ABSTRACT
The term "inflammatory bowel disease" (IBD) describes a class of relapse-remitting conditions that affect the gastrointestinal (GI) tract. Among these, Crohn's disease (CD) and ulcerative colitis (UC) are two of the most globally prevalent and debilitating conditions. Several articles have brought attention to the significant role that inflammation and oxidative stress cooperatively play in the development of IBD, offering a different viewpoint both on its etiopathogenesis and on strategies for the effective treatment of these conditions. Marine ecosystems may be a significant source of physiologically active substances, supporting the search for new potential clinical therapeutics. Based on this evidence, this review aims to comprehensively evaluate the activity of marine algae and deriving biomolecules in decreasing pathological features of CD and UC. To match this purpose, a deep search of the literature on PubMed (MEDLINE) and Google Scholar was performed to highlight primary biological mechanisms, the modulation of inflammatory and oxidative stress biochemical parameters, and potential clinical benefits deriving from marine species. From our findings, both macroalgae and microalgae have shown potential as therapeutic solutions for IBD due to their bioactive compounds and their anti-inflammatory and antioxidant activities which are capable of modulating markers such as cytokines, the NF-κB pathway, reactive oxidative and nitrosative species (ROS and RNS), trefoil factor 3 (TFF3), lactoferrin, SIRT1, etc. However, while we found promising preclinical evidence, more extensive and long-term clinical studies are necessary to establish the efficacy and safety of marine algae for IBD treatment.
Subject(s)
Inflammatory Bowel Diseases , Oxidative Stress , Humans , Oxidative Stress/drug effects , Inflammatory Bowel Diseases/drug therapy , Inflammatory Bowel Diseases/metabolism , Animals , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Biomarkers/metabolism , Seaweed/chemistry , Microalgae/chemistry , Antioxidants/pharmacology , Antioxidants/therapeutic use , Aquatic Organisms , Inflammation/drug therapyABSTRACT
Brain tumors are a heterogeneous group of brain neoplasms that are highly prevalent in individuals of all ages worldwide. Within this pathological framework, the most prevalent and aggressive type of primary brain tumor is glioblastoma (GB), a subtype of glioma that falls within the IV-grade astrocytoma group. The death rate for patients with GB remains high, occurring within a few months after diagnosis, even with the gold-standard therapies now available, such as surgery, radiation, or a pharmaceutical approach with Temozolomide. For this reason, it is crucial to continue looking for cutting-edge therapeutic options to raise patients' survival chances. Pentraxin 3 (PTX3) is a multifunctional protein that has a variety of regulatory roles in inflammatory processes related to extracellular matrix (ECM). An increase in PTX3 blood levels is considered a trustworthy factor associated with the beginning of inflammation. Moreover, scientific evidence suggested that PTX3 is a sensitive and earlier inflammation-related marker compared to the short pentraxin C-reactive protein (CRP). In several tumoral subtypes, via regulating complement-dependent and macrophage-associated tumor-promoting inflammation, it has been demonstrated that PTX3 may function as a promoter of cancer metastasis, invasion, and stemness. Our review aims to deeply evaluate the function of PTX3 in the pathological context of GB, considering its pivotal biological activities and its possible role as a molecular target for future therapies.
ABSTRACT
BACKGROUND: Pseudohypoparathyroidism (PHP) is caused by loss-of-function mutations at the GNAS gene (as in the PHP type 1A; PHP1A), de novo or inherited at heterozygous state, or by epigenetic alterations at the GNAS locus (as in the PHP1B). The condition of PHP refers to a heterogeneous group of disorders that share common clinical and biological features of PTH resistance. Manifestations related to resistance to other hormones are also reported in many patients with PHP, in association with the phenotypic picture of Albright hereditary osteodystrophy characterized by short stature, round facies, subcutaneous ossifications, brachydactyly, mental retardation and, in some subtypes, obesity. The purpose of our study is to report a new mutation in the GNAS gene and to describe the significant phenotypic variability of three sisters with PHP1A bearing the same mutation. CASE PRESENTATION: We describe the cases of three sisters with PHP1A bearing the same mutation but characterized by a significantly different phenotypic picture at onset and during follow-up in terms of clinical features, auxological pattern and biochemical changes. Clinical exome sequencing revealed a never before described heterozygote mutation in the GNAS gene (NM_000516.5 c.118_139 + 51del) of autosomal dominant maternal transmission in the three siblings, confirming the diagnosis of PHP1A. CONCLUSIONS: This study reported on a novel mutation of GNAS gene and highlighted the clinical heterogeneity of PHP1A characterized by wide genotype-phenotype variability. The appropriate diagnosis has crucial implications for patient care and long-term multidisciplinary follow-up.
