{"title":"DNA‑PKcs phosphorylation specific inhibitor, NU7441, enhances the radiosensitivity of clinically relevant radioresistant oral squamous cell carcinoma cells.","authors":"Kentaro Ohuchi, Ryo Saga, Kazuki Hasegawa, Eichi Tsuruga, Yoichiro Hosokawa, Manabu Fukumoto, Kazuhiko Okumura","doi":"10.3892/br.2023.1610","DOIUrl":"https://doi.org/10.3892/br.2023.1610","url":null,"abstract":"<p><p>Radioresistant cancer cells lead to poor prognosis after radiotherapy. However, the mechanisms underlying cancer cell radioresistance have not been fully elucidated. Thus, the DNA damage response of clinically relevant radioresistant oral squamous cell carcinoma HSC2-R cells, established by long-term exposure of parental HSC2 cells to fractionated radiation, was investigated. The DNA double-strand break (DSB) repair protein-specific inhibitor, NU7441, which targets DNA-dependent protein kinase catalytic subunit (DNA-PKcs) phosphorylation, and IBR2, which targets Rad51, were administered to HSC2 and HSC2-R cells. NU7441 administration eliminated colony formation in both cell lines under 6 Gy X-ray irradiation, whereas IBR2 did not affect colony formation. NU7441 and IBR2 significantly enhanced 6 Gy X-ray irradiation-induced apoptosis in HSC2-R cells. In HSC2-R cells, cell cycle arrest released earlier than in HSC2 cells, and phosphorylated-H2A histone family member X (γH2AX) expression rapidly decreased. Following NU7441 administration, γH2AX expression and the cell percentages of the G2/M phase were not decreased at 48 h after treatment in HSC2-R cells. DNA-PKcs has been demonstrated to regulate non-homologous end-joining (NHEJ) and homologous recombination (HR) repair, and the later phase of DSB repair is dominated by HR. Therefore, the results of the present study indicated that the DSB repair mechanism in HSC2-R cells strongly depends on NHEJ and loss of HR repair function. The present study revealed a potential mechanism underlying the acquired radioresistance and therapeutic targets in radioresistant cancer cells.</p>","PeriodicalId":8863,"journal":{"name":"Biomedical reports","volume":"18 4","pages":"28"},"PeriodicalIF":2.3,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10011949/pdf/br-18-04-01610.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9188047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Dynamic changes in radiological parameters, immune cells, selected miRNAs, and cytokine levels in peripheral blood of patients with severe COVID‑19.","authors":"Tetiana Bukreieva, Vitalii Kyryk, Viktoriia Nikulina, Hanna Svitina, Alyona Vega, Oleksii Chybisov, Iuliia Shablii, Oksana Mankovska, Galyna Lobyntseva, Petro Nemtinov, Inessa Skrypkina, Volodymyr Shablii","doi":"10.3892/br.2023.1615","DOIUrl":"10.3892/br.2023.1615","url":null,"abstract":"<p><p>The present study aimed to investigate the dynamic changes in peripheral blood leucocyte subpopulations, cytokine and miRNA levels, and changes in computed tomography (CT) scores in patients with severe coronavirus disease 2019 (COVID-19) (n=14) and age-matched non-COVID-19 volunteers (n=17), which were included as a reference control group. All data were collected on the day of patient admission (day 0) and on the 7th, 14th and 28th days of follow-up while CT of the lungs was performed on weeks 2, 8, 24 and 48. On day 0, lymphopenia and leucopenia were detected in most patients with COVID-19, as well as an increase in the percentage of banded neutrophils, B cells, and CD4<sup>+</sup> Treg cells, and a decrease in the content of PD-1<sup>low</sup> T cells, classical, plasmacytoid, and regulatory dendritic cells. On day 7, the percentage of T and natural killer cells decreased with a concurrent increase in B cells, but returned to the initial level after treatment discharge. The content of different T and dendritic cell subsets among CD45<sup>+</sup> cells increased during two weeks and remained elevated, suggesting the activation of an adaptive immune response. The increase of PD-1-positive subpopulations of T and non-T cells and regulatory CD4 T cells in patients with COVID-19 during the observation