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Abstract Background The aim of this study was to assess the ability of radiologic factors such as mean computed tomography (mCT) value, consolidation/tumor ratio (C/T ratio), solid tumor size, and the maximum standardized uptake (SUVmax) value by F-18 fluorodeoxyglucose positron emission tomography to predict the presence of spread through air spaces (STAS) of lung adenocarcinoma. Methods A retrospective study was conducted on 118 patients those diagnosed with clinically without lymph node metastasis and having a pathological diagnosis of adenocarcinoma after undergoing surgery. Receiver operating characteristics (ROC) analysis was used to assess the ability to use mCT value, C/T ratio, tumor size, and SUVmax value to predict STAS. Univariate and multiple logistic regression analyses were performed to determine the independent variables for the prediction of STAS. Results Forty-one lesions (34.7%) were positive for STAS and 77 lesions were negative for STAS. The STAS positive group was strongly associated with a high mCT value, high C/T ratio, large solid tumor size, large tumor size and high SUVmax value. The mCT values were − 324.9 ± 19.3 HU for STAS negative group and − 173.0 ± 26.3 HU for STAS positive group (p

Lipids in the stratum corneum play an important role in the formation of the skin permeability barrier. The causative gene for congenital ichthyosis, NIPAL4, encodes a Mg2+ transporter and is involved in increases in intracellular Mg2+ concentrations that depend on keratinocyte differentiation. However, the role of this increased Mg2+ concentration in skin barrier formation and its effect on the lipid composition of the stratum corneum has remained largely unknown. Therefore, in the present study, we performed a detailed analysis of epidermal lipids in Nipal4 KO mice via TLC and MS. Compared with WT mice, the Nipal4 KO mice showed compositional changes in many ceramide classes (including decreases in ω-O-acylceramides and increases in ω-hydroxy ceramides), together with increases in ω-hydroxy glucosylceramides, triglycerides, and free fatty acids and decreases in ω-O-acyl hydroxy fatty acids containing a linoleic acid. We also found increases in unusual ω-O-acylceramides containing oleic acid or palmitic acid in the KO mice. However, there was little change in levels of cholesterol or protein-bound ceramides. The TLC analysis showed that some unidentified lipids were increased, and the MS analysis showed that these were special ceramides called 1-O-acylceramides. These results suggest that elevated Mg2+ concentrations in differentiated keratinocytes affect the production of various lipids, resulting in the lipid composition necessary for skin barrier formation.

Spontaneous regression (SR) of cancer is very rare, especially of small cell lung cancer (SCLC). Recently, an association of paraneoplastic neurological syndrome (PNS) has been reported as a cause of SR of cancer, and onconeural antibodies are a possible factor in the SR of cancer associated with PNS. We herein report the first case of SR of SCLC combined with anti-P/Q-type of voltage-gated calcium channel (VGCC) antibody-positive Lambert-Eaton myasthenic syndrome (LEMS), a subtype of PNS. This case report suggests that SCLC may be spontaneously reduced by an autoimmune response induced by VGCC antibodies associated with LEMS. Our finding may help elucidate the mechanisms that inhibit tumor growth and cause the regression of tumors.

Abstract Low‐grade fibromyxoid sarcoma (LGFMS) is a rare mesenchymal tumor that primarily arises in the limbs and trunk of young adults, and rarely in the thoracic cavity. An 84‐year‐old Japanese woman presented with a right intrathoracic mass which was 8 cm in size. CT‐guided needle biopsy did not provide a definitive diagnosis. Perioperatively, a mass was found in the right lower lobe of the lung and was suspected to have invaded the chest wall at the sixth–eighth ribs. A right lower lobectomy and combined chest wall resection were performed. Microscopic examination revealed that the tumor was a low‐grade spindle cell tumor originating from the pleura demonstrating focal invasion of the lung. The tumor exhibited positivity for MUC4, and FUS gene translocation was confirmed through fluorescence in situ hybridization. Unfortunately, 10 months postoperatively, tumor recurrence was noted as peritoneal dissemination, and the patient passed away 13 months postoperatively. Although LGFMS may be diagnosed histologically as a low‐grade tumor by needle biopsy, in this case, it was highly malignant. Postoperative long‐term regular medical follow‐up is recommended considering the highly malignant nature of the tumor and the high risk of local recurrence and pulmonary metastasis.

