1.SARS‑CoV‑2 Omicron variant causes brain infection with lymphoid depletion in a mouse COVID‑19 model
Na Yun LEE ; Youn Woo LEE ; Seung‑Min HONG ; Dain ON ; Gyeong Min YOON ; See‑He AN ; Ki Taek NAM ; Jun‑Young SEO ; Jeon‑Soo SHIN ; Yang‑Kyu CHOI ; Seung Hyun OH ; Jun‑Won YUN ; Ho Young LEE ; Kang‑Seuk CHOI ; Je Kyung SEONG ; Jun Won PARK
Laboratory Animal Research 2023;39(2):165-171
Background:
The Omicron variant has become the most prevalent SARS-CoV-2 variant. Omicron is known to induce milder lesions compared to the original Wuhan strain. Fatal infection of the Wuhan strain into the brain has been well documented in COVID-19 mouse models and human COVID-19 cases, but apparent infections into the brain by Omicron have not been reported in human adult cases or animal models. In this study, we investigated whether Omicron could spread to the brain using K18-hACE2 mice susceptible to SARS-CoV-2 infection.
Results:
K18-hACE2 mice were intranasally infected with 1 × 105 PFU of the original Wuhan strain and the Omicron variant of SARS-CoV-2. A follow-up was conducted 7 days post infection. All Wuhan-infected mice showed > 20% body weight loss, defined as the lethal condition, whereas two out of five Omicron-infected mice (40%) lost > 20% body weight. Histopathological analysis based on H&E staining revealed inflammatory responses in the brains of these two Omicron-infected mice. Immunostaining analysis of viral nucleocapsid protein revealed severe infection of neuron cells in the brains of these two Omicron-infected mice. Lymphoid depletion and apoptosis were observed in the spleen of Omicron-infected mice with brain infection.
Conclusion
Lethal conditions, such as severe body weight loss and encephalopathy, can occur in Omicron-infected K18-hACE2 mice. Our study reports, for the first time, that Omicron can induce brain infection with lymphoid depletion in the mouse COVID-19 model.
2.Extract from Zanthoxylum piperitum Induces Apoptosis of AGS Gastric Cancer Cells Through Akt/MDM2/p53 Signaling Pathway.
Ye Seul PARK ; Gun He NAM ; Kyung Jo JO ; Hye Won KAWK ; Sang Yung KIM ; Young Min KIM
Chinese journal of integrative medicine 2021;27(10):752-759
OBJECTIVE:
To determine the effect of Zanthoxylum piperitum extracet (ZPE) on apoptosis and analyze anticancer substances in ZPE, changes in proteins related to apoptosis, and pathological changes in tumors in mouse.
METHODS:
Fifteen 4-week-old female BALB/c nu/nu mice were divided into 3 groups depending on ZPE dose, with 5 in each group. AGS gastric carcinoma cells (1 × 10
RESULTS:
High performance liquid chromatography (HPLC) analysis showed that ZPE contained organic sulfur compounds such as alliin and S-allylcysteine. MTT assay results revealed that ZPE (10-85 µ g/mL) could effectively inhibit the growth of AGS gastric cancer cells at higher concentrations (P<0.05, P<0.01). The annexin V & dead cell staining assay and cell cycle arrest assay confirmed a dose-dependent increase in the apoptosis rate and G
CONCLUSION
ZPE decreases AGS cell proliferation and induces apoptosis by inhibiting Akt and MDM2 expression.
Animals
;
Apoptosis
;
Cell Line, Tumor
;
Cell Proliferation
;
Female
;
Mice
;
Mice, Inbred BALB C
;
Plant Extracts/therapeutic use*
;
Proto-Oncogene Proteins c-akt/metabolism*
;
Signal Transduction
;
Stomach Neoplasms/drug therapy*
;
Tumor Suppressor Protein p53/metabolism*
;
Zanthoxylum/metabolism*
3.Corni Fructus attenuates testosterone-induced benign prostatic hyperplasia by suppressing 5α-reductase and androgen receptor expression in rats.
