Parkinson's disease (PD) is a severe neurodegenerative disorder marked by progressive dopaminergic loss, oxidative stress, metabolic dysregulation, and neuroinflammation. Umbilical cord blood-derived exosomes (UCB-Exos) have emerged as a promising cell-free therapeutic strategy, yet the precise molecular mechanisms underlying their neuroprotective properties remain largely unknown. This study highlights Peroxiredoxin-2 (PRDX2) as an important antioxidant protein within UCB-Exos that mediates their neuroprotective effects in PD models. Using advanced multi-omics approaches, including proteomics, metabolomics, and transcriptomics, we demonstrate that PRDX2 is selectively enriched in UCB-Exos compared to peripheral blood-derived exosomes. UCB-Exos, through the delivery of PRDX2, partially restore antioxidant defenses in neurons, attenuate neuroinflammation, and promote cellular survival. Moreover, UCB-Exos were found to modulate arachidonic acid metabolism by upregulating the levels of 8,9-epoxyeicosatrienoic acid (8,9-EET), a key metabolite with anti-inflammatory properties. Mechanistically, PRDX2 appears to protect the enzyme CYP2J2 from oxidative degradation, facilitating the production of 8,9-EET and reducing the NF-κB/COX-2-driven inflammatory response, thus potentially mitigating neurodegeneration. This study provides evidence for a potential pathway, the PRDX2-mediated metabolic regulatory pathway, and highlights the therapeutic potential of UCB-Exos, offering a novel strategy in the development of exosome-based treatments targeting oxidative stress and neuroinflammation in neurodegenerative diseases.

Malignant tumors represent a major threat to human life and health, posing persistent challenges in medical research. While chimeric antigen receptor T (CAR-T) cell therapy has demonstrated breakthrough efficacy in hematological malignancies such as leukemia and lymphoma, its application in solid tumors, including hepatocellular carcinoma, lung cancer, and pancreatic cancer, remains constrained by multiple bottlenecks. These limitations encompass the immunosuppressive tumor microenvironment, insufficient in vivo persistence of CAR-T cells, long-term treatment-induced exhaustion, and off-target toxicity. The interleukin (IL)-2 family cytokines, IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21, also known as gamma chain (γc) cytokines, share the γc (CD132)-Janus kinase 1/3-signal transducer and activator of transcription signaling axis. These cytokines precisely regulate the survival, proliferation, and functional differentiation of immune cells, including T cells and natural killer cells. In CAR-T immunotherapy, γc cytokines are applied in four core scenarios: Facilitating efficient in vitro CAR-T cell expansion to meet therapeutic dosing requirements; enhancing in vivo persistence to extend the therapeutic window; reinforcing effector functions to counteract tumor microenvironment-mediated suppression; and enabling precise cytokine release to mitigate toxicity risks. Technological strategies have evolved from early recombinant protein administration (in vitro and in vivo ) to second-generation “armored” CAR-T cells engineered for autocrine cytokine secretion and further to third-generation programmable cytokine circuits using synthetic biology for spatiotemporal control. This review systematically summarizes the mechanistic roles, research progress, and technological evolution of γc cytokines in optimizing CAR-T cell function. It critically analyzes the advantages and limitations of different application strategies and explores their potential to overcome solid tumor treatment bottlenecks while improving CAR-T therapy safety and efficacy. These insights aim to inform basic research and clinical translation in this field.

Abstract Background Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive degeneration of midbrain substantia nigra dopaminergic neurons, resulting in striatal dopamine depletion and motor dysfunction. While this pathological cascade is well‐established, its underlying mechanisms remain elusive. Methods To further investigate the pathological mechanisms of PD, we performed single‐cell RNA sequencing of the midbrain and striatum from Hua‐Syn (SNCA*A53T) transgenic (A53T) mice as a PD model. Results Analysis of 22 865 midbrain and 32 117 striatal cells revealed cell‐type‐specific risk association. Glial populations (astrocytes, microglia, oligodendrocytes) showed significant enrichment for PD‐risk genes. Variance‐based clustering identified PD‐enriched subclusters exhibiting upregulated inflammatory pathways, apoptotic pathways, proteostasis disruption, glutamatergic signaling dysregulation, and mitochondrial respiratory chain defects. Transcriptional regulation analysis identified genes associated with PD specific activity, including Rorb and Foxc1 in the midbrain and Dbx2 and Klf13 in the striatum. Cell–cell interactions showed that cell‐to‐cell signaling was enhanced, and the SEMA and CCL neuroinflammatory axes were specifically activated in the PD group. Conclusions Our integrative analysis delineates the cellular and molecular architecture of the pathological process triggered by the expression of A53T mutant α‐synuclein, and provides a framework for targeted therapeutic development.

