Combined dasatinib and quercetin treatment contributes to skin rejuvenation through selective elimination of senescent cells in vitro and in vivo.

The skin's protective functions are compromised over time by both endogenous and exogenous aging. Senescence is well-documented in skin phenotypes, such as wrinkling and sagging, a consequence of the senescence-associated secretory phenotype (SASP) that involves the accumulation of senescent fibroblasts, chronic inflammation, and collagen remodeling. Although therapeutic approaches for eliminating senescent cells from the skin are available, their efficacy remains unclear. Accordingly, we aimed to examine the effects of dasatinib in combination with quercetin (D + Q) on senescent human skin fibroblasts and aging human skin. Senescence was induced in human dermal fibroblasts (HDFs) using approaches such as long-term passaging, ionizing radiation, and doxorubicin treatment. The generated senescent cells were treated with D + Q or vehicle. Additionally, a mouse-human chimera model was generated by subcutaneously transplanting whole-skin grafts of aged individuals onto nude mice. Mouse models were administered D + Q or vehicle by oral gavage for 30 days. Subsequently, skin samples were harvested and stained for senescence-associated beta-galactosidase. Senescence-associated markers were assessed by western blotting, reverse transcription-quantitative PCR and histological analyses. Herein, D + Q selectively eliminated senescent HDFs in all cellular models of induced senescence. Additionally, D + Q-treated aged human skin grafts exhibited increased collagen density and suppression of the SASP compared with control grafts. No adverse events were observed during the study period. Collectively, D + Q could ameliorate skin aging through selective elimination of senescent dermal fibroblasts and suppression of the SASP. Our findings suggest that D + Q could be developed as an effective therapeutic approach for combating skin aging.

Treatment of Cicatricial Lower Eyelid Ectropion with Suture of Horner Muscle Combined with Fascia Transplantation.

This case series aimed to describe a new technique for correcting contractures and deformities that reliably addresses lacrimal punctum deviation and severe cicatricial lower eyelid ectropion. This was a technical description and a retrospective interventional case series. Eyelid ectropion and lacrimal punctum deviation were treated surgically by grafting the fascia lata and suturing the tarsus-Horner muscle. In total, three patients underwent this surgery: one for burns, one for lower eyelid tumor resection, and the other for an orbital floor fracture following a motorcycle accident, all resulting in ectropion. All patients previously had failed ectropion correction procedures, including scar revision, skin grafting, auricular cartilage grafting, and lateral tarsal strips. The mean follow-up was 15.8 (12.5-18.5) months. Furthermore, all patients showed resolution of lower eyelid ectropion and significant improvement in lower eyelid contracture, with a mean increase of 4.0 (2.5-5) mm. No severe complications were observed, and they reported a significant improvement in ocular surface symptoms. Our study shows that tacking of the tarsus and Horner muscles in combination with fascia lata grafting is effective in correcting refractory cicatricial lower eyelid ectropion with deviation of the tear punctum.

Regulation of ENPP5, a senescence-associated secretory phenotype factor, prevents skin aging.

Aging negatively affects the appearance and texture of the skin owing to the accumulation of senescent fibroblasts within the dermis. Senescent cells undergo abnormal remodeling of collagen and the extracellular matrix through an inflammatory histolytic senescence-associated secretory phenotype (SASP). Therefore, suppression of SASP in senescent cells is essential for the development of effective skin anti-aging therapies. Ectonucleotide pyrophosphatase/phosphodiesterase family member 5 (ENPP5), an extracellular signaling molecule, has been implicated in vascular aging and apoptosis; however, its role in SASP remains unclear. Therefore, this study aimed to investigate the role of ENPP5 in SASP and skin aging using molecular techniques. We investigated the effects of siRNA-mediated ENPP5 knockdown, human recombinant ENPP5 (rENPP5) treatment, and lentiviral overexpression of ENPP5 on SASP and aging in human skin fibroblasts. Additionally, we investigated the effect of siRNA-mediated ENPP5 knockdown on the skin of C57BL/6 mice. We found that ENPP5 was significantly expressed in replication-aged and otherwise DNA-damaged human skin fibroblasts and that treatment with human rENPP5 and lentiviral overexpression of ENPP5 promoted SASP and senescence. By contrast, siRNA-mediated knockdown of ENPP5 suppressed SASP and the expression of skin aging-related factors. Additionally, ENPP5 knockdown in mouse skin ameliorated the age-related reduction of subcutaneous adipose tissue, the panniculus carnosus muscle layer, and thinning of collagen fibers. Conclusively, these findings suggest that age-related changes may be prevented through the regulation of ENPP5 expression to suppress SASP in aging cells, contributing to the development of anti-aging treatments for the skin.

