1,721,038 research outputs found
Photobiomodulation Therapy: in vivo and in vitro Models for Applications in Pediatric Oncology
Full text linkPhotobiomodulation (PBM) Therapy is a form of treatment that exploits laser light to elicit bio-stimulation, promoting cellular metabolism, reducing inflammation, driving analgesia and with an antimicrobial action at blue wavelength. PBM is currently used for the management of oral mucositis (OM) a severe side effect of chemo-radiotherapy characterized by painful atrophic / ulcerative lesions of oral mucosa that can affect pediatric and adult oncologic patients. Although the successful clinical employment of PBM, some issues remain regarding its mechanisms of action, moreover, a universal agreement regarding the most efficacious protocols is still lacking.In this PhD project different aspects of PBM were investigated with the aim of describing the properties of laser light, and consecutively amplifying the scientific knowledge in the laser field.Firstly, PBM effect on oxidative stress was inquired.In OM patients, the clinical parameters improved with PBM at 970nm with the amelioration of clinical scores and with the healing of oral ulcerations, moreover, PBM reduced salivary total oxidant status.In an in vitro model of skin keratinocytes treated with 5-fluorouracil (5-FU), mimicking OM condition, PBM at 970, 905, 800 and 660 nm was able to increment the viability of 5-FU treated cells and to reduce reactive oxygen species (ROS) and gene expression of two antioxidant enzymes.Secondly, PBM was tested for its immunoregulatory actions.PBM was not able to impact on salivary beta-defensins proteins production in OM patients.However, in an oral mucosa epithelial cell line, PBM at 970, 800 and 660 nm reduced mRNA expression of DEFB1, DEFB4, DEFB103 genes. Furthermore, when the cells were pre-treated with lipopolysaccharide, PBM at660nm reduced the expression of DEFB103. Moreover, PBM at 970nm increased IL1B expression and decreased NLRP3 one, meanwhile at 660nm increased NLRP1 expression.Thirdly, the analgesic activities of PBM were investigated.PBM at 970nm was able to decrease the painful sensation referred by OM patients.In primary murine sensory neurons from dorsal root ganglia, PBM at 970 and 800 nm reduced ATP and nitric oxide production and increased ROS level; PBM at 800nm increased also superoxide anion and mitochondrial membrane potential, while at 970nm decreased the calcium flow after capsaicin administration.When capsaicin, as a painful stimulus, were subplantarly injected in mice, PBM at 970nm reduced the pain related behavior.Fourthly, the blue PBM was studied for its antibacterial properties.PBM inhibited Pseudomonas aeruginosa growth on agar plate and in broth, inducing wall damaging. Blue light caused a lethal increment of ROS, that was rescued through a pre-treatment with a ROS scavenger. P. aeruginosa mutants for enzymes of the porphyrin biosynthetic pathway, producing less porphyrins, resulted less susceptible to irradiation.Finally, PBM was able to inhibit bacterial replication in a murine in vivo model of skin abrasion infection. Blue PBM did not result cytotoxic for eukaryotic cells, rather it reduced the inflammatory infiltrate in the murine skin.Lastly, blue PBM was examined for its antiviral activities.Blue PBM was tested on an in vitro model of human skin keratinocytes infected with Herpes simplex virus type 1 (HSV-1).The virus was irradiated alone and then the cells were infected: PBM exerted an antiviral effect, decreasing the viral load and increasing the viability of the cells infected with irradiated virus.The plaque forming unit assay corroborated these results, proven the less infectivity capacity of irradiated HSV-1.So, our results highlighted a pleiotropic action of PBM as anti-oxidant, immunoregulatory, analgesic, antibacterial and antiviral agent. These data corroborated the useful medical interventions based on laser light, possibly helping to increment a clinical thoughtful and justified usage of PBM in OM patients for routinely applications, especially in pediatric oncologic subjects
Is FURIN gene expression in salivary glands related to SARS-CoV-2 infectivity through saliva?
No full textUnravelling the SARS-CoV-
2 mechanism of entry
into host cells is engaging the endeavours of
researchers worldwide and, although angiotensin-converting
enzyme 2 (ACE2) is recognised as
the primary receptor, many issues remain to be
investigated.1
Remarkably, the interaction between ACE2 and the
spike (S) glycosylated protein of SARS-CoV-
2 necessary
for viral entry has been discovered by employing
crystallography. S protein presents a receptor binding
domain (RBD) and more specifically a receptor
binding motif (RBM) which mediates the attachment
to two virus-binding
hotspots within ACE2 surface.
