X-linked ichthyosis (XLI) is an inherited disorder of keratinization resulting from a deficiency of steroid sulfatase (STS), for which no effective therapy is currently available. E-cadherin, a key upstream regulator of keratinocyte differentiation, has been found to be markedly overexpressed in STS-deficient HaCaT cells, suggesting its potential as a therapeutic target in XLI. To investigate the functional role of E-cadherin and explore its therapeutic potential, we introduced mutations into the N-terminal region of Ecadherin and examined the resulting effects on keratinocyte differentiation. In addition, a microRNA (miR-6766) and a rationally designed gapmer antisense oligonucleotide (gASO) targeting the same E-cadherin mRNA sequence were employed to modulate E-cadherin expression in HaCaT cells. Mutations within the N-terminal region of E-cadherin significantly reduced keratin 1 expression, underscoring the critical role of this domain in regulating keratinocyte differentiation. Treatment with miR-6766 led todownregulation of both early and terminal differentiation markers. Building on this, the gASO modified with 2′-O-methoxyethyl andphosphorothioate linkages exhibited enhanced potency and stability, resulting in stronger suppression of E-cadherin and keratin 1 expression compared with miR-6766 (maintained 37.7% greater inhibition of E-cadherin at 96 h and 35.7% greater inhibition of keratin 1 at 96 h). Furthermore, gASO treatment induced a concentration-dependent reduction in early (keratin 1 and keratin 10) and terminal (transglutaminase 1, involucrin, and loricrin) differentiation markers. These findings demonstrate that an E-cadherin– targeting gASO effectively suppresses abnormal keratinocyte differentiation and may serve as a promising therapeutic strategy for X-linked ichthyosis.

Purpose: We present a case of central anticholinergic syndrome following the administration of atropine eye drops.Case summary: A 60-year-old male presented with decreased visual acuity in his left eye and was diagnosed with intraocular lens dislocation. Preoperatively, Isopto atropine® eye drops (1 drop at 15-minutes intervals) were used for pupil dilation. Within an hour of the first instillation, the patient exhibited drowsiness, disorientation, agitation, and urinary retention. Laboratory tests and computed tomography of the brain were unremarkable. Considering the recent administration of atropine eye drops, a diagnosis of central anticholinergic syndrome was made. The surgery was postponed and the patient recovered fully after 3 hours of observation. He remained asymptomatic during an additional day of hospitalization. Conclusions A small dose of atropine eye drops even at a therapeutic dose can induce central anticholinergic syndrome. Therefore, ophthalmologists should be aware of this rare and severe complication.

Background: The use of electric scooters (e-scooters) continues to increase as a simple, inexpensive means of transport, resulting in a sharp increase in the incidence of scooter-related accidents. No study to date has closely examined the injury extent to the lower leg, joints, and extremities from e-scooter-related accidents. Here, we investigated the epidemiology and injury patterns of such accidents, focusing on injuries to the ankle and foot. Methods: Based on data from a single tertiary hospital’s database, the demographics of 563 patients with scooter-associated injuries were analyzed retrospectively. Among the patients, 229 patients who were injured by e-scooter riding were further investigated. Based on the data, the general demographics of whole scooter-associated injuries and the injury characteristics and fracture cases of the lower leg, ankle, and foot were analyzed. Results: During the 4-year study period, the number of patients injured by e-scooters increased every year. Lower extremities were the most common injury site (67.2%) among riders, whereas injuries to the head and neck (64.3%) were more common in riders of non-electric scooters. Among the lower leg, ankle, and foot injuries of riders (52 cases), the ankle joint (53.8%) was the most commonly injured site, followed by the foot (40.4%) and lower leg (21.2%). The fracture group scored significantly higher on the Abbreviated Injury Scale than the non-fracture group (p < 0.001). Among the fracture group (20 cases), ankle fractures (9 cases) were most common, including pronation external rotation type 4 injuries (4 cases) and pilon fractures (2 cases). Five patients (25%) had open fractures, and 12 patients (60%) underwent surgical treatment. Conclusions The ankle and foot are the most common injury sites in e-scooter-related accidents. Given the high frequency and severity of e-scooter-related ankle and foot injuries, we suggest that more attention be paid to preventing these types of injuries with greater public awareness of the dangers of using e-scooters.

