摘要：
MiRNAs are small endogenous non-coding RNAs that have been demonstrated to be involved in post-transcriptional gene silencing, regulating a number of metabolic functions in the human body, including immune response, cellular physiology, organ development, angiogenesis, signaling, and other aspects. As popular molecules that have been studied in previous years, given their extensive regulatory functions, miRNAs hold considerable promise as non-invasive biomarkers. Sexually transmitted infections(STIs) are still widespread and have an adverse effect on individuals, communities, and society worldwide. miRNAs in the regulatory networks are generally involved in their molecular processes of formation and development. In this review, we discuss the value of miRNAs for the diagnosis of STIs.
作者机构：
[Ma, Pengcheng; Liang, Shengxing; Xu, Jun] Southern Med Univ, Sch Publ Hlth, Guangzhou, Peoples R China.;[Ma, Pengcheng; Li, Zeyang; Xu, Jun] Southern Med Univ, Sch Hlth Management, Guangzhou, Peoples R China.;[Ma, Pengcheng; Xu, Jun] Southern Med Univ, Nanfang Hosp, Guangzhou, Peoples R China.;[Liu, Li; He, Jingzhe; Wang, Jiaren; Li, Ruining; Zeng, Lin; Xiao, Lushan; Li, Yan; Hong, Chang; Cui, Hao] Southern Med Univ, Nanfang Hosp, Hepatol Unit, Guangdong Prov Key Lab Viral Hepatitis Res, Guangzhou, Peoples R China.;[Liu, Li; He, Jingzhe; Wang, Jiaren; Li, Ruining; Zeng, Lin; Xiao, Lushan; Li, Yan; Hong, Chang; Cui, Hao] Southern Med Univ, Nanfang Hosp, Dept Infect Dis, Guangzhou, Peoples R China.
通讯机构：
[Xiao, LS ; Xu, J ; Liu, L] S;Southern Med Univ, Nanfang Hosp, Guangzhou 510515, Peoples R China.;Southern Med Univ, Nanfang Hosp, Hepatol Unit, Guangdong Prov Key Lab Viral Hepatitis Res, Guangzhou 510515, Peoples R China.;Southern Med Univ, Nanfang Hosp, Dept Infect Dis, Guangzhou 510515, Peoples R China.
关键词：
Mendelian randomization;cholelithiasis;hand grip strength;sarcopenia;skeletal muscle index;walking pace
摘要：
Cholelithiasis is a common digestive disease that drives a myriad of adverse complications. The correlation between sarcopenia and various digestive disorders has been extensively researched, whereas its association with cholelithiasis remains unreported. We aimed to investigate the association through prospective and Mendelian randomization (MR) analyses and establish a quantitative score reflecting the impact of sarcopenia-related markers on cholelithiasis. The prospective study involved 448 627 participants from the UK Biobank. Cox proportional hazard models were employed to investigate the correlation between sarcopenia-related markers and cholelithiasis. To quantitatively assess cholelithiasis risk, the SARCHO score was derived from a multivariable Cox model. Bidirectional two-sample MR analysis was conducted to validate the causal association. A total of 16 738 individuals developed cholelithiasis during a median follow-up of 12 years. Hazard ratios (HRs) of cholelithiasis decreased stepwise over skeletal muscle index tertiles (highest tertile: reference; middle tertile: 1.23, p < .001; lowest tertile: 1.33, p < .001). The tertiles of grip strength showed a similar pattern. Individuals with slow walking pace had a higher risk of cholelithiasis compared to those with normal walking pace (HR 1.23; p < .001). Our SARCHO score better quantifies the risk of cholelithiasis. MR analysis showed a causal relationship between muscle mass and cholelithiasis (OR 0.81; p < .001). No causal effect of cholelithiasis on lean mass was observed. Prospective and MR analyses have consistently demonstrated an increased risk of cholelithiasis in individuals with decreased muscle mass. Additionally, SARCHO score further quantified the cholelithiasis occurrence risk. These findings provide compelling evidence for muscle strengthening in preventing cholelithiasis.
