Unveiling a Potent Small Molecule Disruptor for RNA G-Quadruplexes Tougher Than DNA G-Quadruplex Disruption.

This research presents a unique small molecule characterized by its ability to effectively disrupt RNA G-quadruplexes (G4s), which are notably more stable than their DNA counterparts. We conducted a comprehensive series of in vitro experiments to thoroughly assess the disruptive capabilities of this molecule on RNA G4s. These experiments included comparisons with established G4 stabilizers and DNA G4 disruptors, providing a multifaceted evaluation of the molecule's efficacy. Our extensive in vitro analyses demonstrated that this molecule effectively alters G4 structures and interactions with the BG4 protein, a well-recognized G4-specific antibody. These findings underscore the molecule's potential to modulate G4-protein interactions, indicating promising applications for manipulating cellular functions associated with G4 dynamics in future research.

Warning of severe pulmonary embolism after cerebral angiography: A case report and literature review.

RATIONALE: Acute pulmonary embolism (PE), which can lead to cardiac and respiratory arrest, is a rare complication of cerebral angiography. However, neurologists do not pay attention to this. PATIENT CONCERNS: A 47-year-old male with a history of type 2 diabetes was admitted to our hospital for evaluation of surgical indications for unruptured ophthalmic aneurysms. After cerebral angiography, a fatal PE occurred. Through rapid identification and effective drug treatment, the patient recovered and was discharged. DIAGNOSES: A diagnosis of fatal PE was made based on the bedside ultrasonography and blood d-dimer level. INTERVENTIONS: Cardiopulmonary resuscitation and intravenous thrombolysis of "50 mg alteplase" for continuous intravenous drip for 2 hours. OUTCOMES: The patient was recovered and no special discomfort was reported. LESSONS: PE is a rare complication of cerebral angiography, but the fatality rate is very high. Neurologists must not only early identify and effectively treat this complication, but more importantly, pay attention to this complication, prevent it in advance, and reduce the occurrence of catastrophic events.

LH promotes the proliferation of porcine primordial germ cell-like cells (pPGCLCs) by regulating the ceRNA network related to the TGF-ß signaling pathway.

Primordial germ cells (PGCs), as the precursors of gametes found in early embryos, provide a new direction for solving the problem of reproductive disorders. In vitro, conversion of adult stem cells (ASCs) into primordial germ cell-like cells (PGCLCs) is feasible. The means of increasing PGCLCs number in vitro has been a focus of recent stem cell research. In this study, we found that luteinizing hormone (LH) could promote porcine PGCLCs (pPGCLCs) proliferation. To investigate the proliferation regulatory network, whole transcriptome sequencing technology was employed. Results showed that the TGF-ß signaling pathway played a key role. In addition, we found that TGFßR1 and SMAD4, TGF-ß signaling pathway-related genes, were significantly upregulated after LH treatment. Subsequently, we predicted their target microRNAs (miRNAs) and long non-coding RNAs (lncRNAs): ssc-miR-128, ssc-miR-146b, ssc-miR-361-3p, MSTRG.11473, MSTRG.11475, MSTRG.11553, and MSTRG.11554, and constructed the competitive endogenous RNAs (ceRNA) network. Finally, to further verify the ceRNA network, the miRNA-inhibitors were transfected into cells. RT-qPCR results indicated a significant increase in the expression of MSTRG.11473, MSTRG.11475, MSTRG.11553, MSTRG.11554, TGFßR1, and SMAD4 compared to the negative control (NC) group. In conclusion, these results highlight that LH could regulate the pPGCLCs proliferation by modulating the expression of TGF-ß signaling pathway-related ncRNAs.

Application of smart-responsive hydrogels in nucleic acid and nucleic acid-based target sensing: A review.

