Early Assessment of Voice Problems in Post-Thyroidectomy Syndrome Using Cepstral Analysis.

Post-thyroidectomy syndrome (PTS), characterized by voice issues after thyroidectomy without recurrent laryngeal nerve injury, was investigated in this study. The Voice Fatigue Index (VFI) and cepstral analysis were employed for subjective and objective voice evaluation. Retrospective analysis involved 96 patients (37 males, 59 females) who underwent thyroidectomy without nerve injury from April 2018 to June 2022. Assessments pre- and post-thyroidectomy included the Voice Handicap Index (VHI) and VFI, along with auditory perceptual, acoustic (including cepstral), aerodynamic, and glottal vibration analyses. In females, although the GRBAS scale showed no significant change, both VHI and VFI increased post-thyroidectomy. Significant correlations were observed between the VHI and VFI in females. Acoustic analysis indicated a decrease in the cepstral peak prominence (CPP) of vowels (/a/) and sentences in females, with significant correlations between changes in the CPP/a/ and VHI/VFI. The maximum fundamental frequency (F0max) exhibited a significant decrease, correlating with the VHI and VFI changes. The VFI demonstrated effectiveness in subjective PTS voice evaluation, comparable to the VHI. The present study highlights the potential of cepstral analysis as an index reflecting subjective voice discomfort, suggesting its promise for a comprehensive PTS voice evaluation.

Lysophosphatidic acid induces proliferation and osteogenic differentiation of human dental pulp stem cell through lysophosphatidic acid receptor 3/extracellular signal-regulated kinase signaling axis.

Background/purpose: Human dental pulp stem cells (hDPSCs) possess excellent proliferative and osteogenic differentiation potentials. This study aimed to elucidate the role of lysophosphatidic acid (LPA) signaling in the proliferation and osteogenic differentiation of hDPSCs. Materials and methods: hDPSCs were treated with LPA and proliferation was measured using the cell counting kit-8 assay. Following the osteogenic differentiation of hDPSCs using osteogenic medium in the presence or absence of LPA, alkaline phosphatase (ALP) staining, ALP activity measurements, and RT-qPCR were performed to analyze the osteoblast differentiation. Small interfering RNA (siRNA)-mediated LPAR3 silencing and extracellular signal-regulated (ERK)/mitogen-activated protein (MAP) kinase inhibitors were used to elucidate the molecular mechanisms underlying LPA-induced proliferation and differentiation of hDPSCs. Results: LPA treatment significantly induced proliferation and osteogenic differentiation of hDPSCs. The depletion of LPAR3 expression by LPAR3-speicifc siRNA in hDPSCs diminished LPA-induced proliferation and osteogenic differentiation. The LPAR3-mediated proliferation and osteogenic differentiation of hDPSCs in response to LPA were significantly suppressed by U0126, a selective inhibitor of ERK. Conclusion: These findings suggest that LPA induces the proliferation and osteogenic differentiation of hDPSCs via LPAR3-ERK-dependent pathways.

Vasohibin-1 promotes osteoclast differentiation in periodontal disease by stimulating the expression of RANKL in gingival fibroblasts.

Vasohibin-1 (VASH1) is a key inhibitor of vascular endothelial growth factor-induced angiogenesis. Although the involvement of VASH1 in various pathological processes has been extensively studied, its role in periodontal disease (PD) remains unclear. We aimed to investigate the role of VASH1 in PD by focusing on osteoclastogenesis regulation. We investigated VASH1 expression in PD by analyzing data from the online Gene Expression Omnibus (GEO) database and using a mouse ligature-induced periodontitis model. The effects of VASH1 on osteoclast differentiation and osteoclastogenesis-supporting cells were assessed in mouse bone marrow-derived macrophages (BMMs) and human gingival fibroblasts (GFs). To identify the stimulant of VASH1, we used culture broth from Porphyromonas gingivalis (Pg), a periopathogen. The GEO database and mouse periodontitis model revealed that VASH1 expression was upregulated in periodontitis-affected gingival tissues, which was further supported by immunohistochemistry and qRT-PCR analyses. VASH1 expression was significantly stimulated in GFs after treatment with the Pg broth. Direct treatment with recombinant VASH1 protein did not stimulate osteoclast differentiation in BMMs but did contribute to osteoclast differentiation by inducing RANKL expression in GFs through a paracrine mechanism. Small interfering RNA-mediated silencing of VASH1 in GFs abrogated RANKL-mediated osteoclast differentiation in BMMs. Additionally, VASH1-activated RANKL expression in GFs was significantly suppressed by MK-2206, a selective inhibitor of AKT. These results suggest that Pg-induced VASH1 may be associated with RANKL expression in GFs in a paracrine manner, contributing to osteoclastogenesis via an AKT-dependent mechanism during PD progression.