摘要：
Microbial degradation is a cost-effective and environmentally friendly method for removing microcystin-LR (MC-LR). However, the application of free bacteria has limitations due to low operational stability and difficulties in recovery. In a previous study, our group successfully isolated a highly efficient MC-LR-degrading bacterium, Sphingopyxis sp. YF1, from Taihu. To enhance its practical potential in addressing MC-LR-contaminated water pollution, a novel biological material named polyacrylonitrile-based carbon fiber @Sphingopyxis sp. YF1 (PAN-CF@YF1) was synthesized. The immobilization conditions of strain Sphingopyxis sp. YF1 on PAN-CF surfaces were optimized using Box–Behnken design and response surface methodology (RSM), which turned out to be an optimal pH of 7.6 for the culture medium, a ratio of 0.038 g of supporting materials per 100 mL of culture media, and an incubation time of 53.4 h. The resultant PAN-CF@YF1 showed a great degradation effect both for low and high concentrations of MC-LR and exhibited satisfactory cyclic stability (85.75% after six cycles). Moreover, the application of PAN-CF@YF1 in the bioreactors demonstrated effective and sustainable MC-LR removal, with a removal efficiency of 78.83% after three consecutive treatments. Therefore, PAN-CF@YF1 with high degradation activity, environmental compatibility, straightforward preparation, and recyclability shows significant application potential for the bioremediation of MC-LR-contaminated water bodies.
摘要：
Corticosterone (CORT) damages hippocampal neurons as well as induces neuroinflammation. The tricarboxylic acid cycle metabolite itaconate has an anti-inflammatory role. Necroptosis is a form of programmed cell death, also known as inflammatory cell death. Menin is a multifunctional scaffold protein, which deficiency aggravates neuroinflammation. In this study, we explored whether itaconate inhibits CORT-induced neuroinflammation as well as necroptosis and further investigated the mediatory role of Menin in this protective effect of itaconate by using an exposure of CORT to HT22 cells (a hippocampal neuronal cell line). The viability of HT22 cells was examined by the cell counting kit 8 (CCK-8). The morphology of HT22 cells was observed by transmission electron microscope (TEM). The expressions of necroptosis-related proteins (p-RIP1/RIP1, p-RIP3/RIP3, and p-MLKL/MLKL) were evaluated by western blotting. The contents of inflammatory factors were detected by an enzyme-linked immunosorbent assay (ELISA) kit. Our results showed that CORT increases the contents of pro-inflammatory factors (IL-1β, TNF-α) as well as decreases the contents of anti-inflammatory factors (IL-4, IL-10) in HT22 cells. We also found that CORT increases the expressions of necroptosis-related proteins (p-RIP1/RIP1, p-RIP3/RIP3, and p-MLKL/MLKL) and decreases the cell viability in HT22 cells, indicating that CORT induces necroptosis in HT22 cells. Itaconate improves CORT-induced neuroinflammation and necroptosis. Furthermore, itaconate upregulates the expression of Menin in CORT-exposed HT22 cells. Importantly, silencing Menin abolishes the antagonistic effect of itaconate on CORT-induced necroptosis and neuroinflammation. In brief, these results indicated that itaconate protects HT22 cells against CORT-induced neuroinflammation and necroptosis via upregulating Menin.
摘要：
Abnormal activation of macrophage and gut Bacteroides fragilis (BF) are the important induction factors in the occurrence of type 2 diabetes (T2D) and vascular complications. However, it remains unknown whether BF involves in macrophage polarization. In this study, we found that BF extracellular vesicles (EV) can be uptaken by macrophage. BF-EV promote macrophage M1/M2 polarization significantly, and increase Sting expression significantly. Bioinformatics analysis found that Sema7a is an important gene involving in macrophage polarization. The expression of Sema7a can be induced by BF-EV and can be inhibited after C-176 treated. The inhibition expression of Sema7a prevent BF-EV to induce macrophage polarization. Further analysis reveals that there is no direct interaction between Sting and Sema7a, but Sgpl1 can interact with Sting or Sema7a. BF-EV promote the expression of Sgpl1, which the phenomenon can be inhibited after C-176 treated. Importantly, overexpression of Sgpl1 reversed the effect of C-176 for Sema7a expression, while inhibit Sema7a expression has limitation influence for Sting and Sgpl1 expression. In conclusion, this study confirms that Sting-Sgpl1-Sema7a is a key mechanism by which BF-EV regulates macrophage polarization.
期刊：
Indian Journal of Hematology and Blood Transfusion,2024年:1-10 ISSN：0971-4502
通讯作者：
Deng, J
作者机构：
[Li, Yike] Hunan Normal Univ, Changsha Hosp Maternal & Child Hlth Care, Dept Clin Lab, Changsha 410007, Hunan, Peoples R China.;[Deng, Jun] Univ South China, Affiliated Changsha Cent Hosp, Hengyang Med Sch, Dept Clin Lab, Changsha 410004, Hunan, Peoples R China.
通讯机构：
[Deng, J ] U;Univ South China, Affiliated Changsha Cent Hosp, Hengyang Med Sch, Dept Clin Lab, Changsha 410004, Hunan, Peoples R China.