In recent years, nucleic acid-related sensing and detection have become essential in clinical diagnostics, treatment and genotyping, especially in connection with the Human Genome Project and the COVID-19 pandemic. Many traditional nucleic acid-related sensing strategies have been employed in analytical chemistry, including fluorescence, colorimetric and chemiluminescence methods. However, their key limitation is the lack of understanding of the interaction during analysis, particularly at the 3D matrix level close to biological tissue. To address this issue, smart-responsive hydrogels are increasingly used in biosensing due to their hydrophilic and biocompatible properties. By combining smart-responsive hydrogels with traditional nucleic acid-related sensing, biological microenvironments can be mimicked, and targets can be easily accessed and diffused, making them ideal for nucleic acid sensing. This review focuses on utilizing smart-responsive hydrogels for nucleic acid-related sensing and detection, including nucleic acid detection, other nucleic acid-based analyte detection and nucleic acid-related sensing platforms applying nucleic acid as sensing tools in hydrogels. Additionally, the analytical mechanisms of smart-responsive hydrogels with the combination of various detection platforms such as optical and electrochemical techniques are described. The limitations of using smart-responsive hydrogels in nucleic acid-related sensing and proposed possible solutions are also discussed. Lastly, the future challenge of smart-responsive hydrogels in nucleic acid-related sensing is explored. Smart-responsive hydrogels can be used as biomimetic materials to simulate the extracellular matrix, achieve biosensing, and exhibit great potential in nucleic acid-related sensing. They serve as a valuable complement to traditional detection and analytical methods.

Prevalence and Clinical Relevance of Anti-FcεRI Autoantibody in Crohn's Disease.

Background: Mast cells can be activated in various ways and were shown to be involved in the development of Crohn's disease (CD). The diagnosis of CD is still challenging, and seeking novel biomarkers is a worthwhile endeavor. Methods: An indirect enzyme-linked immunosorbent assay (ELISA) was successfully established for semi-quantitative detection of IgG anti-FcεRI in serum using human FcεRIα coated microplates and an enzyme-labeled anti-human IgG as secondary antibodies. The optimal working conditions were explored, followed by conducting the method evaluation. The serum samples and clinical data of 117 CD patients and 75 healthy controls were collected. IgE was measured by the rate turbidity turbidimetry; IgG anti-IgE and IgG anti-FcεRI were detected by ELISA. IgG anti-pancreatic antibody (PAB) and anti-Saccharomyces cerevisiae antibody (ASCA) were determined by indirect immunofluorescence assay. Data were analyzed concerning the clinical characteristics. Results: IgG anti-FcεRI was an effective marker for CD (P < 0.001), but IgE and IgG anti-IgE (P = 0.089, 0.219, respectively) were not. There was a positive correlation between anti-IgE and anti-FcεRI (R = 0.380, P < 0.001). Anti-FcεRI positive patients behaved with higher disease activity [OR: 1.478 (1.200~1.821), P < 0.001], but were less likely to be located in L4 among Montreal classification [OR: 0.253 (0.077~0.837), P = 0.024]. Existing indicators, PAB and ASCA, behaved with high specificity (both > 95%) with low sensitivity (both < 30%). The combination of anti-FcεRI with existing markers significantly improved the diagnostic efficiency [AUC: 0.879 (0.831~0.928)]. Conclusion: An ELISA for the detection of anti-FcεRI was established and validated, which may contribute to facilitating research on Crohn's diseases. Anti-FcεRI positive CD patients were associated with higher disease activity indices, suggesting its potential value in the diagnosis and management of CD.

Blood urea nitrogen-to-albumin ratio independently predicts 30-day mortality in acute respiratory failure patients: a retrospective cohort study.