Diabetes mellitus, a global epidemic, represents a major public health threat. Stem cell therapy, with its regenerative capacity, has emerged as a promising approach for diabetes mellitus management. This paper reviews recent advancements, prospects, and challenges in stem cell-based treatments for diabetes mellitus, focusing on the applications of induced pluripotent stem cells and mesenchymal stem cells, the development of pancreatic islet organoids, and the potential for personalized medicine. The review critically assesses the efficacy and safety of stem cell therapies in clinical trials and examines their applications in both type 1 and type 2 diabetes mellitus. Despite the promising potential, challenges such as safety concerns, transplantation efficiency, ethical considerations, and immune rejection remain prevalent. Lastly, the paper discusses future directions, including the integration of stem cell therapy with other treatments and the advancement of personalized therapeutic strategies, offering new perspectives and hope for diabetes mellitus management.

BACKGROUND:Withaferin A (WFA), a naturally occurring compound, has shown promise as a therapeutic agent for Parkinson's disease (PD), a neurodegenerative disorder associated with motor and gastrointestinal dysfunctions. However, its effects on gut microbiota metabolism remain poorly understood. PURPOSE:This study aimed to elucidate the neuroprotective mechanisms of WFA in a PD mouse model by investigating its regulation of gut microbiota composition, metabolic pathways, and correlations with brain spatial metabolomics. METHODS:Human SNCA-transgenic (A53T) mice were treated with WFA and evaluated using behavioral tests, immunohistochemistry, Western blot, and ELISA to assess motor/cognitive functions and PD-related pathology. Gut microbiota composition was analyzed via 16S rRNA sequencing, while untargeted fecal metabolomics and brain spatial metabolomics were employed to identify metabolic alterations. RESULTS:WFA significantly improved motor performance, alleviated cognitive deficits, restored intestinal barrier integrity, and reduced neuroinflammation. It elevated the abundance of anti-inflammatory gut bacteria (e.g., Bifidobacterium, Dubosiella, Akkermansia) and reversed 55 fecal metabolites linked to sphingolipid metabolism, serotonergic synapses, and neuroactive ligand- receptor interactions. Spatial metabolomics revealed WFA's regulation of sphingolipid signaling pathways, including sphingosine kinase (Sphk1), ceramidase, sphingosine 1-phosphate receptor (S1PR5), and endocannabinoid receptor CB2 expression. Correlation analysis indicated a link between brain metabolite content and gut microbiota abundance. CONCLUSION:Our findings highlight a potential mechanism of WFA that repairs neurons by modulating the sphingolipid signaling pathway within the microbiota-gut-brain axis.

The emergence of MDR K. pneumoniae poses a critical challenge in treating respiratory-associated pneumonia. Bacteriophages are promising antibiotic alternatives with unique features. This study aimed to isolate new bacteriophages from the hospital environment and investigate their therapeutic potential and mechanisms. We employed plaque assays, transmission electron microscopy, and whole-genome sequencing to systematically characterize the biological properties, morphology, and genomic profiles of the phages in parallel. The bacteriostatic curve, biofilm staining quantification, and biofilm inhibition rate assay were employed to evaluate the in vitro lytic efficacy of the phage. More importantly, we established the murine pneumonia infection models through nasal instillation, assessed the therapeutic potential of the phage in vivo by observing pathological morphology via HE staining, detecting pro-inflammatory cytokine levels via qPCR and ELISA, and monitoring bacterial load changes in lung tissue through PCR analysis. Phages vB_KpnP_XY3 and vB_KpnP_XY4, taxonomically classified as Siphoviridae, demonstrated broad temperature (4–60 °C), pH (4–11) tolerance, chloroform resistance, latent periods of 40/35 min, and burst sizes of 340/126 PFU/cell. Both genomes contained circular dsDNA genomes (47,466 bp/50,036 bp) without virulence or antibiotic resistance genes. The bacterial concentration markedly decreased at 2 h post-treatment, reaching its biological nadir by 6 h. Concurrent biofilm assays demonstrated 80