关键词：
ABO hemolytic disease of the newborn;L score;Differential diagnosis;Blood routine examination;Early diagnosis
摘要：
Purpose This study aimed to evaluate the diagnostic efficacy of the L score, a novel scoring system, in distinguishing between ABO hemolytic disease of the newborn (ABO-HDN) and non-hemolytic disease of newborn hyperbilirubinemia (NHDNH).Methods A cross-sectional prospective study was conducted to assess the effectiveness of the L score in distinguishing between ABO-HDN (n = 118) and NHDNH (n = 213). Blood routine examination results were collected, and relevant statistical analyses were performed to identify clinically significant parameters. Binary logistic regression analysis was employed to assess the relationship between the L score and the development of these conditions, considering relevant variables.Results Our study identified the red blood cell count, mean corpuscular volume, red blood cell distribution width-coefficient of variation, and red blood cell distribution width-standard deviation as independent risk factors for distinguishing ABO-HDN from other high bilirubinemia conditions (P < 0.001). The L score demonstrated superior predictive performance for ABO-HDN, exhibiting an area under the curve (AUC) of 0.746, with an optimal cutoff value of - 3.0816. The RBC-L score exhibited superior predictive performance (z: 5.596, P < 0.0001) compared to the single-factor RBC indicator, indicating its efficacy in accurately identifying the desired outcome.Conclusion The L score represents a valuable tool for predicting neonatal hyperbilirubinemia and hemolytic disease, facilitating differentiation, and guiding early intervention for improved outcomes. Further research is warranted to validate and expand the applicability of the L score in clinical practice.
期刊：
FRONTIERS IN IMMUNOLOGY,2024年15:1289644 ISSN：1664-3224
通讯作者：
Li, ZY
作者机构：
[Li, Zhongyu; Fang, Chunxia; Li, ZY; Wang, Xinglv; Wu, Hongrong] Univ South China, Inst Pathogen Biol, Hengyang Med Coll, Sch Nursing,Hunan Prov Key Lab Special Pathogens P, Hengyang, Peoples R China.
通讯机构：
[Li, ZY ] U;Univ South China, Inst Pathogen Biol, Hengyang Med Coll, Sch Nursing,Hunan Prov Key Lab Special Pathogens P, Hengyang, Peoples R China.
关键词：
Chlamydia trachomatis;immune evasion;innate immune cells;innate immunity;survival and growth
摘要：
Chlamydia trachomatis, is a kind of obligate intracellular pathogen. The removal of C. trachomatis relies primarily on specific cellular immunity. It is currently considered that CD4(+) Th1 cytokine responses are the major protective immunity against C. trachomatis infection and reinfection rather than CD8(+) T cells. The non-specific immunity (innate immunity) also plays an important role in the infection process. To survive inside the cells, the first process that C. trachomatis faces is the innate immune response. As the "sentry" of the body, mast cells attempt to engulf and remove C. trachomatis. Dendritic cells present antigen of C. trachomatis to the "commanders" (T cells) through MHC-I and MHC-II. IFN-γ produced by activated T cells and natural killer cells (NK) further activates macrophages. They form the body's "combat troops" and produce immunity against C. trachomatis in the tissues and blood. In addition, the role of eosinophils, basophils, innate lymphoid cells (ILCs), natural killer T (NKT) cells, γδT cells and B-1 cells should not be underestimated in the infection of C. trachomatis. The protective role of innate immunity is insufficient, and sexually transmitted diseases (STDs) caused by C. trachomatis infections tend to be insidious and recalcitrant. As a consequence, C. trachomatis has developed a unique evasion mechanism that triggers inflammatory immunopathology and acts as a bridge to protective to pathological adaptive immunity. This review focuses on the recent advances in how C. trachomatis evades various innate immune cells, which contributes to vaccine development and our understanding of the pathophysiologic consequences of C. trachomatis infection.
期刊：
JOURNAL OF INFECTIOUS DISEASES,2024年 ISSN：0022-1899
通讯作者：
Qu, XW
作者机构：
[Zheng, Xingyu; Liu, Fen; Qu, Xiaowang; Wu, Chanfeng; Lu, Rui; Xie, Tianyi; Liu, Wenpei] Univ South China, Coll Basic Med, Hengyang Med Sch, Hengyang, Peoples R China.;[Zheng, Xingyu; Chen, Jun; Wang, You; Liu, Fen; Tang, Jinyong; Pan, Dong; Tang, Yinggen; Wu, Chanfeng; Teng, Shishan; Peng, Liting; Lu, Rui; He, Rongzhang; Hu, Yabin; Rong, Xiaohan; Xie, Tianyi] Univ South China, Peoples Hosp Chenzhou 1, Translat Med Inst, Hengyang Med Sch, Chenzhou, Peoples R China.;[Wang, You] Univ South China, Sch Publ Hlth, Hengyang, Peoples R China.;[Qu, Xiaowang] Univ South China, Coll Basic Med, Hengyang Med Sch, 28 West Changsheng Rd, Hengyang 421001, Peoples R China.