Background: It is crucial to identify patients at high risk for acute respiratory failure (ARF) to provide appropriate and optimal clinical treatment. While previous studies have explored the use of prognostic biomarkers based on a combination of blood urea nitrogen (BUN) and albumin levels, no reports to date have evaluated its utility across a wide range of ARF etiologies in a large and diverse critical care population. Therefore, we aimed to ascertain the association between the BUN-to-albumin ratio (BAR) and mortality in these patients. Methods: Data recorded in the first 24 h following intensive care unit (ICU) admission, including demographics, vital signs, laboratory test results, comorbidities, and score systems were retrieved from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. A general additive model was used to determine whether there was a non-linear relationship between BAR and 30-day mortality. A multivariate Cox analysis was performed to measure the association between them. Results: The study enrolled 9,734 patients with ARF. In comparison to survivors, non-survivors exhibited higher BAR [10.79 (6.25-18.81) vs. 7.35 (4.48-13.62), P<0.001]. The correlation between baseline BAR and 30-day all-cause mortality in patients with ARF was non-linear, with a significant inflection point (11.76 mg/g). The Kaplan-Meier curve demonstrated that ARF patients had higher 30-day all-cause mortality rates when they had higher BAR levels (>11.76 mg/g) with hazard ratio (HR) 1.54 [95% confidence interval (CI): 1.39-1.70]. Conclusions: A high BAR was linked to a higher risk of mortality in ARF patients. BAR is a straightforward and possibly useful prognostic biomarker for ARF.

Transcriptional profile changes caused by noise-induced tinnitus in the cochlear nucleus and inferior colliculus of the rat.

INTRODUCTION: Tinnitus is a prevalent and disabling condition characterized by the perception of sound in the absence of external acoustic stimuli. The hyperactivity of the auditory pathway is a crucial factor in the development of tinnitus. This study aims to examine genetic expression variations in the dorsal cochlear nucleus (DCN) and inferior colliculus (IC) following the onset of tinnitus using transcriptomic analysis. The goal is to investigate the relationship between hyperactivity in the DCN and IC. METHODS: To confirm the presence of tinnitus behavior, we utilized the gap pre-pulse inhibition of the acoustic startle (GPIAS) response paradigm. In addition, we conducted auditory brainstem response (ABR) tests to determine the baseline hearing thresholds, and repeated the test one week after subjecting the rats to noise exposure (8-16 kHz, 126 dBHL, 2 h). Samples of tissue were collected from the DCN and IC in both the tinnitus and non-tinnitus groups of rats. We employed RNA sequencing and quantitative PCR techniques to analyze the changes in gene expression between these two groups. This allowed us to identify any specific genes or gene pathways that may be associated with the development or maintenance of tinnitus in the DCN and IC. RESULTS: Our results demonstrated tinnitus-like behavior in rats exposed to noise, as evidenced by GPIAS measurements. We identified 61 upregulated genes and 189 downregulated genes in the DCN, along with 396 upregulated genes and 195 downregulated genes in the IC. Enrichment analysis of the DCN revealed the involvement of ion transmembrane transport regulation, synaptic transmission, and negative regulation of neuron apoptotic processes in the development of tinnitus. In the IC, the enrichment analysis indicated that glutamatergic synapses and neuroactive ligand-receptor interaction pathways may significantly contribute to the process of tinnitus development. Additionally, protein-protein interaction (PPI) networks were constructed, and 9 hub genes were selected based on their betweenness centrality rank in the DCN and IC, respectively. CONCLUSIONS: Our findings reveal enrichment of differential expressed genes (DEGs) associated with pathways linked to alterations in neuronal excitability within the DCN and IC when comparing the tinnitus group to the non-tinnitus group. This indicates an increased trend in neuronal excitability within both the DCN and IC in the tinnitus model rats. Additionally, the enriched signaling pathways within the DCN related to changes in synaptic plasticity suggest that the excitability changes may propagate to IC. NEW AND NOTEWORTHY: Our findings reveal gene expression alterations in neuronal excitability within the DCN and IC when comparing the tinnitus group to the non-tinnitus group at the transcriptome level. Additionally, the enriched signaling pathways related to changes in synaptic plasticity in the differentially expressed genes within the DCN suggest that the excitability changes may propagate to IC.