period suggests the development of an inflammation control mechanism. The levels of interferon γ-induced protein 10 (IP-10), tumor necrosis factor-α (TNF-α) and interleukin (IL)-6 decreased on day 7, but increased again on days 14 and 28. C-reactive protein and granulocyte colony-stimulating factor (G-CSF) levels decreased gradually throughout the observation period. The relative expression levels of microRNA (miR)-21-5p, miR-221-3p, miR-27a-3p, miR-146a-5p, miR-133a-3p, and miR-126-3p were significantly higher at the beginning of hospitalization compared to non-COVID-19 volunteers. The plasma levels of all miRs, except for miR-126-3p, normalized within one week of treatment. At week 48, CT scores were most prominently correlated with the content of lymphocytes, senescent memory T cells, CD127<sup>+</sup> T cells and CD57<sup>+</sup> T cells, and increased concentrations of G-CSF, IP-10, and macrophage inflammatory protein-1α.</p>","PeriodicalId":8863,"journal":{"name":"Biomedical reports","volume":"18 5","pages":"33"},"PeriodicalIF":2.3,"publicationDate":"2023-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10074022/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9326585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Pinostrobin alleviates chronic restraint stress‑induced cognitive impairment by modulating oxidative stress and the function of astrocytes in the hippocampus of rats.","authors":"Sitthisak Thongrong, Serm Surapinit, Tichanon Promsrisuk, Jinatta Jittiwat, Ratchaniporn Kongsui","doi":"10.3892/br.2023.1602","DOIUrl":"https://doi.org/10.3892/br.2023.1602","url":null,"abstract":"<p><p>Chronic stress has been recognized to induce the alterations of neuronal and glial cells in the hippocampus, and is thus implicated in cognitive dysfunction. There is increasing evidence to indicate that natural compounds capable of exerting neuroprotective and antioxidant activities, may function as potential therapeutic agents for cognitive impairment. The present study examined the neuroprotective effects of pinostrobin from <i>Boesenbergia rotunda</i> (L.) against chronic restraint stress (CRS)-induced cognitive impairment associated with the alterations of oxidative stress, neuronal density and glial fibrillary acidic protein (GFAP) of astrocytes in the hippocampus. For this purpose, male Wistar rats were administered once daily with pinostrobin (20 and 40 mg/kg, <i>per os</i>) prior to exposure to CRS (6 h/day) for 21 days. The cognitive behaviors, the concentration of malondialdehyde, and the activities of superoxide dismutase and catalase were determined. Histologically, the alterations in astrocytic GFAP and excitatory amino acid transporter 2 (EAAT2) in the hippocampus were examined. The results revealed that pinostrobin potentially attenuated cognitive impairment in the Y-maze and in novel object recognition tests, with a reduction in oxidative stress. Furthermore, pinostrobin effectively increased neuronal density, as well as the immunoreactivities of GFAP and EAAT2 in the hippocampus. Taken together, these findings indicate that treatment with pinostrobin alleviates chronic stress-induced cognitive impairment by exerting antioxidant effects, reducing neuronal cell damage, and improving the function of astrocytic GFAP and EAAT2. Thus, pinostrobin may have potential for use as a neuroprotective agent to protect against chronic stress-induced brain dysfunction and cognitive deficits.</p>","PeriodicalId":8863,"journal":{"name":"Biomedical reports","volume":"18 3","pages":"20"},"PeriodicalIF":2.3,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/27/71/br-18-03-01602.PMC9922797.