通讯机构：
[Qu, XW ] U;Univ South China, Coll Basic Med, Hengyang Med Sch, 28 West Changsheng Rd, Hengyang 421001, Peoples R China.
关键词：
COVID-19;Circulating T-Follicular Helper Cell;Neutralizing Antibody;Regulatory T cell
摘要：
Regulatory T (Treg) cells are involved in the antiviral immune response in patients with coronavirus disease 2019 (COVID-19); however, whether Treg cells are involved in the neutralizing antibody (nAb) response remains unclear. Here, we found that individuals who recovered from mild but not severe COVID-19 had significantly greater frequencies of Treg cells and lower frequencies of CXCR3+ circulating T follicular helper (cTfh) cells than healthy controls. Furthermore, the frequencies of Treg and CXCR3+ cTfh cells were negatively and positively correlated with the nAb responses, respectively, and Treg cells was inversely associated with CXCR3+ cTfh cells in individuals who recovered from mild COVID-19 but not in those with severe disease. Mechanistically, Treg cells inhibited memory B-cell differentiation and antibody production by limiting the activation and proliferation of cTfh cells, especially CXCR3+ cTfh cells, and functional molecule expression. This study provides novel insight showing that mild COVID-19 elicits concerted nAb responses, which are shaped by both Treg and Tfh cells.
摘要：
BACKGROUND: With cancer-associated fibroblasts (CAFs) as the main cell type, the rich myxoid stromal components in chordoma tissues may likely contribute to its development and progression. METHODS: Single-cell RNA sequencing (scRNA-seq), spatial transcriptomics, bulk RNA-seq, and multiplexed quantitative immunofluorescence (QIF) were used to dissect the heterogeneity, spatial distribution, and clinical implication of CAFs in chordoma. RESULTS: We sequenced here 72 097 single cells from 3 primary and 3 recurrent tumor samples, as well as 3 nucleus pulposus samples as controls using scRNA-seq. We identified a unique cluster of CAF in recurrent tumors that highly expressed hypoxic genes and was functionally enriched in endoplasmic reticulum stress (ERS). Pseudotime trajectory and cell communication analyses showed that this ERS-CAF subpopulation originated from normal fibroblasts and widely interacted with tumoral and immune cells. Analyzing the bulk RNA-seq data from 126 patients, we found that the ERS-CAF signature score was associated with the invasion and poor prognosis of chordoma. By integrating the results of scRNA-seq with spatial transcriptomics, we demonstrated the existence of ERS-CAF in chordoma tissues and revealed that this CAF subtype displayed the most proximity to its surrounding tumor cells. In subsequent QIF validation involving 105 additional patients, we confirmed that ERS-CAF was abundant in the chordoma microenvironment and located close to tumor cells. Furthermore, both ERS-CAF density and its distance to tumor cells were correlated with tumor malignant phenotype and adverse patient outcomes. CONCLUSIONS: These findings depict the CAF landscape for chordoma and may provide insights into the development of novel treatment approaches.
作者机构：
[Zhang, Jing; He, Rongfang; Li, Jianping; Li, JP; Lan, Zhihua] Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Pathol, Hengyang, Peoples R China.
通讯机构：
[Li, JP ] U;Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Pathol, Hengyang, Peoples R China.
