Effect of a Wearable Device-Based Physical Activity Intervention in North Korean Refugees: Pilot Randomized Controlled Trial.

BACKGROUND: Effective health interventions for North Korean refugees vulnerable to metabolic disorders are currently unelucidated. OBJECTIVE: This study aimed to evaluate the effects of digital health interventions in North Korean refugees using a wearable activity tracker (Fitbit device). METHODS: We conducted a prospective, randomized, open-label study on North Korean refugees aged 19-59 years between June 2020 and October 2021 with a 12-week follow-up period. The participants were randomly assigned to either an intervention group or a control group in a 1:1 ratio. The intervention group received individualized health counseling based on Fitbit data every 4 weeks, whereas the control group wore the Fitbit device but did not receive individualized counseling. The primary and secondary outcomes were the change in the mean daily step count and changes in the metabolic parameters, respectively. RESULTS: The trial was completed by 52 North Korean refugees, of whom 27 and 25 were in the intervention and control groups, respectively. The mean age was 43 (SD 10) years, and 41 (78.8%) participants were women. Most participants (44/52, 95.7%) had a low socioeconomic status. After the intervention, the daily step count in the intervention group increased, whereas that in the control group decreased. However, there were no significant differences between the 2 groups (+83 and -521 steps in the intervention and control groups, respectively; P=.500). The effects of the intervention were more prominent in the participants with a lower-than-average daily step count at baseline (<11,667 steps/day). After the 12-week study period, 85.7% (12/14) and 46.7% (7/15) of the participants in the intervention and control groups, respectively, had an increased daily step count (P=.05). The intervention prevented the worsening of the metabolic parameters, including BMI, waist circumference, fasting blood glucose level, and glycated hemoglobin level, during the study period. CONCLUSIONS: The wearable device-based physical activity intervention did not significantly increase the average daily step count in the North Korean refugees in this study. However, the intervention was effective among the North Korean refugees with a lower-than-average daily step count; therefore, a large-scale, long-term study of this intervention type in an underserved population is warranted. TRIAL REGISTRATION: Clinical Research Information Service KCT0007999; https://cris.nih.go.kr/cris/search/detailSearch.do/23622.

Rutin Prevents Dexamethasone-Induced Muscle Loss in C2C12 Myotube and Mouse Model by Controlling FOXO3-Dependent Signaling.

One of the causes of sarcopenia is that homeostasis between anabolism and catabolism breaks down due to muscle metabolism changes. Rutin has shown antioxidant and anti-inflammatory effects in various diseases, but there are few studies on the effect on muscle loss with aging. The effect of rutin on muscle loss was evaluated using dexamethasone-induced muscle loss C2C12 myoblast and mouse model. In the group treated with dexamethasone, the muscle weight of gastrocnemius (GA), tibialis anterior (TA), and extensor digitorum longus (EDL) in the mouse model were significantly decreased (p < 0.0001 in GA, p < 0.0001 in TA, and p < 0.001 in EDL) but recovered (p < 0.01 in GA, p < 0.0001 in TA, and p < 0.01 in EDL) when treated with rutin. MAFbx, MuRF1, and FOXO3 protein expression of C2C12 myoblast were significantly increased (p < 0.01 in MAFbx, p < 0.01 in MuRF1, and p < 0.01 in FOXO3) when treated with dexamethasone, but it was recovered (p < 0.01 in MAFbx, p < 0.01 in MuRF1, and p < 0.01 in FOXO3) when rutin was treated. In addition, MAFbx and FOXO3 protein expression in GA of mouse model was significantly increased (p < 0.0001 in MAFbx and p < 0.001 in FOXO3) when treated with dexamethasone, but it was also recovered (p < 0.01 in MAFbx and p < 0.001 in FOXO3) when rutin was treated. The present study shows that rutin blocks the FOXO3/MAFbx and FOXO3/MuRf1 pathways to prevent protein catabolism. Therefore, rutin could be a potential agent for muscle loss such as sarcopenia through the blocking ubiquitin-proteasome pathway associated with catabolic protein degradation.

Complete Mitochondrial Genome Sequences of Korean Phytophthora infestans Isolates and Comparative Analysis of Mitochondrial Haplotypes.