Hyun HWANGBO ; Da He KWON ; Eun Ok CHOI ; Min Yeong KIM ; Kyu Im AHN ; Seon Yeong JI ; Jong Sik KIM ; Kyung Il KIM ; No Jin PARK ; Bum Hoi KIM ; Gi Young KIM ; Su Hyun HONG ; Cheol PARK ; Ji Suk JEONG ; Yung Hyun CHOI
Nutrition Research and Practice 2018;12(5):378-386
BACKGROUND/OBJECTIVES: Benign prostatic hypertrophy (BPH) is a major cause of abnormal overgrowth of the prostate mainly in the elderly. Corni Fructus has been reported to be effective in the prevention and treatment of various diseases because of its strong antioxidant effect, but its efficacy against BPH is not yet known. This study was designed to evaluate the therapeutic efficacy of Corni Fructus water extract (CF) in testosterone-induced BPH rats. MATERIALS/METHODS: To induce BPH, rats were intraperitoneal injected with testosterone propionate (TP). Rats in the treatment group were orally administered with CF with TP injection, and finasteride, which is a selective inhibitor of 5α-reductase type 2, was used as a positive control. RESULTS: Our results showed that the increased prostate weight and histopathological changes in BPH model rats were suppressed by CF treatment. CF, similar to the finasteride-treated group, decreased the levels of testosterone and dihydrotestosterone by TP treatment in the serum, and it also reduced 5α-reductase expression and concentration in prostate tissue and serum, respectively. In addition, CF significantly blocked the expression of the androgen receptor (AR), AR co-activators, and proliferating cell nuclear antigen in BPH rats, and this blocking was associated with a decrease in prostate-specific antigen levels in serum and prostate tissue. CONCLUSIONS: These results suggest that CF may weaken the BPH status through the inactivation of at least 5α-reductase and AR activity and may be useful for the clinical treatment of BPH.
Aged
;
Animals
;
Antioxidants
;
Cornus*
;
Dihydrotestosterone
;
Finasteride
;
Humans
;
Proliferating Cell Nuclear Antigen
;
Prostate
;
Prostate-Specific Antigen
;
Prostatic Hyperplasia*
;
Rats*
;
Receptors, Androgen*
;
Testosterone
;
Testosterone Propionate
;
Water
4.Risperidone Monotherapy in Children and Adolescents with Autism Spectrum Disorders: A Naturalistic Study.
Eun Kyung WON ; Jin Park PARK ; Young Ryul LEE ; Yoon Young NAM ; He Ji MIN ; Yeni KIM
Journal of the Korean Academy of Child and Adolescent Psychiatry 2015;26(4):273-278
OBJECTIVES: We retrospectively investigated the efficacy and tolerability of risperidone monotherapy in subjects with autism spectrum disorder (ASD). In addition, we did mixed effect model analysis of the effects of risperidone in patients with ASDs naturalistically treated in a routine clinical setting to determine whether the clinical effects were maintained and the side effects were tolerable. METHODS: This retrospective study assessed children and adolescents with ASD, who were on risperidone monotherapy from July 2010 to July 2011 at the Child and Adolescent ASD Clinic at Seoul National Hospital. Outcome measures included the Clinical Global Impression-Severity of Illness (CGI-S) and the CGI-Improvement (CGI-I) scales along with other clinical indices: dosage, target symptoms, and side effects. RESULTS: The mean dose of risperidone in 47 children and adolescents with ASD (40 males, 7 females; age range 5-19 years) who were on risperidone monotherapy was 1.6+/-0.8 mg/day, and the mean duration of the treatment period was 20.2+/-17.3 months. Aggressive behavior, stereotypic behavior, irritability, and self-injurious behavior were the most frequent target symptoms of risperidone. The most common side effects were weight gain followed by somnolence and extrapyramidal symptoms. In a mixed effects model analysis of CGI-I scores, the mean CGI-I score at the 1 month follow-up was significantly different from the mean CGI-I score of the 3-month follow-up (p=.046), and the CGI-I scores were equally maintained over 3 to 48 months [F(6, 28.9)=4.393, p=.003]. Of the 47 patients, 33 patients (70.2%) were identified as the response group, showing an end point CGI-I rating of 3 or under and having continued risperidone treatment for at least 6 months. The baseline CGI-S score showed significant association with clinical response to risperidone (p=.005), the mean baseline CGI-S was higher in the response group compared to the non-response group. CONCLUSION: In this study, clinical improvement of risperidone stabilized around 3 months and was equally maintained up to 48 months with tolerable side effects, supporting maintenance of risperidone treatment in children and adolescents with ASDs.
Adolescent*
;
Autistic Disorder*
;
Autism Spectrum Disorder*
;
Child*
;
Female
;
Follow-Up Studies
;
Humans
;
Male
;
Outcome Assessment (Health Care)
;
Retrospective Studies
;
Risperidone*
;
Self-Injurious Behavior
;
Seoul
;
Weight Gain
;
Weights and Measures
5.A Case of Congenital Gastric Outlet Obstruction with Serosal Fibrous Band in Prematurity.
