Rosmarinic acid suppresses the progression of COPD via Syk by modulating airway inflammation and epithelial apoptosis in vivo and in vitro.

Rosmarinic acid (RosA), a hydrophilic phenolic compound found in various plants, has several biological effects such as anti-inflammatory and anti-apoptosis activities. However, its potential impact on chronic obstructive pulmonary disease (COPD) and its underlying mechanism has not been investigated. In this study, we explored the potential therapeutic effects and mechanism of RosA on COPD airway inflammation and alveolar epithelial apoptosis in vivo and in vitro. Our data suggested that RosA may be a therapeutic candidate for COPD with low toxicity. The corresponding mechanism lies in its anti-inflammatory effect on macrophage and bronchial epithelial cells, as well as protective effect on lung epithelial apoptosis via the jointly cross-target spleen tyrosine kinase (Syk).

[Traditional Chinese medicine and active ingredients regulate M1/M2 macrophage polarization balance to treat chronic obstructive pulmonary disease: a review].

Chronic obstructive pulmonary disease(COPD) is a progressive lung dysfunction(disease) caused by long-term inhalation of toxic particles, especially smoking. The continued exposure to harmful substances triggers an abnormal inflammatory response, which causes permanent damage to the respiratory system, ultimately leading to irreversible pathological changes. Lung macrophages(LMs) are key innate immune effectors involved in the recognition, phagocytosis, and clearance of pathogens, as well as in the processing of inhaled hazardous particulate matter(e. g., cigarette smoke and particulate matter). LMs are polarized toward the M1 or M2 phenotype in response to the activation of inflammatory mediators to exert pro-/anti-inflammatory effects, respectively, thus being involved in the pulmonary parenchymal damage(emphysema) and repair(airway remodeling) throughout the process of COPD.In addition, they are responsible for phagocytosis and clearance of apoptotic or necrotic tissue cells, which helps to maintain the stability of the microenvironment in the lungs of COPD patients. Modern studies have revealed that macrophage polarization plays a pivotal role in the pathogenesis and development of COPD and is considered a potential target for treating COPD because of its ability to reduce airway inflammation, inhibit tissue remodeling, and combat oxidative stress. In recent years, traditional Chinese medicine(TCM) and its active ingredients have become a hot area in the treatment of COPD by targeting the balance of M1/M2 macrophage polarization. TCM and its active ingredients can intervene in the inflammatory response to promote the repair of the lung tissue in the patients with COPD. This paper reviews the research achievements of TCM and its active ingredients in this field in recent years,aiming to provide a scientific basis and strong support for the precise diagnosis and treatment of COPD.

Exploring the transcriptomic landscape of moyamoya disease and systemic lupus erythematosus: insights into crosstalk genes and immune relationships.

Background: Systemic Lupus Erythematosus (SLE) is acknowledged for its significant influence on systemic health. This study sought to explore potential crosstalk genes, pathways, and immune cells in the relationship between SLE and moyamoya disease (MMD). Methods: We obtained data on SLE and MMD from the Gene Expression Omnibus (GEO) database. Differential expression analysis and weighted gene co-expression network analysis (WGCNA) were conducted to identify common genes. Subsequently, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on these shared genes. Hub genes were further selected through the least absolute shrinkage and selection operator (LASSO) regression, and a receiver operating characteristic (ROC) curve was generated based on the results of this selection. Finally, single-sample Gene Set Enrichment Analysis (ssGSEA) was utilized to assess the infiltration levels of 28 immune cells in the expression profile and their association with the identified hub genes. Results: By intersecting the important module genes from WGCNA with the DEGs, the study highlighted CAMP, CFD, MYO1F, CTSS, DEFA3, NLRP12, MAN2B1, NMI, QPCT, KCNJ2, JAML, MPZL3, NDC80, FRAT2, THEMIS2, CCL4, FCER1A, EVI2B, CD74, HLA-DRB5, TOR4A, GAPT, CXCR1, LAG3, CD68, NCKAP1L, TMEM33, and S100P as key crosstalk genes linking SLE and MMD. GO analysis indicated that these shared genes were predominantly enriched in immune system process and immune response. LASSO analysis identified MPZL3 as the optimal shared diagnostic biomarkers for both SLE and MMD. Additionally, the analysis of immune cell infiltration revealed the significant involvement of activation of T and monocytes cells in the pathogenesis of SLE and MMD. Conclusion: This study is pioneering in its use of bioinformatics tools to explore the close genetic relationship between MMD and SLE. The genes CAMP, CFD, MYO1F, CTSS, DEFA3, NLRP12, MAN2B1, NMI, QPCT, KCNJ2, JAML, MPZL3, NDC80, FRAT2, THEMIS2, CCL4, FCER1A, EVI2B, CD74, HLA-DRB5, TOR4A, GAPT, CXCR1, LAG3, CD68, NCKAP1L, TMEM33, and S100P have been identified as key crosstalk genes that connect MMD and SLE. Activation of T and monocytes cells-mediated immune responses are proposed to play a significant role in the association between MMD and SLE.