Subject(s)
Chromogranins , GTP-Binding Protein alpha Subunits, Gs , Pseudohypoparathyroidism , Humans , GTP-Binding Protein alpha Subunits, Gs/genetics , Pseudohypoparathyroidism/genetics , Pseudohypoparathyroidism/diagnosis , Chromogranins/genetics , Female , Child , Phenotype , Pedigree , Mutation , Adolescent , Child, PreschoolABSTRACT
Parkinson's disease (PD) is recognized as the second most common neurodegenerative disease worldwide. Even if PD etiopathogenesis is not yet fully understood, in recent years, it has been advanced that a chronic state of inflammation could play a decisive role in the development of this pathology, establishing the close link between PD and neuroinflammation. In the broad panorama of inflammation and its several signaling pathways, the C-C chemokine receptor type 1 (CCR1) could play a key pathogenic role in PD progression, and could constitute a valuable target for the development of innovative anti-PD therapies. In this study, we probed the neuroprotective properties of the CCR1 antagonist BX471 compound in a mouse model of MPTP-induced nigrostriatal degeneration. BX471 treatments were performed intraperitoneally at a dose of 3 mg/kg, 10 mg/kg, and 30 mg/kg, starting 24 h after the last injection of MPTP and continuing for 7 days. From our data, BX471 treatment strongly blocked CCR1 and, as a result, decreased PD features, also reducing the neuroinflammatory state by regulating glial activation, NF-κB pathway, proinflammatory enzymes, and cytokines overexpression. Moreover, we showed that BX471's antagonistic action on CCR1 reduced the infiltration of immune cells, including mast cells and lymphocyte T activation. In addition, biochemical analyses carried out on serum revealed a considerable increase in circulating levels of CCR1 following MPTP-induced PD. In light of these findings, CCR1 could represent a useful pathological marker of PD, and its targeting could be a worthy candidate for the future development of new immunotherapies against PD.
Subject(s)
Parkinson Disease , Receptors, CCR1 , Receptors, CCR1/metabolism , Receptors, CCR1/antagonists & inhibitors , Animals , Mice , Parkinson Disease/metabolism , Parkinson Disease/drug therapy , Male , Disease Models, Animal , Biomarkers , Mice, Inbred C57BL , Neuroinflammatory Diseases/drug therapy , Neuroinflammatory Diseases/metabolism , Neuroprotective Agents/pharmacology , Neuroprotective Agents/therapeutic use , Signal Transduction/drug effectsABSTRACT
Since the inception of the SARS-CoV-2 pandemic, healthcare systems around the world observed an increased rate of Acute Limb Ischemia (ALI) in patients with a COVID-19 infection. Despite several pieces of evidence suggesting that COVID-19 infection may also worsen the prognosis associated with ALI, only a small number of published studies include a direct comparison regarding the outcomes of both COVID-19 and non-COVID-19 ALI patients. Based on the above, a systematic review and a meta-analysis of the literature were conducted, evaluating differences in the incidence of two major outcomes (amputation and mortality rate) between patients concurrently affected by COVID-19 and negative ALI subjects. PubMed (MEDLINE), Web of Science, and Embase (OVID) databases were scrutinized from January 2020 up to 31 December 2023, and 7906 total articles were recovered. In total, 11 studies (n: 15,803 subjects) were included in the systematic review, and 10 of them (15,305 patients) were also included in the meta-analysis. Across all the studies, COVID-19-positive ALI patients experienced worse outcomes (mortality rates ranging from 6.7% to 47.2%; amputation rates ranging from 7.0% to 39.1%) compared to non-infected ALI patients (mortality rates ranging from 3.1% to 16.7%; amputation rates ranging from 2.7% to 18%). Similarly, our meta-analysis shows that both the amputation rate (OR: 2.31; 95% CI: 1.68-3.17; p < 0.00001) and mortality (OR: 3.64; 95% CI: 3.02-4.39; p < 0.00001) is significantly higher in COVID-19 ALI patients compared to ALI patients.
ABSTRACT
In the original publication [...].