Purpose: We present a case of central anticholinergic syndrome following the administration of atropine eye drops.Case summary: A 60-year-old male presented with decreased visual acuity in his left eye and was diagnosed with intraocular lens dislocation. Preoperatively, Isopto atropine® eye drops (1 drop at 15-minutes intervals) were used for pupil dilation. Within an hour of the first instillation, the patient exhibited drowsiness, disorientation, agitation, and urinary retention. Laboratory tests and computed tomography of the brain were unremarkable. Considering the recent administration of atropine eye drops, a diagnosis of central anticholinergic syndrome was made. The surgery was postponed and the patient recovered fully after 3 hours of observation. He remained asymptomatic during an additional day of hospitalization. Conclusions A small dose of atropine eye drops even at a therapeutic dose can induce central anticholinergic syndrome. Therefore, ophthalmologists should be aware of this rare and severe complication.

Purpose: We present a case of central anticholinergic syndrome following the administration of atropine eye drops.Case summary: A 60-year-old male presented with decreased visual acuity in his left eye and was diagnosed with intraocular lens dislocation. Preoperatively, Isopto atropine® eye drops (1 drop at 15-minutes intervals) were used for pupil dilation. Within an hour of the first instillation, the patient exhibited drowsiness, disorientation, agitation, and urinary retention. Laboratory tests and computed tomography of the brain were unremarkable. Considering the recent administration of atropine eye drops, a diagnosis of central anticholinergic syndrome was made. The surgery was postponed and the patient recovered fully after 3 hours of observation. He remained asymptomatic during an additional day of hospitalization. Conclusions A small dose of atropine eye drops even at a therapeutic dose can induce central anticholinergic syndrome. Therefore, ophthalmologists should be aware of this rare and severe complication.

Purpose: In colorectal cancer surgery, it is important to have accurate resection margins. However, it is challenging to localize lesions during laparoscopy. Therefore, to reduce surgical errors, many preoperative localizing methods have been introduced. In this study, we aimed to assess the preoperative feasibility and safety of autologous blood tattooing. Methods: A total of 11 patients underwent preoperative colonoscopic autologous blood tattooing from August 2017 to February 2020. At the start of the surgery, the surgeon assessed the patients for the precision of visibility and other complications such as abscess or spillage. The patients’ characteristics, outcomes, and complications were collected retrospectively. Results: The study comprised 8 men and 3 women, with an average age of 63 years. Ten patients showed precise visibility, and no localization errors were observed during surgery. No complication was observed in all patients. Conclusion Preoperative autologous blood tattooing is a very useful and safe technique because it has high visibility with no complications. This method does not require additional agents or facilities. A large-scale study will be required to develop standard guidelines.

Axl receptor tyrosine kinase has been implicated in cancer progression, invasion, and metastasis in various cancer types. Axl overexpression has been observed in many cancers, and selective inhibitors of Axl, including R428, may be promising therapeutic agents for several human cancers, such as breast, lung, and pancreatic cancers. Here, we examined the cell growth inhibition mediated by R428 and auranofin individually as well as in combination in the human breast cancer cell lines MCF-7 and MDAMB-231 to identify new advanced combination treatments for human breast cancer. Our data showed that combination therapy with R428 and auranofin markedly inhibited cancer cell proliferation. Isobologram analyses of these cells indicated a clear synergism between R428 and auranofin with a combination index value of 0.73. The combination treatment promoted apoptosis as indicated by caspase 3 activation and poly (ADP-ribose) polymerase cleavage. Cancer cell migration was also significantly inhibited by this combination treatment. Moreover, we found that combination therapy significantly increased the expression level of Bax, a mitochondrial proapoptotic factor, but decreased that of the X-linked inhibitor of apoptosis protein. Furthermore, the suppression of cell viability and induction of Bax expression by the combination treatment were recovered by treatment with N-acetylcysteine. In conclusion, our data demonstrated that combined treatment with R428 and auranofin synergistically induced apoptosis in human breast cancer cells and may thus serve as a novel and valuable approach for cancer therapy.