Potato late blight caused by Phytophthora infestans is a destructive disease in Korea. To elucidate the genomic variation of the mitochondrial (mt) genome, we assembled its complete mt genome and compared its sequence among different haplotypes. The mt genome sequences of four Korean P. infestans isolates were revealed by Illumina HiSeq. The size of the circular mt genome of the four major genotypes, KR_1_A1, KR_2_A2, SIB-1, and US-11, was 39,872, 39,836, 39,872, and 39,840 bp, respectively. All genotypes contained the same 61 genes in the same order, comprising two RNA-encoding genes, 16 ribosomal genes, 25 transfer RNA, 17 genes encoding electron transport and ATP synthesis, 11 open reading frames of unknown function, and one protein import-related gene, tatC. The coding region comprised 91% of the genome, and GC content was 22.3%. The haplotypes were further analyzed based on sequence polymorphism at two hypervariable regions (HVRi), carrying a 2 kb insertion/deletion sequence, and HVRii, carrying 36 bp variable number tandem repeats (VNTRs). All four genotypes carried the 2 kb insertion/deletion sequence in HVRi, whereas HVRii had two VNTRs in KR_1_A1 and SIB-1 but three VNTRs in US-11 and KR_2_A2. Minimal spanning network and phylogenetic analysis based on 5,814 bp of mtDNA sequences from five loci, KR_1_A1 and SIB-1 were classified as IIa-6 haplotype, and isolates KR_1_A2 and US-11 as haplotypes IIa-5 and IIb-2, respectively. mtDNA sequences of KR_1_A1 and SIB-1 shared 100% sequence identity, and both were 99.9% similar to those of KR_2_A2 and US-11.

Mitochondrial genome recombination in somatic hybrids of Solanum commersonii and S. tuberosum.

Interspecific somatic hybridization has been performed in potato breeding experiments to increase plant resistance against biotic and abiotic stress conditions. We analyzed the mitochondrial and plastid genomes and 45S nuclear ribosomal DNA (45S rDNA) for the cultivated potato (S. tuberosum, St), wild potato (S. commersonii, Sc), and their somatic hybrid (StSc). Complex genome components and structure, such as the hybrid form of 45S rDNA in StSc, unique plastome in Sc, and recombinant mitogenome were identified. However, the mitogenome exhibited dynamic multipartite structures in both species as well as in the somatic hybrid. In St, the mitogenome is 756,058 bp and is composed of five subgenomes ranging from 297,014 to 49,171 bp. In Sc, it is 552,103 bp long and is composed of two sub-genomes of 338,427 and 213,676 bp length. StSc has 447,645 bp long mitogenome with two subgenomes of length 398,439 and 49,206 bp. The mitogenome structure exhibited dynamic recombination mediated by tandem repeats; however, it contained highly conserved genes in the three species. Among the 35 protein-coding genes of the StSc mitogenome, 21 were identical for all the three species, and 12 and 2 were unique in Sc and St, respectively. The recombinant mitogenome might be derived from homologous recombination between both species during somatic hybrid development.

Identifying serum miRNA biomarkers for radiation exposure in hematopoietic humanized NSG-SGM3 mice.

BACKGROUND: Humans are commonly exposed to ionizing radiation. The conventional approach for estimating radiation exposure is to integrate physical and clinical measurements for optimizing the dose calculation. However, these methods have several limitations. The present study attempted to identify candidate microRNA (miRNA) biomarkers for radiation exposure in a hematopoietic humanized NSGS (hu-NSGS) mouse model. METHODS: We grafted human CD34+ hematopoietic stem cells into NSG-SGM3 (NSGS) mice. The hu-NSGS mice underwent total body irradiation at doses of 2, 3, and 4 Gy. Tissues from the spleen, thymus, and lymph nodes of hu-NSGS mice were prepared to analyze levels of CD45+ and CD3+ T cells and CD 20+ B cells using flow cytometry and immunohistochemistry. Serum miRNAs were profiled using a digital multiplexed NanoString n-Counter. RESULTS: The expression of 45 miRNAs was upregulated/downregulated hu-NSGS mice. The miRNAs hsa-mir-188-5p, hsa-let-7a-5p, hsa-mir-612, hsa-mir-671-5p, and hsa-mir-675-5p were highly radiation-responsive in irradiated hu-NSGS mice. When compared with control mice, radiation-exposed mice exhibited significant upregulated of hsa-let-7a-5p expression and significant downregulation of hsa-mir-188-5p expression. CONCLUSIONS: Single miRNAs or combinations of hsa-mir-188-5p, hsa-let-7a-5p, hsa-mir-675-5p, hsa-mir-612, and hsa-mir-671-5p can be used as biomarkers for predicting the impact of radiation exposure. The current findings suggest the usefulness of hu-NSGS models for investigating radiation biomarkers.