A male patient (age: 85 -years) with lung cancer underwent basal segmentectomy. Subsequently, he underwent emergency open window thoracotomy for a bronchial stump fistula. The general and nutritional conditions of the patient improved; nevertheless, natural closure of the fistula did not occur. Therefore, the patient underwent fistula closure using an endobronchial Watanabe spigot, polyglycolic acid sheet and N-butyl-2-cyanoacrylate. Nine months later, the fistula had enlarged. The air leak was treated by applying pressure with gauze; however, this approach was not sufficiently effective, and the patient became unable to expectorate phlegm or speak. One side of a straight-type silicone stent with an outer diameter measuring 9mm was closed, and the stent was inserted into the fistula through the fenestration with the closed side at the tip. The L-sized endobronchial Watanabe spigot was placed into the lumen of the stent to reinforce it. Air leak from the fistula was significantly reduced, making breathing and expectoration easier. Retrograde closure of a bronchial fistula using a unilaterally closed silicon stent can be an effective treatment for large, refractory bronchial fistulas.

Abstract An 84‐year‐old man underwent right basal segmentectomy for primary lung cancer and developed empyema accompanied by a bronchopleural fistula (BPF). Emergency open‐window thoracotomy was performed. Although the general and nutritional conditions improved, the fistula did not close naturally, and we planned to close it 6 months after surgery. In this report, we describe, for the first time, a novel method for closing BPF using an endobronchial Watanabe spigot (EWS), polyglycolic acid (PGA) sheet and N‐butyl‐2‐cyanoacrylate (NBCA). We named this method the“sandwich method.”

The increasing need for pulmonary resection by video‐assisted thoracoscopic surgery (VATS) has presented a greater opportunity to detect small‐sized pulmonary nodules by computed tomography (CT). In cases where it is difficult to identify tumor localization intraoperatively, it is necessary to place the VATS marker near the pulmonary nodules before surgery. Conventional percutaneous or bronchoscopic VATS marker placement under local anesthesia is accompanied by patient pain. We clinically applied a new technique to place VATS markers using a bronchoscope under general anesthesia in a hybrid operating room. Multiple pulmonary nodules were successfully marked and securely excised simultaneously by VATS. This technique enables secure, minimally invasive resection of multiple small‐sized pulmonary nodules without causing distress to the patient.

Objective To determine the appropriate amount of indocyanine green for bronchial insufflation. Methods We enrolled 20 consecutive patients scheduled for anatomical segmentectomy in the Kochi Medical School Hospital. After inducing general anesthesia, 6 to 60 mL of 200-fold-diluted indocyanine green (0.0125 mg/mL) was insufflated into the subsegmental bronchi in the targeted pulmonary segmental bronchus. The volume of the targeted pulmonary segments was calculated using preoperative computed tomography. Fluorescence spread in the segmental alveoli was visualized using a dedicated near-infrared thoracoscope. Results The targeted segment was uniformly visualized by indocyanine green fluorescence in 16/20 (80.0%) cases after insufflating indocyanine green. A receiver operating characteristic curve indicated that the area under the curve was 0.984; the optimal cut-off volume of diluted indocyanine green for insufflation was 8.91% of the calculated targeted pulmonary segment volume. Conclusions The setting for indocyanine green insufflation was optimized for near-infrared fluorescence image-guided anatomical segmentectomy. By injecting the correct amount of indocyanine green, fluorescence-guided anatomical segmentation may be performed more appropriately.