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10798472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Potential prognostic and predictive value of UBE2N, IMPDH1, DYNC1LI1 and HRASLS2 in colorectal cancer stool specimens.","authors":"Yu-Nung Chen, Cheng-Yen Shih, Shu-Lin Guo, Chih-Yi Liu, Ming-Hung Shen, Shih-Chang Chang, Wei-Chi Ku, Chi-Cheng Huang, Chi-Jung Huang","doi":"10.3892/br.2023.1604","DOIUrl":"https://doi.org/10.3892/br.2023.1604","url":null,"abstract":"<p><p>Colorectal cancer (CRC) is the most common gastrointestinal malignancy worldwide. The poor specificity and sensitivity of the fecal occult blood test has prompted the development of CRC-related genetic markers for CRC screening and treatment. Gene expression profiles in stool specimens are effective, sensitive and clinically applicable. Herein, a novel advantage of using cells shed from the colon is presented for cost-effective CRC screening. Molecular panels were generated through a series of leave-one-out cross-validation and discriminant analyses. A logistic regression model following reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry was used to validate a specific panel for CRC prediction. The panel, consisting of ubiquitin-conjugating enzyme E2 N (UBE2N), inosine monophosphate dehydrogenase 1 (IMPDH1), dynein cytoplasmic 1 light intermediate chain 1 (DYNC1LI1) and phospholipase A and acyltransferase 2 (HRASLS2), accurately recognized patients with CRC and could thus be further investigated as a potential prognostic and predictive biomarker for CRC. UBE2N, IMPDH1 and DYNC1LI1 expression levels were upregulated and HRASLS2 expression was downregulated in CRC tissues. The predictive power of the panel was 96.6% [95% confidence interval (CI), 88.1-99.6%] sensitivity and 89.7% (95% CI, 72.6-97.8%) specificity at a predicted cut-off value at 0.540, suggesting that this four-gene panel testing of stool specimens can faithfully mirror the state of the colon. On the whole, the present study demonstrates that screening for CRC or cancer detection in stool specimens collected non-invasively does not require the inclusion of an excessive number of genes, and colonic defects can be identified via the detection of an aberrant protein in the mucosa or submucosa.</p>","PeriodicalId":8863,"journal":{"name":"Biomedical reports","volume":"18 3","pages":"22"},"PeriodicalIF":2.3,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/8f/a2/br-18-03-01604.PMC9945078.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9358047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"(-)‑Epigallocatechin‑3‑<i>O</i>‑gallate upregulates the expression levels of miR‑6757‑3p, a suppressor of fibrosis‑related gene expression, in extracellular vesicles derived from human umbilical vein endothelial cells.","authors":"Motoki Murata, Yuki Marugame, Mai Morozumi, Kyosuke Murata, Motofumi Kumazoe, Yoshinori Fujimura, Hirofumi Tachibana","doi":"10.3892/br.2023.1601","DOIUrl":"https://doi.org/10.3892/br.2023.1601","url":null,"abstract":"<p><p>As pulmonary fibrosis (PF), a severe interstitial pulmonary disease, has such a poor prognosis, the development of prevention and treatment methods is imperative. (-)-Epigallocatechin-3-<i>O</i>-gallate (EGCG), one of the major catechins in green tea, exerts an antifibrotic effect, although its mechanism remains unclear. Recently, it has been reported that microRNAs (miRNAs or miRs) transported by extracellular vesicles (EVs) from vascular endothelial cells (VECs) are involved in PF. In the present study, the effects of EGCG on the expression of miRNAs in EVs derived from human umbilical vein endothelial cells (HUVECs) were assessed and miRNAs with antifibrotic activity were identified. miRNA microarray analysis revealed that EGCG modulated the expression levels of 31 miRNAs (a total of 27 miRNAs were upregulated, and 4 miRNAs were downregulated.) in EVs from HUVECs. Furthermore, TargetScan analysis indicated that miR-6757-3p in particular, which exhibited the highest degree of change, may target transforming growth factor-β (TGF-β) receptor 1 (TGFBR1). To evaluate the effects of miR-6757-3p on TGFBR1 expression, human fetal lung fibroblasts (HFL-1) were transfected with an miR-6757-3p mimic. The results demonstrated that the miR-6757-3p mimic downregulated the expression of TGFBR1 as well the expression levels of fibrosis-related genes including fibronectin and α-smooth muscle actin in TGF-β-treated HFL-1 cells. In summary, EGCG upregulated the expression levels of miR-6757-3p, which may target TGFBR1 and downregulate fibrosis-related genes, in EVs derived from VECs.