Supernatant of activated platelet-rich plasma rejuvenated aging-induced hyposalivation in mouse.

Hyposalivation is a common complaint among the elderly, but no established treatment prevents age-induced hyposalivation. Platelet derivatives such as platelet-rich plasma (PRP), platelet-rich fibrin (PRF), and plasma rich in growth factor (PRGF), are used widely in different areas of regenerative medicine to enhance the wound healing processes. This study examined whether the local injection of the supernatant of activated PRP (saPRP) into the salivary gland (SG) could help prevent aging-induced SG dysfunction and explored the mechanisms responsible for the protective effects on the SG hypofunction. The platelets were separated from the blood of male SD rats (220 ± 20 g). saPRP was manufactured by removing the fibrin clot after activating platelet with calcium ionophore 10 µM (A23187). The total protein and TGF-ß1 levels were significantly higher in saPRP than in PRP. Human salivary gland epithelial cell(hSGEC) was treated with saPRP or PRP after senescence through irradiation. The significant proliferation of hSGEC was observed in saPRP treated group compared to irradiation only group and irradiation + PRP group. Cellular senescence, apoptosis, and inflammation significantly reduced in saPRP group. The SG function and structural tissue remodeling by the saPRP were investigated with naturally aged mice. The mice were divided into three groups: 3 months old (3 M), 22 months old (22 M), and 22 months old treated with saPRP (22 M + saPRP). Salivary flow rate and lag time were significantly improved in 22 M + saPRP group compared to 22 M group. The histologic examinations showed the significant proliferation of acinar cell in 22 M + saPRP group. The decrease of senescence, apoptosis, and inflammation observed by western blot in 22 M + saPRP group. The saPRP induced the proliferation of hSGECs, leading to a significant decrease in cellular senescence via decrease inflammation and apoptosis, in vitro. Moreover, the acini cells of the salivary gland were regenerated, and the salivary function increased in aged mice. These results showed that saPRP could be a treatment agent against aging-induced SG dysfunction.

Effect of statin use on head and neck cancer prognosis in a multicenter study using a Common Data Model.

Few studies have found an association between statin use and head and neck cancer (HNC) outcomes. We examined the effect of statin use on HNC recurrence using the converted Observational Medical Outcome Partnership (OMOP) Common Data Model (CDM) in seven hospitals between 1986 and 2022. Among the 9,473,551 eligible patients, we identified 4669 patients with HNC, of whom 398 were included in the target cohort, and 4271 were included in the control cohort after propensity score matching. A Cox proportional regression model was used. Of the 4669 patients included, 398 (8.52%) previously received statin prescriptions. Statin use was associated with a reduced rate of 3- and 5-year HNC recurrence compared to propensity score-matched controls (risk ratio [RR], 0.79; 95% confidence interval [CI], 0.61-1.03; and RR 0.89; 95% CI 0.70-1.12, respectively). Nevertheless, the association between statin use and HNC recurrence was not statistically significant. A meta-analysis of recurrence based on subgroups, including age subgroups, showed similar trends. The results of this propensity-matched cohort study may not provide a statistically significant association between statin use and a lower risk of HNC recurrence. Further retrospective studies using nationwide claims data and prospective studies are warranted.

Assessment of Radiologic Extranodal Extension Using Combinatorial Analysis of Nodal Margin Breakdown and Metastatic Burden in Oropharyngeal Cancer.