Right ventricle to pulmonary artery (RV-PA) conduits have been used for the surgical repair of congenital heart defects. These conduits frequently become stenosed or develop insufficiency with time, necessitating reoperations. Percutanous pulmonary valve implantation (PPVI) can delay the need for repeated surgeries in patients with congenital heart defects and degenerated RV-PA conduits. We presented our first experience with PPVI and described in detail the procedural methods and the considerations that are needed for this intervention to be successful. Immediate and short-term clinical outcomes of our patients were reported. Good haemodynamic results were obtained, both angiographically and on echocardiography. PPVI provides an excellent alternative to repeat open-heart surgery for patients with congenital heart defects and degenerated RV-PA conduits. This represents a paradigm shift in the management of congenital heart disease, which is traditionally managed by open-heart surgery.

Human breast cancer cell line, MDA-MB-231, is highly invasive and aggressive, compared to less invasive cell line, MCF-7. To explore the genes that might influence the malignancy of MDA-MB-231, DNA microarray analysis was performed. The results showed that G0/G1 switch 2 (G0S2) was one of the most highly expressed genes among the genes upregulated in MDA-MB-231. Although G0S2 acts as a direct inhibitor of adipose triglyceride lipase, action of G0S2 in cancer progression is not yet understood. To investigate whether G0S2 affects invasiveness of MDA-MB-231 cells, G0S2 expression was inhibited using siRNA, which led to decreased cell proliferation, migration, and invasion of MDA-MB-231 cells. Consequently, G0S2 inhibition inactivated integrin-regulated FAK-Src signaling, which promoted Hippo signaling and inactivated ERK1/2 signaling. In addition, G0S2 downregulation decreased β-catenin expression, while E-cadherin expression was increased. It was demonstrated for the first time that G0S2 mediates the Hippo pathway and induces epithelial to mesenchymal transition (EMT). Taken together, our results suggest that G0S2 is a major factor contributing to cell survival and metastasis of MDA-MB-231 cells.
Breast Neoplasms ; Breast ; Cadherins ; Cell Line ; Cell Proliferation ; Cell Survival ; Down-Regulation ; Humans ; Lipase ; Neoplasm Metastasis ; Oligonucleotide Array Sequence Analysis ; RNA, Small Interfering ; Signal Transduction

Mitochondria continuously fuse and divide to maintain homeostasis. An impairment in the balance between the fusion and fission processes can trigger mitochondrial dysfunction. Accumulating evidence suggests that mitochondrial dysfunction is related to neurodegenerative diseases such as Parkinson's disease (PD), with excessive mitochondrial fission in dopaminergic neurons being one of the pathological mechanisms of PD. Here, we investigated the balance between mitochondrial fusion and fission in the substantia nigra of a non-human primate model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD. We found that MPTP induced shorter and abnormally distributed mitochondria. This phenomenon was accompanied by the activation of dynamin-related protein 1 (Drp1), a mitochondrial fission protein, through increased phosphorylation at S616. Thereafter, we assessed for activation of the components of the cyclin-dependent kinase 5 (CDK5) and extracellular signal-regulated kinase (ERK) signaling cascades, which are known regulators of Drp1(S616) phosphorylation. MPTP induced an increase in p25 and p35, which are required for CDK5 activation. Together, these findings suggest that the phosphorylation of Drp1(S616) by CDK5 is involved in mitochondrial fission in the substantia nigra of a non-human primate model of MPTP-induced PD.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine ; Cyclin-Dependent Kinase 5 ; Cyclin-Dependent Kinases ; Dopaminergic Neurons ; Homeostasis ; Mitochondria ; Mitochondrial Dynamics ; Neurodegenerative Diseases ; Parkinson Disease ; Phosphorylation ; Phosphotransferases ; Primates ; Substantia Nigra