Effect of telmisartan on an experimental model of periodontitis in mice.

OBJECTIVE: This study was performed to explore the impact of telmisartan on experimental periodontitis in mice, in terms of alveolar bone destruction, by using micro-computed tomography analysis. MATERIALS AND METHODS: Male BALB/c mice were divided into four groups of 7 to 9 mice each: control (C) group; experimental periodontitis (E) group; experimental periodontitis-plus-telmisartan 5 mg/kg (ET5) group; and experimental periodontitis-plus-telmisartan 10 mg/kg (ET10) group. The mice in Group C were not subjected to experimental periodontitis. The other mice from Groups E, ET5 and ET10 were exposed to periodontitis. Periodontitis was induced by inoculation with Porphyromonas gingivalis. RESULTS: Telmisartan significantly suppressed both the reduction in alveolar bone height and increase of root exposure caused by P. gingivalis infection. When mice were treated with telmisartan, the decrease in the bone volume fraction induced by the infection was notably recovered. In addition, telmisartan reversed P. gingivalis-induced alterations in the microstructural parameters of trabecular bone, except trabecular thickness.No significant difference was evident between Groups ET5 and ET10 in both the extent of alveolar bone loss and microstructural parameters assessed, except bone volume fraction and trabecular number. CONCLUSION: Telmisartan may have potential benefits as a host modulation agent for the therapy of periodontitis.

Prevalence of Dysphonia in Children with Adenotonsillar Problems and the Impact of Surgery on Voice.

OBJECTIVE/HYPOTHESIS: Adenotonsillar problems might affect the voices of patients with pediatric dysphonia, which is very common. This study aimed to evaluate the prevalence of dysphonia in patients with adenotonsillar problems and to demonstrate the impact of tonsillectomy and adenoidectomy (T & A) on their voice postoperatively. STUDY DESIGN: Single-institution retrospective study. METHODS: Subjects were recruited from those children admitted for the purpose of T & A, and all underwent the auditory-perceptual assessment by speech therapists preoperatively. If children demonstrated scores >2 in the G parameter, we performed subjective (pediatric voice handicap index [pVHI], severity, talkativeness scale) and objective (Multi-Dimensional Voice Program) voice analyses preoperatively and 1 and 3 months postoperatively. RESULTS: Among the 1,197 patients, 91 (7.6%) patients showed dysphonia with a score >2 in the G parameter preoperatively. The follow-up voice analysis was completed in 51 and 22 patients after 1 and 3 months, respectively. Although there were no significant differences in the amount of speech preoperatively and postoperatively, the average visual analog scale score for dysphonia severity was significantly decreased at postoperative 1 month and postoperative 3 months. The average total pVHI score, jitter, shimmer, noise-to-harmonic ratio, and soft phonation index were significantly decreased at 1 and 3 months postoperatively. Subjective scores given by parents did not correlate with the acoustic parameters; however, the postoperative subjective parameters were significantly correlated with objective parameters. CONCLUSIONS: Voice problems were significantly improved after T & A in the short term and long term. In those with pediatric dysphonia, decreased mouth breathing and compliance with vocal hygiene would be helpful for voice improvement. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:2369-2375, 2021.

Effect of nifedipine, a calcium channel blocker, on the generation of nitric oxide and interleukin-1ß by murine macrophages activated by lipopolysaccharide from Prevotella intermedia.

Nifedipine, a calcium channel blocker, has been reported to possess anti-inflammatory and immunosuppressive effects. The current study was undertaken to explore the influence of nifedipine on the generation of proinflammatory mediators by murine macrophages activated by lipopolysaccharide (LPS) prepared from Prevotella intermedia, a putative periodontal pathogen, and associated mechanisms of action as well. LPS was purified by employing phenol-water extraction protocol. Culture supernatants were analyzed for nitric oxide (NO) and interleukin (IL)-1ß. Real-time PCR and immunoblotting were conducted to quantify mRNA and protein expression, respectively. NF-κB-dependent secreted embryonic alkaline phosphatase (SEAP) levels were estimated by reporter assay. Nifedipine markedly suppressed the generation of iNOS-derived NO and IL-1ß together with their mRNA expressions in murine macrophages activated by P. intermedia LPS. LPS-stimulated cells exposed to nifedipine notably increased the mRNA levels of Arg-1, Ym-1, FIZZ1, and TGF-ß, which are typical markers for M2 macrophage polarization. Nifedipine induced HO-1 at both gene and protein levels in cells challenged with P. intermedia LPS, and the nifedipine-mediated inhibition of NO generation was significantly abrogated by adding SnPP, an HO-1 inhibitor. Nifedipine inhibited LPS-evoked generation of NO and IL-1ß in a PPAR-γ-independent manner. In addition, NF-κB activation as well as phosphorylation of STAT1/3 induced by P. intermedia LPS was suppressed by nifedipine. Nifedipine is an inhibitor of P. intermedia LPS-evoked production of NO and IL-1ß in murine macrophages and encourages macrophage polarization toward the M2 phenotype. Nifedipine possibly has potential to be used for host modulation of periodontal disease and is worth being further researched.