Preoperative photoacoustic versus indocyanine green lymphography in lymphaticovenular anastomosis outcomes for lower extremity lymphedema: A pilot study.

BACKGROUND: Identification of the proper lymphatics is important for successful lymphaticovenular anastomosis (LVA) for lymphedema; however, visualization of lymphatic vessels is challenging. Photoacoustic lymphangiography (PAL) can help visualize lymphatics more clearly than other modalities. Therefore, we investigated the usefulness of PAL and determined whether the clear and three-dimensional image of PAL affects LVA outcomes. METHODS: We recruited 22 female patients with lower extremity lymphedema. The operative time, number of incisions, number of anastomoses, lymphatic vessel detection rate (number of functional lymphatics identified during the operation/number of incisions), and limb volume changes preoperatively and 3 months postoperatively were compared retrospectively. The patients were divided according to whether PAL was performed or not, and results were compared between those undergoing PAL (PAL group; n = 10) and those who did not (near-infrared fluorescence [NIRF] group, n = 12). RESULTS: The mean age of the patients was 55.9 ± 15.1 years in the PAL group and 50.7 ± 14.9 years in the NIRF group. One patient in the PAL group and three in the NIRF group had primary lymphedema. Eighteen patients (PAL group, nine; and NIRF group, nine) had secondary lymphedema. Based on preoperative evaluation using the International Society of Lymphology (ISL) classification, eight patients were determined to be in stage 2 and two patients in late stage 2 in the PAL group. In contrast, in the NIRF group, one patient was determined to be in stage 0, three patients each in stage 1 and stage 2, and five patients in late stage 2. Lymphatic vessel detection rates were 93% (42 LVAs and 45 incisions) and 83% (50 LVAs and 60 incisions) in the groups with and without PAL, respectively (p = 0.42). Limb volume change was evaluated in five limbs of four patients and in seven limbs of five patients in the PAL and NIRF groups as 336.6 ± 203.6 mL (5.90% ± 3.27%) and 52.9 ± 260.7 mL (0.71% ± 4.27%), respectively. The PAL group showed a significant volume reduction. (p = .038). CONCLUSIONS: Detection of functional lymphatic vessels on PAL is useful for treating LVA.

Ligustilide, A Novel Senolytic Compound Isolated from the Roots of Angelica Acutiloba.

Senescent cells accumulate with age and contribute to age-related diseases and organ dysfunctions. Early evidence suggests that removal of senescent cells using senolytic drugs improves the aging phenotype in mice and may improve the health of individuals with chronic diseases. Signs of skin aging, including wrinkles, and sagging, occur largely due to the accumulation of senescent fibroblasts within the dermis; However, there is currently no skin treatment that eliminates senescent cells. In this study, human fibroblasts subjected to replicative aging and ionizing radiation exposure are used to screen plant extracts for potential senescent cell-destructive and/or senescent cell-forming activities. Angelica acutiloba-a traditional Chinese herbal medicine-selectively kills senescent cells without affecting the proliferating cells. Among the major components of this herb, ligustilide shows promising senescent cell-destructive properties, and selectively eliminates senescent cells by inducing an apoptosis. Moreover, ligustilide markedly inhibits senescence-associated secretory phenotypes. Administration of ligustilide to mouse skin eliminates senescent cells and increases dermal collagen density and subcutaneous adipose tissue content; it selectively promotes death of senescent cells without affecting non-senescent cells. These results provide evidence that a natural compound-ligustilide-may exhibit therapeutic effects on the skin aging phenotype by specifically inducing apoptosis in senescent cells.