ABSTRACT
Brain tumors are a diverse collection of neoplasms affecting the brain with a high prevalence rate in people of all ages around the globe. In this pathological context, glioblastoma, a form of glioma that belongs to the IV-grade astrocytoma group, is the most common and most aggressive form of the primary brain tumors. Indeed, despite the best treatments available including surgery, radiotherapy or a pharmacological approach with Temozolomide, glioblastoma patients' mortality is still high, within a few months of diagnosis. Therefore, to increase the chances of these patients surviving, it is critical to keep finding novel treatment opportunities. In the past, efforts to treat glioblastoma have mostly concentrated on customized treatment plans that target specific mutations such as epidermal growth factor receptor (EGFR) mutations, Neurotrophic Tyrosine Receptor Kinase (NTRK) fusions, or multiple receptors using multi-kinase inhibitors like Sunitinib and Regorafenib, with varying degrees of success. Here, we focused on the receptor tyrosine kinase AXL that has been identified as a mediator for tumor progression and therapy resistance in various cancer types, including squamous cell tumors, small cell lung cancer, and breast cancer. Activated AXL leads to a significant increase in tumor proliferation, tumor cell migration, and angiogenesis in different in vitro and in vivo models of cancer since this receptor regulates interplay with apoptotic, angiogenic and inflammatory pathways. Based on these premises, in this review we mainly focused on the role of AXL in the course of glioblastoma, considering its primary biological mechanisms and as a possible target for the application of the most recent treatments.
Subject(s)
Axl Receptor Tyrosine Kinase , Glioblastoma , Humans , Axl Receptor Tyrosine Kinase/metabolism , Glioblastoma/metabolism , Proto-Oncogene Proteins/metabolism , Receptor Protein-Tyrosine Kinases/metabolism , Signal TransductionABSTRACT
Migraine is one of the most common neurological illnesses, and it is characterized by complicated neurobiology. It was confirmed the influence of inflammation and oxidative stress in migraines and also in distal organs such as the intestine. Indeed, the constant bidirectional communication between the Central Nervous System (CNS) and the gastrointestinal (GI) tract, known as the gut-brain axis, has become an attractive target involved in different human disorders. Herein, we explored the role of NADPH oxidase 2 (NOX2) in nitroglycerin (NTG)-induced migraine in mice models to discover the mechanism by which, during migraine attack, oxidative stress is sustained within trigeminal neurons and GI. Considering the inverse relationship between NOX2 and Nrf2, Nrf2 upregulation seems to be a promising approach to decrease NOX2 expression and consequently limit oxidative stress and inflammation spread in neurological and non-neurological diseases. With this aim, we exploited tempol's Nrf2-inducer ability to better understand the involvement of Nrf2/NOX2 axis in migraine and associated GI comorbidities. Behavioral tests confirmed that tempol, in a dose-dependent manner, moderated clinical signs of migraine and abdominal pain. Moreover, we demonstrated that the decrease in migraine-related symptomatology was strongly linked to the modulation of Nrf2/NOX2 signaling pathway in the brain and colon. In the brain, the rebalancing of Nrf2/NOX2 prevented neuronal loss, decreased glia reactivity while inhibiting NF-κB and NLRP3 inflammasome activation. In the colon, Nrf2 upregulation and consequent NOX2 decrease reduced the histological damage, mast cells infiltration as well as tumor necrosis factor (TNF)-α and interleukin (IL)-1ß release. Furthermore, the attenuation of inflammation and oxidative stress led to the restoration of the intestinal barrier through TJs replacement. Taken as a whole, data suggested that the regulation of Nrf2/NOX2 balance is a successful way to reduce neurological and related intestinal impairments during migraine and could be of relevance for migraine-like attacks in humans.