Abstract Background Minimally invasive video-assisted thoracoscopic surgery for small-sized pulmonary nodules is challenging, and image-guided preoperative localisation is required. Near-infrared indocyanine green fluorescence is capable of deep tissue penetration and can be distinguished regardless of the background colour of the lung; thus, indocyanine green has great potential for use as a near-infrared fluorescent marker in video-assisted thoracoscopic surgery. Methods Thirty-seven patients with small-sized pulmonary nodules, who were scheduled to undergo video-assisted thoracoscopic wedge resection, were enrolled in this study. A mixture of diluted indocyanine green and iopamidol was injected into the lung parenchyma as a marker, using either computed tomography-guided percutaneous or bronchoscopic injection techniques. Indications and limitations of the percutaneous and bronchoscopic injection techniques for marking nodules with indocyanine green fluorescence were examined and compared. Results In the computed tomography-guided percutaneous injection group (n = 15), indocyanine green fluorescence was detected in 15/15 (100%) patients by near-infrared thoracoscopy. A small pneumothorax occurred in 3/15 (20.0%) patients, and subsequent marking was unsuccessful after a pneumothorax occurred. In the bronchoscopic injection group (n = 22), indocyanine green fluorescence was detected in 21/22 (95.5%) patients. In 6 patients who underwent injection marking at 2 different lesion sites, 5/6 (83.3%) markers were successfully detected. Conclusion Either computed tomography-guided percutaneous or bronchoscopic injection techniques can be used to mark pulmonary nodules with indocyanine green fluorescence. Indocyanine green is a safe and easily detectable fluorescent marker for video-assisted thoracoscopic surgery. Furthermore, the bronchoscopic injection approach enables surgeons to mark multiple lesion areas with less risk of causing a pneumothorax. Trial Registration UMIN-CTR R000027833 accepted by ICMJE. Registered 5 January 2013.

The extent of spontaneous recovery in patients with a spinal cord injury (SCI) has not been thoroughly investigated. It is essentially not known whether SCI animals exhibit full recovery from both motor and sensory deficits as well. Here, we developed an appropriate condition to produce a mild SCI in mice. Mice given a mild contusion SCI showed transient low performances in the Basso Mouse Scale for locomotion (BMS), rotarod and beam walking tests after the SCI, which was followed by complete restoration in a short time. The SCI mice also showed functional full recovery from low sensitivity to light touch using dynamic touch test. Nevertheless, the fully-recovered SCI mice still exhibited significant loss of myelin in the spinal cord. These results suggest a high potential of adaptation of motor and sensory systems in mice and might provide insight into the prognoses of SCI patients.

A critical role for mitochondrial dysfunction has been shown in the pathogenesis of fibromyalgia. It is a chronic pain syndrome characterized by neuroinflammation and impaired oxidative balance in the central nervous system. Boswellia serrata (BS), a natural polyphenol, is a well-known able to influence the mitochondrial metabolism. The objective of this study was to evaluate the mitochondrial dysfunction and biogenesis in fibromyalgia and their modulation by BS. To induce the model reserpine (1 mg/Kg) was subcutaneously administered for three consecutive days and BS (100 mg/Kg) was given orally for twenty-one days. BS reduced pain like behaviors in reserpine-injected rats and the astrocytes activation in the dorsal horn of the spinal cord and prefrontal cortex that are recognized as key regions associated with the neuropathic pain. Vulnerability to neuroinflammation and impaired neuronal plasticity have been described as consequences of mitochondrial dysfunction. BS administration increased PGC-1α expression in the nucleus of spinal cord and brain tissues, promoting the expression of regulatory genes for mitochondrial biogenesis (NRF-1, Tfam and UCP2) and cellular antioxidant defence mechanisms (catalase, SOD2 and Prdx 3). According with these data BS reduced lipid peroxidation and the GSSG/GSH ratio and increased SOD activity in the same tissues. Our results also showed that BS administration mitigates cytochrome-c leakage by promoting mitochondrial function and supported the movement of PGC-1α protein into the nucleus restoring the quality control of mitochondria. Additionally, BS reduced Drp1 and Fis1, preventing both mitochondrial fission and cell death, and increased the expression of Mfn2 protein, facilitating mitochondrial fusion. Overall, our results showed important mitochondrial dysfunction in central nervous system in fibromyalgia syndrome and the role of BS in restoring mitochondrial dynamics., Competing Interests: Declaration of competing interest The authors declare no conflicting financial interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The genus Eutreptiella (Euglenophyceae/Euglenozoa) comprises unicellular organisms known for their photosynthetic capacity and significant role in marine ecosystems. This review highlights the taxonomic, ecological, and biotechnological characteristics of Eutreptiella species, emphasizing their morphological and genomic adaptations. Eutreptiella species exhibit high phenotypic plasticity, enabling adaptation to various environmental conditions, from nutrient-rich waters to high-salinity conditions. They play a crucial role in primary production and nutrient cycling in marine ecosystems. Genetic and transcriptomic studies have revealed their complex regulatory mechanisms and potential for biofuel and nutraceutical production. Eutreptiella blooms significantly impact local ecosystems, influencing nutrient availability and community dynamics. Additionally, interactions with associated bacteria enhance their growth and metabolic capabilities. The genus shows substantial genetic variability, suggesting potential misidentifications or a polyphyletic nature. Further comprehensive studies are needed to clarify their taxonomy and evolutionary relationships. Understanding and managing Eutreptiella populations is essential to leverage their biotechnological potential and ensure the health of marine ecosystems., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s). Ecology and Evolution published by John Wiley & Sons Ltd.)