Fisetin, a potential skin rejuvenation drug that eliminates senescent cells in the dermis.

Accumulation of senescent fibroblasts, chronic inflammation, and collagen remodeling due to aging-related secretory phenotypes have been hypothesized to cause age-related skin aging, which results in wrinkles and loss of skin elasticity, thus compromising appearance attractiveness. However, the rejuvenating effects of removing senescent cells from the human skin and the efficacy of related therapeutic agents remain unclear. Here, we investigated the effects of fisetin, a potential anti-aging component found in various edible fruits and vegetables, on senescent human dermal fibroblasts (HDFs) and aging human skin. Senescence was induced in primary HDFs using long-term passaging and treatment with ionizing radiation, and cell viability was assessed after treatment with fisetin and a control component. A mouse/human chimeric model was established by subcutaneously transplanting whole skin grafts from aged individuals into nude mice, which were treated intraperitoneally with fisetin or control a component for 30 d. Skin samples were obtained and subjected to senescence-associated-beta-galactosidase staining; the extent of aging was evaluated using western blotting, reverse transcription-quantitative PCR, and histological analysis. Fisetin selectively eliminated senescent dermal fibroblasts in both senescence-induced cellular models; this effect is attributable to cell death induction by caspases 3, 8, and 9-mediated endogenous and exogenous apoptosis. Fisetin-treated senescent human skin grafts showed increased collagen density and decreased senescence-associated secretory phenotypes (SASP), including matrix metalloproteinases and interleukins. No apparent adverse events were observed. Thus, fisetin could improve skin aging through selective removal of senescent dermal fibroblasts and SASP inhibition, indicating its potential as an effective novel therapeutic agent for combating skin aging.

Hemostatic Efficacy of Oxidized Regenerated Cellulose Powder in Le Fort 1 Osteotomy.

A challenging aspect of Le Fort I osteotomy is bleeding control. Osteotomy techniques, devices, drugs, and anesthetic management have been reported to reduce bleeding; however, there are no reports on the use of hemostatic agents. We aimed to evaluate the hemostatic efficacy of a new topical absorbent hemostatic agent, Surgicel Powder, consisting of oxidized regenerated cellulose (ORC). We reviewed the records of 40 patients who underwent Le Fort I surgery for jaw deformities, with or without cleft lip and palate. Twenty of the 40 patients did not have cleft lips or cleft palates (CLCP); the remaining 20 had CLCP. In each group, an absorbent hemostatic agent was used in 10 patients but not in the other 10. Total blood loss and operative time for each group were evaluated. In the jaw deformity without CLCP group, the amount of bleeding with or without ORC was 112.0±33.8 and 158.6±75.3 mL, respectively, with a significant difference between groups ( P <0.05). Operative time with or without ORC was 206.4±31.3 and 238.3±42.5 minutes, respectively, with a significant difference observed between groups ( P <0.05). In the jaw deformity with CLCP group, the amount of bleeding with or without ORC was 199.7±64.6 and 476.8±104.8 mL, respectively, with a significant difference between groups ( P <0.05). Operative time with or without ORC was 213.7±27.6 and 220.8±41.5 minutes, respectively, with no significant difference between groups ( P =0.329). In conclusion, oxidized regenerated cellulose powder may be a beneficial hemostatic agent for reducing blood loss during Le Fort I osteotomy.

Regeneration of Panniculus Carnosus Muscle in Fetal Mice Is Characterized by the Presence of Actin Cables.