Subject(s)
Cyclic N-Oxides , Migraine Disorders , NF-E2-Related Factor 2 , Spin Labels , Animals , Humans , Mice , Brain-Gut Axis , Inflammation/metabolism , Migraine Disorders/genetics , Migraine Disorders/chemically induced , Migraine Disorders/metabolism , NADPH Oxidase 2/genetics , NADPH Oxidase 2/metabolism , NF-E2-Related Factor 2/genetics , NF-E2-Related Factor 2/metabolism , Oxidative Stress , Tumor Necrosis Factor-alpha/metabolismABSTRACT
Gastroesophageal reflux disease (GERD) is the most common foregut disease, affecting about 20% of the adult population. Esophageal epithelial barrier plays a fundamental role in the pathophysiology of GERD; however, pharmacological therapies mainly aim to reduce the acidity of the gastroesophageal environment rather than to protect esophageal tissue integrity. This study aims to evaluate the efficacy of an oral solution containing xyloglucan and pea proteins (XP) in reestablishing gastroesophageal tissue integrity and biochemical markers. To induce GERD, C57BL/6 mice were alternatively overfed and fasted for 56 days and then treated with XP, sodium alginate, omeprazole, or omeprazole+XP twice daily for 7 days. Gastric pain and inflammatory markers were evaluated after 3 and 7 days of treatment. After sacrifice, the esophagi and stomachs were surgically removed for macroscopic and histological examination. Gastric pain was significantly reduced at days 3 and 7 by XP, omeprazole, and omeprazole+XP, while alginates were ineffective at day 3. XP was able to diminish gastric macroscopic damage and demonstrated the same efficacy as omeprazole in reducing esophageal damage. XP significantly reduced histological damage, with an efficacy comparable to that of omeprazole, but superior to alginates. Inflammatory markers were significantly reduced by XP, with superior efficacy compared with alginates at day 7. Interestingly, XP was also able to significantly increase gastric pH. This study demonstrated that XP restored gastric homeostasis, improved esophageal integrity, and decreased inflammation and pain with a similar efficacy to omeprazole and greater than alginates.
Subject(s)
Gastroesophageal Reflux , Glucans , Pea Proteins , Xylans , Animals , Mice , Pea Proteins/therapeutic use , Disease Models, Animal , Mice, Inbred C57BL , Gastroesophageal Reflux/drug therapy , Omeprazole/pharmacology , Omeprazole/therapeutic use , Pain/drug therapyABSTRACT
Intraocular pressure (IOP) positively correlates with both normal and high-tension glaucoma. To date, IOP targeting remains the validated pharmacological approach in counteracting glaucoma progression as well as in halting vision loss. Among the different adjuvant compounds, evidence highlighted the potential effectiveness of Palmitoylethanolamide (PEA), an endogenous fatty acid amide. Thus, a systematic review of the literature was conducted, thoroughly evaluating PEA treatment regimen in decreasing IOP in patients with eye disorders. We checked for articles across the scientific databases Pubmed (MEDLINE), Embase (OVID), and Web of Science from the inception to 30 August 2023, and a total of 828 articles were recovered. Six of these studies (199 patients) were included in the systematic review after the study selection process, and three studies for meta-analysia. Overall, PEA showed significant efficacy in reducing IOP in patients, this encourages its clinical use in glaucoma as well as across different forms of eye disorders.
ABSTRACT
BACKGROUND: Distal chromosome 16 duplication syndrome (also known as 16q partial trisomy) is a very rare genetic disorder recently described in few clinical reports. 16q trisomy is generally associated with a multisystemic phenotype including intrauterine growth restriction (IUGR), brain and cardiac defects, intellectual disability (ID) and an increased risk of both prenatal and postnatal lethality. Smaller copy number variants (CNV) within the 16q region create partial trisomies, which occur less frequently than full trisomy 16q. CASE PRESENTATION: We present the clinical case of a 12-years-old male with a 16q22.3q24.1 de novo heterozygous duplication whose phenotype was characterized by ID, facial dysmorphisms, stature and weight overgrowth. To date, only five other cases of this syndrome have been reported in scientific literature, and none of them comprised overgrowth. CONCLUSIONS: Our case report highlights the great heterogeneity in clinical manifestations and provides new evidence for better defining the phenotypic picture for smaller 16q distal CNVs, suggesting unusual features.
Subject(s)
Intellectual Disability , Trisomy , Pregnancy , Female , Humans , Male , Child , Trisomy/genetics , Intellectual Disability/genetics , Fetal Growth Retardation , Chromosomes, Human, Pair 16/genetics , BrainABSTRACT
We present a case of bidirectional ventricular tachycardia in a 15-year-old boy asymptomatic for arrhythmias, whose major complaint was muscle weakness. At our first evaluation he was receiving sotalol for his ventricular arrhythmias. In addition to bidirectional tachycardia, electrocardiogram during sinus rhythm showed prominent U waves and prolonged QT-U interval. These electrocardiographic signs, along with the evidence of clinodactyly and mild hypertelorism, led us to the diagnosis of Andersen-Tawil syndrome, confirmed by genetic analysis that revealed a "de novo" missense mutation of KCNJ2 gene. Monotherapy with flecainide was rapidly effective and almost eliminated ventricular arrhythmias. After a 4-year follow-up there were no adverse events, flecainide has been well tolerated without significant modification of the QRS or repolarization, and ventricular arrhythmias have not been relapsed to date. The case highlights the importance of a correct clinical diagnosis, which is crucial for the optimal selection of the most appropriate drug therapy, which is expected not to be harmful, before being beneficial.