Delayed simvastatin treatment improves neurological recovery after cryogenic traumatic brain injury through downregulation of ELOVL1 by inhibiting mTOR signaling.

Statins are well-tolerated and widely available lipid-lowering medications with neuroprotective effects against traumatic brain injury (TBI). However, whether delayed statin therapy starting in the subacute phase promotes recovery after TBI is unknown. Elongation of the very long-chain fatty acid protein 1 (ELOVL1) is involved in astrocyte-mediated neurotoxicity, but its role in TBI and the relationship between ELOVL1 and statins are unclear. We hypothesized that delayed simvastatin treatment promotes neurological functional recovery after TBI by regulating the ELOVL1-mediated production of very long-chain fatty acids (VLCFAs). ICR male mice received daily intragastric administration of 1, 2 or 5mg/kg simvastatin on Days 1-14, 3-14, 5-14, or 7-14 after cryogenic TBI (cTBI). The results showed that simvastatin promoted motor functional recovery in a dose-dependent manner, with a wide therapeutic window of at least 7 days postinjury. Meanwhile, simvastatin inhibited astrocyte and microglial overactivation and glial scar formation, and increased total dendritic length, neuronal complexity and spine density on day 14 after cTBI. The up-regulation of ELOVL1 expression and saturated VLCFAs concentrations in the cortex surrounding the lesion caused by cTBI was inhibited by simvastatin, which was related to the inhibition of the mTOR signaling. Overexpression of ELOVL1 in astrocytes surrounding the lesion using HBAAV2/9-GFAP-m-ELOVL1-3xFlag-EGFP partially attenuated the benefits of simvastatin. These results showed that delayed simvastatin treatment promoted functional recovery and brain tissue repair after TBI through the downregulation of ELOVL1 expression by inhibiting mTOR signaling. Astrocytic ELOVL1 may be a potential target for rehabilitation after TBI.

Amelioration of immunoglobulin A vasculitis by suppression of the pathological expansion of T follicular helper 17 cells.

The main pathogenic features of immunoglobulin A vasculitis (IgAV) are overactive B cells and elevated production of IgA, which requires help from T follicular helper 17 (Tfh17) cells. To evaluate the pathological role of Tfh17 cells in IgAV, we investigated the mechanism responsible for Tfh17 differentiation and explored how to ameliorate IgAV by modulating Tfh17 generation. Peripheral blood mononuclear cells from IgAV patients were analyzed by flow cytometry. In vitro culture was performed to assess the modulation of cytokine-induced phenotypes. IgAV rats were used to explore the therapeutic effects of IL-6 blockade and the regulatory functions of IL-6 in Tfh17 cells. Serum cytokine and IgA levels were measured by ELISA while histopathological changes were evaluated by H&E,PAS or immunofluorescence staining. Frequency of CD4+CXCR5+CCR6+ Tfh17 cells were increased in IgAV patients and associated with disease severity. There was also a significant infiltration of Tfh17 cells in the kidney of human IgAV nephritis patients. IL-6 promoted the dendritic cell production of TGF-ß and Tfh17 differentiation. In IgAV rats, the in vivo blockade of IL-6 signaling inhibited Tfh17 differentiation, resulting in reduction of the germinal center and IgA production. Suppression of Tfh17 cells using IL-6 blockade greatly ameliorated clinical symptoms such as hemorrhagic rash and bloody stool and decreased IgA deposition and mesangial proliferation in the kidney in IgAV rats. Our findings suggest that suppression of Tfh17 differentiation can alleviate IgA-mediated vasculitis and may permit the development of tailored medicines for treating IgAV.

