a 65-nm CMOS process and consumes 6nW power. It has a linear dynamic range of 26dB and exhibits an error of ±0.5dB with a wide bandwidth of 750MHz. A detailed analysis of the RSSI circuit is presented and verified with simulation and measurement results. The high detection accuracy with ultra-low power consumption of our RSSI circuit is favourable for IoT applications including localization, beamforming, hardware security and other low-power applications.

Video-Assisted Thoracoscopy for Vertebral Body Tethering of Juvenile and Adolescent Idiopathic Scoliosis: Tips and Tricks of Surgical Multidisciplinary Management.

VATS (video assisted thoracoscopic surgery) is routinely and successfully performed in minor and major complex thoracic procedures. This technique has been recently introduced for the treatment of severe forms of idiopathic scoliosis (IS) with the aim to repair the deformity, reduce morbidity and to prevent its progression in patients with skeletal immaturity. This study aims to present VATS in anterior vertebral body tethering (AVBT) approach to support the pediatric orthopedic surgeons during vertebral body fixation. Surgical and anesthesiologic tips and tricks are reported to assure a safe procedure. The study includes preadolescents with IS and a grade of scoliosis >40° that had a high probability of deterioration due to remaining growth (December 2018 to April 2021). Skeletal immaturity of enrolled patients was assessed by Sanders classification and Risser sign. Patients had a Risser score between 0 and 1 and a Sanders score >2 and <5. AVBT technique using VATS was performed by a senior pediatric surgeon assisting the pediatric orthopedic surgeon. Twenty-three patients have been submitted to VATS AVBT in the period of study (age range 9-14 years). The patients had a classified deformity Lenke 1A or B convex right and all types of curves were treated. In all patients, the vertebrae submitted to tethering surgery ranged from D5 to D12; mean curve correction was 43%. Three postoperative complications occurred: one late postoperative bleeding requiring a chest tube positioning on 12th postoperative day; one screw dislodged and needed to be removed; one child showed worsening of the scoliosis and needed a posterior arthrodesis. Initial results of VATS AVBT in growing patients with spinal deformities are encouraging. An appropriate selection of patients and a pediatric dedicated multidisciplinary surgical approach decrease intraoperative complications, time of operation and postoperative sequelae and guarantee an optimal outcome.

Anterior vertebral body tethering as a treatment for scoliosis in skeletally immature patients.

A relatively new surgical procedure called Anterior Vertebral Body Tethering (AVBT) is used to treat scoliosis in patients with immature skeletons. It is a growth modulation fusionless system that Crowford and Lenke first described in 2010. We present our observations from 25 patients. Improvement in the mean coronal Cobb angle, from mean 57° preoperative to mean 34° postoperative, was 40%. Additionally, we noted that the mean thoracic hypokyphosis improved from 16° to 24° on average after surgery. Complication rates were 16% and surgical revision rates were 12%. All patients who demonstrated improvement in pain, function, and self-image underwent administration of the SRS-24 questionnaire. These data, according to the literature, show that AVBT is a reliable technique that enables scoliosis correction in skeletally immature patients and maintains that correction while utilizing remaining growth potential to achieve further correction, avoiding spinal fusion, and maintaining spine mobility.

High-Figure-of-Merit X-Cut Lithium Niobate MEMS Resonators Operating Around 50 MHz for Large Passive Voltage Amplification in Radio Frequency Applications.

This article reports on the modeling, design, fabrication, and testing of high-performance X-cut lithium niobate (LN) laterally vibrating resonators (LVRs) operating around 50 MHz. The objective of this work is to exploit the high figure of merit (FoM)-product of quality factor at series resonance ( Qs ) and electromechanical coupling ( kt2 )-to provide for large passive voltage amplification in the front end of emerging radio frequency (RF) applications, i.e., wake-up radio receivers (WuRx). Finite-element analysis (FEA) is performed to optimize the devices' geometry and ensure simultaneous high Qs and kt2 . Resonators exhibiting and % are demonstrated, with FoM >1650-the highest value recorded for resonators in the megahertz range to the best of our knowledge. Finally, passive voltage gains between 35 and 57 V/V are showcased for capacitive loads ranging from 400 fF to 1 pF.