关键词：
axillary lymph node;breast cancer patients;fine-needle aspiration;GATA-3 immunocytochemistry
摘要：
BACKGROUND: Ultrasound-guided fine-needle aspiration cytology (FNAC) is a routine preoperative method for evaluating suspicious axillary lymph nodes (ALNs) in patients with breast cancer. However, a range of reasons such as morphological pitfalls, technical artifacts, and sampling errors restrict the sensitivity and accuracy of FNAC. This retrospective study investigated the diagnostic value of GATA-binding protein 3 (GATA-3) immunocytochemistry for FNAC. METHODS: Breast cancer patients who underwent preoperative FNAC for suspicious ALNs, relevant GATA-3 immunocytochemistry, and postoperative status of ALNs were reviewed from the period of March 2020 to February 2022. Altogether, 102 patients were included in the study. FNAC material smears stained with hematoxylin and eosin was initially assessed by two cytopathologists and categorized into five groups: nondiagnostic, negative, atypical, suspicious, and positive for malignancy. Only group of cells positive for malignancy was considered positive. For each case, two selected slides were digitized (whole slide imaged) at ×40 magnification and decolored for GATA-3 immunocytochemistry. The expression of GATA-3 was scored ranging from 0 to 9 (Score ≥3: Positive, Score ≤2: Negative). If either FNAC or GATA-3 immunocytochemistry was positive or the combined test positive, then the case was considered positive. The sensitivity, specificity, and accuracy of FNAC, GATA-3 immunocytochemistry, and combined FNAC/GATA-3 immunocytochemistry were analyzed by χ(2) and Fisher's tests. RESULTS: The mean age of the study participants was 50.62 (ranging: 30-73 years). Invasive breast carcinoma (not otherwise specified) accounted for most histological subtypes, and grade 2 was the leading Nottingham grade. Sixteen cases directly underwent mastectomy while the other 86 patients had neoadjuvant therapy. A more serious diagnosis was made based on GATA-3 detection in 22.5% (n = 23) of 102 cases. Of the 23 cases, metastasis was confirmed by GATA-3 detection in 21 cases, and an uncertain diagnosis was ascertained based on GATA-3 immunocytochemistry in 2 with nondiagnostic FNAC results. The sensitivity (77/87, 88.5%) of GATA-3 detection for distinguishing malignancies from benign lesions was higher than that of FNAC alone (62/87, 71.3%) (p < .05). CONCLUSIONS: GATA-3 immunocytochemistry exhibited high diagnostic efficacy in distinguishing malignant breast cancer cells. Moreover, combined FNAC and GATA-3 immunocytochemistry achieved optimal results in terms of reducing the false-negative rate and promoting accuracy.
期刊：
Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy,2024年17:343-362 ISSN：1178-7007
通讯作者：
Wang, J;Kuang, TD
作者机构：
[Deng, Wenying; Wang, Jing; Zhao, Zeyi] Univ South China, Sch Basic Med Sci, Hengyang 421001, Hunan, Peoples R China.;[Zou, Tao] Univ South China, Affiliated Hosp 1, Dept Cardiovasc Med, Hengyang 421001, Hunan, Peoples R China.;[Kuang, Tongdong] Guilin Med Univ, Guangxi Key Lab Diabetic Syst Med, Guilin 541199, Guangxi, Peoples R China.
通讯机构：
[Kuang, TD ] G;[Wang, J ] U;Univ South China, Sch Basic Med Sci, Hengyang 421001, Hunan, Peoples R China.;Guilin Med Univ, Guangxi Key Lab Diabetic Syst Med, Guilin 541199, Guangxi, Peoples R China.
关键词：
Fc protein;albumin;diabetes mellitus;fusion protein;glucagon-like peptide 1 receptor agonists;transferrin
摘要：
Diabetes mellitus (DM) is a chronic metabolic disease characterized by elevated blood glucose levels, resulting in multi-organ dysfunction and various complications. Fusion proteins can form multifunctional complexes by combining the target proteins with partner proteins. It has significant advantages in improving the performance of the target proteins, extending their biological half-life, and enhancing patient drug compliance. Fusion protein-based drugs have emerged as promising new drugs in diabetes therapeutics. However, there has not been a systematic review of fusion protein-based drugs for diabetes therapeutics. Hence, we conducted a comprehensive review of published literature on diabetic fusion protein-based drugs for diabetes, with a primary focus on immunoglobulin G (IgG) fragment crystallizable (Fc) region, albumin, and transferrin (TF). This review aims to provide a reference for the subsequent development and clinical application of fusion protein-based drugs in diabetes therapeutics.
摘要：
BACKGROUND: Endothelial-mesenchymal transition (EndMT) induced by low shear stress plays an important role in the development of atherosclerosis. However, little is known about the correlation between hydrogen sulfide (H(2)S), a protective gaseous mediator in atherosclerosis and the process of EndMT. METHODS: We constructed a stable low-shear-stress-induced(2dyn/cm(2)) EndMT model, acombined with the pretreatment method of hydrogen sulfide slow release agent(GYY4137). The level of MEST was detected in the common carotid artery of ApoE(-/-) mice with local carotid artery ligation. The effect of MEST on atherosclerosis development in vivo was verified using ApoE(-/-) mice were given tail-vein injection of endothelial-specific overexpressed and knock-down MEST adeno-associated virus (AAV). RESULTS: These findings confirmed that MEST is up-regulated in low-shear-stress-induced EndMT and atherosclerosis. In vivo experiments showed that MEST gene overexpression significantly promoted EndMT and aggravated the development of atherosclerotic plaques and MEST gene knockdown significantly inhibited EndMT and delayed the process of atherosclerosis. In vitro, H(2)S inhibits the expression of MEST and EndMT induced by low shear stress and inhibits EndMT induced by MEST overexpression. Knockdown of NFIL3 inhibit the up regulation of MEST and EndMT induced by low shear stress in HUVECs. CHIP-qPCR assay and Luciferase Reporter assay confirmed that NFIL3 binds to MEST DNA, increases its transcription and H(2)S inhibits the binding of NFIL3 and MEST DNA, weakening NFIL3's transcriptional promotion of MEST. Mechanistically, H(2)S increased the sulfhydrylation level of NFIL3, an important upstream transcription factors of MEST. In part, transcription factor NFIL3 restrain its binding to MEST DNA by sulfhydration. CONCLUSIONS: H(2)S negatively regulate the expression of MEST by sulfhydrylation of NFIL3, thereby inhibiting low-shear-stress-induced EndMT and atherosclerosis.
