1.Transforming growth factor beta/Smad signaling pathway and targeted therapy of keloid scars
Siqi YAO ; Wenzheng LI ; Hong WANG
Chinese Journal of Tissue Engineering Research 2024;28(16):2619-2624
BACKGROUND:There are many studies focusing on keloid scars,but the pathogenesis is not fully understood.In recent years,there have been some new research advances in the pathogenesis of keloids,including transforming growth factor-β(TGF-β)/Smad signaling pathway,ischemic hypoxia,hypoxia-inducible factor 1(HIF-1),and mitogen-activated protein kinase(MAPK)pathway.The TGF-β/Smad pathway is now more clearly studied,and activation of the TGF-β/Smad pathway promotes the development of keloid scars. OBJECTIVE:To review the TGF-β/Smad signaling pathway and evaluate the main therapeutic strategies targeting this pathway,with the aim of contributing to the development of more effective clinical treatments. METHODS:PubMed and Web of Science,CNKI and WanFang databases were searched by computer for relevant literature published from January 2017 to April 2023 with the search terms of"keloid,fibroblasts,TGF-β/Smad,extracellular matrix,collagen,treatment measures"in English and Chinese.Seventy-two articles were finally included according to the inclusion and exclusion criteria. RESULTS AND CONCLUSION:The mechanism of TGF-β/Smad signaling pathway in the occurrence and development of keloids is summarized:TGF-β1 and TGF-β2 are overexpressed in keloids,while TGF-β3 shows antifibrotic effects.Smad2/3 and Smad1/5/8 are combined with Smad4 to form a complex that enters the nucleus and plays a fibrotic role,while Smad6/7 can inhibit keloid hyperplasia.The TGF-β/Smad signaling pathway is currently the most clearly studied pathway in keloids,and there are many pathways targeted to inhibit the activation of this pathway,which can inhibit the occurrence and development of keloids to a greater extent.Currently,there is no single clinical gold standard treatment for keloids,and inhibition of the TGF-β/Smad pathway alone cannot completely inhibit the development of keloids.A comprehensive consideration of the association between all systemic systems and keloids is needed.Although many promising targets have been identified in the fibrosis cascade,more research is needed to translate this into targeted therapies in the clinic.
2.Network Correlation Analysis Between Components of Shuanghuanglian Injection and Allergy-like Targets
Weilong ZHANG ; Hong HE ; Ru QIAO ; Peng HE ; Wenjiao LI ; Liangqi ZHANG ; Xiaoxuan LIU ; Siqi HUANG ; Xue PAN ; Fuyuan HE
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(19):190-197
ObjectiveBased on the network pharmacology system and quantitative spectroscopy of traditional Chinese medicine(TCM) compounds, a topological network analysis method with equilibrium constant as the core was established to further explore the interaction between allergenic components and their network targets in Shuanghuanglian injection(SHLI), in order to provide new ideas and experimental basis for identifying and screening potential allergens of SHLI. MethodAfter one week of adaptive feeding, 72 SPF-grade SD male rats were randomly divided into blank group, SHLI standard group, Lonicerae Japonicae Flos(LJF) group, Scutellariae Radix(SR) group, Forsythiae Fructus(FF) group, and 7 groups of SHLI matching groups(groups 1-7), with 6 rats in each group. Rats in each group were administered the drug intravenously and blood samples were taken after steady state, high performance liquid chromatography(HPLC) characterization profiles of the testing drugs and plasma components in each group were established, and the peak area changes of the drugs and plasma components in each group were calculated after the component groups were classified. Enzyme-linked immunosorbent assay(ELISA) was used to determine the changes of immunoglobulin E(IgE), histamine(HIS), tryptase(TPS), total complement(CH50) and terminal complement complex(C5b-9) in animal blood samples. MATLAB R2020b v9.9.0 software was used to calculate the network balance constants of the component groups with the targets, and the eigenvalues of the matrices composed of network equilibrium constants were calculated and ranked according to their values. ResultELISA results showed that, compared with the blank group, groups 1-3 could significantly increase the IgE level, groups 1-2, groups 4-6 and SHLI standard group could significantly increase the HIS level, group 4 could significantly increase the CH50 level, groups 1, 3-4, LJF group and FF group could significantly increase the TPS level, SR group could significantly increase the C5b-9 level, and the differences were all statistically significant(P<0.05). According to the retention time of chromatographic peaks, it was classified into 6 component groups from C1 to C6 by HPLC. The order of the network balance constants of each component group was C6>C4>C1>C5>C3>C2, indicating that C6 had the greatest effect on the allergic reaction, and was most likely to be the allergen. The sequence of eigenvalues was C2>C5b-9>C3>C1>CH50>C6>C5>IgE>TPS>C4>HIS, indicating that component group C2 had the greatest contribution to the whole network. ConclusionBased on the correlation analysis of SHLI component group and allergy-like target network, this study clarified that component group C6 may be a potential allergen in SHLI, and the component group C2 may be a key node in the mechanism of drug action, which can provide new strategies and methods for the screening of allergens in TCM injections.