Clinical Efficacy of Electroacupuncture at Sacral Four Points Combined with Moxibustion at Abdominal Three Points for Treating Post-Stroke Urinary Incontinence: Observations on Urodynamics, Quality of Life, and Safety.

BACKGROUND: Urinary incontinence is a common complication following a stroke. No specific drugs are available in Western medicine, and surgical treatment is highly traumatic, limiting its clinical application. This study aimed to observe the clinical efficacy of electroacupuncture at the "Sacral Four Points" combined with moxibustion at the "Abdominal Three Points" on post-stroke urinary incontinence, exploring its impact on urodynamics and quality of life. METHODS: Patients with post-stroke urinary incontinence treated at our Hospital from January 2021 to December 2023 were recruited. The study included 117 patients: 57 in the electroacupuncture group and 60 in the combined group. Urodynamic parameters were measured, and scores from the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI SF) and the Incontinence Quality of Life Questionnaire (I-QOL) were recorded before, and after the first and third courses of treatment. Clinical efficacy and adverse reactions were evaluated post-treatment. RESULTS: The study found no significant differences in clinical characteristics between the groups (p > 0.05), providing a baseline for comparison. Both groups showed substantial decreases in leakage volume after one course of treatment (p < 0.05), with a reduction in the ICIQ-UI SF score (p < 0.05) and an increase in the I-QOL score (p < 0.05). After three courses of treatment, the leakage volume of patients in both groups significantly decreased (p < 0.05), the ICIQ-UI SF score decreased (p < 0.05), and the I-QOL score increased (p < 0.05). The combined group showed a lower leakage volume compared to the electroacupuncture group (p < 0.05), with lower ICIQ-UI SF scores (p = 0.027) and higher I-QOL scores (p = 0.048). Importantly, the total effective rate was significantly higher in the combined group (88.33% vs 64.91%, p = 0.037), demonstrating the safety and efficacy of the treatment. CONCLUSIONS: Electroacupuncture at the "Sacral Four Points" combined with moxibustion at the "Abdominal Three Points" improves the clinical symptoms and enhances the quality of life for patients with post-stroke urinary incontinence, showing superior results compared to electroacupuncture alone.

CD36-mediated ferroptosis destabilizes CD4+ T cell homeostasis in acute Stanford type-A aortic dissection.

Acute type A aortic dissection (ATAAD) is a lethal pathological process within the aorta with high mortality and morbidity. T lymphocytes are perturbed and implicated in the clinical outcome of ATAAD, but the exact characteristics of T cell phenotype and its underlying mechanisms in ATAAD remain poorly understood. Here we report that CD4+ T cells from ATAAD patients presented with a hypofunctional phenotype that was correlated with poor outcomes. Whole transcriptome profiles showed that ferroptosis and lipid binding pathways were enriched in CD4+ T cells. Inhibiting ferroptosis or reducing intrinsic reactive oxygen species limited CD4+ T cell dysfunction. Mechanistically, CD36 was elevated in CD4+ T cells, whose blockade effectively alleviated palmitic acid-induced ferroptosis and CD4+ T cell hypofunction. Therefore, targeting the CD36-ferroptosis pathway to restore the functions of CD4+ T cells is a promising therapeutic strategy to improve clinical outcomes in ATAAD patients.

An updated molecular diagnostic for surveillance of tetM in Neisseria gonorrhoeae.

Doxycycline post-exposure prophylaxis (doxy-PEP) for sexually transmitted bacterial infections reduces the risk of syphilis and chlamydia, but effectiveness against gonorrhea is variable, likely attributable to varying resistance rates. As doxy-PEP is incorporated into clinical practice, an urgent unanswered question is whether increased doxycycline use will drive tetracycline-class resistance in Neisseria gonorrhoeae. Here, we report an updated RT-PCR molecular diagnostic to detect the tetM gene that confers high-level tetracycline resistance in N. gonorrhoeae.