Endocrine disruptors (EDs) pose significant risks to human and environmental health, with potential implications for neurotoxicity. This study investigates the synergistic neurotoxic effects of perfluorooctane sulfonate (PFOS) and glyphosate (GLY), two ubiquitous EDs, using SHSY5Y neuronal and C6 astrocytic cell lines. While individual exposures to PFOS and glyphosate at non-toxic concentrations did not induce significant changes, their combination resulted in a marked increase in oxidative stress and neuroinflammatory responses. Specifically, the co-exposure led to elevated levels of interleukin-6, tumor necrosis factor alpha, and interferon gamma, along with reduced interleukin-10 expression, indicative of heightened neuroinflammatory processes. These findings underscore the importance of considering the synergistic interactions of EDs in assessing neurotoxic risks and highlight the urgent need for further research to mitigate the adverse effects of these compounds on neurological health., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Traumatic brain injury (TBI) is described as a structural damage or physiological disturbance of brain function that occurs after trauma and causes disability or death in people of all ages. New treatment targets for TBI are being explored because current medicines are frequently ineffectual and poorly tolerated. There is increasing evidence that following TBI, there are widespread changes in autophagy-related proteins in both experimental and clinical settings. The current study investigated if Boswellia Sacra Gum Resin (BSR) treatment (500 mg/kg) could modulate post-TBI neuronal autophagy and protein expression, as well as whether BSR could markedly improve functional recovery in a mouse model of TBI. Taken together our results shows for the first time that BSR limits histological alteration, lipid peroxidation, antioxidant, cytokines release and autophagic flux alteration induced by TBI., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Interdonato, Marino, Impellizzeri, D’Amico, Siracusa, Fusco, Cammilleri, Pantano, Modafferi, Abdelhameed, Fritsch, Rashan, Cuzzocrea, Calabrese, Cordaro and Di Paola.)

Introduction: Feline idiopathic cystitis is a common, chronic-relapsing disorder of the lower urinary tract. In addition to environmental modification/enrichment, long-term and safe treatment targeting specific pathophysiological changes may be of help. In this context, effective dietary interventions hold clinical promise. Palmitoyl-glucosamine (PGA) and hesperidin (HSP) are safe and authorized feed ingredients for animal nutrition under European regulations., Methods: The current study aimed to investigate whether a 3:1 mixture of micronized PGA and HSP could represent a novel mechanism-oriented approach to chronic cystitis management. A newly validated rat model of cyclophosphamide (CYP)-induced chronic cystitis was used (40 mg/kg, three intraperitoneal injections every 3rd day). Animals were randomized to orally receive either vehicle or PGA-HSP at a low (72 + 24 mg/kg) or high (doubled) dose for 13 days, starting 3 days before the chronic CYP protocol, with mesna (2-mercaptoethane-sulfonate) being used as a reference drug., Results: Higher PGA-HSP dose was effective at relieving chronic visceral pain, as measured by mechanical allodynia test (von Frey test). The severity of cystitis was also significantly improved, as shown by the reduced sonographic thickening of the bladder wall, as well as the decrease in edema, bleeding and bladder to body weight ratio compared to the vehicle treated group. A significant decrease of MPO activity, MDA level and fibrosis at Masson's trichrome staining was also observed in animals administered PGA-HSP in comparison to vehicle treated ones. The CYP-induced increase in bladder mRNA expression of pro-inflammatory cytokines was also significantly counteracted by the study mixture. Moreover, CYP-induced bladder mast cell accumulation and releasability were significantly decreased by PGA-HSP (even at the low dose), as determined by metachromatic staining, chymase and tryptase immunostaining as well as enzyme-linked immunosorbent assay for histamine and 5-hydoxytriptamine., Discussion: PGA-HSP is able to block CYP-induced decrease of tight junction proteins, claudin-1 and occludin, thus preserving the urothelial bladder function. Finally, neuroinflammatory changes were investigated, showing that dietary supplementation with PGA-HSP prevented the activation of neurons and non-neuronal cells (i.e., microglia, astrocytes and mast cells) at the spinal level, and counteracted CYP-induced increase of spinal mRNA encoding for pro-inflammatory cytokines. Altogether, the present findings confirm the uroprotective and pain-relieving effect of PGA-HSP and pave the way to potential and relevant clinical applications of the study supplement in feline idiopathic cystitis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer CI declared a shared affiliation with the authors to the handling editor at the time of review., (Copyright © 2024 Gugliandolo, Franco, Marino, Peritore, Impellizzeri, Cordaro, Siracusa, Fusco, D’Amico, Macrì, Di Paola, Cuzzocrea and Crupi.)