The aminoacidic constitution of SARS-CoV-
2 RBM
is highly homologous to that of SARS-CoV
but shows
some differences, specifically a four-residue
motif at
482–485 (Gly-Val-
Glu-
Gly)
that confers more affinity
for ACE2 resulting in a tight relation between the two
molecules
HLA-G and susceptibility to develop celiac disease
No full textThe Human Leukocyte Antigen-G has immunomodulatory function and its expression has been associated with several diseases. In our study we analyzed HLA-G polymorphisms in order to evaluate their possible association with susceptibility to celiac disease development. A total of 420 celiac patients and 509 controls were genotyped for HLA-G polymorphisms. We sequenced 800bp upstream the ATG codon (5' upstream regulatory region) and the whole 3' untranslated region of the HLA-G gene, whereas the ΔC deletion at exon 3 was detected by RFLP-PCR. Five polymorphisms (namely -477 C>G, -369 C>A, 14bp del/ins, 3187 A>G, 3196 C>G) and one haplotype (TCGGTACGAAITCCCGAG) were significantly more frequent in celiac patients than controls and associated with increased disease susceptibility. The 14bp I/I, 3187 G/G, 3196 G/G genotypes and TCGGTACGAAITCCCGAG haplotype, were still significantly associated with increased disease susceptibility (and in addition also the 3003 C/C genotype) when the analysis was restricted to patients and controls presenting the DQ2.5 or DQ8 HLA-DQ celiac disease risk haplotypes. Our findings indicate an association between HLA-G gene polymorphisms and susceptibility to celiac disease development, suggesting that HLA-G molecule is possibly involved in the pathogenesis of the disease
Interleukin-18 gene promoter polymorphisms and celiac disease in Italian patients.
No full textCeliac disease (CD) is the most common food-sensitive enteropathy in genetically susceptible individuals. The major genetic risk factors known are specific human leukocyte antigen (HLA)-DQ haplotypes, but other genetic factors are supposed to be involved. Interleukin-18 (IL-18) is a pro-inflammatory cytokine that has an important role in the immune defense and it has the potential to influence inflammatory disorders. IL-18 is able to promote Th1 cell development and it is expressed in the mucosa of the small intestine in celiac patients. Given the IL-18 biological role, and since a few studies have previously suggested its involvement in CD, in order to investigate the role of IL18 gene in the susceptibility to CD we have performed a case-control study, analyzing two IL18 gene promoter polymorphisms, previously reported to impair the transcriptional activity of the gene, (-137G > C and -607C > A, rs187238 and rs1946518 respectively). A total of 556 CD Italian patients and 582 controls, further stratified for HLA class II (DQ) CD risk haplotypes were enrolled. The -607A > C A allele and A/A genotype, as well as the combination of this allele with the -137G allele in the AG haplotype, were associated with an increased risk towards CD development, in particular in HLA-DQ2.2 patients. Although the association was very moderate, our results indicate the possible involvement of IL18 gene in the susceptibility to CD, and for this reason we do think it should deserve further investigation
SARS-CoV-2 and the next generations: which impact on reproductive tissues?