BACKGROUND:Umbilical cord blood (UCB) is a rich source of multifunctional stem cells characterized by low immunogenicity. Recent research in the fields of aging and regenerative medicine has revealed the potential of human umbilical cord blood-derived exosomes (UCB-Exos) in promoting wound healing, anti-aging, and regeneration. However, their role in neurodegenerative diseases, specifically Parkinson's disease (PD), remains unexplored. This study investigates the potential therapeutic effects and underlying mechanisms of UCB-Exos on PD. METHODS:Large extracellular vesicles (LEv), Exos, and soluble fractions (SF) of human UCB plasma were extracted to investigate their effects on motor dysfunction of the MPTP-induced PD mouse model and identify the key components that improve PD symptoms. UCB-Exos were administered by the caudal vein to prevent or treat the PD mouse model. The motor function and pathological markers were detected. Differentially expressed gene and KEGG enrichment pathways were screened by transcriptome sequence. MN9D and SH-SY5Y cells were cultured and evaluated for cell viability, oxidative stress, cell cycle, and aging-related indexes by qRT-PCR, western blot, immunofluorescence, and flow cytometry. The protein expression level of the MAPK p38 and ERK1/2 signaling pathway was detected by western blot. RESULTS:We observed that LEv, Exos, and SF all exhibited potential in ameliorating motor dysfunction in MPTP-induced PD model mice, with UCB-Exos demonstrating the most significant effect. UCB-Exos showed comparable efficacy in preventing and treating motor dysfunction, cognitive decline, and substantia nigra pathological damage in PD mice. Further investigations revealed that UCB-Exos could potentially alleviate oxidative damage, aging and degeneration, and energy metabolism disorders in neurons. Transcriptome sequencing results corroborated that genes differentially expressed due to UCB-Exos were primarily enriched in the neuroactive ligand-receptor interaction, Dopaminergic synapse, and MAPK signaling pathway. We also observed that UCB-Exos significantly inhibited the hyperphosphorylation of the MAPK p38 and ERK1/2 signaling pathways both in vitro and in vivo. CONCLUSIONS:Our study provides a comprehensive evaluation of UCB-Exos on the neuroprotective effects and suggests that inhibition of hyperphosphorylation of MAPK p38 and ERK 1/2 signaling pathways by regulating transcription levels of HspB1 and Ppef2 may be the key mechanism for UCB-Exos to improve PD-related pathological features.

An increase in α-synuclein (α-syn) levels and mutations in proteins associated with mitochondria contribute to the development of familial Parkinson’s disease (PD); however, the involvement of α-syn and mitochondria in idiopathic PD remains incompletely understood. The voltage-dependent anion channel I (VDAC1) protein, which serves as a crucial regulator of mitochondrial function and a gatekeeper, plays a pivotal role in governing cellular destiny through the control of ion and respiratory metabolite flux. The ability of resveratrol (RES), which is a potent phytoalexin with antioxidant and anti-inflammatory properties, to regulate VDAC1 in PD is unknown. The objective of this study was to evaluate the role of VDAC1 in the pathological process of PD and to explore the mechanism by which resveratrol protects dopaminergic neurons by regulating VDAC1 to maintain the mitochondrial permeability transition pore (mPTP) and calcium ion balance. The effects of RES on the motor and cognitive abilities of A53T mice were evaluated by using small animal behavioral tests. Various techniques, including immunofluorescence staining, transmission electron microscopy, enzyme-linked immunoadsorption, quantitative polymerase chain reaction (PCR), and Western blotting, among others, were employed to assess the therapeutic impact of RES on neuropathy associated with PD and its potential in regulating mitochondrial VDAC1. The findings showed that RES significantly improved motor and cognitive dysfunction and restored mitochondrial function, thus reducing oxidative stress levels in A53T mice. A significant positive correlation was observed between the protein expression level of VDAC1 and mitochondrial α-syn expression, as well as disease progression, whereas no such correlation was found in VDAC2 and VDAC3. Administration of RES resulted in a significant decrease in the protein expression of VDAC1 and in the protein expression of α-syn both in vivo and in vitro. In addition, we found that RES prevents excessive opening of the mPTP in dopaminergic neurons. This may prevent the abnormal aggregation of α-syn in mitochondria and the release of mitochondrial apoptosis signals. Furthermore, the activation of VDAC1 reversed the resveratrol-induced decrease in the accumulation of α-syn in the mitochondria. These findings highlight the potential of VDAC1 as a therapeutic target for PD and identify the mechanism by which resveratrol alleviates PD-related pathology by modulating mitochondrial VDAC1.