Endometriosis is a chronic disease characterized by pelvic inflammation. This study aimed at investigating the molecular mechanisms underlying the pathology and how they can be modulated by the administration of a natural compound, Actaea racemosa (AR). We employed an in vivo model of endometriosis in which rats were intraperitoneally injected with uterine fragments from donor animals. During the experiment, rats were monitored by abdominal high-frequency ultrasound analysis. AR was able to reduce the lesion's size and histological morphology. From a molecular point of view, AR reduced hyperproliferation, as shown by Ki-67 and PCNA expression and MAPK phosphorylation. The impaired apoptosis pathway was also restored, as shown by the TUNEL assay and RT-PCR for Bax, Bcl-2, and Caspase levels. AR also has important antioxidant (reduced Nox expression, restored SOD activity and GSH levels, and reduced MPO activity and MDA levels) and anti-inflammatory (reduced cytokine levels) properties. Moreover, AR demonstrated its ability to reduce the pain-like behaviors associated with the pathology, the neuro-sensitizing mediators (c-FOS and NGF) expression, and the related central astrogliosis (GFAP expression in the spinal cord, brain cortex, and hippocampus). Overall, our data showed that AR was able to manage several pathways involved in endometriosis suppression.

Myocarditis is an inflammatory cardiac disorder and the primary cause of heart failure in young adults. Its origins can be attributed to various factors, including bacterial or viral infections, exposure to toxins or drugs, endocrine disruptors (EDs), and autoimmune processes. Tebuconazole (TEB), which is a member of the triazole fungicide family, is utilized to safeguard agricultural crop plants against fungal pathogens. Although TEB poses serious threats to mammal health, the information about how it induces toxic effects through various pathways, particularly in autoimmune diseases, are still limited. Thus, the aim of this paper was to evaluate the effect of TEB exposure in autoimmune myocarditis (AM). To induce AM, rats were immunized with porcine cardiac myosin and exposed to TEB for 21 days. Thereafter, animals were sacrificed, and histological, biochemical, and molecular analyses were performed. TEB exposure increased heart weight, systolic blood pressure and heart rate already augmented by AM. Additionally, it significantly increased creatine phosphokinase heart (CK-MB), creatine phosphokinase (CPK), cardiac troponin T (cTnT), and cardiac troponin I (cTnI), as compared to the control. From the histological perspective, TEB exacerbates the histological damage induced by AM (necrosis, inflammation and cell infiltration) and increased fibrosis and collagen deposition. TEB exposure strongly increased pro-inflammatory cytokines and prooxidant levels (O2 - , H 2 O 2 , NO 2 - , lipid peroxidation) and reduced antioxidant enzyme levels, which were already dysregulated by AM. Additionally, TEB increased NOX-4 expression and the TGFβ1-Smads pathway already activated by AM. Overall, our results showed that TEB exposure strongly aggravated the cardiotoxicity induced by AM.