Novel collagen gradient membranes with multiphasic structures: Preparation, characterization, and biocompatibility.

Scaffolds with multiphasic structures are considered to be superior for guided tissue regeneration. Two types of tilapia skin collagen gradient membranes (stepped gradient and linear gradient) with multiphasic structures were prepared by controlling the collagen concentrations and the freezing rates. The results revealed that collagen gradient membranes were more capable of guiding tissue regeneration compared to homogeneous membranes. These two gradient membranes featured a dense outer layer and a loose inner layer, with good mechanical properties as indicated by tensile strengths of more than 250 Kpa and porosities exceeding 85 %. Additionally, these membranes also showed good hydrophilicity and water absorption, with an inner layer contact angle of less than 91° and a water absorption ratio greater than 40 times. Furthermore, the multiphasic scaffolds were proved to be biocompatible by the acute toxicity assay, the intradermal irritation test and so on. Gradient membranes could effectively promote the adhesion and proliferation of fibroblasts and osteoblasts, through elevating the TGF-ß/Smad signaling pathway by TGF-ß and Smads, and activating the Wnt/ß-catenin signaling pathway by LRP5 and ß-catenin, similar to homogenous membranes. Therefore, collagen gradient membranes from tilapia skin show important application value in guiding tissue regeneration.

Accumulation of mitochondrial DNA with a point mutation in tRNALeu(UUR) gene induces brain dysfunction in mice.

Brain functions are mediated via the complex interplay between several complex factors, and hence, identifying the underlying cause of an abnormality within a certain brain region can be challenging. In mitochondrial disease, abnormalities in brain function are thought to be attributed to accumulation of mitochondrial DNA (mtDNA) with pathogenic mutations; however, only few previous studies have directly demonstrated that accumulation of mutant mtDNA induced abnormalities in brain function. Herein, we examined the effects of mtDNA mutations on brain function via behavioral analyses using a mouse model with an A2748G point mutation in mtDNA tRNALeu(UUR). Our results revealed that mice with a high percentage of mutant mtDNA showed a characteristic trend toward reduced prepulse inhibition and memory-dependent test performance, similar to that observed in psychiatric disorders, such as schizophrenia; however, muscle strength and motor coordination were not markedly affected. Upon examining the hippocampus and frontal lobes of the brain, mitochondrial morphology was abnormal, and the brain weight was slightly reduced. These results indicate that the predominant accumulation of a point mutation in the tRNALeu(UUR) gene may affect brain functions, particularly the coordination of sensory and motor functions and memory processes. These abnormalities probably caused by both direct effects of accumulation of the mutant mtDNA in neuronal cells and indirect effects via changes of systemic extracellular environments. Overall, these findings will lead to a better understanding of the pathogenic mechanism underlying this complex disease and facilitate the development of optimal treatment methods.

Gd-EOB-DTPA enhanced MRI nomogram model to differentiate hepatocellular carcinoma and focal nodular hyperplasia both showing iso- or hyperintensity in the hepatobiliary phase.

