Jae-Ho Shin's research while affiliated with CHA University and other places

Triple‐negative breast cancer (TNBC) patients harboring wild‐type breast cancer susceptibility gene 1 (BRCA1) account for most TNBC patients but lack adequate targeted therapeutic options. Although radiotherapy (RT) is the primary treatment modality for TNBC patients, radioresistance is one of the major challenges. RT‐induced increase in cathepsin S (CTSS) causes radioresistance through suppressing BRCA1‐mediated apoptosis of tumor cells, which was induced by CTSS‐mediated degradation of BRCA1. Targeting CTSS may provide a novel therapeutic opportunity for TNBC patients. Publicly available data and human tissue microarray slides were analyzed to investigate the relationship between CTSS and BRCA1 in breast cancer patients. A CTSS enzyme assay and in silico docking analysis were conducted to identify a novel CTSS inhibitor. RO5461111 was used first to confirm the concept of targeting CTSS for radiosensitizing effects. The MDA‐MB‐231 TNBC cell line was used for in vitro and in vivo assays. Western blotting, promoter assay, cell death assay, clonogenic survival assay, and immunohistochemistry staining were conducted to evaluate novel CTSS inhibitors. CTSS inhibitors were further evaluated for their additional benefit of inhibiting cell migration. A novel CTSS inhibitor, TS‐24, increased BRCA1 protein levels and showed radiosensitization in TNBC cells with wild‐type BRCA1 and in vivo in a TNBC xenograft mouse model. These effects were attributed by BRCA1‐mediated apoptosis facilitated by TS‐24. Furthermore, TS‐24 demonstrated the additional effect of inhibiting cell migration. Our study suggests that employing CTSS inhibitors for the functional restoration of BRCA1 to enhance RT‐induced apoptosis may provide a novel therapeutic opportunity for TNBC patients harboring wild‐type BRCA1.

Regdanvimab, a monoclonal antibody pharmaceutical, is the first Korean drug approved for treating coronavirus disease 2019 (COVID-19). We analyzed the therapeutic efficacy of regdanvimab in patients with the COVID-19 delta variant infection. We retrospectively reviewed the electronic medical records of patients hospitalized at two Korean tertiary COVID-19 hospitals with COVID-19 delta variant infection between May 26, 2021, and January 30, 2022. To analyze the therapeutic efficacy of regdanvimab, the patients were divided into regdanvimab and non-regdanvimab groups and were 1:1 propensity-score (PS)-matched on age, severity at admission, and COVID-19 vaccination history. Of 492 patients, 262 (53.3%) and 230 (46.7%) were in the regdanvimab and non-regdanvimab groups, respectively. After PS matching the groups on age, severity at admission, and COVID-19 vaccination history, each group comprised 189 patients. The 30-day hospital mortality rates (0.0% vs. 1.6%, p = 0.030), proportions of patients with exacerbated conditions to severe/critical/died (9.5% vs. 16.4%, p = 0.047), proportions who received oxygen therapy because of pneumonia exacerbation (7.4% vs. 16.4%, p = 0.007), and proportions with a daily National Early Warning Score ≥ 5 from hospital day 2 were significantly lower in the regdanvimab group. We showed that regdanvimab reduced the exacerbation rates of conditions and mortality in patients with the COVID-19 delta variant infection. Thus, it is recommended to streamline the drug approval system during epidemics of new variant viruses to improve the availability and usage of therapeutics for patients. To facilitate this, relevant institutional support is required.

Background Gastrodia elata Blume (GEB), a traditional medicinal herb, has been reported to have pharmacological effect including protection against liver, neuron and kidney toxicity. However, explanation of its underlying mechanisms remains a great challenge. This study investigated the protective effects of GEB extract on vancomycin (VAN)-induced nephrotoxicity in rats and underlying mechanisms with emphasis on the anti-oxidative stress, anti-inflammation and anti-apoptosis. The male Sprague-Dawley rats were randomly divided three groups: control (CON) group, VAN group and GEB group with duration of 14 days. Results The kidney weight and the serum levels of blood urea nitrogen and creatinine in the GEB group were lower than the VAN group. Histological analysis using hematoxylin & eosin and periodic acid Schiff staining revealed pathological changes of the VAN group. Immunohistochemical analysis revealed that the expression levels of N-acetyl-D-glucosaminidase, myeloperoxidase and tumor necrosis factor-alpha in the GEB group were decreased when compared with the VAN group. The number of terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling-positive cells, phosphohistone and malondialdehyde levels were lower in the GEB group than VAN group. The levels of total glutathione in the GEB group were higher than the VAN group. Conclusions The findings of this study suggested that GEB extract prevents VAN-induced renal tissue damage through anti-oxidation, anti-inflammation and anti-apoptosis.

Purpose: To report a case of herpes zoster ophthalmicus with corneal involvement and rarely occurred ophthalmoplegia.Case summary: A 74-year-old man visited to the dermatology clinic for the pain and blistering of the forehead and around the right eye, which started 4 days ago. After the diagnosis of herpes zoster, he referred to our clinic to evaluate the ophthalmologic abnormality. At the initial visit, the skin around the right eye was scuffed, lid swelling was observed, and epiphora was noted. One week later, he complained of decreased visual acuity in his right eye and diplopia. On ophthalmic examination, there was ophthalmoplegia including complete ptosis in his right eye. By slit lamp biomicroscopy, corneal edema and conjunctival injection were observed. Oral antiviral agents were maintained and topical antiviral agent and steroid were administrated. Two months after the onset of skin lesion, ophthalmoplegia and ptosis were recovered except for lateral gaze limitation. All ocular abnormalities were fully recovered after 5 months of skin lesion.Conclusions: Ophthalmoplegia after herpes zoster ophthalmicus is very rare but it should be considered as one of the major complications that may occur. We experienced a case of ophthalmoplegia accompanied by corneal invasion and complete recovery after topical agent and oral antiviral therapy so we want to report this case with a review of the literature.