(1) Background: Vinclozolin is a popular fungicide used in fruit, ornamental plants, and vegetable crops. It has recently been seen that prolonged exposure to VZN can cause human or animal health damage to various organs, but little is known to date about its cardiovascular effects. In this study, we addressed the chronic effects of VZN on the myocardium and the enzymes involved in the cardiovascular function. (2) Methods: The animals were divided into four groups: group 1 served as the control, group 2 received 1 mg/kg of VZN by gavage, group 3 received 30 mg/kg of VZN by gavage, and group 4 received 100 mg/kg of VZN by gavage, for 30 days. (3) Results: Results showed that 100 mg/kg VZN markedly increased the plasma concentration of cardiac markers (CK-MB, cTnT, ANP, BNP). Moreover, compared to the control group, VZN treatment decreased the activity of SOD, CAT, and GPx, and downregulated the mRNA expression levels of Nrf2. Furthermore, collagen deposition was amplified owing to 100 mg/kg VZN cardiotoxicity. This harmful effect was confirmed by a histological study using hematoxylin and eosin (H&E) and Masson's trichrome staining. (4) Conclusion: Overall, our results proved the cardiotoxicity caused by chronic exposure to VZN.

A chronic, painful, and inflammatory condition known as endometriosis is defined by the extra-uterine development of endometrial tissue. The aim of this study was to evaluate the beneficial effects of fisetin, a naturally occurring polyphenol that is frequently present in a variety of fruits and vegetables. Uterine fragments were injected intraperitoneally to cause endometriosis, and fisetin was given orally every day. At 14 days of treatment, laparotomy was performed, and the endometrial implants and peritoneal fluids were collected for histological, biochemical, and molecular analyses. Rats subjected to endometriosis presented important macroscopic and microscopic changes, increased mast cell (MC) infiltration, and fibrosis. Fisetin treatment reduced endometriotic implant area, diameter, and volumes, as well as histological alterations, neutrophil infiltration, cytokines release, the number of MCs together with the expression of chymase and tryptase, and diminished α smooth muscle actin (α-sma) and transforming growth factor beta (TGF β) expressions. In addition, fisetin was able to reduce markers of oxidative stress as well as nitrotyrosine and Poly ADP ribose expressions and increase apoptosis in endometrial lesions. In conclusion, fisetin could represent a new therapeutic strategy to control endometriosis perhaps by targeting the MC-derived NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome pathway and oxidative stress.

Background: Fibromyalgia is a medical condition that affects a small percentage of the population, with no known effective treatment. There is evidence to suggest that inflammation is a key factor in the nerve sensitization that characterizes the disorder. Therefore, this paper concentrates on the role of IL-6 in fibromyalgia and the related pain-like symptoms., Methods: This work aimed to evaluate Sprague-Dawley rats, which were injected for three consecutive days with 1 mg/kg of reserpine; IL-6-R Ab was intraperitoneally injected at 1.5 mg/kg seven days after the first reserpine injection. Behavioral analyses were conducted at the beginning of the experiment and at seven and twenty-one days from the first reserpine injection. At this timepoint, the animals were sacrificed, and tissues were collected for molecular and histological analysis., Results: Our data showed the analgesic effect of IL-6-R-Ab administration on mechanical allodynia and thermal hyperalgesia. Additionally, the reserpine + IL-6-R-Ab group showed a reduced expression of the pain-related mediators cFOS and NFG and reduced levels of pro-inflammatory cytokines (TNF-α, IL-1β and IL-6) and chemokines (Cxcl5, Cxcl10 and Cx3cl1). From the molecular point of view, the IL-6-R-Ab administration reduced the gp130 phosphorylation and the activation of the Jak/STAT3 pathway. Additionally, the IL-6-R Ab reduced the activation of neuroinflammatory cells., Conclusions: Our study showed that IL-6 plays a crucial role in fibromyalgia by triggering the Jak/STAT3 pathway, leading to an increase in chemokine levels and activating glial cells.