Effects of magnetically controlled growing rods surgery on pulmonary function in young subjects with spinal muscular atrophy type 2 and other neuromuscular scoliosis.

BACKGROUND: The aim of this study was to determine the effects of magnetically controlled growing rods surgery (MCGRS) of the scoliosis on pulmonary function in children with neuromuscular scoliosis. METHODS: Seven patients, 85.7% female (mean±SD age: 6.7±1.2 years), with neuromuscular scoliosis (4 SMA II, 2 congenital myopathies and 1 VACTER syndrome), received MCGRS of the spine in the thoraco-lumbar area. The outcome measures were clinical features and pulmonary function (forced vital capacity [FVC] and forced expiratory volume in 1st second [FEV1], were collected. All measures were collected at pre-, post-intervention and follow-up (short-term [0-6 months], mid-term [7-12 months], and long-term [13-24 months]). RESULTS: MCGRS reduced Cobb angle after intervention in 100% in subjects and this result was maintained at 24-month follow-up (all, P=0.001). There was no significant difference in FVC or FEV1 between preoperative and each postoperative period, (P>0.05). Analyses of the correlation coefficients indicated no significant associations between changes in pulmonary function and scoliosis. CONCLUSIONS: The current study found that MCGRS addressed to the scoliosis maintained pulmonary function during long-term follow-up; However, pulmonary function was not associated with scoiosis in children with neuromuscular scoliosis.

A bio-guided approach for the development of a chestnut-based proanthocyanidin-enriched nutraceutical with potential anti-gastritis properties.

Gastritis is a widely spread inflammatory disease, mostly caused by Helicobacter pylori infection. Release of IL-8 by the stomach epithelium is a hallmark of gastritis and contributes to the amplification of the inflammatory state. Pharmacological modulation of IL-8 release is a strategy to relieve gastric inflammation and prevent more severe clinical outcomes. In search of nutraceuticals with potential anti-gastritis properties we used a bio-guided approach based on IL-8 secretion by gastric cells to characterize extracts from the fruits of different chestnut varieties. We found that the ability to inhibit IL-8 secretion correlated with the amount of proanthocyanidins and was associated to the not edible parts of chestnut in all the tested varieties. We also found that the anti-inflammatory activity is preserved upon mild thermal treatment and after in vitro simulated gastric digestion. By combining a robust bio-guided approach with a comprehensive analysis of the tannin fraction of chestnut extracts, we provide evidence for the potential use of chestnut-based nutraceuticals in human gastritis. The bioactive components of chestnut fruits inhibit IL-8 secretion by impairing NF-κB signaling and by other mechanisms, thus opening new applications of proanthocyanidins for inflammation-based diseases.

Revision of surgical correction of scoliosis in pediatric patients affected by neuromuscular pathology using Unit Rod instrumentation.

PURPOSE: The purpose of this study is to present a large consecutive series of pediatric patients affected by neuromuscular scoliosis treated with Unit Rod instrumentation. METHODS: Retrospective review of 160 children treated with Unit Rod instrumentation between 2003 and 2010. This review analyzed complications, radiographic outcome, time surgery, average blood loss, hospital staying and functional outcome of patients and parents after surgery. The follow-up of 80 patients is at more than 5 years. RESULTS: Scoliosis was corrected from a mean of 56° range 21° to 76° Cobb (68 %). Pelvic obliquity was corrected from a mean of 24° to 5° (74 %). Major complications are not related to the technique but to the pathology. CONCLUSION: Unit Rod instrumentation is a common standard technique, is considerably less expensive than the other system, and remains a good indication for the treatment of the spinal deformity in children affected by neuromuscular disease.