BACKGROUND: To develop and validate a nomogram model based on Gd-EOB-DTPA enhanced MRI for differentiation between hepatocellular carcinoma (HCC) and focal nodular hyperplasia (FNH) showing iso- or hyperintensity in the hepatobiliary phase (HBP). METHODS: A total of 75 patients with 49 HCCs and 26 FNHs randomly divided into a training cohort (n = 52: 34 HCC; 18 FNH) and an internal validation cohort (n = 23: 15 HCC; 8 FNH). A total of 37 patients (n = 37: 25 HCC; 12 FNH) acted as an external test cohort. The clinical and imaging characteristics between HCC and FNH groups in the training cohort were compared. The statistically significant parameters were included into the FAE software, and a multivariate logistic regression classifier was used to identify independent predictors and establish a nomogram model. Receiver operating characteristic (ROC) curves were used to evaluate the prediction ability of the model, while the calibration and decision curves were used for model validation. Subanalysis was used to compare qualitative and quantitative characteristics of patients with chronic hepatitis and cirrhosis between the HCC and FNH groups. RESULTS: In the training cohort, gender, age, enhancement rate in the arterial phase (AP), focal defects in uptake were significant predictors for HCC showing iso- or hyperintensity in the HBP. In the training cohort, area under the curve (AUC), sensitivity and specificity of the nomogram model were 0.989(95%CI: 0.967-1.000), 97.1% and 94.4%. In the internal validation cohort, the above three indicators were 0.917(95%CI: 0.782-1.000), 93.3% and 87.5%. In the external test cohort, the above three indicators were 0.960(95%CI: 0.905-1.000), 84.0% and 100.0%. The results of subanalysis showed that age was the independent predictor in the patients with chronic hepatitis and cirrhosis between HCC and FNH groups. CONCLUSIONS: Gd-EOB-DTPA enhanced MRI nomogram model may be useful for discriminating HCC and FNH showing iso- or hyperintensity in the HBP before surgery.

Stability of oil-in-water emulsion and immunomodulating activity in S180 tumor-bearing mice.

The stability and nutritional integrity of emulsions are susceptible to various factors including thermal treatment, solid-liquid ratio, and sterilization. In this study, the physicochemical stability and immunomodulatory activities of an oil-in-water emulsion containing immune peptides (TUFSE) were assessed through particle size, zeta potential, related cytokines, and so on. When the temperature was 70°C and a solid-liquid ratio of 1:4, the emulsion revealed stability at high-pressure homogenization, with the small particle size. The loss rates of vitamins were 8.57%-62.26% in 6 months at 25°C. After treatment with cyclophosphamide (CTX), lymphocyte proliferation activity in TUFSE-H group increased (p < 0.05), and immune globulin levels were notably elevated (p < 0.05) in TUFSE groups compared to model group. It confirms the parameters of the emulsion, suggesting its ability to be prepared with minimal vitamin loss while simultaneously improving the disease status in CTX-treated tumor-bearing mice. It shows potential as an immune-enhancing supplement with significant potential value. PRACTICAL APPLICATION: This study validated the parameters of the oil-in-water emulsion and showed that it can be stably prepared with minor vitamin loss while simultaneously improving the disease status in CTX-treated tumor-bearing mice. TUFSE-H group exhibited a notable increase in lymphocytes proliferation activity, whereas serum cytokines and immune globulin levels were elevated compared to MC group, indicating its potential as an immune-enhancing supplement with substantial value.

Investigation of tumour environments through advancements in microtechnology and nanotechnology.

Cancer has a significant negative social and economic impact on both developed and developing countries. As a result, understanding the onset and progression of cancer is critical for developing therapies that can improve the well-being and health of individuals with cancer. With time, study has revealed, the tumor microenvironment has great influence on this process. Micro and nanoscale engineering techniques can be used to study the tumor microenvironment. Nanoscale and Microscale engineering use Novel technologies and designs with small dimensions to recreate the TME. Knowing how cancer cells interact with one another can help researchers develop therapeutic approaches that anticipate and counteract cancer cells' techniques for evading detection and fighting anti-cancer treatments, such as microfabrication techniques, microfluidic devices, nanosensors, and nanodevices used to study or recreate the tumor microenvironment. Nevertheless, a complicated action just like the growth and in cancer advancement, and their intensive association along the environment around it that has to be studied in more detail.