The black soldier fly (BSF), Hermetia illucens, has been recognized as one of the most promising insect species for its ability to valorize organic waste while producing a valuable larval biomass with a great potential as a sustainable source of nutrients, including proteins and bioactive molecules. In the present study, BSF larvae were used to produce and characterize the protein hydrolysates (BPHs) that were then evaluated for their potential biological activity in vitro. The BPHs obtained from the BSF larvae proteins by enzymatic digestion were characterized by Nuclear Magnetic Resonance (NMR) and polyacrylamide gel electrophoresis and assessed for their antioxidant activity (BPHs in the range of 0.1 to 1.5 mg/mL) in L-929 cells. Our findings show that BPHs can exert a dose-dependent cytoprotective role against H 2 O 2 -iduced oxidative stress in cells. This antioxidant activity relies on the reduction of ROS levels in challenged cells as measured by flow cytometry and fluorescence microscopy, together with the induction and nuclear translocation of Nrf2, as evaluated by qPCR and indirect immunofluorescence analysis, respectively. Overall, our findings on the remarkable biological activity of the BPHs obtained in a large-scale process strongly suggest the application of BPHs as ingredients promoting animal health in feed formulations.

In recent years, the phytoconstituents of foods in the Mediterranean diet (MD) have been the subject of several studies for their beneficial effects on human health. The traditional MD is described as a diet heavy in vegetable oils, fruits, nuts, and fish. The most studied element of MD is undoubtedly olive oil due precisely to its beneficial properties that make it an object of interest. Several studies have attributed these protective effects to hydroxytyrosol (HT), the main polyphenol contained in olive oil and leaves. HT has been shown to be able to modulate the oxidative and inflammatory process in numerous chronic disorders, including intestinal and gastrointestinal pathologies. To date, there is no paper that summarizes the role of HT in these disorders. This review provides an overview of the anti-inflammatory and antioxidant proprieties of HT against intestinal and gastrointestinal diseases.

Recently, wound healing has received increased attention from both a scientific and clinical point of view. It is characterized by an organized series of processes: angiogenesis, cell migration and proliferation, extracellular matrix production, and remodeling. Many of these processes are controlled by the Wnt pathway, which activates them. The aim of the study was to evaluate the molecular mechanism of açai berry administration in a mouse model of wound healing. CD1 male mice were used in this research. Two full-thickness excisional wounds (5 mm) were performed with a sterile biopsy punch on the dorsum to create two circular, full-thickness skin wounds on either side of the median line on the dorsum. Açai berry was administered by oral administration (500 mg/kg dissolved in saline) for 6 days after induction of the wound. Our study demonstrated that açai berry can modulate the Wnt pathway, reducing the expression of Wnt3a, the cysteine-rich domain of frizzled (FZ)8, and the accumulation of cytosolic and nuclear β-catenin. Moreover, açai berry reduced the levels of TNF-α and IL-18, which are target genes strictly downstream of the Wnt/β-catenin pathway. It also showed important anti-inflammatory activities by reducing the activation of the NF-κB pathway. Furthermore, Wnt can modulate the activity of growth factors, such as TGF-β, and VEGF, which are the basis of the wound-healing process. In conclusion, we can confirm that açai berry can modulate the activity of the Wnt/β-catenin pathway, as it is involved in the inflammatory process and in the activity of the growth factor implicated in wound healing.

Endometriosis (Endo) is a chronic gynecological disease. This paper aimed to evaluate the modulation of autophagy, oxidative stress and apoptosis with Açai Berries in a rat model of endometriosis. Endometriosis was induced with an intraperitoneal injection of minced uterus tissue from a donor rat into a recipient one. The abdominal high-frequency ultrasound (hfUS) analysis was performed at 7 and 14 days from the endometriosis induction to evaluate the growth of the lesion during the experiment. Seven days from the induction, once the lesions were implanted, an Açai Berry was administered daily by gavage for the next seven days. At the end of the experiment, the hfUS analysis showed a reduced lesion diameter in animals given the Açai Berry. A macroscopical and histological analysis confirmed this result. From the molecular point of view, Western blot analyses were conducted to evaluate the autophagy induction. Samples collected from the Endo group showed impaired autophagy, while the Açai Berry administration inhibited PI3K and AKT and ERK1/2 phosphorylation and promoted autophagy by inactivating mTOR. Additionally, Açai Berry administration dephosphorylated ATG1, promoting the activity of the ATG1/ULK1 complex that recruited Ambra1/Beclin1 and Atg9 to promote autophagosome nucleation and LC3II expression. Açai Berry administration also restored mitophagy, which increased Parkin cytosolic expression. The Açai Berry increased the expression of NRF2 in the nucleus and the expression of its downstream antioxidant proteins as NQO-1 and HO-1, thereby restoring the oxidative imbalance. It also restored the impaired apoptotic pathway by reducing BCL-2 and increasing BAX expression. This result was also confirmed by the TUNEL assay. Overall, our results displayed that Açai Berry administration was able to modulate autophagy, oxidative stress and apoptosis during endometriosis.