ABSTRACT
Currently, biological markers for COVID-19 disease severity still constitute the main goal of enhancing an efficient treatment to reduce critical consequences such as an abnormal systemic inflammatory response. In this regard, the latest research has shown that Pentraxin 3 (PTX3), a highly conserved innate immunity protein, may serve as a valuable biochemical marker. Based on this evidence, we conducted a case-control study to compare the PTX3 serum levels and several immune-inflammatory mediators of 80 healthcare workers who were subdivided into subjects who were previously infected with SARS-CoV-2 (n = 40) and individuals who were never infected (n = 40). Using a commercially available Enzyme-Linked Immunosorbent Assay (ELISA), PTX3 and various immune-inflammatory protein levels were assessed in serum samples, while also considering possible variables (e.g., gender-related differences). We have shown elevated levels of PTX3 and other inflammatory proteins in previously infected COVID-19-positive subjects (p < 0.001). Moreover, the obtained data also indicate a degree of severity influenced by gender, as shown by the subgroup analysis, in which PTX3 expression was more pronounced in previously COVID-19-positive males (p < 0.001) than in females (p < 0.05) compared to the respective controls. In addition, our data further validate, through a direct comparison of previously COVID-19-positive subjects, greater pro-inflammatory levels in males than in females. Overall, our results may support the validity of PTX3 as a systemic biomarker in prolonged systemic inflammatory responses in the context of COVID-19. Thus, PTX3 modulation could constitute an effective therapeutic strategy for improving the recovery from COVID-19 and its systemic long-term consequences.
ABSTRACT
Post-Covid Olfactory Dysfunction (PCOD) is characterized by olfactory abnormalities, hyposmia, and anosmia, which are among the most often enduring symptoms in individuals who have recovered from SARS-CoV-2 infection. This disorder has been reported to persist in subsets of patients well after 12 months following infection, significantly affecting their quality of life. Despite the high prevalence of PCOD among patients who suffered from SARS-CoV-2 infection, specific therapeutic strategies are still limited. Among these, emerging evidence seems to indicate the administration of CoUltraPEALut, a combination of micronized Palmitoylethanolamide (PEA), an endogenous fatty acid amide, and Luteolin, a natural antioxidant flavonoid, as a viable therapy, especially when given as an adjuvant to olfactory training. Based on the above, a systematic review and a meta-analysis of the literature were conducted, with the aim of evaluating the efficacy of CoUltraPEALut as an addition to olfactory training (OT), in treating PCOD symptoms. Pubmed (MEDLINE), Embase (OVID), and Web of Science scientific databases were screened from the inception until 31 May 2023, and a total of 407 articles were recovered; only five of these studies (441 total patients between treated and control groups) were included in the systematic review. CoUltraPEALut demonstrated significant efficacy in the overall recovery of the olfactory function, compared to the conventional therapy, suggesting that it could represent a possible future adjuvant treatment for PCOD.
ABSTRACT
Parkinson's disease (PD) is a disorder that is characterized by progressive and selective neuronal injury and cell death. Recent studies have provided accumulating evidence for a significant role of the immune system and neuroinflammation in PD pathogenesis. On this basis, many scientific articles have highlighted the anti-inflammatory and neuroprotective properties of Antrodia camphorata (AC), an edible fungus containing various bioactive compounds. This study aimed to evaluate the inhibitory effect of AC administration on neuroinflammation and oxidative stress in a murine model of MPTP-induced dopaminergic degeneration. AC (10, 30, 100 mg/kg) was administered daily by oral gavage starting 24 h after the first administration of MPTP, and mice were sacrificed 7 days after MPTP induction. In this study, treatment with AC significantly reduced the alteration of PD hallmarks, increasing tyrosine hydroxylase expression and reducing the number of alpha-synuclein-positive neurons. In addition, AC treatment restored the myelination process of neurons associated with PD and attenuated the neuroinflammatory state. Furthermore, our study demonstrated that AC was able to reduce the oxidative stress induced by MPTP injection. In conclusion, this study highlighted that AC could be a potential therapeutic agent for the treatment of neurodegenerative disorders such as PD.