Botulinum toxin type A inhibits the formation of hypertrophic scar through the JAK2/STAT3 pathway.

Hypertrophic scar (HS) is a fibrous proliferative disorder that occurs in the dermis after skin injury. Studies have confirmed that Botulinum toxin type A (BTA) is effective in scar prevention and treatment. However, the specific mechanism remains uncertain. Hypertrophic scar fibroblasts (HSFs) and normal skin fibroblasts (NSFs) from the skin tissues of HS patients were isolated and cultured. Western blot analysis was conducted to measure the expression of JAK2/STAT3 pathway-related proteins. HSFs were treated with the JAK2 inhibitor (AG490) or agonist (C-A1). The CCK-8 assay, EdU staining, scratch-wound assay and transwell assay were used to examine the biological properties of HSFs. Western blot, immunofluorescence, and Sirius red staining were used to assess the fibrosis of HSFs. Additionally, a mouse full-thickness wound model was constructed to investigate the role of BTA in wound healing. The results showed that the JAK2 and STAT3 phosphorylation levels were markedly increased in HS tissues and HSFs. AG490 treatment reduced cell viability, proliferation and migration capacity, and inhibited the fibrosis of HSFs, whereas C-A1 treatment had the opposite effect. BTA treatment inhibited the JAK2/STAT3 pathway. BTA reduced cell viability, proliferation and migration ability, and inhibited the fibrosis of HSFs, while C-A1 intervention weakened the impact of BTA. Meanwhile, BTA promoted wound healing and reduced collagen deposition in vivo. In conclusion, BTA inhibited the JAK2/STAT3 pathway, which in turn hindered the proliferation, migration and fibrosis of HSFs, and promoted wound healing in mice.

Typical structural characteristics and hepatoprotective effects of novel high Fischer ratio oligopeptides from Antarctic krill on acute alcoholic liver injury.

High Fischer ratio oligopeptides derived from Antarctic krill (HFOPs-AK) were screened, and their hepatoprotective effects and potential mechanisms were investigated. Herein, HFOPs-AK, with a Fischer ratio of 29 g/g (40.22 mol/mol) (MW < 1000 Da), were prepared via two-step enzymatic hydrolysis using chymotrypsin and flavourzyme and aromatic amino acid removal. Seventy-eight characteristic peptides were identified from HFOPs-AK through UHPLC-Q/TOF, with peptides containing Leu, Val, or Ile accounting for 79%. High hepatoprotective peptides were purified using GFC and RP-HPLC and identified as SDELGW and LLGWDDM. Furthermore, a murine model of acute liver injury induced by alcohol was successfully established. It was demonstrated that the oral administration of HFOPs-AK (800 mg per kg bw per d) remarkably increased the contents of ADH and ALDH compared with the model group, reaching 3.40 and 5.10 U mg-1 prot, respectively. Further, it was revealed that HFOPs-AK could effectively mitigate hepatic oxidative stress by increasing the levels of GSH-Px (p < 0.01) and decreasing the level of MDA (p < 0.05). Additionally, HFOPs-AK (800 mg per kg bw per d) attenuated liver inflammation by down-regulating the mRNA levels of TNF-α, IL-1ß, and IL-6 by 40.45%, 38.48%, and 35.83%, respectively. Therefore, HFOPs-AK may have the potential as a new nutritional supplement for the treatment of alcoholic liver injury.

Novel EGFR inhibitors against resistant L858R/T790M/C797S mutant for intervention of non-small cell lung cancer.