Atopic dermatitis (AD) is an inflammatory and allergic disease, whose multifactorial etiopathogenesis is the consequence of the link between the genetic, immunological and environmental components. The complexity and difficulty in understanding the causes that trigger or exacerbate this pathology makes it difficult, once diagnosed, to proceed with a targeted and effective therapeutic process. Today, the new frontiers of research look to natural and innovative treatments to counteract the different manifestations of dermatitis. From this point of view, the mucus secreted by Helix aspersa Muller has proven, since ancient times, to be able to neutralize skin diseases. To study canine atopic dermatitis (cAD), we used cell lines of canine epidermal keratinocytes (CPEK) that are optimal to understand the biological reactivity of keratinocytes in vitro. The data obtained from our study demonstrate the anti-inflammatory capacity of snail secretion filtrate (SSF) in counteracting the production of proinflammatory cytokines produced during cAD, highlighting the opportunities for further studies to be able to identify new, natural and safe treatments for cAD and to open new frontiers for veterinarians and owners.

Background: Fibromyalgia is a clinical condition that affects 1% to 5% of the population. No proper therapy has been currently found. It has been described that inflammation plays a central role in the nerve sensitizations that characterize the pathology., Methods: This paper aimed to evaluate the efficacy of etanercept and infliximab in the management of pain sensitization. Fibromyalgia was induced by three injections once a day of reserpine at the dose of 1 mg/kg. Etanercept (3 mg/kg) and infliximab (10 mg/kg) were administered the day after the last reserpine injection and then 5 days after that. Behavioral analyses were conducted once a week, and molecular investigations were performed at the end of the experiment., Results: Our data confirmed the major effect of infliximab administration as compared to etanercept: infliximab administration strongly reduced pain sensitization in thermal hyperalgesia and mechanical allodynia. From the molecular point of view, infliximab reduced the activation of microglia and astrocytes and the expression of the purinergic P2X7 receptor ubiquitously expressed on glia and neurons. Downstream of the P2X7 receptor, infliximab also reduced p38-MAPK overexpression induced by the reserpine administration., Conclusion: Etanercept and infliximab treatment caused a significant reduction in pain. In particular, rats that received infliximab showed less pain sensitization. Moreover, infliximab reduced the activation of microglia and astrocytes, reducing the expression of the purinergic receptor P2X7 and p38-MAPK pathway.

Pharmaceuticals are widely acknowledged to be a threat to aquatic life. Over the last two decades, the steady use of biologically active chemicals for human health has been mirrored by a rise in the leaking of these chemicals into natural environments. The aim of this work was to detect the toxicity of sodium fluoride (NaF) exposure and platinum-derived drugs in an ecological setting on aquatic organism development. From 24 to 96 h post-fertilization, zebrafish embryos were treated to dosages of NaF 10 mg/L -1 + cisplatin (CDDP) 100 μM, one with NaF 10 mg/L -1 + carboplatin (CARP) 25 μM, one with NaF 10 mg/L -1 + CDDP 100 μM + CARP 25 μM. Fluoride exposure in combination with Cisplatin and Carboplatin (non-toxic concentration) had an effect on survival and hatching rate according to this study. Additionally, it significantly disturbed the antioxidant defense system and increased ROS in zebrafish larvae. NaF 10 mg/L -1 associated with CDDP 100 μM and CARP 25 μM, increased the production of apoptosis-related proteins (caspase 3, bax, and bcl-2) and the downregulation of acetylcholinesterase (AChE) activity, while no effect was seen for the single exposure.