摘要：
BACKGROUND: The DLG3 gene encodes disks large membrane-associated guanylate kinase scaffold protein 3, which plays essential roles in the clustering of N-methyl-D-aspartate receptors (NMDARs) at excitatory synapses. Previously, DLG3 has been identified as the causative gene of X-linked intellectual developmental disorder-90 (XLID-90; OMIM# 300850). This study aims to explore the phenotypic spectrum of DLG3 and the genotype-phenotype correlation. METHODS: Trios-based whole-exome sequencing was performed in patients with epilepsy of unknown causes. To analyze the genotype-phenotype correlations, previously reported DLG3 variants were systematically reviewed. RESULTS: DLG3 variants were identified in seven unrelated cases with epilepsy. These variants had no hemizygous frequencies in controls. All variants were predicted to be damaging by silico tools and alter the hydrogen bonds with surrounding residues and/or protein stability. Four cases mainly presented with generalized seizures, including generalized tonic-clonic and myoclonic seizures, and the other three cases exhibited secondary generalized tonic-clonic seizures and focal seizures. Multifocal discharges were recorded in all cases during electroencephalography monitoring, including the four cases with generalized discharges initially but multifocal discharges after drug treating. Protein-protein interaction network analysis revealed that DLG3 interacts with 52 genes with high confidence, in which the majority of disease-causing genes were associated with a wide spectrum of neurodevelopmental disorder (NDD) and epilepsy. Three patients with variants locating outside functional domains all achieved seizure-free, while the four patients with variants locating in functional domains presented poor control of seizures. Analysis of previously reported cases revealed that patients with non-null variants presented higher percentages of epilepsy than those with null variants, suggesting a genotype-phenotype correlation. SIGNIFICANCE: This study suggested that DLG3 variants were associated with epilepsy with/without NDD, expanding the phenotypic spectrum of DLG3. The observed genotype-phenotype correlation potentially contributes to the understanding of the underlying mechanisms driving phenotypic variation.
作者：
Vu, Nguyen Trung;Kim, Hyeongsoon;Lee, Soohong;Hwang, In Sun;Kwon, Choon-Tak;...
期刊：
Applied Microbiology and Biotechnology,2024年108(1):17-17 ISSN：0175-7598
通讯作者：
Zeng, YH
作者机构：
[Vu, Nguyen Trung; Lee, Soohong; Kwon, Choon-Tak] Kyung Hee Univ, Dept Green Bio Sci, Yongin 17104, South Korea.;[Hwang, In Sun; Kim, Hyeongsoon; Oh, Chang-Sik] Seoul Natl Univ, Res Inst Agr & Life Sci, Seoul 08826, South Korea.;[Oh, Chang-Sik] Seoul Natl Univ, Coll Agr & Life Sci, Dept Agr Biotechnol, Seoul 08826, South Korea.;[Oh, Chang-Sik] Seoul Natl Univ, Plant Genom & Breeding Inst, Seoul 08826, South Korea.
通讯机构：
[Oh, CS ] S;Seoul Natl Univ, Res Inst Agr & Life Sci, Seoul 08826, South Korea.;Seoul Natl Univ, Coll Agr & Life Sci, Dept Agr Biotechnol, Seoul 08826, South Korea.;Seoul Natl Univ, Plant Genom & Breeding Inst, Seoul 08826, South Korea.