No full textCoronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2) is a
severe global pandemic, affecting mostly the respiratory system. Understandably, attention is also being directed towards the
urogenital tract. In this work, expression patterns of various host molecules possibly involved in viral entry and replication were
investigated in human female and male reproductive systems by inquiring online repositories, including the Human Protein Atlas,
GTEx, FANTOM5. Our findings highlight that male reproductive tissues could be targeted by SARS-CoV-2, particularly the
testis since it co-expresses the receptor (ACE2) and the protease (TMPRSS) needed for viral entry. We hypothesized that SARSCoV-
2 infection could have repercussions on the fertility status of male individuals Potential infectivity of SARS-CoV-2 in
reproductive tissues should be considered in reproductive medicine and management of in vitro fertilization in present and future
generation
Lactoferrin gene polymorphisms in Italian patients with recurrent tonsillitis
No full textRecurrent tonsillitis is an oral pathology characterized by inflammation of tonsils. The disease susceptibility depends upon environmental and host factors, specifically the innate immune response, the first line of host defence could play an important role. Among innate immunity members, lactoferrin, known for its antimicrobial properties, was previously correlated with the risk of oral pathology as periodontitis and dental caries
Candida Infections and Human Defensins
Full text linkCandida species infections are an important worldwide health issue since they do not only affect immunocompromised patients but also healthy individuals. Indeed Candida spp. are present as commensal flora in the host human body but they can switch into a pathological form inducing cellular damage and disease. Among Candida strains, C. albicans is the most prevalent in both mucosal and systemic infections. The host developed different mechanisms of protection against Candida infections; specifically the immune system and the innate immune response are the first line of defence. Defensis are a group of antimicrobial peptides, components of the innate immunity, produced at mucosal level and known to be active against bacteria, virus but also fungi. Defensins are able to recognize the pathogens cell wall (different in composition from the human ones), and disrupt it through membrane permeabilization. Although the exact mechanisms of defensins anti-fungal action are not completely elucidated, the findings of the reviewed studies highlight the pivotal role of these peptides in the immune response against Candida infections
sensory neurons
Full text linkPhotobiomodulation therapy (PBMT) is known as a complementary tool to alleviate pain sensation in patients, nevertheless, there is still a gap of knowledge on its mechanism of action, thus limiting its clinical employment. In this study, a possible molecular mechanism of the 905 nm PBMT (0.25 W/cm2; 3, 6, 12, and 18 J/cm2, 5 Hz) analgesic effect was tested on 50B11 cells, by investigating its impact on mitochondria. A decrement of adenosine triphosphate was detected, moreover, an increment of total reactive oxygen species and mitochondrial superoxide anion was found after PBMT with all protocols tested. PBMT at 18 J diminished the mitochondrial membrane potential, and influenced mitochondrial respiration, decreasing the oxygen consumption rate. Finally, a decrement of extracellular signal-regulated kinase 1/2 phosphorylation was observed with the protocol using 12 J. Taken together these findings highlighted the intracellular effects, mainly correlated to mitochondrial, induced by 905 nm PBMT in sensory neurons, indicating the central role of this organelle in the cellular response to 905 nm near-infrared laser light. (Figure presented.).This work was supported by the Italian Ministry of Health, through the contribution given to the Institute for Maternal and Child Health IRCCS Burlo Garofolo, Trieste, Italy (RC 15/17 and RC 29/23)
NLRC5 polymorphism is associated with susceptibility to chronic periodontitis
No full textPeriodontitis is a chronic oral pathology caused by impaired immune response against oral bacteria resulting in tissue inflammation and damage. Among the members of innate immune response, the first line of defence against pathogens, inflammasomes are macro-molecular protein complexes that can be activated by different stimuli, comprised bacteria infections. Different proteins are involved in inflammasoma formation; the most important are molecules belonging from the family of nucleotide-binding and oligomerization domain (NOD)-like receptors (NLRs). In this study, polymorphisms within 20 NLRs related genes were analysed in order to investigate their possible association with periodontitis susceptibility in a population from North-East Italy. One polymorphism, namely rs289723, in NLRC5 gene resulted associated with chronic slight and chronic localized periodontitis susceptibility, specifically A/A genotype was correlated with increased risk of disease development. Our study, for the first time, identified the possible involvement of a polymorphism within NLRC5 gene as a possible biomarker for periodontitis condition susceptibility among Italian individuals from genetic isolates
Ketorolac analgesia in the emergency department in adults: systematic review and meta-analysis
No full textBackground and objective: Acute painful conditions are a common reason to emergency department (ED) referral, and a broad variety of analgesic drugs may be used. Among them, ketorolac is a Non-Steroidal Anti-Inflammatory Drug (NSAID) increasingly used in the last two decades. In order to clarify the available evidence about the use of ketorolac in the ED setting, a systematic review and meta-analysis was performed. Databases and data treatment: A search was performed in PubMed for English written articles updated to February 2023. Only randomized controlled trials regarding adult patients with acute painful conditions treated in the ED were selected. A meta-analysis was performed to evaluate the effectiveness of ketorolac in different pain conditions. Results: : Forty randomized controlled trials were selected including studies focused on acute renal colic, headache, traumatic and non-traumatic musculoskeletal pain, and biliary colic. In these studies, ketorolac was mainly compared to opioids and in general showed a similar analgesic efficacy. On the other hand, when compared to other NSAIDs, ketorolac does not seem to have a stronger analgesic effect. Conclusion: s: This systematic review indicates that ketorolac is a valuable option, alternative to opioids, to induce analgesia in adult ED patients, as our meta-analysis showed no significant difference in efficacy compared to opioids or other NSAIDs. Nevertheless, the evidence regarding its efficacy compared to other commonly NSAIDs is still limited and should be further explored in future studies
- …