To overcome C797S mutation, the latest and most common resistance mechanism in the clinical treatment of third-generation EGFR inhibitor, a novel series of substituted 6-(2-aminopyrimidine)-indole derivatives were designed and synthesized. Through the structure-activity relationship (SAR) study, compound 11eg was identified as a novel and potent EGFR L858R/T790M/C797S inhibitor (IC50 = 0.053 µM) but had a weak effect on EGFRWT (IC50 = 1.05 µM). 11eg significantly inhibited the proliferation of the non-small cell lung cancer (NSCLC) cells harboring EGFRL858R/T790M/C797S with an IC50 of 0.052 µM. 11eg also showed potent inhibitory activity against other NSCLC cell lines harboring main EGFR mutants. Furthermore, 11eg exhibited much superior activity in arresting cell cycle and inducing apoptosis of NSCLC cells with mutant EGFRC797S. It blocked cellular EGFR signaling. Importantly, 11eg markedly suppressed the tumor growth in in vivo xenograft mouse model with good safety. Additionally, 11eg displayed good microsomal stability. These results demonstrated the potential of 11eg with novel scaffold as a promising lead compound targeting EGFRC797S to guide in-depth structural optimization.

Effects of compound emulsifiers on the characteristics and stability of nano-emulsions from pollock bones.

To improve the stability of pollock bone broth, compound emulsifiers were employed and evaluated in nano-emulsions from pollock bones (PBNs). The microstructure, creaming index, particle size, zeta potential, and viscosity of PBNs were characterized and the stability of PBNs was investigated. It revealed that the concentration of compound emulsifiers is one of the principal factors for particle size, zeta potential, and viscosity of PBNs, and 0.9% of sodium caseinate and sucrose fatty acid ester (CS-SE) can make the PBN display good stability. Its particle size changed from 81.17 ± 1.33 nm to 19.62 ± 0.21 nm when the temperature ranged from 40 °C to 80 °C, and its creaming index could reach a maximum (90.83%) among all PBNs in 4 months of freeze-thaw assays. PBN stability could be improved by the compound emulsifier (CS-SE), which offers a theoretical basis for the application of pollock bone broth.

Establishment of a normal control model of children's brain 18-fluorodeoxyglucose positron emission tomography and analysis of the changing pattern in patients aged 0-14 years.

Background: It is difficult to obtain 18-fluorodeoxyglucose positron emission tomography (18FDG-PET) data from normal children, and changes in brain metabolism in children due to growth and development are poorly understood. For the first time, we established a normal control model of brain 18FDG-PET in children and evaluated its feasibility. The association of PET with age in children aged 0-14 years was analyzed. This study aimed to establish a normal control model of brain 18FDG-PET in children for the first time and to verify its feasibility, and to analyze the trend of PET with age in children aged 0-14 years. Methods: In this retrospective cohort study, the 18FDG-PET imaging data of patients with no epileptiform discharge involvement contralateral to the epileptogenic zone were consecutively collected from January 2015 to June 2022 according to strictly defined screening criteria. For the normal control data, the hemisphere contralateral to the epileptogenic zone was mirrored and spliced to form an intact brain. The cohort of children aged 0-14 years was divided into 14 groups according age by year. Subsequently, patients who underwent lesionectomy with clear hypometabolism that roughly coincided with the extent of surgical resection were examined. The PET scan was compared with the control model, and the ratio of overlapping parts (hypometabolic areas ∩ surgical resection area) to hypometabolic parts (ROH) was calculated. Multiple regression analysis was performed on the normal control model for every 3- to 4-year age interval. Results: A total of 159 normal control models were established. Five patients were randomly selected to verify the reliability of each yearly model. The average ROH was 0.968. Metabolism increasing with age in the different brain regions was observed at ages 0-2~, 3-5~, and 6-10 years. No age-related metabolic increase or decrease was found in the 10- to 14-year-old group. The metabolism in the 7- to 8-year-old group was higher than that in the 13- to 14-year-old group. Conclusions: With strict screening criteria, the method of mirroring the contralateral hemisphere of the epileptic zone and splicing it into a complete brain as a means of creating a normal control group is feasible. The method offers convenience to the studies that lack healthy pediatric controls. Children under 10 years of age (especially 0-6 years old) experience considerable metabolic changes year on year. After the age of 10 years, the changes in metabolism gradually decrease, and metabolism also slowly decreases. Our findings provide guidance the clinical interpretation of areas with hypometabolism and emphasize the importance of establishing a normal control model of the child's brain, which should not be replaced by an adult model.

