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These findings imply that rapamycin prevents cognitive impairment and protects hippocampus neurons from AD-like pathology and mitochondrial abnormality, and also that rapamycin treatment could normalize these STZ-induced alterations by decreasing hippocampus mTOR/p70S6K hyperactivity.Recurrent aphthous stomatitis (RAS) is a common disease with ulcers in oral cavity which may trigger chewing, speaking, and swallowing difficulties to patients. Treatment of RAS is primarily aimed at pain relief and the promotion of wound healing. However, few agents have been found to have definite effect in the management of RAS and most of the medicinal products may cause adverse reactions or other disadvantages, which makes their clinical usage questionable. The purpose of this randomized controlled clinical trial (RCT) was to assess the clinical effect of diode laser and traditional medication treatment on RAS. In this study, 56 patients were randomly assigned to two groups (n = 28). Laser group was treated using diode laser (810 nm, 1.0 W, CW, irradiation time 20 s for 3 applications) once daily for continuous 3 days. Medication group was treated with triamcinolone acetonide 0.1% three times a day until the lesion was healed. Spontaneous and functional pain level on the third day of treatment was significantly less in the laser group. Significant difference was observed with respect to healing time; however, the order of difference is small albeit of statistical significance. Diode laser with the chosen parameters had better effects on pain relief and no distinct advantage on wound healing comparing with medication. Trial registration number ChiCTR2000030298; date of registration 26 February 2020 (retrospectively registered).
The objective of this review was to assess the efficacy of non-pharmacological interventions on endometrial cancer (EC) survivors' QOL, and their use of patient-reported outcome measures (PROMs).
We conducted a systematic review of randomized controlled trials (RCTs) of non-pharmacological interventions that assessed the impact of intervention on EC survivors' general and domain-specific QOL (i.e., physical, psychological, and social well-being) using PROMs.
Of the 3178 studies identified, 28 full-text articles were reviewed, and 10 were included in the review. Nine RCTs assessed at least one PROM as a primary outcome and six assessed a PROM as a secondary outcome, but few studies used validated PROMs. Significant improvements in general QOL were found in two studies, domain-specific QOL in three studies, and both general and domain-specific QOL in three studies; however, effect sizes ranged from small to large and no significant effects were found for social well-being and few were found for psychological well-being.
Few non-pharmacological interventions for EC survivors targeted QOL, even though QOL was assessed as either a primary or secondary outcome of the RCT. Despite this, findings suggest that non-pharmacological interventions for EC survivors hold promise for improving general and domain-specific QOL. Use of validated PROMs would greatly enhance outcome reporting and facilitate comparisons across studies. More interventions are also needed that address social and psychological functioning in this population.
Our review highlights a need to (1) expand non-pharmacological RCTs for EC survivors, (2) increase the use of validated PROMs measuring QOL, and (3) address psychosocial domains of QOL when developing interventions for this population.
Our review highlights a need to (1) expand non-pharmacological RCTs for EC survivors, (2) increase the use of validated PROMs measuring QOL, and (3) address psychosocial domains of QOL when developing interventions for this population.Thyroid gland involvement of Langerhans cell histiocytosis (LCH) is extremely rare in both systemic and isolated disease. The role of viral infection in LCH development is not yet fully understood. Although several viruses are proposed as etiologic factors, such as Epstein-Barr virus (EBV) and human herpesvirus 6 (HHV-6), they seem to play a bystander role in LCH. A 29-year old female patient with a prior history of multisystemic LCH (pituitary gland and skull bone), presented with a thyroid nodule. The patient underwent a total thyroidectomy and the histological examination revealed nodular lesions composed of sheets and clusters of histiocytes in the inflammatory background. The histiocytes stained positive for S-100 and CD1a and were negative for HHV-8, cytomegalovirus, and VE1 (anti-BRAFV600E) on immunohistochemistry. The EBER in situ hybridization for EBV showed frequent positive-stained cells. The conventional PCR analysis for EBV was positive and qPCR analysis confirmed a significant DNA copy number difference (p = 0.02) between the tumor and adjacent non-neoplastic thyroid tissue. PCR analysis for HHV-6, HPV, HSV was negative in both tumor and benign samples. In conclusion, the presented case showed a rare thyroid involvement by LCH associated with EBV infection, which has not been reported before. Further studies are required to investigate a possible etiologic link between EBV infection and LCH.
Rapamycin and its semi-synthetic analogues (rapalogues) are frequently used in combination with other prescribed medications in clinical settings. Although the inhibitory effects of rapalogues on cytochrome P450 enzymes (CYPs) have been well examined, the inhibition potentials of rapalogues on human esterases have not been investigated. Herein, the inhibition potentials and inhibitory mechanisms of six marketed rapalogues on human esterases are investigated.
The inhibitory effects of six marketed rapalogues (rapamycin, zotarolimus, temsirolimus, everolimus, pimecrolimus and tacrolimus) on three major esterases, including human carboxylesterases 1 (hCES1A), human carboxylesterases 2 (hCES2A) and butyrylcholinesterase (BuChE), were assayed using isozyme-specific substrates. TEN-010 Inhibition kinetic analyses and docking simulations were performed to investigate the inhibitory mechanisms of the rapalogues with strong hCES2A inhibition potency.
Zotarolimus and pimecrolimus displayed strong inhibition of human hCES2A but these agents did not inhibit hCES1A or BuChE.
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