Parkinson's disease (PD) is a neurological disorder characterized by motor and gastrointestinal dysfunctions. Resveratrol is a potent antioxidant and anti-inflammatory phytoalexin known for its health-promoting benefits. However, little is known about its potential in treating PD by modulating the microbial gut-brain axis, and its clinical application has been limited due to poor water solubility, rapid metabolism, and limited systemic bioavailability. Our study aimed to evaluate the therapeutic potential of RHSD, a resveratrol-cyclodextrin inclusion complex, in treating PD through the gut-brain axis in human SNCA-transgenic (A53T) mice PD models. Building on our previous study, we prepared RHSD and compared its efficacy with uncoated resveratrol for PD treatment. The study results demonstrated that RHSD exhibited several advantages in improving motor function, alleviating cognitive impairment, restoring intestinal barrier function, and inhibiting neuropathy. Subsequently, a series of analyses, including fecal microbiota metagenomic sequencing, non-target metabolic assays, host transcriptome sequencing, and integrative analysis were performed to reveal the potential therapeutic pathways of RHSD in A53T mice. The metagenomic sequencing results indicated a significant increase in the levels of Lactobacillus murinus, Lactobacillus reuteri, Enterorhabduscaecimuris, Lactobacillus taiwanensis, and Lactobacillus animals following RHSD administration. Furthermore, metabolomics profiling showed that the levels of gut microbiome metabolites were reversed after RHSD treatment, and differential metabolites were significantly correlated with motor function and intestinal function in PD mice. The integrated analysis of microbial metabolites and host transcriptomics suggested that abnormal amino acid metabolism, mitochondrial dysfunction, oxidative stress, and neuroinflammation in the PD model were associated with the diffusion of abnormal metabolites. This study illustrates the profound impact of RHSD administration on rectifying gut microbiota dysbiosis and improving the A53T mouse model. Notably, we observed significant alterations in the proliferation and metabolism of multiple probiotic strains of Lactobacillus. Furthermore, our research supports the hypothesis that microbiota-related metabolites may regulate the transcription of host genes, including dopamine receptors and calcium stabilization. Consequently, our findings underscore the potential of RHSD as a promising therapeutic candidate for the treatment of PD through the modulation of several signaling pathways within the microbiota-gut-brain axis.