Psychophysiological responses to hookah tobacco public education messages among young adults.

OBJECTIVE: Hookah tobacco use among young adults may be driven by misperceptions of health harms and addictiveness, appealing flavors, and social use. This study examined the effects of hookah prevention messages on participants' cognitive and emotional processing in a lab setting. METHOD: One hundred twenty participants (61 susceptible never-users, 59 current users) were exposed to messages representing six categories: health risks only, health risks of social use, health risks of flavors, addiction risks only, addiction risks of social use, and addiction risks of flavors. Guided by the Limited Capacity Model of Motivated Mediated Message Processing, participants' psychophysiological responses (heart rate, skin conductance, facial action coding) were recorded while participants viewed the messages. Recognition memory and counterarguing were measured postexposure. RESULTS: The combination of heart rate, skin conductance, both positive and negative facial action coding, and recognition memory indicated that social themed messages were more defensively processed than the other message types. Addiction-social messages, in particular, were least likely to be encoded. Further, defensive processing indicated by the psychophysiological and recognition data did not vary according to user status. Counterarguing was higher for users than for never-users across all message themes and risks. DISCUSSION: Messages about health risks and addiction, whether or not they included information on flavors, evoked relatively similar responses. But social themed messages stand out as potentially problematic, especially addiction-social messages. Using psychophysiological and self-report measures extend opportunities to identify optimal hookah tobacco public education message features. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Development of a Bioluminescent Human Osteosarcoma Model in Humanized NSG Mice: A Pilot Study.

BACKGROUND/AIM: Osteosarcoma is the most common type of bone cancer, but current therapeutic interventions remain largely insufficient. The development of new treatment strategies is needed, and moreover, optimal rodent models are necessary for testing the efficacy of new treatment modalities of osteosarcoma. Humanized mice carry human hematopoietic and immune systems, and are considered an ideal tool to study human diseases including cancer immunology. Herein, we performed a preliminary study toward developing an in vivo bioluminescent osteosarcoma model using humanized immunodeficient (NSG) mice. MATERIALS AND METHODS: To establish the xenograft and orthotopic mouse model, NSG mice engrafted with human CD34+ hematopoietic stem cells were injected with luciferase-expressing KHOS/NP cells at two different time points. Bioluminescence images were obtained to monitor in vivo tumor growth and metastasis. Influence of the degree of human cell engraftment on tumor growth and metastatic behavior was analyzed and compared between the two groups. RESULTS: KHOS/NP-luc cells injected in humanized NSG mice formed macroscopic tumors. The percentage of human CD45+ cells in these models was similar, but the percentage of human CD45+CD3+ and their subset was higher in the late-injection group compared to that of the early-injection group. The rate of KHOS/NP tumor growth was higher in the early-injection group than in the late-injection group. In the present study, human hematopoietic cell engraftment was not influenced by KHOS/NP cell injection, but KHOS/NP osteosarcoma showed more aggressive behavior in the early-injection group than that in the late-injection group, forming larger tumor volumes and earlier metastases. CONCLUSION: The results indicated that tumor growth and progression in humanized NSG mice may have been influenced by higher levels of human cell engraftment, especially T cells. Although there exist some limitations to our study, our preliminary results can provide the basis for the development of a humanized osteosarcoma mouse model.

Improved Genome Sequence and Gene Annotation Resource for the Potato Late Blight Pathogen Phytophthora infestans.

Phytophthora infestans is a devastating pathogen causing potato late blight (Solanum tuberosum). Here we report the sequencing, assembly and genome annotation for two Phytophthora infestans isolates sampled in Republic of Korea. Genome sequencing was carried out using long read (Oxford Nanopore) and short read (Illumina Nextseq) sequencing technologies that significantly improved the contiguity and quality of P. infestans genome assembly. Our resources would help researchers better understand the molecular mechanisms by which P. infestans causes late blight disease in the future.

Lentivirus-Mediated VEGF Knockdown Suppresses Gastric Cancer Cell Proliferation and Tumor Growth in vitro and in vivo.