</p>","PeriodicalId":8863,"journal":{"name":"Biomedical reports","volume":"18 3","pages":"19"},"PeriodicalIF":2.3,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a4/8b/br-18-03-01601.PMC9912138.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10764706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Measurement of exhaled breath temperature in patients under general anesthesia: A feasibility study.","authors":"Libo Guo, Jinghui Shi, Desheng Liu, Yue Wang, Hongshuang Tong, Yue Feng, Pulin Yu, Yanji Lv, Enyou Li, Changsong Wang","doi":"10.3892/br.2023.1600","DOIUrl":"https://doi.org/10.3892/br.2023.1600","url":null,"abstract":"<p><p>The aim of the present study was to investigate the respiratory parameters that influence the exhaled breath temperature (EBT) and the feasibility of using the latter to monitor the core temperature under general endotracheal anesthesia. A total of 20 patients undergoing abdominal surgery were included in the present study. At the first stage of the experiment, the respiratory rate was adjusted, while the other respiratory parameters [tidal volume, inspiratory and expiratory time ratio (TI:TE), and positive end expiratory pressure (PEEP)] were maintained at a constant level. At the second stage, the tidal volume was adjusted, while the other respiratory parameters were maintained at a constant level. At the third stage, the TI:TE was adjusted, while the other parameters were maintained at a constant level. At the fourth stage, PEEP was adjusted, while the other parameters were maintained at a constant level. In each experiment, the EBT, the maximum temperature of exhaled air in each min, the inhaled air temperature and the nasopharyngeal temperature (T nose) were recorded every min. During the first stage of the experiment, no significant difference was noted in the EBT at different levels of respiratory rate. During the second, third and fourth stage, no significant difference was noted in the EBT at different tidal volumes, TI:TE and PEEP, respectively. The EBT was significantly correlated with the T nose. Overall, the present study demonstrated that the EBT of patients undergoing abdominal surgery under general endotracheal anesthesia was not affected by the examined respiratory parameters and that it could be considered a feasible method of monitoring core temperature.</p>","PeriodicalId":8863,"journal":{"name":"Biomedical reports","volume":"18 3","pages":"18"},"PeriodicalIF":2.3,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/86/09/br-18-03-01600.PMC9912139.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10764709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mahanthesh Vasudha, Chakra S Prashantkumar, Mallika Bellurkar, Vishwas Kaveeshwar, Devaraja Gayathri
{"title":"Probiotic potential of β‑galactosidase‑producing lactic acid bacteria from fermented milk and their molecular characterization.","authors":"Mahanthesh Vasudha, Chakra S Prashantkumar, Mallika Bellurkar, Vishwas Kaveeshwar, Devaraja Gayathri","doi":"10.3892/br.2023.1605","DOIUrl":"https://doi.org/10.3892/br.2023.1605","url":null,"abstract":"<p><p>Probiotics have attained significant interest in recent years as a result of their gut microbiome modulation and gastrointestinal health benefits. Numerous fermented foods contain lactic acid bacteria (LAB) which are considered as GRAS and probiotic bacteria. The present study aimed to investigate indigenous LAB from homemade fermented milk samples collected in remote areas of Karnataka (India), in order to isolate the most potent and well-adapted to local environmental conditions bacteria, which were then evaluated using a step-by-step approach focused on the evaluation of probiotic traits and β-galactosidase-producing ability. LAB were screened using 5-bromo-4-chloro-3-indole-D-galactopyranoside (X-Gal) and <i>O</i>-nitrophenyl-β-D-galactopyranoside (ONPG) as substrate, and exhibited β-galactosidase activity ranging from 728.25 to 1,203.32 Miller units. The most promising isolates were selected for 16S rRNA gene sequence analysis and identified as <i>Lactiplantibacillus plantarum</i>, <i>Limosilactobacillus fermentum</i>, <i>Lactiplantibacillus pentosus</i> and <i>Lactiplantibacillus</i> sp. Furthermore, these isolates were evaluated by <i>in vitro, viz.