Mammalian skin, including human and mouse skin, does not regenerate completely after injury; it is repaired, leaving a scar. However, it is known that skin wounds up to a certain stage of embryonic development can regenerate. The mechanism behind the transition from regeneration to scar formation is not fully understood. Panniculus carnosus muscle (PCM) is present beneath the dermal fat layer and is a very important tissue for wound contraction. In rodents, PCM is present throughout the body. In humans, on the other hand, it disappears and becomes a shallow fascia on the trunk. Fetal cutaneous wounds, including PCM made until embryonic day 13 (E13), regenerate completely, but not beyond E14. We visualized the previously uncharacterized development of PCM in the fetus and investigated the temporal and spatial changes in PCM at different developmental stages, ranging from full regeneration to non-regeneration. Furthermore, we report that E13 epidermal closure occurs through actin cables, which are bundles of actomyosin formed at wound margins. The wound healing process of PCM suggests that actin cables may also be associated with PCM. Our findings reveal that PCM regenerates through a similar mechanism.

Modified Urethral Graciloplasty Cross-Innervated by the Pudendal Nerve for Postprostatectomy Urinary Incontinence: Cadaveric Simulation Surgery and a Clinical Case Report.

An artificial sphincter implanted in the bulbous urethra to treat severe postprostatectomy urinary incontinence is effective, but embedding-associated complications can occur. We assessed the feasibility, efficacy, and safety of urethral graciloplasty cross-innervated by the pudendal nerve. A simulation surgery on three male fresh cadavers was performed. Both ends of the gracilis muscle were isolated only on its vascular pedicle with proximal end of the obturator nerve severed and transferred to the perineum. We examined whether the gracilis muscle could be wrapped around the bulbous urethra and whether the obturator nerve was long enough to suture with the pudendal nerve. In addition, surgery was performed on a 71-year-old male patient with severe urinary incontinence. The postoperative 12-month outcomes were assessed using a 24-hour pad test and urodynamic study. In all cadaveric simulations, the gracilis muscles could be wrapped around the bulbous urethra in a γ-loop configuration. The length of the obturator nerve was sufficient for neurorrhaphy with the pudendal nerve. In the clinical case, the postoperative course was uneventful. The mean maximum urethral closure pressure and functional profile length increased from 40.7 to 70 cm H 2 O and from 40.1 to 45.3 mm, respectively. Although urinary incontinence was not completely cured, the patient was able to maintain urinary continence at night. Urethral graciloplasty cross-innervated by the pudendal nerve is effective in raising the urethral pressure and reducing urinary incontinence.

Cistanche deserticola Polysaccharide Reduces Inflammation and Aging Phenotypes in the Dermal Fibroblasts through the Activation of the NRF2/HO-1 Pathway.

Dermal fibroblasts maintain the skin homeostasis by interacting with the epidermis and extracellular matrix. Their senescence contributes to functional defects in the skin related to aging. Therefore, there is an urgent need for novel therapeutic agents that could inhibit fibroblast senescence. In this study, we investigated the effects of Cistanche deserticola polysaccharide (CDP), a natural anti-inflammatory component, on the progression of senescence in human dermal fibroblasts. Normal human dermal fibroblasts (NHDFs) were cultured in passages, and highly senescent cells were selected as senescent cells. CDP treatment increased the cell proliferation in senescent NHDFs and decreased the proportion of senescence-associated-ß-galactosidase-positive cells. The treatment suppressed the senescence-related secretory phenotype, and reactive oxygen species (ROS) production was reduced, alleviating H2O2-induced oxidative stress. CDP mitigated ROS formation via the nuclear factor erythroid 2-related factor/heme oxygenase-1 pathway in senescent cells and was involved in the suppression of upstream p-extracellular signal-regulated kinase. These results indicate that CDP is an antioxidant that can alleviate age-related inflammation and may be a useful compound for skin anti-aging.

False-positive diagnoses of damaged breast implants on imaging: a report of two cases.