PURPOSE: Gastric cancer has a high mortality rate worldwide. Although treatments, such as molecular-targeted therapy, have been introduced, the resulting long-term survival and prognosis remain unsatisfactory. Downregulation of the target genes using lentivirus-mediated short hairpin RNA (shRNA) can be an effective therapeutic strategy for patients with gastric cancer. Overexpressed vascular endothelial growth factor A (VEGF) in human gastric cancer cells can be an effective novel therapeutic target for human gastric cancer. Thus, this study aimed to evaluate the therapeutic effects of lentivirus-mediated knockdown of VEGF gene expression in human gastric cancer growth. MATERIALS AND METHODS: Specific shRNA sequences targeting VEGF were designed to construct a lentiviral expression vector. After human gastric carcinoma cells (cell line NCI-N87) were infected with the lentiviral vector, the therapeutic effects of the lentivirus-mediated shRNA targeting VEGF were analyzed both in vitro and in vivo. RESULTS: Stable suppression of VEGF gene expression in NCI-N87 cells using shRNA (ShVEGF) showed significant inhibition of cell proliferation, clonogenicity, and cell motility. ShVEGF also showed increased G0/G1 cell cycle arrest and apoptosis. In addition, in vivo results from nude mice xenografted ShVEGF showed significant inhibition of tumor growth. Assessing the therapeutic effects of intratumoral injection of lentivirus-targeting VEGF (Virus_VEGF) revealed that it significantly inhibited tumor growth compared to that in the Virus_Scramble or saline injection control groups. CONCLUSION: The constructed ShVEGF showed significant inhibition of NCI-N87 gastric cancer cell growth both in vitro and in vivo. These experimental results suggest a novel therapeutic strategy for patients with gastric cancer using lentivirus-mediated shRNA targeting VEGF.

Physical exercise ameliorates psychiatric disorders and cognitive dysfunctions by hippocampal mitochondrial function and neuroplasticity in post-traumatic stress disorder.

Post-traumatic stress disorder (PTSD) is a stress-related condition that can be triggered by witnessing or experiencing a life-threatening event, such as a war, natural disaster, terrorist attack, major accident, or assault. PTSD is caused by dysfunction of the hippocampus and causes problems associated with brain functioning, such as anxiety, depression, and cognitive impairment. Exercise is known to have a positive effect on brain function, especially in the hippocampus. In this study, we investigated the effect of aerobic exercise on mitochondrial function and neuroplasticity in the hippocampus as well as behavioral changes in animal models of PTSD. Exposure to severe stress resulted in mitochondrial dysfunction in the hippocampus, including impaired Ca2+ homeostasis, an increase in reactive oxygen species such as H2O2, a decrease in the O2 respiration rate, and overexpression of membrane permeability transition pore-related proteins, including voltage-dependent anion channel, adenine nucleotide translocase, and cyclophilin-D. Exposure to extreme stress also decreased neuroplasticity by increasing apoptosis and decreasing the brain-derived neurotrophic factor level and neurogenesis, resulting in increased anxiety, depression, and cognitive impairment. The impairments in mitochondrial function and neuroplasticity in the hippocampus, as well as anxiety, depression, and cognitive impairment, were all improved by exercise. Exercise-induced improvement of the brain-derived neurotrophic factor level in particular might alter mitochondrial function, neuroplasticity, and the rate of apoptosis in the hippocampus. Therefore, exercise might be an important non-pharmacological intervention for the prevention and treatment of the pathobiology of PTSD.

[Influence of Physical Symptoms and Lifestyle on Suicidal Ideation of Senior Grade Students in Elementary School]. / 초등학교 ê³ í•™ë „ 아동의 ì‹ ì²´ì¦ìƒ 및 생활습관이 자살생각에 미치는 영향.

PURPOSE: This study was conducted to analyze physical symptom-related and life-style factors affecting suicidal ideation of senior grade students in elementary school. METHODS: Physical symptom-related and life-style factors were used to investigate suicidal ideation among 663 elementary school students. From February 11 to 15, 2018, data were collected using a structured questionnaire and analyzed using the x2 test, Pearson correlation analysis, and logistic regression analysis in SPSS for Windows version 22.0. RESULTS: The factors affecting suicidal ideation were gender, family structure, economic status, academic performance, exposure to school violence during the past year, physical symptoms, drinking experience, smoking experience, sleeping time, and ramen noodle consumption. The regression analysis showed that exposure to school violence during the past year (odds ratio [OR]: 102.99, 95% confidence interval [CI]: 51.19~207.19, p=.001), number of physical symptoms (OR: 1.25, 95% CI: 1.12~1.41, p=.001), drinking experience (OR: 3.17, 95% CI: 1.66~6.06, p=.001), and game and internet usage time (OR: 2.08, 95% CI: 1.08~4.01, p=.029) affected suicidal ideation. CONCLUSION: This study revealed that physical symptoms and life-style significantly influenced suicidal ideation. Therefore, interventions to reduce suicidal ideation in children must focus on improving children's physical symptoms and life-style.