3.Immunological effects of human tonsil organoids after influenza virus infection
Siqi LI ; Yun XU ; Hong LI ; Lei FEI ; Xiaoyong HUANG ; Yongwen CHEN
Journal of Army Medical University 2024;46(9):978-987
Objective To establish a human tonsil organoid model and investigate the immunological effects of this tonsil organoid infected by influenza virus.Methods Human tonsil tissue removed by adenoid hypertrophy surgery were subjected to gradient centrifugation,and then the obtain cells were cultured in vitro with using a 2.5D-Transwell chamber in combination with IL-2 and B cell activating factor(Baff)to construct a human tonsil organoid.Single cell transcriptome sequencing(scRNA-seq)was used to analyze the distribution of influenza virus receptors in different cell subsets of the tonsil organoid.Immunofluorescence assay and flow cytometry were applied to detect the immunological effects of the tonsil organoid in 48 h after influenza virus infection.Results The tonsil organoids were established successfully using this 2.5D-Transwell culture technique.scRNA-seq analysis showed that the receptors for influenza virus were extensively distributed in nearly all of cell subsets of tonsil organoids.In 48 h after influenza virus infection,the tonsil organoids could generate a large amount of plasma cells and memory B cells to produce specific IgG antibodies.In addition,direct infection of the virus promoted the production of TNF-α and IL-2 from CD8+T cells and the secretion of TNF-α,IFN-γ and IL-2 by CD4+T cells.Conclusion The tonsil organoids can be established successfully and reach maturity at about the 6th day after culture.The receptors for influenza virus are widely distributed in human tonsil organoids.Influenza virus directly infects human T cells,leading to T cell activation and cytokine releasing.Moreover,influenza virus infection also promotes B cells differentiate into plasma cells and induce the secretion of IgG as well as the formation of memory B cells.
4.New trends in the development of artificial intelligence-assisted cerebrospinal fluid morphologic examination
Hui ZHAO ; Kun CHEN ; Hong LYU ; Siqi HAN ; Yunzhuan ZHAO ; Ping HAN ; Bei SONG ; Yang LIU ; Yishan HUO ; Ming GUAN ; Guojun ZHANG
Chinese Journal of Laboratory Medicine 2024;47(5):480-485
Cerebrospinal fluid morphology examination is an important method of diagnosing central nervous system diseases, but manual microscopy has shortcomings such as low efficiency, long staff training period, and poor homogeneity of test results. In recent years, the application of artificial intelligence in the medical field has developed rapidly, providing new technical means for cerebrospinal fluid morphology examination. In the future, AI-assisted morphological examination of cerebrospinal fluid will not only realize digitalization and networking, but also improve the level and efficiency of intelligent diagnosis of cerebrospinal fluid morphology, which has a broad application prospect in the intelligent assisted diagnosis of cerebrospinal fluid.