Rationale Posterior reversible encephalopathy syndrome is a neurological condition characterized by headache, convulsions, altered consciousness, and visual disturbance with specific radiological features, which is characterized by contrast enhancement in the occipital lobe on T2-weighted image. We report a case of sudden visual impairment of both eyes 6 days after childbirth diagnosed as postpartum preeclampsia and posterior reversible encephalopathy syndrome (PRES) through radiological examination. Patient concerns A 31-year-old female patient with headache and visual disturbance visited the clinic. Diagnosis Visual acuity was light perception in the right eye and hand motion in the left eye; pupillary light reflections of both eyes were normal. In the field of view test, the waveform was not observed in the defect pattern visual field power test, and the amplitude was greatly reduced in the visual field test. 1+ proteinuria was observed on urine test and magnetic resonance imaging showed contrast enhancement under both parietal and occipital cortex. Interventions Hospitalization was done for blood pressure control and examination of related disease under suspicion of PRES caused by postpartum preeclampsia. Outcomes Four weeks after diagnosis, vision and visual field defects recovered to normal, and the previously observed lesion on magnetic resonance imaging completely improved 3 months after the initial visit, and it was diagnosed as PRES. Lessons PRES in postpartum preeclampsia can cause rapid vision and symptoms, visual field loss, and accurate follow-up diagnosis with relevant imaging and clinical patterns can improve vision.

Cancer cachexia is a metabolic disease involving multiple organs, which is accompanied by the depletion of muscle tissue and is associated with ~20% of cancer-related deaths. Muscle wasting is a critical factor in cancer cachexia. β-carotene (BC) has been shown to increase muscle mass and hypertrophy in healthy mice. However, its effects on muscle tissue dysregulation in cancer cachexia have yet to be studied. In the present study, 5-week-old male C57BL/6J mice were injected with 1×10⁶ Lewis lung carcinoma (LLC) cells to induce cancer cachexia; then the mice were administered BC (4 or 8 mg/kg) for 22 days to assess its effects on muscle atrophy in the gastrocnemius muscles. The effects of BC on inflammatory cytokines, myogenesis and muscle atrophy were evaluated using C2C12 myotubes treated with LLC-conditioned media. BC supplementation significantly suppressed tumor growth, inflammatory cytokines, and hepatic gluconeogenesis in the LLC-induced cancer cachexia mouse model, while also improving muscle weight and grip strength. These effects are considered to be mediated by the PI3K/Akt pathway and through regulation of muscle atrophy. Moreover, BC treatment was associated with the recovery of LLC-conditioned media-induced muscle differentiation deficits and muscle atrophy in C2C12 myotubes. These findings indicate BC as a potential novel therapeutic agent for cancer cachexia.

Rationale: Plasmacytoma is a disease caused by the proliferation of monoclonal immunoglobulin-producing plasma cells and divided into multiple myeloma, solitary bone plasmacytoma, and extramedullary plasmacytoma. We report a case of orbital extramedullary plasmacytoma invading the dura mater in a patient with exophthalmos and diplopia. Patient concerns: A 35-year-old female patient with exophthalmos in the right eye and diplopia visited the clinic. Diagnoses: The thyroid function tests showed nonspecific results. Orbital computed tomography and magnetic resonance imaging revealed a homogeneously enhancing orbital mass infiltrating the right maxillary sinus and adjacent brain tissue in the middle cranial fossa through the superior orbital fissure. Interventions: To diagnose and alleviate the symptoms, an excisional biopsy was performed, which revealed a plasmacytoma. Outcomes: One month after the surgery, the protruding symptoms and eye movement restriction in the right eye improved, and the visual acuity in the right eye was restored. Lessons: In this case report, we present a case of an extramedullary plasmacytoma that originated in the inferior wall of the orbit and invaded the cranial cavity. To our knowledge, no previous reports have described a solitary plasmacytoma that originated in the orbit, causing exophthalmos and invading the cranial cavity at the same time.

In the present study, we aimed to investigate age-, cryptorchidism-, and testicular tumor-related changes in miRNAs in the testis and epididymis of dogs. Twelve healthy male dogs were divided into two groups: young (<1 year, n = 8) and old (>3 years, n = 4). Five dogs with unilateral cryptorchidism, one with a Sertoli cell tumor, and one with seminoma were referred to a veterinary hospital. After surgery, the testes and epididymis tails were collected. A high-throughput miRNA array analysis was performed to identify miRNAs affected by age, cryptorchidism, and testicular tumors. The expression of only cfa-miR-503 was downregulated in the epididymis of younger dogs, whereas the expression of 64 miRNAs was upregulated. Among them, the top five miRNAs were cfa-miR-26a, cfa-miR-200c, cfa-let-7c, cfa-let-7b, and cfa-let-7a. The expression of cfa-miR-148a and cfa-miR-497 was considerably lower in cryptorchid testis than in healthy dog testis. In the epididymis, the cfa-miR-1841 level was significantly decreased. We observed a significant difference in the expression of 26 cfa-miRNAs between testicular tumors and normal tissues. This study demonstrated that aging and cryptorchidism have a causal relationship with miRNA expression. The identified miRNAs may be candidate genes for male reproductive traits and could be applied in molecular breeding programs.