Treadmill exercise alleviates stress-induced anxiety-like behaviors in rats.

Stress is the physiological responses of organisms to harmful or threatening stimuli that allow appropriate behavioral responses to the stressor. In the present study, the effect of treadmill exercise on stress-induced anxiety was evaluated using rats. To induce stress, the rats were exposed to an inescapable electric foot shock. Exposure of rats to the electric foot shock was performed for 7 days. The rats in the exercise groups were made to run on a motorized treadmill for 30 min once a day for 4 weeks stating one day after last electric food shock. Anxiety-like behaviors were determined by open field test and elevated plus-maze test. The expressions of c-Fos and neuronal nitric oxide synthase (nNOS) in the hypothalamus and locus coeruleus were detected by immunohistochemistry. In the present results, locomotor activity in the center of the open field test and the number of entries and time in the open arms of the elevated plus-maze test were reduced in the rats with stress-induced anxiety. Treadmill running enhanced these locomotor activities, the number of entries and time in the stress-induced anxiety rats. c-Fos and nNOS expressions in the hypothalamus and locus coeruleus were increased in the stress-induced rats. Treadmill exercise reduced c-Fos and nNOS overexpressions in the stress-induced rats. In the present study, treadmill exercise ameliorated anxiety-like behaviors in the stress-induced rats. The improving effect of treadmill exercise on anxiety-like behaviors might be ascribed to the suppressing effect of exercise on c-Fos and nNOS expressions.

HSP60 is required for stemness and proper differentiation of mouse embryonic stem cells.

Embryonic stem cells (ESCs) are metabolically distinct from their differentiated counterparts. ESC mitochondria are less complex and fewer in number than their differentiated progeny. However, few studies have examined the proteins responsible for differences in mitochondrial structure and function between ESCs and somatic cells. Therefore, in this study, we aimed to investigate the differences between mitochondrial proteins in these two cell types. We demonstrate that HSP60 is more abundant in mouse ESC mitochondria than in mouse embryonic fibroblasts. Depletion of HSP60 inhibited mouse ESC proliferation and self-renewal, characterized by decreased OCT4 expression. HSP60 depletion also enhanced apoptosis during mouse ESC differentiation into embryoid bodies. Our results suggest that HSP60 expression has an essential role in ESC self-renewal and survival of differentiated cells from ESCs.

Low-frequency electroacupncture improves locomotor function after sciatic crushed nerve injury in rats.

Sciatic crushed nerve injury (SCI) causes pain-related gait and swelling in the affected limb. Electroacupuncture (EA) is a modified acupuncture technique, and analgesic effect of EA on different types of pain has been documented. Scientific functional index (SFI) is a mathematical formula to represent parameters of normal and experimental footprints. We investigated the effect of low-frequency EA on functional recovery following SCI in rats. For this study, immunohistochemistry for c-Fos in the ventral lateral periaqueductal gray (vlPAG) and paraventricular nucleus (PVN) and western blot for neurofilament (NF) and brain-derived neurotrophic factor (BDNF) in the sciatic nerve were conducted. To induce crush injury on the sciatic nerve, sciatic nerve was crushed for 30 sec using a surgical clip. The rats in the acupuncture groups received acupuncture bilaterally at respective site, once a day for 14 days. The rats in the EA group received 100-Hz electrical stimulation for 10 min once a day during 14 days. SCI decreased SFI value, in contrast, EA increased SFI value. c-Fos expression in the vlPAG and PVN was increased following SCI, in contrast, EA suppressed c-Fos expression. NF expression in the sciatic nerve was decreased by SCI, in contrast, EA increased NF expression. BDNF expression in the sciatic nerve was increased by SCI, in contrast, EA suppressed BDNF expression. In the present study, EA showed effectiveness on functional recovery from SCI.

The relationship between communication competence and exercise participation type: focusing on joining clubs and using fitness applications.