</i>, survival in gastrointestinal tract, antibiotic susceptibility, antimicrobial activity, cell surface characteristics, and haemolytic activity. All eight isolates demonstrated strong adherence and prevented pathogen penetration into HT-29 cells, indicating potential of the bacteria to scale up industrial level production of milk products for lactose intolerants.</p>","PeriodicalId":8863,"journal":{"name":"Biomedical reports","volume":"18 3","pages":"23"},"PeriodicalIF":2.3,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/38/b3/br-18-03-01605.PMC9945298.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9358044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Experimental conditions and protein markers for redifferentiation of human coronary artery smooth muscle cells.","authors":"Ryota Shinozaki, Ryoji Eguchi, Ichiro Wakabayashi","doi":"10.3892/br.2023.1606","DOIUrl":"https://doi.org/10.3892/br.2023.1606","url":null,"abstract":"<p><p>A phenotype switch from contractile type to proliferative type of arterial smooth muscle cells is known as dedifferentiation, but to the best of our knowledge, little is known about redifferentiation of coronary artery smooth muscle cells. The purpose of the present study was to determine <i>in vitro</i> culture conditions for inducing redifferentiation of coronary artery smooth muscle cells. In addition, the present study aimed to determine protein markers for detection of redifferentiated arterial smooth muscle cells. Human coronary artery smooth muscle cells (HCASMCs) were cultured in the presence or absence of growth factors, including epidermal growth factor, fibroblast growth factor-B and insulin. Protein expression and migration activity of HCASMCs were evaluated using western blotting and migration assay, respectively. In HCASMCs 5 days after 100% confluency, expression levels of α-smooth muscle actin (α-SMA), calponin, caldesmon and SM22α were significantly increased, while expression levels of proliferation cell nuclear antigen (PCNA) and S100A4 and migration activity were significantly decreased, compared with the corresponding levels just after reaching 100% confluency, indicating that redifferentiation occurred. Redifferentiation was also induced in a low-density culture of HCASMCs in the medium without growth factors. When the culture medium for confluent cells was replaced daily with fresh medium, the expression levels of α-SMA, caldesmon, SM22α, PCNA and S100A4 and migration activity were not significantly different but the calponin expression was significantly increased compared with the levels in dedifferentiated cells just after reaching 100% confluency. Thus, redifferentiation was induced in HCASMCs by deprivation of growth factors from culture medium. The results suggested that α-SMA, caldesmon and SM22α, but not calponin, are markers of redifferentiation of HCASMCs.</p>","PeriodicalId":8863,"journal":{"name":"Biomedical reports","volume":"18 3","pages":"24"},"PeriodicalIF":2.3,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/76/3c/br-18-03-01606.PMC9944247.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9358045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Biomedical reportsPub Date : 2023-02-14eCollection Date: 2023-03-01DOI: 10.3892/br.2023.1607
Laura Grosu, Alin Ionut Grosu, Dana Crisan, Alexandru Zlibut, Lacramioara Perju-Dumbrava