The importance of risk stratification in the management of oropharyngeal squamous cell carcinoma (OPSCC) is becoming increasingly obvious with the growing evidence of its variable prognosis. We identified and evaluated imaging characteristics predictive of extranodal extension (ENE) in OPSCC. Preoperative computed tomography and histopathologic results of 108 OPSCC patients who underwent neck dissection as primary treatment were analyzed. Imaging characteristics were reassessed for factors associated with nodal margin breakdown and metastatic burden. Moreover, the predictability of pathological ENE (pENE) was analyzed. Univariate and multivariate binomial logistic regression analyses were performed to examine the predictive power of ENE-related radiologic features. Imaging-based characteristics showed variable degrees of association with pENE. Factors associated with nodal margin breakdown (indistinct capsular contour, irregular margin, and perinodal fat stranding) and factors associated with nodal burden (nodal matting, lower neck metastasis, and presence of >4 lymph node metastases) were significantly predictive of ENE (odds ratio (OR) = 11.170 and 12.121, respectively). The combined utilization of the nodal margin and burden factors further increased the predictive ability (OR = 14.710). Factors associated with nodal margin breakdown and nodal burden were associated with pENE, demonstrating the use of combinatorial analysis for more accurate ENE prediction.

Liquid plasma as a treatment for cutaneous wound healing through regulation of redox metabolism.

The skin functions as the outermost protective barrier to the internal organs and major vessels; thus, delayed regeneration from acute injury could induce serious clinical complications. For rapid recovery of skin wounds, promoting re-epithelialization of the epidermis at the initial stage of injury is essential, wherein epithelial keratinocytes act as leading cells via migration. This study applied plasma technology, which has been known to enable wound healing in the medical field. Through in vitro and in vivo experiments, the study elucidated the effect and molecular mechanism of the liquid plasma (LP) manufactured by our microwave plasma system, which was found to improve the applicability of existing gas-type plasma on skin cell migration for re-epithelialization. LP treatment promoted the cytoskeletal transformation of keratinocytes and migration owing to changes in the expression of integrin-dependent focal adhesion molecules and matrix metalloproteinases (MMPs). This study also identified the role of increased levels of intracellular reactive oxygen species (ROS) as a driving force for cell migration activation, which was regulated by changes in NADPH oxidases and mitochondrial membrane potential. In an in vivo experiment using a murine dorsal full-thickness acute skin wound model, LP treatment helped improve the re-epithelialization rate, reaffirming the activation of the underlying intracellular ROS-dependent integrin-dependent signaling molecules. These findings indicate that LP could be a valuable wound management material that can improve the regeneration potential of the skin via the activation of migration-related molecular signaling within the epithelial cell itself with plasma-driven oxidative eustress.

Preoperative perforator localization in anterolateral thigh free flap using acoustic doppler and computed tomography angiography.

Objectives: Our aim in this study was to investigate if we could predict perforator localization during ALTF elevation, using information from acoustic Doppler (AD) and computed tomography angiography (CTA). Methods: Prospective observational data were collected from H&N cancer patients who received reconstruction with ALTF in Ajou University Hospital Cancer Center from June to December, 2021. Total of 21 cases were included in the analysis. Lower extremity angio-CT scans were used to determine the course and depth of the perforator before surgery. During intraoperative design of the ALTF, the possible location of the perforator was identified by AD. After flap elevation, the distance between the actual and Doppler-identified location of the perforator was measured. Results: The average distance from the actual location to the Doppler-identified location was 1.29 ± 1.26 cm. Among 21 cases, almost all perforators (20 cases) were identified in a circle with a radius equivalent to the depth of the perforator. Perforator depth measured by CTA showed a significant positive correlation with the distance from the actual to Doppler-identified location, regardless of skin thickness or body mass index (BMI). Conclusions: A circle with a radius equivalent to the CTA-assessed depth of the perforator successfully predicted the location of the perforator in almost all cases. Depth of the perforator measured by CTA combined with Doppler-identified location can help safely locate the perforator during ALTF harvesting.Level of Evidence: 4.

Cell-derived vesicles from adipose-derived mesenchymal stem cells ameliorate irradiation-induced salivary gland cell damage.