The purpose of this study was to determine the effects of the differences in subfactors of communication competence on exercise participation types (clubs, applications use). Communication competence focus on the communication part of the individual's interpersonal competence. Therefore, communication competence can be predicted to be related to the type of exercise participation. Accordingly, the targets of this study were clubs, which had group characteristics, and fitness applications, which had individual characteristics. There was a significant difference as a result of the association between communication competence and the type of exercise participation. In terms of club membership, significant differences were found in communication competence skills according to exercise participation types in that self-disclosure of subjects who joined clubs was significant, social relaxation of subjects who intend to join a club was significant, and the immediacy of fitness applications users was significant.

Effects of colostrum serum on the serotonergic system in the dorsal raphe nuclei of exercised rats.

PURPOSE: The central fatigue hypothesis suggests that exhaustion, or the maximum level of exercise, induces excessive stress and increases serotonin concentrations in the brain, which in turn decreases central nervous system (CNS) function and induces fatigue. Our aim was to determine the effects of colostrum serum on the serotonergic system in the dorsal raphe nuclei during exhaustive exercise. METHODS: Animals were randomly divided into five groups: control, exercise, exercise and treatment with 50, 100, and 200 mg/kg of colostrum serum. The rats in the colostrum serum treatment groups were fed colostrum serum at three different doses of 50, 100, and 200 mg/kg per day for seven days. The rats in the control and exercise groups received water by oral gavage once per day for seven days. RESULTS: The time to exhaustion in response to treadmill running increased after treatment with colostrum serum. These results show that exhaustive exercise led to over activation of the serotonergic system in the dorsal raphe nuclei, and that treatment with colostrum serum suppressed of the exercise-induced expression of tryptophan hydroxylase (TPH) and serotonin (5-HT). The results also indicated that exhaustive exercise induced 5-HT1A autoreceptor and serotonin transporter (5-HTT) overexpression in the dorsal raphe nuclei, and that colostrum serum treatment suppressed exhaustive exercise-induced 5-HT1A and 5-HTT expression in the dorsal raphe nuclei. The most effective dose of colostrum serum was 100 mg/kg. CONCLUSION: Overall, our study suggests that colostrum serum has positive effects on exercise performance and recovery by increasing the resistance to fatigue.

Knockout of krüppel-like factor 10 suppresses hepatic cell proliferation in a partially hepatectomized mouse model.

The liver has marked regenerative capabilities, and numerous signaling pathways are involved in liver regeneration. The transforming growth factor-ß (TGF-ß)/Smad pathway, which is also involved in liver regeneration, regulates numerous biological processes. Krüppel-like factor 10 (KLF10) has been reported to activate the TGF-ß/Smad signaling pathway; however, the exact functions of KLF10 under various pathophysiological conditions remain unclear. In the present study, the role of KLF10 in liver regeneration following partial hepatectomy (PH) was investigated using KLF10-knockout (KO) mice. KLF10-KO mice exhibited lower liver/body weight ratios and 5-bromo-2-deoxy-uridine labeling indices compared with wild-type (WT) mice, and significant differences (P=0.028) were obtained at 72 h after PH. To understand the causes of the gross and histopathological findings, the expression levels of the components of the TGF-ß/Smad pathway were examined using reverse transcription-quantitative polymerase chain reaction and western blot analysis. The mRNA and protein levels of Smad3, p15, TGF-ß1 and TGF-ß receptor 1 were significantly increased, while those of cMyc and cyclin D1 (proliferation-associated genes) were significantly lower in the liver tissues of the KLF10-KO mice compared with those of the WT mice at 72 h post-PH. These results indicated that KLF10-KO may exhibit antiproliferative effects on liver regeneration following PH, through strengthening the TGF-ß/Smad signaling pathway in a delayed manner.

Humanizing NOD/SCID/IL-2Rγnull (NSG) mice using busulfan and retro-orbital injection of umbilical cord blood-derived CD34(+) cells.