Subject(s)
MPTP Poisoning , Neuroprotective Agents , Parkinson Disease , Mice , Animals , Parkinson Disease/metabolism , NF-E2-Related Factor 2/metabolism , Disease Models, Animal , Neuroinflammatory Diseases , Mice, Inbred C57BL , Dopaminergic Neurons/metabolism , Neuroprotective Agents/pharmacology , Neuroprotective Agents/therapeutic use , Neuroprotective Agents/metabolism , 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine/pharmacology , MPTP Poisoning/metabolismABSTRACT
Oral squamous cell carcinoma (OSCC) is a commonly occurring head and neck cancer and it is characterized by a high metastasis grade. The aim of this study was to evaluate for the first time the effect of BAY-117082, a selective NLRP3 inflammasome inhibitor, in an in vivo orthotopic model of OSCC and its role in the invasiveness and metastasis processes in neighbor organs such as lymph node, lung, and spleen tissues. Our results demonstrated that BAY-117082 treatment, at doses of 2.5 mg/kg and 5 mg/kg, was able to significantly reduce the presence of microscopic tumor islands and nuclear pleomorphism in tongue tissues and modulate the NLRP3 inflammasome pathway activation in tongue tissues, as well as in metastatic organs such as lung and spleen. Additionally, BAY-117082 treatment modulated the epithelial-mesenchymal transition (EMT) process in tongue tissue as well as in metastatic organs such as lymph node, lung, and spleen, also reducing the expression of matrix metalloproteinases (MMPs), particularly MMP2 and MMP9, markers of cell invasion and migration. In conclusion, the obtained data demonstrated that BAY-117082 at doses of 2.5 mg/kg and 5 mg/kg were able to reduce the tongue tumor area as well as the degree of metastasis in lymph node, lung, and spleen tissues through the NLRP3 inflammasome pathway inhibition.
ABSTRACT
Atopic dermatitis (AD) is the most common chronically relapsing inflammatory skin disease, predominantly common in children; it is characterized by an eczematous pattern generally referable to skin dryness and itchy papules that become excoriated and lichenified in the more advanced stages of the disease. Although the pathophysiology of AD is not completely understood, numerous studies have demonstrated the complex interaction between genetic, immunological, and environmental factors, which acts to disrupt skin barrier function. Free radicals play a key role by directly damaging skin structure, inducing inflammation and weakening of the skin barrier. Tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl) is a membrane-permeable radical scavenger, known to be a stable nitroxide, which exhibits excellent antioxidant effects in several human disorders, such as osteoarthritis and inflammatory bowel diseases. Considering the few existing studies on dermatological pathologies, this study aimed to evaluate tempol, in a cream formulation, in a murine model of AD. Dermatitis was induced in mice via dorsal skin application of 0.5% Oxazolone, three times a week for two weeks. After induction, mice were treated with tempol-based cream for another two weeks at three different doses of 0.5%, 1% and 2%. Our results demonstrated the ability of tempol, at the highest percentages, to counteract AD by reducing the histological damage, decreasing mast cell infiltration, and improving the skin barrier properties, by restoring the tight junction (TJs) and filaggrin. Moreover, tempol, at 1% and 2%, was able to modulate inflammation by reducing the nuclear factor kappa-light-chain-enhancer of the activated B cell (NF-κB) pathway, as well as tumor necrosis factor (TNF)-α and interleukin (IL)-1ß expression. Topical treatment also attenuated oxidative stress by modulating nuclear factor erythroid 2-related factor 2 (Nrf2), manganese superoxide dismutase (MnSOD), and heme oxygenase I (HO-1) expression levels. The obtained results demonstrate the numerous advantages provided by the topical administration of a tempol-based cream formulation, in reducing inflammation and oxidative stress through modulation of the NF-κB/Nrf2 signaling pathways. Therefore, tempol could represent an alternative anti-atopic approach to treating AD, thereby improving skin barrier function.