Computer-Based Experiment for the Motion of Spring Oscillator on a Linear Air Track Using Ultrasonic Sensor.

In the present paper, an affordable innovative physical experimental equipment consisting of an upper computer, an ultrasonic sensor module, and an Arduino microcontroller has been designed. The relationship between the position of the slider fixed on two springs and time is measured by using the ultrasonic sensor module. A system for slider motion data and image acquisition is constructed by using the LabVIEW interface of Arduino UNO R3. The purpose of this experiment is to demonstrate and interpret the propagation of waves represented by harmonic motion. The spring oscillator system including a slider and two springs is measured and recorded, and the motion can be realized using curve fitting to the wave equation in Sigmaplot. The vibration periods obtained from experimental measurements and curve fitting of the wave equation are 1.130 s and 1.165 s, respectively. The experimental data are in good agreement with the theoretical model. The experimental measurement results show that the maximum kinetic energy is 0.0792 J, the maximum potential energy is 0.0795 J, and the total energy at the position of half the amplitude is 0.0791 J. The results verify the mechanical energy conservation of spring oscillator system in a short time. This self-made instrument has improved the visualization and the automation level of the corresponding experiments.

18F-FDG PET/CT findings of paratesticular alveolar rhabdomyosarcoma.

Rhabdomyosarcoma (RMS) originates from primitive mesenchymal cells and is the most common soft tissue tumor in childhood. 18F-fluoro-deoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) has been reported to be valuable in RMS staging and risk stratification. Paratesticular RMS is a relatively uncommon form of RMS, most of which are of the embryonal histologic type. Paratesticular alveolar RMS is associated with aggressive behavior, high metastatic potential, and poor outcomes. To the best of our knowledge, 18F-FDG PET/CT imaging findings of paratesticular alveolar RMS have never been described. Here, we report on a 16-year-old boy's rare paratesticular alveolar RMS with multiple metastases and its findings on 18F-FDG PET/CT. This case also demonstrates the potential value of 18F-FDG PET/CT in RMS staging and treatment decisions, and may aid in the differential diagnosis.

Uncovering novel mechanisms of chitinase-3-like protein 1 in driving inflammation-associated cancers.

Chitinase-3-like protein 1 (CHI3L1) is a secreted glycoprotein that is induced and regulated by multiple factors during inflammation in enteritis, pneumonia, asthma, arthritis, and other diseases. It is associated with the deterioration of the inflammatory environment in tissues with chronic inflammation caused by microbial infection or autoimmune diseases. The expression of CHI3L1 expression is upregulated in several malignant tumors, underscoring the crucial role of chronic inflammation in the initiation and progression of cancer. While the precise mechanism connecting inflammation and cancer is unclear, the involvement of CHI3L1 is involved in chronic inflammation, suggesting its role as a contributing factor to in the link between inflammation and cancer. CHI3L1 can aggravate DNA oxidative damage, induce the cancerous phenotype, promote the development of a tumor inflammatory environment and angiogenesis, inhibit immune cells, and promote cancer cell growth, invasion, and migration. Furthermore, it participates in the initiation of cancer progression and metastasis by binding with transmembrane receptors to mediate intracellular signal transduction. Based on the current research on CHI3L1, we explore introduce the receptors that interact with CHI3L1 along with the signaling pathways that may be triggered during chronic inflammation to enhance tumorigenesis and progression. In the last section of the article, we provide a brief overview of anti-inflammatory therapies that target CHI3L1.