Abstract Background Mammary carcinoma, a pervasive and potentially lethal affliction, is conjectured to be profoundly influenced by physical exercise, both in prophylaxis and therapeutic contexts. This study endeavors to explore the repercussions of exercise training on the progression of mammary carcinoma, particularly the mechanisms by which the amalgamation of an exercise regimen and doxorubicin induces tumor cell apoptosis. Methods Female BALB/c mice were categorized into four distinct groups: A sedentary group (SED), an exercise group (Ex), a doxorubicin group (Dox, 5 mg/kg), and a combined treatment group (Dox + Ex). The exercise training lasted for 21 days and included aerobic rotarod exercise and resistance training. The impact of exercise training on tumor growth, immune cell proportions, inflammatory factor levels, and cell apoptosis pathway was assessed. Results Exercise training significantly curtailed tumor growth in a mouse model of breast cancer. Both the Ex and Dox groups exhibited significant reductions in tumor volume and weight (p < 0.01) in comparison to the SED group, while the Dox + Ex group had a significantly lower tumor volume and weight than the Dox group (p < 0.01). Exercise training also significantly increased the proportion of NK and T cells in various parts of the body and tumor tissue, while decreasing tumor blood vessels density. Exercise training also increased IL‐6 and IL‐15 levels in the blood and altered the expression of apoptosis‐related proteins in tumor tissue, with the combined treatment group showing even more significant changes. Conclusions Physical training improves the effectiveness of doxorubicin in treating breast cancer by activating cytotoxic immune cells, releasing tumor suppressor factors, and initiating mt‐apoptosis, all while mitigating the adverse effects of chemotherapy.

BackgroundThe diagnosis of Parkinson's disease (PD) is complex and there are no biomarkers for early identification. Many studies have reported altered gut microbiota in patients with PD compared with healthy individuals. However, results from previous studies vary across countries. AimsThe aim of this study was to identify gut microbiota biomarkers that could be used as a marker for the diagnosis of PD. MethodsFirstly, the differential gut microbiota was obtained by meta-analysis, and then the results of meta-analysis were validated through metagenomic cohort. Finally, the ROC curve was drawn based on the metagenomic validation results. ResultsThe meta-analysis showed a lower relative abundance of Prevotellaceae (p < 0.00001) and Lachnospiraceae (p = 0.002), and a higher of Ruminococcaceae (p < 0.00001), Christensenellaceae (p = 0.03), Bifidobacteriaceae (p < 0.00001), and Verrucomicrobiaceae (p = 0.02) in patients with PD. Only Bifidobacteriaceae was also at high levels in the validation cohort of the metagenome. Meanwhile, three species from the Bifidobacteriaceae, including Scardovia_inopinata (p = 0.022), Bifidobacterium_dentium (p = 0.005), and Scardovia_wiggsiae (p = 0.024) were also high. The ROC curve showed that the three species (71.2%) from Bifidobacteriaceae had good predictive efficiency for PD. ConclusionElevated Bifidobacteriaceae may be associated with PD. Elevated three species from the Bifidobacteriaceae, including Scardovia_inopinata, Bifidobacterium_dentium and Scardovia_wiggsiae may provide new potential biomarkers for the diagnosis of PD.

Abstract Background: Physical exercise is believed to play a vital role in the prevention and treatment of cancer and its complications. However, the molecular mechanisms underlying this effect remain unclear. Methods: BALB/c female mice (n=24) were randomly divided into sedentary group (SED), exercise group (Ex), Doxorubicin group (Dox, 5 mg/kg), and Doxorubicin + exercise group (Dox + Ex) after 7 days of 4T1 cell implantation. Exercise training lasted for 28 days and included rotarod experiments and resistance training. H&E staining was used to observe histopathological changes in the tumor, spleen, and heart; The proportion of NK cells and T cells in peripheral and immune organs was analyzed by flow cytometry; The infiltration of NK and CD8 T cells and the expression levels of CD31 and VEGF in tumor tissues were evaluated by immunohistochemical; The mRNA expression levels of IL-6, IL-1β, TNF-α, TNF-α R, IFN-γ, and IFN-γ R were detected by q-PCR, and the protein expression levels of Bax, Bcl2 and cleaved caspase3 were detected by Western blot. Results: The chemotherapeutic effect of Doxorubicin on breast cancer was significantly promoted by exercise training, and its mechanism might be that exercise activates the maturation of tumor killer cells in the immune system and releases tumor suppressor factors, such as TNF-α and IFN-γ, which induces the activation of Caspase3/Bax/Bcl2 signaling pathway in tumor cells. Conclusions: It is suggested that exercise training improves chemotherapy efficacy while reducing side effects, which provides experimental evidence for the establishment of new clinical treatment strategies for breast cancer.