BACKGROUND: Humanized mouse models are still under development, and various protocols exist to improve human cell engraftment and function. METHODS: Fourteen NOD/SCID/IL-2Rγnull (NSG) mice (4‒5 wk old) were conditioned with busulfan and injected with human umbilical cord blood (hUCB)-derived CD34(+) hematopoietic stem cells (HSC) via retro-orbital sinuses. The bone marrow (BM), spleen, and peripheral blood (PB) were analyzed 8 and 12 weeks after HSC transplantation. RESULTS: Most of the NSG mice tolerated the regimen well. The percentage of hCD45(+) and CD19(+) cells rose significantly in a time-dependent manner. The median percentage of hCD45(+)cells in the BM was 55.5% at week 8, and 67.2% at week 12. The median percentage of hCD45(+) cells in the spleen at weeks 8 and 12 was 42% and 51%, respectively. The median percentage of hCD19(+) cells in BM at weeks 8 and 12 was 21.5% and 39%, respectively (P=0.04). Similarly, the median percentage of hCD19(+) cells in the spleen at weeks 8 and 12 was 10% and 24%, respectively (P=0.04). The percentage of hCD19(+) B cells in PB was 23% at week 12. At week 8, hCD3(+) T cells were barely detectable, while hCD7(+) was detected in the BM and spleen. The percentage of hCD3(+) T cells was 2‒3% at week 12 in the BM, spleen, and PB of humanized NSG mice. CONCLUSION: We adopted a simplified protocol for establishing humanized NSG mice. We observed a higher engraftment rate of human CD45(+) cells than earlier studies without any significant toxicity. And human CD45(+) cell engraftment at week 8 was comparable to that of week 12.

Combined exercise ameliorates ovariectomy-induced cognitive impairment by enhancing cell proliferation and suppressing apoptosis.

OBJECTIVE: Estrogen plays an important role in cognitive function, including attention, learning, and memory, and affects the structure and function of brain areas. We investigated the effects of combined exercise on memory deficits induced by ovariectomy (OVX) in relation to cell proliferation and apoptosis in the hippocampus. METHODS: Rats were randomly divided into four groups: sham, sham and exercise, OVX, and OVX and exercise. Rats in combined exercise groups were subjected to 3 days of resistance training and 3 days of running (for a total of 6 d/wk) for eight consecutive weeks. Rats were tested in step-down avoidance task and Morris water maze task to verify the effects of OVX on short-term and spatial working memory. RESULTS: In the present study, the number of BrdU-positive and doublecortin-positive cells and expression of brain-derived neurotrophic factor, TrkB, and Bcl-2 decreased; expression of Bax and the number of caspase-3-positive and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling-positive cells increased; and short-term and spatial working memory decreased in the OVX group compared with the sham group. Conversely, when the combined exercise group was compared with the OVX group, the number of BrdU-positive and doublecortin-positive cells and expression of brain-derived neurotrophic factor, TrkB, and Bcl-2 increased; expression of Bax and the number of caspase-3-positive and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling-positive cells decreased; and short-term and spatial working memory increased. CONCLUSIONS: Combined exercise increases cell proliferation and inhibits apoptosis in the hippocampus and improves cognitive function despite estrogen deficiency.

Treadmill exercise alleviates stress-induced impairment of social interaction through 5-hydroxytryptamine 1A receptor activation in rats.

Brain-derived neurotrophic factor (BDNF) and its receptors tyrosine kinase B (trkB), and cyclic adenosine monophosphate response element binding protein (CREB) have been suggested as the neurobiological risk factors causing depressive disorder. Serotonin (5-hydroxytryptamine, 5-HT) plays an important role in the pathogenesis of depression. We in-vestigated the effect of treadmill exercise on social interaction in relation with BDNF and 5-HT expressions following stress in rats. Stress was induced by applying inescapable 0.2 mA electric foot shock to the rats for 7 days. The rats in the exercise groups were forced to run on a motorized treadmill for 30 min once a day for 4 weeks. Social interaction test and western blot for BDNF, TrkB, pCREB, and 5-HT1A in the hippocampus were performed. The results indicate that the spend time with unfamiliar partner was decreased by stress, in contrast, treadmill exercise increased the spending time in the stress-induced rats. Expressions of BDNF, TrkB, and pCREB were decreased by stress, in contrast, treadmill exercise enhanced expressions of BDNF, TrkB, and pCREB in the stress-induced rats. In addition, 5-HT1A receptor expression was de-creased by stress, in contrast, treadmill exercise enhanced 5-HT1A expression in the stress-induced rats. In the present study, treadmill exercise alleviated stress-induced social interaction impairment through enhancing hippocampal plasticity and serotonergic function in the hippocampus. These effects of treadmill exercise are achieved through 5-HT1A receptor activation.