Background: Silicone breast implants (SBIs), used in breast reconstruction, are durable and resistant to breakage and internal gel leakage. However, regular imaging examinations are crucial, as symptoms may not be apparent even if the implant ruptures. There are several known imaging findings that suggest SBI failure. Although artifacts such as moisture and air bubbles or substances similar to the gel extending outside the shell may appear on imaging, no reports have demonstrated false-positive diagnoses of damaged SBIs in detail. Hence, we present two cases in which failure was suspected based on the imaging results but not confirmed. Case Description: In case 1, at the 4-year follow-up after implant-based breast reconstruction, ultrasonography revealed a stepladder sign, and magnetic resonance imaging (MRI) revealed the salad oil sign. Although SBI failure was suggested, intraoperative examination revealed only a small amount of fluid retention within the capsule and no SBI fractures. Consequently, the imaging results were proved to be artifacts. In case 2, at the 7-year follow-up after implant-based breast reconstruction, ultrasonography revealed a subcapsular line sign, and MRI confirmed a keyhole sign. Although SBI failure was suggested, intraoperative examination revealed no implant fractures. Hematogenous serous effusion was found within the capsule, and blood clots and a large amount of fibrinous mass were found deposited at the bottom of the capsule. These findings caused false-positive diagnoses on imaging. Conclusions: In cases of suspected fractures, patients may opt for either observation or surgical removal, or replacement of the implant. When choosing the latter, it is important to inform patients of the possibility of an unbroken implant.

Pediatric-acquired Idiopathic Blepharoptosis with the Eyelids Being Habitually Opened Using the Frontalis Muscle.

Pediatric-acquired idiopathic blepharoptosis is rare, and no studies on surgery for the disease have been reported. We present a case of the disease with an atypical postoperative course. The patient initially underwent levator aponeurosis advancement. However, she cannot sufficiently open the affected eyelid without conscious effort and has developed a habit of opening the eyelids using the frontalis muscle. She underwent secondary frontalis suspension with the fascia latae, and then she was able to open her eyelids well all the time. When the disease duration in pediatric-acquired blepharoptosis is long, the habit of opening the eyelids using the frontalis muscle may be difficult to break. In such cases, we believe that frontalis suspension is the best operation.

Functional and long-lived melanocytes from human pluripotent stem cells with transient ectopic expression of JMJD3.

BACKGROUND: Melanocytes are an essential part of the epidermis, and their regeneration has received much attention because propagation of human adult melanocytes in vitro is too slow for clinical use. Differentiation from human pluripotent stem cells to melanocytes has been reported, but the protocols to produce them require multiple and complex differentiation steps. METHOD: We differentiated human embryonic stem cells (hESCs) that transiently express JMJD3 to pigmented cells. We investigated whether the pigmented cells have melanocytic characteristics and functions by qRT-PCR, immunocytochemical analysis and flow cytometry. We also investigated their biocompatibility by injecting the cells into immunodeficient mice for clinical use. RESULT: We successfully differentiated and established a pure culture of melanocytes. The melanocytes maintained their growth rate for a long time, approximately 200 days, and were functional. They exhibited melanogenesis and transfer of melanin to peripheral keratinocytes. Moreover, melanocytes simulated the developmental processes from melanoblasts to melanocytes. The melanocytes had high engraftability and biocompatibility in the immunodeficient mice. CONCLUSION: The robust generation of functional and long-lived melanocytes are key to developing clinical applications for the treatment of pigmentary skin disorders.

Three-dimensional adipofascial and dermal structures involved in forehead crease formation.

Deeply etched forehead creases indicate aging. Various treatments such as filler injections, fat grafting, and facelift surgery are used to remove them. However, knowledge of the anatomical structures associated with subcutaneous tissue changes and the superficial musculoaponeurotic system is lacking, and there is no consensus about the appropriate treatment. We have investigated the subcutaneous structures involved in forehead creases; this will help to establish selection criteria for improved treatment. The forehead sections of five unfixed adult Asian cadavers were obtained. Tissues containing forehead creases were removed from the periosteum and were examined using gross observation, radiography, histology, and nano-computed tomography. All methods revealed that the dermis in the skin crease area, namely the fold visible from the body surface, was bound to the frontalis muscle by a three-dimensional fibrous structure between the fatty septa. This structure was dense near the skin folds and sparse and thin in other areas. In particular, it was tightly bound to the dermis immediately below the crease, with collagen fibers traversing toward the epidermis. In addition, there were fewer skin appendages near the crease than in the normal area, or they were absent altogether; the epidermis was thicker, and the dermal papillae were more developed. It is thought that the density and firmness of the fibrous fatty septal structures between the dermis-frontalis muscle and the specific structures of the epidermis and dermis immediately below the crease account for the characteristic plastic forehead creases.