5.Phytotherapeutic BS012 and Its Active Component Ameliorate Allergic Asthma via Inhibition of Th2-Mediated Immune Response and Apoptosis
Siqi ZHANG ; Joonki KIM ; Gakyung LEE ; Hong Ryul AHN ; Yeo Eun KIM ; Hee Ju KIM ; Jae Sik YU ; Miso PARK ; Keon Wook KANG ; Hocheol KIM ; Byung Hwa JUNG ; Sung Won KWON ; Dae Sik JANG ; Hyun Ok YANG
Biomolecules & Therapeutics 2024;32(6):744-758
Asthma is a chronic inflammatory disorder of the lungs that results in airway inflammation and narrowing. BS012 is an herbal remedy containing Asarum sieboldii, Platycodon grandiflorum, and Cinnamomum cassia extracts. To elucidate the anti-asthma effect of BS012, this study analyzed the immune response, respiratory protection, and changes in metabolic mechanisms in an ovalbumininduced allergic asthma mouse model. Female BALB/c mice were exposed to ovalbumin to induce allergic asthma. Bronchoalveolar lavage fluid and plasma were analyzed for interleukin and immunoglobulin E levels. Histological analyses of the lungs were performed to measure morphological changes. Apoptosis-related mediators were assayed by western blotting. Plasma and lung tissue metabolomic analyses were performed to investigate the metabolic changes. A T-helper-2-like differentiated cell model was used to identify the active components of BS012. BS012 treatment improved inflammatory cell infiltration, mucus production, and goblet cell hyperplasia in lung tissues. BS012 also significantly downregulated ovalbumin-specific immunoglobulin E in plasma and T-helper-2-specific cytokines, interleukin-4 and -5, in bronchoalveolar lavage fluid. The lungs of ovalbumin-inhaled mice exhibited nerve growth factor-mediated apoptotic protein expression, which was significantly attenuated by BS012 treatment. Ovalbumin-induced abnormalities in amino acid and lipid metabolism were improved by BS012 in correlation with its anti-inflammatory properties and normalization of energy metabolism. Additionally, the differentiated cell model revealed that N-isobutyl-dodecatetraenamide is an active component that contributes to the anti-allergic properties of BS012. The current findings demonstrate the anti-allergic and respiratory protective functions of BS012 against allergic asthma, which can be considered a therapeutic candidate.
6.Phytotherapeutic BS012 and Its Active Component Ameliorate Allergic Asthma via Inhibition of Th2-Mediated Immune Response and Apoptosis
Siqi ZHANG ; Joonki KIM ; Gakyung LEE ; Hong Ryul AHN ; Yeo Eun KIM ; Hee Ju KIM ; Jae Sik YU ; Miso PARK ; Keon Wook KANG ; Hocheol KIM ; Byung Hwa JUNG ; Sung Won KWON ; Dae Sik JANG ; Hyun Ok YANG
Biomolecules & Therapeutics 2024;32(6):744-758
Asthma is a chronic inflammatory disorder of the lungs that results in airway inflammation and narrowing. BS012 is an herbal remedy containing Asarum sieboldii, Platycodon grandiflorum, and Cinnamomum cassia extracts. To elucidate the anti-asthma effect of BS012, this study analyzed the immune response, respiratory protection, and changes in metabolic mechanisms in an ovalbumininduced allergic asthma mouse model. Female BALB/c mice were exposed to ovalbumin to induce allergic asthma. Bronchoalveolar lavage fluid and plasma were analyzed for interleukin and immunoglobulin E levels. Histological analyses of the lungs were performed to measure morphological changes. Apoptosis-related mediators were assayed by western blotting. Plasma and lung tissue metabolomic analyses were performed to investigate the metabolic changes. A T-helper-2-like differentiated cell model was used to identify the active components of BS012. BS012 treatment improved inflammatory cell infiltration, mucus production, and goblet cell hyperplasia in lung tissues. BS012 also significantly downregulated ovalbumin-specific immunoglobulin E in plasma and T-helper-2-specific cytokines, interleukin-4 and -5, in bronchoalveolar lavage fluid. The lungs of ovalbumin-inhaled mice exhibited nerve growth factor-mediated apoptotic protein expression, which was significantly attenuated by BS012 treatment. Ovalbumin-induced abnormalities in amino acid and lipid metabolism were improved by BS012 in correlation with its anti-inflammatory properties and normalization of energy metabolism. Additionally, the differentiated cell model revealed that N-isobutyl-dodecatetraenamide is an active component that contributes to the anti-allergic properties of BS012. The current findings demonstrate the anti-allergic and respiratory protective functions of BS012 against allergic asthma, which can be considered a therapeutic candidate.