Introduction: Salivary gland (SG) damage is commonly caused by aging, irradiation, and some medications, and currently, no damage modifying agent is available. However, cell therapy based on mesenchymal stem cells (MSCs) has been proposed as a therapeutic modality for irradiated SGs. Therefore, we administered cell-derived vesicles (CDVs) of adipose-derived mesenchymal stem cells (ADMSCs) to irradiated SG cells to investigate their radioprotective effects in vitro. Methods: The artificial CDVs were obtained from ADMSC by tangential flow filtration (TFF) purification and ultracentrifugation. Cultured human SG epithelial cells were exposed to 2, 5 or 15 Gy of 4 MV X-rays produced by a linear accelerator. The effects of ADMSC-CDVs on SG epithelial cells damaged by irradiation were tested by proliferation activity, transepithelial electrical resistance (TEER), and amylase activity. Results: Exposure to penetrating radiation inhibited the proliferation of SG epithelial cells, but the radiation intensity required to reduce the proliferation of human submandibular gland epithelial cells (hSMGECs) was greater than required for other SG cells. ADMSC-CDVs restored the proliferative ability of SG epithelial cells reduced by irradiation, and the proliferation capacities of irradiated human parotid gland epithelial cells (hPGECs) and human sublingual gland epithelial cells (hSLGECs) were increased by administering ADMSC-CDVs to non-irradiated SG epithelial cells. Furthermore, amylase activity in irradiated hPGECs, hSMGECs, and hSLGECs was lower than in non-irradiated controls. However, amylase ability was restored in all by ADMSC-CDV treatment. Also, TEER was diminished by irradiation in hPGECs, hSMGECs, and hSLGECs and restored by ADMSC-CDV administration. Conclusion: Overall, our findings demonstrate that ADMSC-CDVs have potent radioprotective effects on irradiated SG cells.

Liquid-type plasma-controlled in situ crosslinking of silk-alginate injectable gel displayed better bioactivities and mechanical properties.

Silk is a promising biomaterial for injectable hydrogel, but its long-gelation time and cytotoxic crosslinking methods are the main obstacles for clinical application. Here, we purpose a new in situ crosslinking technique of silk-alginate (S-A) injectable hydrogel using liquid-type non-thermal atmospheric plasma (LTP) in vocal fold (VF) wound healing. We confirmed that LTP induces the secondary structure of silk in a dose-dependent manner, resulting in improved mechanical properties. Significantly increased crosslinking of silk was observed with reduced gelation time. Moreover, controlled release of nitrate, an LTP effectors, from LTP-treated S-A hydrogel was detected over 7 days. In vitro experiments regarding biocompatibility showed activation of fibroblasts beyond the non-cytotoxicity of LTP-treated S-A hydrogels. An in vivo animal model of VF injury was established in New Zealand White rabbits. Full-thickness injury was created on the VF followed by hydrogel injection. In histologic analyses, LTP-treated S-A hydrogels significantly reduced a scar formation and promoted favorable wound healing. Functional analysis using videokymography showed eventual viscoelastic recovery. The LTP not only changes the mechanical structures of a hydrogel, but also has sustained biochemical effects on the damaged tissue due to controlled release of LTP effectors, and that LTP-treated S-A hydrogel can be used to enhance wound healing after VF injury.

Applications of Plasma-Activated Liquid in the Medical Field.

Much progress has been made since plasma was discovered in the early 1900s. The first form of plasma was thermal type, which was limited for medical use due to potential thermal damage on living cells. In the late 1900s, with the development of a nonthermal atmospheric plasma called cold plasma, profound clinical research began and 'plasma medicine' became a new area in the academic field. Plasma began to be used mainly for environmental problems, such as water purification and wastewater treatment, and subsequent research on plasma and liquid interaction led to the birth of 'plasma-activated liquid' (PAL). PAL is currently used in the fields of environment, food, agriculture, nanoparticle synthesis, analytical chemistry, and sterilization. In the medical field, PAL usage can be expanded for accessing places where direct application of plasma is difficult. In this review, recent studies with PAL will be introduced to inform researchers of the application plan and possibility of PAL in the medical field.