关键词：
Cyclophilin A;Apoptosis;Disease development;Therapeutic target for diseases
摘要：
Cyclophilin A (CypA), the first member of cyclophilins, is distributed extensively in eukaryotic and prokaryotic cells, primarily localized in the cytoplasm. In addition to acting as an intracellular receptor for cyclosporin A (CSA), CypA plays a crucial role in diseases such as aging and tumorigenesis. Apoptosis, a form of programmed cell death, is able to balance the rate of cell viability and death. In this review, we focus on the effects of CypA on apoptosis and the relationship between specific mechanisms of CypA promoting or inhibiting apoptosis and diseases, including tumorigenesis, cardiovascular diseases, organ injury, and microbial infections. Notably, the process of CypA promoting or inhibiting apoptosis is closely related to disease development. Finally, future prospects for the association of CypA and apoptosis are discussed, and a comprehensive understanding of the effects of CypA on apoptosis in relation to diseases is expected to provide new insights into the design of CypA as a therapeutic target for diseases.
关键词：
botulinum toxin;botulinum toxin type A;cancer;pain
摘要：
BACKGROUND: Botulinum toxin type A (BTX-A) is a potential treatment for cancer pain. This study aimed to analyze the effectiveness and safety of BTX-A in the treatment of pain after cancer treatment. PATIENTS AND METHODS: Systematic searches of PubMed, Cochrane Library, and Embase databases were conducted. Randomized controlled trials evaluating the efficacy and safety of BTX-A compared with either placebo or active treatment in patients with pain after cancer treatment were included. The outcomes included pain intensity, quality of life, and adverse events. RESULTS: This systematic review included four studies of which 2 were included in the meta-analysis. Compared with a placebo, BTX-A injection in patients with pain after cancer treatment had a clinically meaningful reduction in self-reported pain post-treatment (mean difference=-1.79 [95% confidence interval (CI), -2.14 to -1.43], P＜0.00001, I²=0%). CONCLUSION: This systematic review and meta-analysis demonstrated that BTX-A is safe and effective for pain relief in patients with pain after cancer treatment.
作者机构：
[Kuang, Wending; Zhang, Yang; Yuan, Mei; Chen, Gang; Luo, Bang; Wang, Yuzheng; Chen, G] Univ South China, Affiliated Hosp 2, Hengyang Med Sch, Dept Neurol, Hengyang 421001, Hunan, Peoples R China.;[Chen, Liucui] Univ South China, Hengyang Med Sch, Sch Pharmaceut Sci, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Chen, G ] U;Univ South China, Affiliated Hosp 2, Hengyang Med Sch, Dept Neurol, Hengyang 421001, Hunan, Peoples R China.
关键词：
Early neurological deterioration;Acute ischemic stroke;Intravenous thrombolysis;Nomogram;Risk prediction
摘要：
OBJECTIVES: Intravenous thrombolysis therapy (IVT) with recombinant tissue plasminogen activator has proven to be a beneficial treatment for acute ischemic stroke (AIS) patients when administered within 4.5h after a stroke. This study aimed to investigate an available and inexpensive predictive tool for early neurological deterioration in AIS. METHODS: Patients admitted to our department with acute stroke who were given IVT with recombinant tissue plasminogen activator within 4.5h of stroke onset were included in the study. The NIH stroke scale (NIHSS) was used to assess patients' neurological state prior to IVT and for 24h after. Early neurological deterioration was defined as occurring if the NIHSS total score increased by≥4 or the NIHSS individual score increased by≥2 compared to baseline. Patients were randomly assigned to training or validation cohorts. RESULTS: Of the 266 AIS patients receiving IVT who were screened, 217 were deemed eligible for the study. Multivariate logistic regression analysis identified smoking history, NIHSS score, homocysteine level, and neutrophil to lymphocyte ratio as independent factors for predicting early neurological deterioration. ROC analysis was used to assess the quality of the resulting nomogram. The AUC for the training dataset was 0.826 (95% CI, 0.719-0.932), and for the validation dataset was 0.887 (95% CI, 0.763-1.000). CONCLUSION: The robustness of this nomogram suggests that it may be a reliable tool for evaluating the progression of AIS after IVT.
作者机构：
[Dou, Chengyun; Xie, Xia] Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Infect Dis, Hengyang 421001, Hunan, Peoples R China.;[Zhu, Hongbo] Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Med Oncol, Hengyang 421001, Hunan, Peoples R China.;[Cao, Chuangjie; Cao, CJ; Huang, Cuiqin] Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Pathol, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Cao, CJ ] U;Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Pathol, Hengyang 421001, Hunan, Peoples R China.