So Min YANG ; Ho Seon EUN ; Soon Min LEE ; He Kyung CHANG ; Kook In PARK ; Ran NAMGUNG
Korean Journal of Perinatology 2014;25(4):302-306
Most of the gastric outlet obstruction symptoms like vomiting and abdominal distension were caused by congenital anatomical abnormality in a neonate. Abnormal structures associated with congenital gastric outlet obstruction have been categorized by its site and extent of obstruction. We report one case of persisting vomiting in a premature infant caused by serosal fibrous band in gastric outlet lesion, excluded from the category of congenital gastric outlet obstruction.
Fibrosis
;
Gastric Outlet Obstruction*
;
Humans
;
Infant, Newborn
;
Infant, Premature
;
Vomiting
6.Delayed-Onset Complete Atrioventricular Block in a Patient with Murine Typhus Myocarditis.
Bo Sung KIM ; Su Young KIM ; Seung Hee HAN ; He Kyung PARK ; Dong Hyun LEE ; Jong Sung PARK
Korean Journal of Medicine 2013;84(5):723-727
Murine typhus is a flea-borne infectious disease caused by Rickettsia typhi, of which myocarditis is a rare complication in the acute disseminating phase. A 62-year-old female presented with a fever and was diagnosed with murine typhus. She was treated with doxycycline and discharged after complete resolution of the fever. However, recurrent presyncope and exertional dyspnea developed 6-8 weeks later. Complete atrioventricular (AV) block with a wide QRS escape rhythm and a left bundle branch block configuration was documented. Subacute myocarditis was diagnosed based on persistent cardiac troponin-I elevation and typical cardiac magnetic resonance imaging findings. A permanent pacemaker was implanted for symptomatic complete AV block. Few reports of myocarditis in murine typhus have been published. We report a case of murine typhus myocarditis complicated by complete AV block in the late convalescence phase.
Atrioventricular Block
;
Bundle-Branch Block
;
Communicable Diseases
;
Convalescence
;
Doxycycline
;
Dyspnea
;
Female
;
Fever
;
Humans
;
Magnetic Resonance Imaging
;
Myocarditis
;
Rickettsia typhi
;
Syncope
;
Troponin I
;
Typhus, Endemic Flea-Borne
;
United Nations
7.A Case of Neurofibromatosis with Invasion of Bladder.
Mi Kyung KIM ; Cheol PARK ; Min Sang KIM ; Hyung Eun YIM ; Kee Hwan YOO ; Young Sook HONG ; Joo Won LEE
Journal of the Korean Society of Pediatric Nephrology 2012;16(1):68-71
Neurofibromatosis is a rare systemic disease, and genitourinary tract involvement is especially uncommon. Bladder is the most frequently involved organ in the genitourinary tract. Bladder neurofibromatosis may present as a diffuse infiltrative process or an isolated neurofibroma. The symptoms vary, ranging from urinary incontinence to retention. Treatment is usually conservative. The patient should be worked up to rule out other manifestation of tumor enlargement and followed to evaluate the development of new lesion. We report a case of the development of invasion of bladder in a patient with neurofibromatosis.
Humans
;
Neurofibroma
;
Neurofibromatoses
;
Neurofibromatosis 1
;
Retention (Psychology)
;
Urinary Bladder
;
Urinary Incontinence
;
Urinary Retention
8.Acute Kidney Injury Accompanied by Acute Pyelonephritis and Renal Abscess in a Child with Vesicoureteral Reflux.
Cheol PARK ; Min Sang KIM ; Mi Kyung KIM ; Hyung Eun YIM ; Kee Hwan YOO ; Young Sook HONG ; Joo Won LEE
Journal of the Korean Society of Pediatric Nephrology 2012;16(1):63-37
Acute pyelonephritis (APN) is a relatively common bacterial infection in children. In previously healthy children, acute kidney injury (AKI) is very rare in the course of APN without urinary tract obstruction, renal hypoperfusion due to hypotension or exposure to nephrotoxic agents. We describe a case of AKI secondary to APN and renal abscess in a child with vesicoureteral reflux. With antibiotic treatment and adequate hydration, the patient was improved. APN should be included in the differential diagnosis of AKI and adequate treatment by proper antibiotics is crucial for full recovery of renal function.
Abscess
;
Acute Kidney Injury
;
Anti-Bacterial Agents
;
Bacterial Infections
;
Child
;
Diagnosis, Differential
;
Humans
;
Hypotension
;
Pyelonephritis
;
Urinary Tract
;
Vesico-Ureteral Reflux
9.Clinical Significance of Extended-Spectrum beta-Lactamase Producing Escherichia coli in Pediatric Patients with Febrile Urinary Tract Infection.