Targeting astrocytic TDAG8 with delayed CO2 postconditioning improves functional outcomes after controlled cortical impact injury in mice.

T-cell death-associated gene 8 (TDAG8), a G-protein-coupled receptor sensing physiological or weak acids, regulates inflammatory responses. However, its role in traumatic brain injury (TBI) remains unknown. Our recent study showed that delayed CO2 postconditioning (DCPC) has neuroreparative effects after TBI. We hypothesized that activating astrocytic TDAG8 is a key mechanism for DCPC. WT and TDAG8-/- mice received DCPC daily by transiently inhaling 10% CO2 after controlled cortical impact (CCI). HBAAV2/9-GFAP-m-TDAG8-3xflag-EGFP was used to overexpress TDAG8 in astrocytes. The beam walking test, mNSS, immunofluorescence and Golgi-Cox staining were used to evaluate motor function, glial activation and dendritic plasticity. DCPC significantly improved motor function; increased total dendritic length, neuronal complexity and spine density; inhibited overactivation of astrocytes and microglia; and promoted the expression of astrocytic brain-derived neurotrophic factor in WT but not TDAG8-/- mice. Overexpressing TDAG8 in astrocytes surrounding the lesion in TDAG8-/- mice restored the beneficial effects of DCPC. Although the effects of DCPC on Days 14-28 were much weaker than those of DCPC on Days 3-28 in WT mice, these effects were further enhanced by overexpressing astrocytic TDAG8. Astrocytic TDAG8 is a key target of DCPC for TBI rehabilitation. Its overexpression is a strategy that broadens the therapeutic window and enhances the effects of DCPC.

Targeting Neuronal GPR65 With Delayed BTB09089 Treatment Improves Neurorehabilitation Following Ischemic Stroke.

BACKGROUND: GPR65 (G protein-coupled receptor 65) can sense extracellular acidic environment to regulate pathophysiological processes. Pretreatment with the GPR65 agonist BTB09089 has been proven to produce neuroprotection in acute ischemic stroke. However, whether delayed BTB09089 treatment and neuronal GPR65 activation promote neurorestoration remains unknown. METHODS: Ischemic stroke was induced in wild-type (WT) or GPR65 knockout (GPR65-/-) mice by photothrombotic ischemia. Male mice were injected intraperitoneally with BTB09089 every other day at days 3, 7, or 14 poststroke. AAV-Syn-GPR65 (adenoassociated virus-synapsin-GPR65) was utilized to overexpress GPR65 in the peri-infarct cortical neurons of GPR65-/- and WT mice. Motor function was monitored by grid-walk and cylinder tests. The neurorestorative effects of BTB09089 were observed by immunohistochemistry, Golgi-Cox staining, and Western blotting. RESULTS: BTB09089 significantly promoted motor outcomes in WT but not in GPR65-/- mice, even when BTB09089 was delayed for 3 to 7 days. BTB09089 inhibited the activation of microglia and glial scar progression in WT but not in GPR65-/- mice. Meanwhile, BTB09089 reduced the decrease in neuronal density in WT mice, but this benefit was abolished in GPR65-/- mice and reemerged by overexpressing GPR65 in peri-infarct cortical neurons. Furthermore, BTB09089 increased the GAP43 (growth-associated protein-43) and synaptophysin puncta density, dendritic spine density, dendritic branch length, and dendritic complexity by overexpressing GPR65 in the peri-infarct cortical neurons of GPR65-/- mice, which was accompanied by increased levels of p-CREB (phosphorylated cAMP-responsive element-binding protein). In addition, the therapeutic window of BTB09089 was extended to day 14 by overexpressing GPR65 in the peri-infarct cortical neurons of WT mice. CONCLUSIONS: Our findings indicated that delayed BTB09089 treatment improved neurological functional recovery and brain tissue repair poststroke through activating neuronal GRP65. GPR65 overexpression may be a potential strategy to expand the therapeutic time window of GPR65 agonists for neurorehabilitation after ischemic stroke.