摘要：
Nonalcoholic fatty liver disease (NAFLD) is a prevalent global liver disorder, posing substantial health risks. Britanin, a bioactive sesquiterpene lactone extracted from Inula japonica, has demonstrated antidiabetic, hypolipidemic, and hepatoprotective attributes. Nonetheless, the precise impact of Britanin on NAFLD and the intricate biological mechanisms underpinning this interaction remain unexplored. We integrated computer-aided methods to unearth shared biological targets and signaling pathways associated with both Britanin and NAFLD. A network was constructed by compiling putative targets associated with Britanin and NAFLD, followed by a stringent screening of key targets and mechanisms through protein-protein interaction analysis along with GO and KEGG pathway enrichment analyses. Molecular docking was integrated as an evaluation tool, culminating in the identification of HO-1 as the pivotal therapeutic target, showcasing a satisfactory binding affinity. The primary mechanism was ascribed to biological processes and pathways linked to oxidative stress, as evidenced by the outcomes of enrichment analyses. Of these, the AMPK/SREBP1c pathway assumed centrality in this mechanism. Furthermore, in vivo experiments substantiated that Britanin effectively curtailed NAFLD development by ameliorating liver injury, modulating hyperlipidemia and hepatic lipid accumulation, and alleviating oxidative stress and apoptosis. In summary, this study demonstrates the potential of Britanin as a promising therapeutic drug against NAFLD.
摘要：
The immune response to Mycoplasma pneumoniae infection plays a key role in clinical symptoms. Previous investigations focused on the pro-inflammatory effects of leukocytes and the pivotal role of epithelial cell metabolic status in finely modulating the inflammatory response have been neglected. Herein, we examined how glycolysis in airway epithelial cells is affected by M. pneumoniae infection in an in vitro model. Additionally, we investigated the contribution of ATP to pulmonary inflammation. Metabolic analysis revealed a marked metabolic shift in bronchial epithelial cells during M. pneumoniae infection, characterized by increased glucose uptake, enhanced aerobic glycolysis, and augmented ATP synthesis. Notably, these metabolic alterations are orchestrated by adaptor proteins, MyD88 and TRAM. The resulting synthesized ATP is released into the extracellular milieu via vesicular exocytosis and pannexin protein channels, leading to a substantial increase in extracellular ATP levels. The conditioned medium supernatant from M. pneumoniae-infected epithelial cells enhances the secretion of both interleukin (IL)-1β and IL-18 by peripheral blood mononuclear cells, partially mediated by the P2X7 purine receptor (P2X7R). In vivo experiments confirm that addition of a conditioned medium exacerbates pulmonary inflammation, which can be attenuated by pre-treatment with a P2X7R inhibitor. Collectively, these findings highlight the significance of airway epithelial aerobic glycolysis in enhancing the pulmonary inflammatory response and aiding pathogen clearance.
期刊：
Biosensors and Bioelectronics,2024年249:116002 ISSN：0956-5663
通讯作者：
Wang, WG
作者机构：
[Tan, Ting; Wang, Weiguo; Yang, Lin; Cao, Qianqian; Liu, Aizhe; Chen, Lijing; Deng, Yuqian] Univ South China, Inst Pharm & Pharmacol, Hengyang 421000, Hunan, Peoples R China.;[Li, Ranhui; Duan, Minghui] Univ South China, Inst Pathogen Biol, Hengyang Med Sch, Hengyang 421000, Hunan, Peoples R China.
通讯机构：
[Wang, WG ] U;Univ South China, Inst Pharm & Pharmacol, Hengyang 421000, Hunan, Peoples R China.
关键词：
Ferrous disulfide;Nickel doping;Oxidase mimics;Total antioxidant capacity;Transition metal sulfides
摘要：
The development of nanomaterials that mimic oxidase-like activities has recently attracted an increasing amount of attention. Obtaining highly active and cost-effective oxidase mimics has posed a significant challenge in this area of research. In this study, we successfully synthesized nickel-doped ferrous disulfide nanocubes (Ni-FeS(2)) via a facile one-step method. Characterization by scanning electron microscopy (SEM) and transmission electron microscopy (TEM) revealed that Ni was predominantly distributed within the surface layer of the Ni-FeS(2) nanocubes. The incorporation of nickel in density functional theory (DFT) calculations effectively reduced the d-band center of Fe, resulting in weakened adsorption to intermediates and thereby enhancing its catalytic efficiency. Moreover, we developed a novel approach based on Ni-FeS(2) (the Ni-FeS(2) method) for detecting reducing substances, which exhibited good sensitivity toward ascorbic acid (AA), glutathione (GSH), and cysteine (Cys). Remarkably, the established Ni-FeS(2) method was successfully employed for in vitro assessment of total antioxidant capacity (TAC) in cellular and organ samples, thereby enabling discrimination between normal, senescent, and malignant cells as well as distinguishing among healthy liver tissue, cancerous liver tissue, and metastatic organs.