7.Phytotherapeutic BS012 and Its Active Component Ameliorate Allergic Asthma via Inhibition of Th2-Mediated Immune Response and Apoptosis
Siqi ZHANG ; Joonki KIM ; Gakyung LEE ; Hong Ryul AHN ; Yeo Eun KIM ; Hee Ju KIM ; Jae Sik YU ; Miso PARK ; Keon Wook KANG ; Hocheol KIM ; Byung Hwa JUNG ; Sung Won KWON ; Dae Sik JANG ; Hyun Ok YANG
Biomolecules & Therapeutics 2024;32(6):744-758
Asthma is a chronic inflammatory disorder of the lungs that results in airway inflammation and narrowing. BS012 is an herbal remedy containing Asarum sieboldii, Platycodon grandiflorum, and Cinnamomum cassia extracts. To elucidate the anti-asthma effect of BS012, this study analyzed the immune response, respiratory protection, and changes in metabolic mechanisms in an ovalbumininduced allergic asthma mouse model. Female BALB/c mice were exposed to ovalbumin to induce allergic asthma. Bronchoalveolar lavage fluid and plasma were analyzed for interleukin and immunoglobulin E levels. Histological analyses of the lungs were performed to measure morphological changes. Apoptosis-related mediators were assayed by western blotting. Plasma and lung tissue metabolomic analyses were performed to investigate the metabolic changes. A T-helper-2-like differentiated cell model was used to identify the active components of BS012. BS012 treatment improved inflammatory cell infiltration, mucus production, and goblet cell hyperplasia in lung tissues. BS012 also significantly downregulated ovalbumin-specific immunoglobulin E in plasma and T-helper-2-specific cytokines, interleukin-4 and -5, in bronchoalveolar lavage fluid. The lungs of ovalbumin-inhaled mice exhibited nerve growth factor-mediated apoptotic protein expression, which was significantly attenuated by BS012 treatment. Ovalbumin-induced abnormalities in amino acid and lipid metabolism were improved by BS012 in correlation with its anti-inflammatory properties and normalization of energy metabolism. Additionally, the differentiated cell model revealed that N-isobutyl-dodecatetraenamide is an active component that contributes to the anti-allergic properties of BS012. The current findings demonstrate the anti-allergic and respiratory protective functions of BS012 against allergic asthma, which can be considered a therapeutic candidate.