Influence of the Number of Revision Surgeries and Nasal Symmetry After Final Rhinoplasty for Patients With Cleft Lip.

The effects of operative intervention on vertical nasal growth in patients with unilateral cleft lips (CLs) are well described. However, the factors influencing nasal symmetry have not been sufficiently evaluated. Therefore, this study aimed to study the factors that cause difficulties in obtaining nasal symmetry postoperatively in patients with CLs. We conducted a retrospective analysis using data from patients with CLs who underwent a series of treatments at Keio University Hospital from 1990 to 2000. We collected data on the patients' sex, cleft type, number and time of revision surgery, palatal fistula incidence, and history of the pharyngeal flap and orthognathic surgery. Nasal symmetry was analyzed as the symmetrical ratio after the final touch-up surgery, and multivariate analysis was conducted using binary logistic regression to determine the factors affecting nasal symmetry. This study included 89 patients with unilateral CL. Multivariate analysis revealed that complete cleft lip and palate ( P < 0.05, odds ratio = 4.37) and repeated revision surgery ( P < 0.05, odds ratio = 9.28) were significant predictors of the final nasal symmetry. Our study showed that cleft type and the number of revision surgeries were identified as important factors for obtaining nasal symmetry after final touch-up rhinoplasty. Revision surgery may be necessary to relieve patients' psychological stress due to nasal deformity, suggesting that this dilemma needs to be overcome.

Reliability-Aware Restoration Framework for 4D Spectral Photoacoustic Data.

Spectral photoacoustic imaging (PAI) is a new technology that is able to provide 3D geometric structure associated with 1D wavelength-dependent absorption information of the interior of a target in a non-invasive manner. It has potentially broad applications in clinical and medical diagnosis. Unfortunately, the usability of spectral PAI is severely affected by a time-consuming data scanning process and complex noise. Therefore in this study, we propose a reliability-aware restoration framework to recover clean 4D data from incomplete and noisy observations. To the best of our knowledge, this is the first attempt for the 4D spectral PA data restoration problem that solves data completion and denoising simultaneously. We first present a sequence of analyses, including modeling of data reliability in the depth and spectral domains, developing an adaptive correlation graph, and analyzing local patch orientation. On the basis of these analyses, we explore global sparsity and local self-similarity for restoration. We demonstrated the effectiveness of our proposed approach through experiments on real data captured from patients, where our approach outperformed the state-of-the-art methods in both objective evaluation and subjective assessment.

Incidence of Otalgia After Orthognathic Surgery.

BACKGROUND: In orthognathic surgery, it is well known that maxillary osteotomies and displacements sometimes affect auditory function. Thus, this study examined the relationship between the direction of maxillary displacement and postoperative otalgia. METHODS: Twenty consecutive patients underwent Le Fort I maxillary osteotomy using advancement, impaction, setback, or a combination of these procedures. The direction of movement and incidence of otalgia were investigated. Patients provided informed consent preoperatively, and postoperative reassurance was prudent. RESULTS: Pure-tone average evaluation based on horizontal or vertical movements did not show significant differences, although vertical movements resulted in fewer changes in the hearing threshold. Specifically, no significant changes were observed in the hearing thresholds of patients after surgery. No significant difference was also observed between horizontal and vertical movements in the tympanometry results. Negative changes were found in the results of the Eustachian tube dysfunction test in vertical movements, which returned to preoperative values in the final test. CONCLUSIONS: The risk of minor changes in hearing function is probable during the first week after orthognathic surgery; however, these negative changes either completely disappear or remain negligible.