Spatiotemporal Mapping of the Oxytocin Receptor at Single-Cell Resolution in the Postnatally Developing Mouse Brain.

The oxytocin receptor (OXTR) has garnered increasing attention for its role in regulating both mature behaviors and brain development. It has been established that OXTR mediates a range of effects that are region-specific or period-specific. However, the current studies of OXTR expression patterns in mice only provide limited help due to limitations in resolution. Therefore, our objective was to generate a comprehensive, high-resolution spatiotemporal expression map of Oxtr mRNA across the entire developing mouse brain. We applied RNAscope in situ hybridization to investigate the spatiotemporal expression pattern of Oxtr in the brains of male mice at six distinct postnatal developmental stages (P7, P14, P21, P28, P42, P56). We provide detailed descriptions of Oxtr expression patterns in key brain regions, including the cortex, basal forebrain, hippocampus, and amygdaloid complex, with a focus on the precise localization of Oxtr+ cells and the variance of expression between different neurons. Furthermore, we identified some neuronal populations with high Oxtr expression levels that have been little studied, including glutamatergic neurons in the ventral dentate gyrus, Vgat+Oxtr+ cells in the basal forebrain, and GABAergic neurons in layers 4/5 of the cortex. Our study provides a novel perspective for understanding the distribution of Oxtr and encourages further investigations into its functions.

Zona Incerta GABAergic Neurons Facilitate Emergence from Isoflurane Anesthesia in Mice.

The zona incerta (ZI) predominantly consists of gamma-aminobutyric acid (GABAergic) neurons, located adjacent to the lateral hypothalamus. GABA, acting on GABAA receptors, serves as a crucial neuromodulator in the initiation and maintenance of general anesthesia. In this study, we aimed to investigate the involvement of ZI GABAergic neurons in the general anesthesia process. Utilizing in-vivo calcium signal optical fiber recording, we observed a decrease in the activity of ZI GABAergic neurons during isoflurane anesthesia, followed by a significant increase during the recovery phase. Subsequently, we selectively ablated ZI GABAergic neurons to explore their role in general anesthesia, revealing no impact on the induction of isoflurane anesthesia but a prolonged recovery time, accompanied by a reduction in delta-band power in mice under isoflurane anesthesia. Finally, through optogenetic activation/inhibition of ZI GABAergic neurons during isoflurane anesthesia, we discovered that activation of these neurons facilitated emergence without affecting the induction process, while inhibition delayed emergence, leading to fluctuations in delta band activity. In summary, these findings highlight the involvement of ZI GABAergic neurons in modulating the emergence of isoflurane anesthesia.

Diabetes and Early Development: Epigenetics, Biological Stress, and Aging.

Pregestational diabetes, either type 1 or type 2 diabetes, induces structural birth defects including neural tube defects and congenital heart defects in human fetuses. Rodent models of type 1 and type 2 diabetic embryopathy have been established and faithfully mimic human conditions. Hyperglycemia of maternal diabetes triggers oxidative stress in the developing neuroepithelium and the embryonic heart leading to the activation of proapoptotic kinases and excessive cell death. Oxidative stress also activates the unfolded protein response and endoplasmic reticulum stress. Hyperglycemia alters epigenetic landscapes by suppressing histone deacetylation, perturbing microRNA (miRNA) expression, and increasing DNA methylation. At cellular levels, besides the induction of cell apoptosis, hyperglycemia suppresses cell proliferation and induces premature senescence. Stress signaling elicited by maternal diabetes disrupts cellular organelle homeostasis leading to mitochondrial dysfunction, mitochondrial dynamic alteration, and autophagy impairment. Blocking oxidative stress, kinase activation, and cellular senescence ameliorates diabetic embryopathy. Deleting the mir200c gene or restoring mir322 expression abolishes maternal diabetes hyperglycemia-induced senescence and cellular stress, respectively. Both the autophagy activator trehalose and the senomorphic rapamycin can alleviate diabetic embryopathy. Thus, targeting cellular stress, miRNAs, senescence, or restoring autophagy or mitochondrial fusion is a promising approach to prevent poorly controlled maternal diabetes-induced structural birth defects. In this review, we summarize the causal events in diabetic embryopathy and propose preventions for this pathological condition. KEY POINTS: · Maternal diabetes induces structural birth defects.. · Kinase signaling and cellular organelle stress are critically involved in neural tube defects.. · Maternal diabetes increases DNA methylation and suppresses developmental gene expression.. · Cellular apoptosis and senescence are induced by maternal diabetes in the neuroepithelium.. · microRNAs disrupt mitochondrial fusion leading to congenital heart diseases in diabetic pregnancy..