8.Analysis of intermittent photic stimulation in children′s video electroencephalography
Yu DENG ; Qiao HU ; Jin CHEN ; Siqi HONG ; Xinghui LAN
Chinese Journal of Applied Clinical Pediatrics 2023;38(2):136-139
Objective:To explore the value of intermittent photic stimulation (IPS) in children′s video electroencephalography (EEG).Methods:The data of 8 994 children aged 1 to 18 years, who received IPS in the video EEG examination at the Liangjiang Campus of the Children′s Hospital of Chongqing Medical University from March 2021 to March 2022, were analyzed retrospectively.Patients were divided into non-epilepsy group and confirmed or suspected epilepsy group.Their IPS responses, clinical and EEG characteristics were collected.Categorical variables were expressed using frequencies and percentages.The relationship between IPS response and age was determined by Chi- square test or Fisher′ s exact probability method. Results:The median age of 8 994 children was 6.3 years.There were 2 310 (25.7%) children in the non-epileptic group, including 1 364 (59.0%) males and 946 (41.0%) females.There were 6 684 (74.3%) children in the confirmed or suspected epileptic group, including 3 842 (57.5%) males and 2 842 (42.5%) females.In the non-epileptic group, 141 cases (6.1%) had IPS photo-driving responses, and 1 case had photo paroxysmal response (PPR). In the confirmed or suspected epilepsy group, IPS photo-driving responses (2.4%) occurred in 160 cases, PPR (1.2%) in 82 cases, photo convulsion responses(0.3%) in 18 cases, and asymmetric photo-driving responses (0.2%) in 14 cases.The IPS photosensitivity responses varied among children of different ages, sexes, epileptic discharge types and seizure types in the confirmed or suspected epilepsy group.The children aged 6 to 18 years showed significantly stronger photosensitivity responses than those aged 1 to <6 years ( P<0.001). The photosensitivity activity in females was 1.9 times higher than that in males.The photosensitivity activity in patients with generalized discharges was 1.7 times more intense than that in patients with focal discharges.The photosensitivity reaction in patients with photo convulsive generalized seizures was 2.5 times stronger than that in patients with focal seizures. Conclusions:Routine standardized IPS is important for the detection of photosensitivity in children diagnosed or suspected with epilepsy.It can effectively guide the medical practice.
9.The mediating effect of depression between social capital and cognitive function of the elderly in nursing institutions
Siqi LI ; Tieying SHI ; Hong GUO ; Jiayu WANG ; Wanqing LI
Chinese Journal of Practical Nursing 2023;39(11):838-844
Objective:To investigate the mechanism of depression between social capital and cognitive function of the elderly in nursing institutions, and provide new ideas for improving the cognitive function of the elderly.Methods:This study was a cross-sectional survey. Using the convenient sampling method to collect the general information questionnaire, the Geriatric Depression Scale (GDS), Social Capital Scale and Montreal Cognitive Assessment Scale (MoCA) of 218 elderly people from three elderly nursing institutions including Shenyang Health Care Centre, Songpu Nursing Home and Colourful Sunshine City Pension Service Centre in Shenyang from July 2020 to January 2021.Results:A total of 218 questionnaires were distributed and 202 valid questionnaires were recovered. The effective recovery rate was 92.7%. The scores of the cognitive function, depression and social capital of the elderly were (23.60 ± 4.25), (6.38 ± 4.35) and (75.41 ± 8.61). Depression scores were negatively correlated with social capital scores and cognitive function scores ( r = - 0.401, - 0.481, both P<0.05); there was a positive correlation between social capital scores with cognitive function scores ( r = 0.338, P<0.05). There was a mediating effect of depression between social capital and cognitive function, accounting for 42.1%. Conclusions:While improving the cognitive function of the elderly in nursing institutions by improving the level of social capital, it is necessary to pay attention to the mediatingeffect of depression, strengthen the psychological counseling of the elderly, promote mental health, and further reduce the occurrence and development of cognitive decline in the elderly.
10.Progress in the application of assessment scales associated with activities of daily living in the disease-modifying treatments of spinal muscular atrophy
International Journal of Pediatrics 2023;50(6):370-373
Spinal muscular atrophy(SMA) is a serious neuromuscular degenerative disease that severely impairs the quality of life for patients and entire families.The emergence of disease-modifying treatments such as nusinersen and risdiplam has gradually changed the natural course of SMA patients.It is particularly important to include the activities of daily living(ADL) ability reported by patients or caregivers in the comprehensive assessment of SMA patients.There are many ADL-related assessment tools, and studies have found that disease-modifying treatments can somewhat improve the ADL ability of SMA children.This article reviews the progress on the effect of disease-modifying treatments on ADL in SMA patients, which can provide a reference for exploring more comprehensive and effective assessment tools and treatment decision-making in subsequent clinical practice.

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