Usefulness of Harmonic ACE+7 Scalpel in Breast Reconstruction with Extended Latissimus Dorsi Flap: An Open-label Single Institution Pilot Study.

The extended latissimus dorsi (ELD) flap is a safe and aesthetically acceptable method to reconstruct small to medium-sized breasts. However, the long time required for flap elevation and intraoperative bleeding contributes to various postoperative complications. We investigated the use of alternative devices, such as the Harmonic ACE+7, which has a long arm that can help simultaneously detach and seal tissues to prevent such complications. Methods: We compared 27 patients who underwent breast reconstruction with the ELD flap using the Harmonic ACE +7 scalpel, and 28 patients who underwent breast reconstruction using an electrocautery scalpel, between May 2019 and March 2022. Data on patient demographics, surgery, and postoperative complications were collected. Surgical outcomes were compared between electrocautery (EC) and Harmonic ACE+7 (HA) groups. Results: The median age of the patients was 50.2 years. The patient demographics between the groups did not show significant differences. Flap necrosis and hematomas did not occur, and seroma was the major postoperative complication (65.7% in the EC group and 70% in the HA group). The time required for flap elevation was significantly shorter in the HA group than in the EC group (286.0 minutes and 179.0 minutes, respectively). Blood loss reduced significantly in the HA and EC groups (138.5 mL and 78.2 mL, respectively). Moreover, decreased drainage was observed for the breast area. There were no significant differences in other end points. Conclusion: In breast reconstruction with ELD flaps, using the Harmonic ACE+7 can help reduce the rate of seroma, operative time, and intraoperative bleeding without further disadvantages.

Identification of resibufogenin, a component of toad venom, as a novel senolytic compound in vitro and for potential skin rejuvenation in male mice.

Senescent cells that accumulate with age have been shown to contribute to age-related diseases and organ dysfunction and have attracted attention as a target for anti-aging therapy. In particular, the use of senescent cell-depleting agents, or senolytics, has been shown to improve the aging phenotype in animal models. Since senescence has been implicated in the skin, particularly in fibroblasts, this study used aged human skin fibroblasts to investigate the effects of resibufogenin. A component of the traditional Chinese medicine toad venom, resibufogenin was investigated for senolytic and/or senomorphic activity. We found that the compound selectively caused senescent cell death without affecting proliferating cells, with a marked effect on the suppression of the senescence-associated secretory phenotype. We also found that resibufogenin causes senescent cell death by inducing a caspase-3-mediated apoptotic program. Administration of resibufogenin to aging mice resulted in an increase in dermal collagen density and subcutaneous fat, improving the phenotype of aging skin. In other words, resibufogenin ameliorates skin aging through selective induction of senescent cell apoptosis without affecting non-aged cells. This traditional compound may have potential therapeutic benefits in skin aging characterized by senescent cell accumulation.

Maxillary Reconstruction With a Rib-attached Free Latissimus Dorsi Muscle Flap.

In defect reconstruction after maxillary tumor resection, filling the dead space created by resection and reconstruction of surrounding areas are crucial for good cosmetic outcomes. Although various procedures have been described in the literature, most are complex and require advanced surgical skills. Therefore, in this study, the authors aimed to identify a simple procedure for successful reconstruction with minimal bone fixation. Three patients who underwent total maxillectomy and reconstruction using the rib-attached free latissimus dorsi flap at Keio University Hospital between 2012 and 2014 were included and followed up with for a minimum of 5 years. After total maxillectomy, the authors used a free latissimus dorsi flap with a portion of the rib to fill the dead space and reconstructed the orbit, nasal cavity, and oral cavity.The authors performed a rigid reconstruction of the zygomatic ridge using only 2-point plate fixations of the ribs at the outer orbit and anterior nasal spine. Patients were followed up for ≥5 years, and the flap successfully survived in all cases. There was an issue with rib fixation in 1 case; however, all patients were highly satisfied with the procedure's cosmetic results.