Cheol PARK ; Min Sang KIM ; Mi Kyung KIM ; Hyung Eun YIM ; Kee Hwan YOO ; Young Sook HONG ; Joo Won LEE
Journal of the Korean Society of Pediatric Nephrology 2012;16(1):38-45
PURPOSE: The incidence of community-acquired urinary tract infection (UTI) due to extended-spectrum beta-lactamase producing Escherichia coli (ESBL(+) E. coli) has increased worldwide. ESBL causes resistance to various types of the newer beta-lactam antibiotics, including the expanded spectrum cephalosporins and monobactams. We aimed to investigate the severity of UTI and associated genitourinary malformations in children with febrile UTI caused by ESBL(+) E. coli. METHODS: We retrospectively reviewed the medical records of 290 patients diagnosed as febrile UTI caused by E. coli between January 2008 and October 2010 at Korea University Medical center. We classified the patients into two groups with ESBL(+) and ESBL(-) E. coli group according to the sensitivity of urine culture. Fever duration, admission period, white blood cell (WBC) counts and C-reactive protein (CRP) in peripheral blood, the presence of hydronephrosis, cortical defects, vesicoureteral reflux (VUR) and renal scar were compared between the two groups. RESULTS: Patients with ESBL(+) E. coli were 32, and those with ESBL(-) E. coli were 258. If we excluded those tested with a sterile urine bag, patients with ESBL(+) E. coli were 22, and those with ESBL(-) E. coli were 212. Whether the results of sterile urine bag tests were included or not, there was no significant difference in all parameters between the two groups statistically. CONCLUSION: Our data shows that ESBL(+) E. coli may not be related to the severity of UTI and associated genitourinary malformations.
Academic Medical Centers
;
Anti-Bacterial Agents
;
beta-Lactamases
;
C-Reactive Protein
;
Cephalosporins
;
Child
;
Cicatrix
;
Escherichia
;
Escherichia coli
;
Fever
;
Humans
;
Hydronephrosis
;
Incidence
;
Korea
;
Leukocytes
;
Medical Records
;
Monobactams
;
Retrospective Studies
;
Urinary Tract
;
Urinary Tract Infections
;
Vesico-Ureteral Reflux
10.Transmission of Synucleinopathies in the Enteric Nervous System of A53T Alpha-Synuclein Transgenic Mice.
He Jin LEE ; Ji Eun SUK ; Kyung Won LEE ; Seung Hwa PARK ; Peter C BLUMBERGS ; Wei Ping GAI ; Seung Jae LEE
Experimental Neurobiology 2011;20(4):181-188
Parkinson's disease (PD) and dementia with Lewy bodies (DLB) are characterized by abnormal deposition of alpha-synuclein aggregates in many regions of the central and peripheral nervous systems. Accumulating evidence suggests that the alpha-synuclein pathology initiates in a few discrete regions and spreads to larger areas in the nervous system. Recent pathological studies of PD patients have raised the possibility that the enteric nervous system is one of the initial sites of alpha-synuclein aggregation and propagation. Here, we evaluated the induction and propagation of alpha-synuclein aggregates in the enteric nervous system of the A53T alpha-synuclein transgenic mice after injection of human brain tissue extracts into the gastric walls of the mice. Western analysis of the brain extracts showed that the DLB extract contained detergent-stable alpha-synuclein aggregates, but the normal brain extract did not. Injection of the DLB extract resulted in an increased deposition of alpha-synuclein in the myenteric neurons, in which alpha-synuclein formed punctate aggregates over time up to 4 months. In these mice, inflammatory responses were increased transiently at early time points. None of these changes were observed in the A53T mice injected with saline or the normal brain extract, nor were these found in the wild type mice injected with the DLB extract. These results demonstrate that pathological alpha-synuclein aggregates present in the brain of DLB patient can induce the aggregation of endogenous alpha-synuclein in the myenteric neurons in A53T mice, suggesting the transmission of synucleinopathy lesions in the enteric nervous system.
alpha-Synuclein
;
Animals
;
Brain
;
Dementia
;
Enteric Nervous System
;
Humans
;
Inflammation
;
Lewy Bodies
;
Mice
;
Mice, Transgenic
;
Nervous System
;
Neurons
;
Parkinson Disease
;
Peripheral Nervous System
;
Tissue Extracts

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