ABSTRACT
This systematic review aimed to compare the efficacy of nonpharmacological therapies for painful temporomandibular joint disorders. The protocol was registered on International Prospective Register of Systematic Reviews (PROSPERO) database (CRD42020171364). The search was performed on the electronic databases PubMed, Google Scholar, Clinical Trials, and Web of Science. The eligibility criteria were randomized controlled trials in patients diagnosed with painful temporomandibular joint disorders comparing the pain relief between conventional treatment and nonpharmacological therapies such as acupuncture, physiotherapy, low-level laser, and massage. Fourteen articles were included in this review. At the overall bias of the studies included, 71.42% exhibited some concerns and 28.57% had high risk. The efficacy of nonpharmacological interventions was found to be moderate in the short term and variable in the long term for pain reduction in patients with temporomandibular joint disorders. The evidence pointed out that acupuncture, laser therapy, and physiotherapy are potentially useful interventions for pain relief in patients with temporomandibular joint disorders. However, there is a lack of consistency and short-term follow-up in the studies to determine the lasting of such effect.
ABSTRACT
O-linked ß-N-acetylglucosaminylation (O-GlcNAcylation) is a reversible post-translational modification on serine and threonine residues of cytosolic, nuclear and mitochondrial proteins. O-GlcNAcylation level is regulated by OGT (O-GlcNAc transferase), which adds GlcNAc on proteins, and OGA (O-GlcNAcase), which removes it. Abnormal level of protein O-GlcNAcylation has been observed in numerous cancer cell types, including cervical cancer cells. In the present study, we have evaluated the effect of increasing protein O-GlcNAcylation on cervical cancer-derived CaSki cells. We observed that pharmacological enhancement of protein O-GlcNAcylation by Thiamet G (an inhibitor of OGA) and glucosamine (which provides UDP-GlcNAc substrate to OGT) increases CaSki cells proliferation, migration and survival. Moreover, we showed that increased O-GlcNAcylation promotes IGF-1 receptor (IGF1R) autophosphorylation, possibly through inhibition of protein tyrosine-phosphatase 1B activity. This was associated with increased IGF-1-induced phosphatidyl-Inositol 3-phosphate production at the plasma membrane and increased Akt activation in CaSki cells. Finally, we showed that protein O-GlcNAcylation and Akt phosphorylation levels were higher in human cervical cancer samples compared to healthy cervix tissues, and a highly positive correlation was observed between O-GlcNAcylation level and Akt phosphorylation in theses tissues. Together, our results indicate that increased O-GlcNAcylation, by activating IGF1R/ Phosphatidyl inositol 3-Kinase (PI-3K)/Akt signaling, may participate in cervical cancer cell growth and proliferation.