Abstract Background Parkinson's disease (PD) is a neurological disorder characterized by motor and gastrointestinal dysfunctions. There is a significant need for more effective treatment options. Resveratrol (RES) is a potent antioxidant and anti-inflammatory phytoalexin known for its health-promoting benefits. However, little is known about its potential in treating PD by modulating the microbial gut-brain axis, and its clinical application has been limited due to poor water solubility, rapid metabolism, and limited systemic bioavailability. Our study aimed to evaluate the therapeutic potential of RHSD, a resveratrol-cyclodextrin inclusion complex, in treating PD through the gut-brain axis in human SNCA-transgenic (A53T) mice PD models.Results We have demonstrated that administering RHSD can prevent neurodegeneration, improve motor skills, and restore the levels of phosphorylated tyrosine hydroxylase in A53T mice, while also leading to a positive impact on gastrointestinal function. Our metagenomic sequencing indicated significant changes in the richness, evenness, and composition of the gut microbiome in A53T mice, with a significant increase in the levels of Lactobacillus murinus, Lactobacillus reuteri, Enterorhabduscaecimuris, Lactobacillus taiwanensis, and Lactobacillus animals following RHSD administration. Furthermore, metabolomics profiling showed that the levels of gut microbiome metabolites were reversed after RHSD treatment, with altered metabolites primarily present in metabolic pathways such as drug metabolism-cytochrome P450, retinol metabolism, purine metabolism, tyrosine metabolism, and methane metabolism. The altered gut microbiota showed significant correlations with microbiota metabolites. With an integrated analysis of microbiota metabolites and host transcriptomics, our research provides insights into the potential interaction between abnormalities in amino acid metabolism, mitochondrial dysfunction, oxidative stress, and neuroinflammation in Parkinson's disease.Conclusions This study illustrates the profound impact of RHSD administration on rectifying gut microbiota dysbiosis and improving the A53T mouse model. We also observed that the proliferation and metabolism of multiple probiotic strains of Lactobacillus were significantly altered. Moreover, our research supports the hypothesis that microbiota-related metabolites could regulate the transcription of host genes, including dopamine receptors and calcium stabilization. Our findings thus highlight the potential of RHSD as a viable therapeutic candidate for treating PD by targeting several signaling pathways of the microbiota-gut-brain axis.

Introduction: Spinocerebellar ataxia (SCA) is an autosomal dominant genetic disease characterized by cerebellar neurological deficits. Specifically, its primary clinical manifestation is ataxia accompanied by peripheral nerve damage. A total of 48 causative genes of SCA have been identified. This study aimed to identify causative genes of autosomal dominant SCA in a four-generation Chinese kindred comprising eight affected individuals. Methods: Genomic DNA samples were extracted from the pedigree members, and genomic whole-exome sequencing was performed, followed by bidirectional Sanger sequencing, and minigene assays to identify mutation sites. Results: A novel pathogenic heterozygous mutation in the splice region of the coiled-coil domain containing the 88C (CCDC88C) gene (NM_001080414:c.3636-4 A>G) was identified in four affected members. The minigene assay results indicated that this mutation leads to the insertion of CAG bases (c.3636-1_3636-3 insCAG). Conclusion: CCDC88C gene mutation leads to SCA40 (OMIM:616053), which is a rare subtype of SCA without symptoms during childhood. Our findings further demonstrated the role of the CCDC88C gene in SCA and indicated that the c.3636-4 A>G (NM_001080414) variant of CCDC88C is causative for a later-onset phenotype of SCA40. Our findings enrich the mutation spectrum of CCDC88C gene and provide a theoretical basis for the genetic counseling of SCA40.