Oxaliplatin-induced upregulation of exosomal miR-424-3p derived from human bone marrow mesenchymal stem cells attenuates progression of gastric cancer cells.

Chemotherapy, particularly with oxaliplatin, is a key treatment for advanced gastric cancer (GC), and exosomes derived from human bone marrow mesenchymal stem cells (hBM-MSCs) play a vital role in the tumor microenvironment. The study aims to elucidate the previously unexplored role of exosomes derived from hBM-MSCs in GC tumorigenesis, especially under the influence of chemotherapy. We conducted an experimental study, utilizing miRNA sequencing and biological experiments, to analyze the tumorigenicity of exosomal miR-424-3p secreted by hBM-MSCs and its target gene RHOXF2 in GC cell lines. The results were confirmed through experimentation using a xenograft mouse model. This study demonstrated the role of hBM-MSCs in the GC microenvironment, focusing on their epithelial-mesenchymal transition (EMT) facilitation through exosomes, which led to enhanced tumorigenicity in GC cells. Intriguingly, this pro-tumor effect was abrogated when hBM-MSCs were treated with oxaliplatin. Exosomal miRNA sequencing revealed that oxaliplatin can upregulate the levels of miR-424-3p in exosomes secreted by hBM-MSCs, thereby inhibiting the EMT process in GC cells. Furthermore, miR-424-3p was identified to target and downregulate RHOXF2 expression, impeding the malignant behavior of GC cells both in vitro and in the mouse model. These findings uncover a potential hidden mechanism of oxaliplatin's anti-tumor action and propose the delivery of miR-424-3p via exosomes as a promising avenue for anti-tumor therapy.

Tumor-associated macrophage clusters linked to immunotherapy in a pan-cancer census.

Transcriptional heterogeneity of tumor-associated macrophages (TAMs) has been investigated in individual cancers, but the extent to which these states transcend tumor types and represent a general feature of cancer remains unclear. We performed pan-cancer single-cell RNA sequencing analysis across nine cancer types and identified distinct monocyte/TAM composition patterns. Using spatial analysis from clinical study tissues, we assessed TAM functions in shaping the tumor microenvironment (TME) and influencing immunotherapy. Two specific TAM clusters (pro-inflammatory and pro-tumor) and four TME subtypes showed distinct immunological features, genomic profiles, immunotherapy responses, and cancer prognosis. Pro-inflammatory TAMs resided in immune-enriched niches with exhausted CD8+ T cells, while pro-tumor TAMs were restricted to niches associated with a T-cell-excluded phenotype and hypoxia. We developed a machine learning model to predict immune checkpoint blockade response by integrating TAMs and clinical data. Our study comprehensively characterizes the common features of TAMs and highlights their interaction with the TME.

Metabolic Engineering of Candida tropicalis for the De Novo Synthesis of ß-Ionone.