{"title":"Parkinson's disease and cardiovascular involvement: Edifying insights (Review).","authors":"Laura Grosu, Alin Ionut Grosu, Dana Crisan, Alexandru Zlibut, Lacramioara Perju-Dumbrava","doi":"10.3892/br.2023.1607","DOIUrl":"10.3892/br.2023.1607","url":null,"abstract":"<p><p>Parkinson's disease (PD) is one of the most common neurodegenerative illnesses, and is a major healthcare burden with prodigious consequences on life-quality, morbidity, and survival. Cardiovascular diseases are the leading cause of mortality worldwide and growing evidence frequently reports their co-existence with PD. Cardiac dysautonomia due to autonomic nervous system malfunction is the most prevalent type of cardiovascular manifestation in these patients, comprising orthostatic and postprandial hypotension, along with supine and postural hypertension. Moreover, many studies have endorsed the risk of patients with PD to develop ischemic heart disease, heart failure and even arrhythmias, but the underlying mechanisms are not entirely clear. As importantly, the medication used in treating PD, such as levodopa, dopamine agonists or anticholinergic agents, is also responsible for cardiovascular adverse reactions, but further studies are required to elucidate the underlying mechanisms. The purpose of this review was to provide a comprehensive overview of current available data regarding the overlapping cardiovascular disease in patients with PD.</p>","PeriodicalId":8863,"journal":{"name":"Biomedical reports","volume":"18 3","pages":"25"},"PeriodicalIF":2.3,"publicationDate":"2023-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/7b/0e/br-18-03-01607.PMC9944619.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9358046","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Biomedical reportsPub Date : 2023-02-06eCollection Date: 2023-03-01DOI: 10.3892/br.2023.1603
Benjamin Bartlett, Silvia Lee, Herbert P Ludewick, Teck Siew, Shipra Verma, Grant Waterer, Vicente F Corrales-Medina, Girish Dwivedi
{"title":"A multiple comorbidities mouse lung infection model in <i>ApoE</i>‑deficient mice.","authors":"Benjamin Bartlett, Silvia Lee, Herbert P Ludewick, Teck Siew, Shipra Verma, Grant Waterer, Vicente F Corrales-Medina, Girish Dwivedi","doi":"10.3892/br.2023.1603","DOIUrl":"10.3892/br.2023.1603","url":null,"abstract":"<p><p>Acute pneumonia is characterised by a period of intense inflammation. Inflammation is now considered to be a key step in atherosclerosis progression. In addition, pre-existing atherosclerotic inflammation is considered to play a role in pneumonia progression and risk. In the present study, a multiple comorbidities murine model was used to study respiratory and systemic inflammation that results from pneumonia in the setting of atherosclerosis. Firstly, a minimal infectious dose of <i>Streptococcus pneumoniae</i> (TIGR4 strain) to produce clinical pneumonia with a low mortality rate (20%) was established. C57Bl/6 <i>ApoE</i> <sup>-/-</sup> mice were fed a high-fat diet prior to administering intranasally 10<sup>5</sup> colony forming units of TIGR4 or phosphate-buffered saline (PBS). At days 2, 7 and 28 post inoculation (PI), the lungs of mice were imaged by magnetic resonance imaging (MRI) and positron emission tomography (PET). Mice were euthanised and investigated for changes in lung morphology and changes in systemic inflammation using ELISA, Luminex assay and real-time PCR. TIGR4-inoculated mice presented with varying degrees of lung infiltrate, pleural effusion and consolidation on MRI at all time points up to 28 days PI. Moreover, PET scans identified significantly higher FDG uptake in the lungs of TIGR4-inoculated mice up to 28 days PI. The majority (90%) TIGR4-inoculated mice developed pneumococcal-specific IgG antibody response at 28 days PI. Consistent with these observations, TIGR4-inoculated mice displayed significantly increased inflammatory gene expression [interleukin (IL)-1β and IL-6] in the lungs and significantly increased levels of circulating inflammatory protein (CCL3) at 7 and 28 days PI respectively. The mouse model developed by the authors presents a discovery tool to understand the link between inflammation related to acute infection such as pneumonia and increased risk of cardiovascular disease observed in humans.</p>","PeriodicalId":8863,"journal":{"name":"Biomedical reports","volume":"18 3","pages":"21"},"PeriodicalIF":2.3,"publicationDate":"2023-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/b6/28/br-18-03-01603.PMC9944256.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10783345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}