目的 研究白藜芦醇(resveratrol,RES)对α-突触核蛋白(α-synuclein,α-Syn)A53T转基因小鼠运动功能障碍及外周免疫的影响.方法 选取8月龄的A53T转基因小鼠,随机分成4组:对照组(WT)、对照治疗组(WT+RES)、模型组(PD)、模型治疗组(PD+RES).治疗组每3 d灌胃RES,用药3个月;对照组和模型组给予等量生理盐水.通过爬杆实验、转棒实验、前脚抓力实验、四肢抱紧实验检测各组小鼠运动水平.流式细胞仪检测小鼠T淋巴细胞亚群,酶联免疫吸附试验(ELISA)检测小鼠血清中白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、白细胞介素-18(IL-18)以及转化生长因子-β(TGF-β)的水平.结果 与对照组相比,模型组运动功能评分均较低;与模型组相比,模型治疗组运动功能评价显著改善.流式结果显示,与对照组比,模型组小鼠外周T细胞占比、CD4+T细胞占比、CD4+/CD8+比值均降低,CD8+T细胞占比无统计学意义.与模型组相比,模型治疗组T淋巴细胞占比和CD4+T细胞占比均显著升高,有统计学意义,CD4+/CD8+比值也升高,但差异无统计学意义.外周血血清ELISA结果显示,与对照组相比,模型组小鼠IL-6、IL-18均升高,TGF-β降低,TNF-α浓度无统计学差异.与模型组相比,模型治疗组IL-6、IL-18浓度显著下降,TGF-β有所上升,结果无统计学意义.结论 RES通过调节小鼠外周免疫,减少神经炎症反应,从而显著改善A53T转基因小鼠的运动功能障碍.

JQ1, a BRD4 protein inhibitor, first identified because of its therapeutic role in cancer, has gradually demonstrated a protective effect on the heart in recent years; however, it is unclear whether JQ1 also plays a role in LPS-induced cardiac dysfunction. This paper aims to investigate the effects of the BRD4 inhibitor JQ1 on LPS-induced cardiac dysfunction and its mechanism. In the experiments, we found that BRD4 was significantly upregulated in the hearts of LPS-treated mice.JQ1 treatment improved survival and cardiac function in LPS-treated mice and reduced cardiomyopathologic injury, inflammation, and oxidative injury.JQ1 treatment similarly reduced the release of lactate dehydrogenase and inflammatory factors in H9C2 cells treated with LPS.JQ1 significantly upregulated silent information regulator 1 (SIRT1) expression and suppressed the upregulation of NOD-like receptor protein 3 (NLRP3), cleaved caspase-1, and GSDMD in heart tissues induced by LPS.Meanwhile, we obtained the same results in H9C2 cells treated with LPS. The administration of the SIRT1 inhibitor (EX527) intervention partially blocked the JQ1-mediated downregulation of NLRP3, cleaved caspase-1, GSDMD in LPS-induced H9C2 cells. Therefore, we propose that JQ1 can improve LPS-induced cardiac dysfunction by inhibiting SIRT1-dependent activation of NLRP3 inflammasomes, which may be a promising strategy for treating sepsis cardiomyopathy.

Raman spectroscopy (RS) has been used in clinical diagnostics, tissue engineering, and toxicology experiments owing to its label-free, low-destructive, high sensitivity, and strong specificity. Nonetheless, their application has been limited because of the integrated analysis of biological experimental methods and RS. In this study, it was challenged that applied RS in combination with biological experiments to distinguish colorectal cancer (CC) cells from which treated with artesunate (ART), which has obvious antitumor effects. Heavy water (D2O) was used to detect changes in colorectal cancer cell metabolism. The Raman spectral intensity of the C-D band at 2100-2300 cm(-1) was significantly weakened in CC (SW480, SW620, and HCT116) treated with ART. According to the CCK-8, wound healing, and Transwell assays, the activity of SW480 and SW620 cells was significantly inhibited by ART. Through literature tracking and transcriptome sequencing, multiple signal pathways of SW480 and SW620 cells have changed significantly after treatment with ART, such as "apoptotic signaling pathway," "cell cycle phase transition," "mitochondrial part," and "mRNA metabolic process." The Raman peak area significantly decreased at 490 cm(-1), 746 cm(-1), 1126 cm(-1), 1311 cm(-1), 1337 cm(-1), and 1582 cm(-1) in SW480 and SW620 cells treated with ART. It showed that these Raman bands are associated with ART-induced apoptosis-related signaling pathways. In addition, we found that application of the RS in cell type identification will be prosperous. By integrating RS with biological mechanisms, its application in the biomedical field is increasing, and its significance in biological sample detection has become more prominent.