ABSTRACT
Inflammatory bowel diseases (IBDs) involving Crohn's disease (CD) and ulcerative colitis (UC) are gastrointestinal (GI) disorders in which abdominal pain, discomfort, and diarrhea are the major symptoms. The immune system plays an important role in the pathogenesis of IBD and, as indicated by several clinical studies, both innate and adaptative immune response has the faculty to induce gut inflammation in UC patients. An inappropriate mucosal immune response to normal intestinal constituents is a main feature of UC, thus leading to an imbalance in local pro- and anti-inflammatory species. Ulva pertusa, a marine green alga, is known for its important biological properties, which could represent a source of beneficial effects in various human pathologies. We have already demonstrated the anti-inflammatory, antioxidant, and antiapoptotic effects of an Ulva pertusa extract in a murine model of colitis. In this study, we aimed to examine thoroughly Ulva pertusa immunomodulatory and pain-relieving properties. Colitis was induced by using the DNBS model (4 mg in 100 µL of 50% ethanol), whereas Ulva pertusa was administered daily at the dosage of 50 and 100 mg/kg by oral gavage. Ulva pertusa treatments have been shown to relieve abdominal pain while modulating innate and adaptative immune-inflammatory responses. This powerful immunomodulatory activity was specifically linked with TLR4 and NLRP3 inflammasome modulation. In conclusion, our data suggest Ulva pertusa as a valid approach to counteract immune dysregulation and abdominal discomfort in IBD.
Subject(s)
Colitis, Ulcerative , Colitis , Inflammatory Bowel Diseases , Ulva , Humans , Animals , Mice , Colitis/chemically induced , Colitis/drug therapy , Colitis, Ulcerative/chemically induced , Colitis, Ulcerative/drug therapy , Abdominal Pain , Immune SystemABSTRACT
Over the last three years, humanity has been facing one of the most serious health emergencies due to the global spread of Coronavirus disease (COVID-19). In this scenario, the research of reliable biomarkers of mortality from COVID-19 represents a primary objective. Pentraxin 3 (PTX3), a highly conserved protein of innate immunity, seems to be associated with a worse outcome of the disease. Based on the above, this systematic review and meta-analysis evaluated the prognostic potential of PTX3 in COVID-19 disease. We included 12 clinical studies evaluating PTX3 in COVID-19 patients. From our research, we found increased PTX3 levels compared to healthy subjects, and notably, PTX3 was even more augmented in severe COVID-19 rather than non-severe cases. Moreover, we performed a meta-analysis to establish if there were differences between ICU and non-ICU COVID-19 patients in PTX3-related death. We combined 5 studies for a total of 543 ICU vs. 515 non-ICU patients. We found high significative PTX3-related death in ICU COVID-19 hospitalized individuals (184 out of 543) compared to non-ICU (37 out of 515), with an overall effect OR: 11.30 [2.00, 63.73]; p = 0.006. In conclusion, we probed PTX3 as a reliable marker of poor outcomes after COVID-19 infection as well as a predictor of hospitalized patients' stratification.
Subject(s)
COVID-19 , Humans , Biomarkers/metabolism , C-Reactive Protein/metabolism , COVID-19/metabolism , COVID-19/mortality , PrognosisABSTRACT
Bacterial vaginosis (BV) is a common vaginal dysbiosis characterized by a malodorous discharge and irritation. The imbalance of the vaginal microbiota plays a key role in the development of BV. It has been demonstrated that Gardnerella vaginalis (GV), a facultative anaerobic bacillus, is involved in BV. Due to the rising number of antimicrobial-resistant species, recurrence of BV is becoming more frequent in women; thus, alternative treatments to antibiotics are needed. Natural substances have recently shown a great efficacy for the treatment of vaginal dysbiosis. Thus, this study aimed to investigate the beneficial effect of a product containing pea protein (PP), grape seed extract (GS) and lactic acid (LA) in an in vivo model of Gardnerella vaginalis-induced vaginosis by intravaginal administration of GV suspension (1 × 106 CFU/20 µL saline). Our results demonstrated that the product containing PP, GS and LA significantly reduced GV proliferation. More specifically, it significantly preserved tissue architecture and reduced neutrophil infiltration, inflammatory markers and sialidase activity when used both as a pre- or a post-treatment. Moreover, the product displayed strong bioadhesive properties. Therefore, our data suggested that the product containing PP, GS and LA could be used as alternative preventive or curative treatment for the management of BV.