Tricarbonyldichlororuthenium(II) dimer, the lipid-soluble carbon monoxide-releasing molecule, attenuates Prevotella intermedia lipopolysaccharide-induced production of nitric oxide and interleukin-1ß in murine macrophages.

Carbon monoxide (CO) is increasingly being appreciated as an important mediator that has pleiotropic biological properties and appears to have a possible therapeutic application for a variety of disorders. Nevertheless, whether this gaseous molecule may be utilized as a therapeutic intervention for periodontal disease is unclear. Here, we examined the potential beneficial effect of CO-releasing molecule-2 (CORM-2), a tricarbonyldichlororuthenium(II) dimer, against the elaboration of proinflammatory mediators by murine macrophages challenged with lipopolysaccharide (LPS) isolated from Prevotella intermedia, a pathogenic bacterium implicated in inflammatory periodontal disease. We found that NO and IL-1ß production, iNOS protein expression and mRNA expressions of iNOS and IL-1ß were significantly down-regulated when LPS-challenged RAW264.7 cells were exposed to CORM-2. In addition, HO-1 expression was upregulated by CORM-2 in cells activated with P. intermedia LPS, and the inhibitory influence of CORM-2 upon NO production was attenuated by tin protoporphyrin IX, an inhibitor of HO activity. PPAR-γ did not function in the attenuation of NO and IL-1ß by CORM-2. JNK and p38 phosphorylation caused by LPS was not altered by CORM-2. CORM-2 reduced NF-κB reporter activity and IκB-α degradation elicited by P. intermedia LPS. Additionally, CORM-2 inhibited LPS-induced phosphorylation of STAT1/3. In conclusion, CORM-2 suppresses NO and IL-1ß production caused by P. intermedia LPS. CORM-2 exerts its effect by a mechanism involving anti-inflammatory HO-1 induction and attenuation of NF-κB and STAT1/3 activation, independently of PPAR-γ as well as JNK and p38. CORM-2 may hold promise as host response modulation agent for periodontal disease, though further research is indicated to verify the therapeutic effect.

Telmisartan, an angiotensin II receptor blocker, attenuates Prevotella intermedia lipopolysaccharide-induced production of nitric oxide and interleukin-1ß in murine macrophages.

Telmisartan, widely prescribed for the treatment of hypertension, has an anti-inflammatory property in addition to being an angiotensin II type 1 receptor antagonist. This study was carried out to explore the influence of telmisartan upon the elaboration of inflammatory mediators in murine macrophages stimulated with lipopolysaccharide (LPS) prepared from Prevotella intermedia, a periodontal pathogen, as well as its molecular mechanisms. Telmisartan significantly inhibited LPS-induced generation of inducible nitric oxide (NO) synthase-derived NO and interleukin-1ß (IL-1ß) as well as their gene expressions in RAW264.7 cells. Telmisartan treatment of LPS-activated cells significantly up-regulated arginase 1 (Arg-1) and chitinase-like 3 (Ym-1), which are specific markers of M2 macrophages. Telmisartan caused a significant increase in heme oxygenase-1 (HO-1) expression in cells stimulated with LPS, and its inhibitory action against NO production was reversed by treatment with SnPP, an HO-1 inhibitor. Phosphorylation of STAT1 and STAT3 induced by LPS was attenuated by telmisartan. Telmisartan inhibited LPS-induced generation of NO and IL-1ß independently of PPAR-γ activation. In addition, activation of NF-κB as well as JNK and p38 signaling induced by LPS was not modulated by telmisartan. In summary, telmisartan is a potent inhibitor of P. intermedia LPS-induced generation of NO and IL-1ß in RAW264.7 cells and promotes macrophage phenotype switching toward the M2 phenotype. Telmisartan may have potential to be developed into host modulatory agent for inflammatory periodontal disease, although additional studies are needed to confirm the therapeutic effect.