Background JQ1, a BRD4 inhibitor, first identified its therapeutic role in cancer, has gradually demonstrated a protective effect on the heart in recent years; however, it is unclear whether JQ1 also plays a role in LPS-induced cardiac dysfunction. Methods and results A total of forty eight mice were randomly divided into control, LPS(7.5 mg/kg), and LPS + JQ1 (50 mg/kg). JQ1 was preprotected for 1 h, and LPS was stimulated for 12 h, mouse survival and cardiac function were observed, and histopathological, serum myocardial injury markers, and inflammatory indicators, and oxidative stress levels in heart tissue were examined. The experiment found that the cardiac BRD4 levels were upregulated and the heart severe damage in the LPS group compared with the control group. While compared with the LPS group, JQ1 preprotected increased survival rate and cardiac function, reducated cardiomypathological injury and CD45 infiltration, and reduced the release of LDH, CK-MB, IL-1, IL-18, reduced MDA generation, and increased SOD viability. In addition, JQ1 preprotected also upregulated SIRT1, and inhibited the expression of NLRP3, caspase-1p20, and GSDMD. Meanwhile, similar results were obtained in LPS-treated H9C2 cells, and further intervention with the SIRT1 inhibitor EX527 partially blocked the JQ1-mediated down regulation of NLRP3, caspase-1p20, and GSDMD. Conclusions We propose that JQ1 may improve LPS-induced cardiac dysfunction by inhibiting SIRT1-dependent activation of NLRP3 inflammasomes, which may be a promising strategy for treating sepsis cardiomyopathy.

目的:使用拉曼光谱技术对比抑郁症患者及健康人血清,寻找差异标志物,判断该技术在抑郁症诊断中应用的可能性.方法:空腹采集21例抑郁症患者与11例年龄匹配的健康人血清,用拉曼光谱仪进行点测量,获得的原始数据扣除荧光背景后,采用origin 2018软件寻找差异光谱数据.考虑到饮食对结果的影响,另采集非空腹6例抑郁症患者与7例年龄匹配的健康人血清,进行相同检测.结果:空腹情况下,抑郁症患者血清的拉曼光谱与健康人血清存在差异,于1150、1155、1157、1518及1524 cm-1位移处的峰强显著低于健康人血清(P<0.001),表明这些峰归属的物质(类胡萝卜素)在抑郁症患者中含量较少.非空腹情况下,仅1150、1157 cm-1处存在显著差异(P<0.05).结论:通过血清拉曼光谱分析方法可以找到健康人和抑郁症患者的差异物,但受饮食影响较大.拉曼光谱技术在抑郁症的鉴别诊断上具有一定的临床应用价值.

Abstract Background: Glioblastoma (GBM) is an invasive brain tumor that lacks effective treatment methods. This study examined the effects and molecular mechanisms of Artesunate (ART) in GBM using both in vivo and in vitro methods and RNA sequencing (RNA-seq). Methods and Results: The effects of ART were assessed in vitro using GBM cells and in vivo using tumor-bearing nude mice. ART significantly suppressed GBM cell proliferation, facilitated apoptosis, and induced excessive reactive oxygen species (ROS) generation. However, ROS scavengers reversed the growth inhibitory and apoptotic effects of ART on GBM cells. In the mouse model of GBM, ART effectively inhibited cancer development without inducing toxicity. RNA-seq of ART-treated and untreated cells revealed 389 differentially expressed genes (DEGs), including 145 upregulated and 244 downregulated DEGs. Furthermore, the DEGs were applied to Gene Ontology and Kyoto Encyclopedia of Gene and Genomes analysis. The downregulated DEGs were mostly related to tumor-related pathways, such as the cell cycle, cell molecule adhesion, and extracellular matrix-receptor interaction. In addition, analyses using the Molecular Complex Detection algorithm and protein-protein interaction network were performed on those DEGs, and HMMR, CDC20, CCNB1, and THBS1, which may play key roles in ART-treated GBM cells, were identified. These results were validated via quantitative PCR and western blot analysis. Conclusions: Overall, our results illustrated the anti-GBM effects of ART and the possible mechanisms involved.