ß-ionone, a norisoprenoid, is a natural aromatic compound derived from plants, which displays various biological activities including anticancer, antioxidant and deworming properties. Due to its large biomass and strong environmental tolerance, the nonconventional oleaginous yeast Candida tropicalis was selected to efficiently synthesize ß-ionone. We initially investigated the capacity of the cytoplasm and subcellular compartments to synthesize ß-ionone independently. Subsequently, through adaptive screening of enzymes, functional identification of subcellular localization signal peptides and subcellular compartment combination strategies, a titer of 152.4 mg/L of ß-ionone was achieved. Finally, directed evolution of rate-limiting enzyme and overexpression of key enzymes were performed to enhance ß-ionone production. The resulting titer was 400.5 mg/L in shake flasks and 730 mg/L in a bioreactor. This study demonstrates the first de novo synthesis of ß-ionone in C. tropicalis, providing a novel cellular chassis for terpenoid fragrances with considerable industrial potential.

Visual Outcome after Anti-Vascular Epithelial Growth Factor Therapy Using New Classification of Diabetic Macular Edema by Optical Coherence Tomography.

INTRODUCTION: The aim of the study was to examine alterations in visual acuity in patients with diabetic macular edema (DME), classified according to the TCED-HFV optical coherence tomography (OCT) system, following anti-vascular epithelial growth factor (VEGF) therapy. METHODS: The medical records of patients with DME receiving anti-VEGF therapy were retrospectively reviewed. Patients were divided into four groups according to the TCED-HFV OCT classification. Patient demographic and clinical characteristics and best-corrected visual acuity (BCVA) before and after treatment were compared among the groups. RESULTS: The BCVA before treatment was 0.49 ± 0.18, 0.81 ± 0.41, 0.83 ± 0.41, and 0.82 ± 0.49 in the early DME, advanced DME, severe DME, and atrophic maculopathy groups, respectively. The BCVA in the early DME group was therefore significantly lower than that in the other three groups (p = 0.042). After treatment, the BCVA improved to 0.15 ± 0.17, 0.52 ± 0.31, 0.62 ± 0.32, and 0.69 ± 0.47 in the early DME, advanced DME, severe DME, and atrophic maculopathy groups, respectively (p < 0.005). There were some differences among patients in the four groups in terms of the duration of diabetes, percentage of hemoglobin A1c, and duration of hypertension. CONCLUSION: The TCED-HFV OCT classification of patients with DME is exact and functional and can allow the severity of DME, and its response to anti-VEGF therapy, to be estimated.

Acupuncture ameliorates depression-like behavior of poststroke depression model rats through the regulation of gut microbiota and NLRP3 inflammasome in the colon.

This study was conducted to examine the effects of acupuncture on gut microbiota and expression of NLRP3 inflammasome in the colon in poststroke depression (PSD) model rats. Sprague-Dawley male rats were randomized into four groups: sham surgery group, poststroke depression group, acupuncture group, and probiotics group. Acupuncture therapy at Baihui (GV20), Shenting (GV24), bilateral Zusanli (ST36) acupoints in the acupuncture group and probiotic gavage therapy in the probiotics group were performed once per day for 2 weeks. Behaviors of depression were assessed by using weight measurements, sucrose preference test, open field test, and forced swimming test. Histopathological alterations in the colon were determined by hematoxylin-eosin staining, the expression of NLRP3/ASC/caspase-1 pathway-related proteins was analyzed by western blotting. Serum levels of IL-1ß and IL-18 were derived from ELISA. The 16S rRNA gene sequencing was performed to examine and analyze the differences of gut microbiota of rats among all groups. Acupuncture was effective to increase weight and ameliorate depressive-like behaviors in PSD rats. Acupuncture increased the diversity of gut microbiota, upregulated the abundance of Bifidobacteriaceae and Lactobacillaceae, and decreased the relative abundance of Peptostreptococcaceae, Rikenellaceae, Eggerthellaceae, and Streptococcaceae at family level. Acupuncture effectively improved the pathological changes in the colon. Meanwhile, acupuncture reduced NLRP3, ASC, caspase-1 protein expressions in the colon, and serum levels of IL-18 and IL-1ß. Acupuncture may reduce depressive-like behaviors of PSD by regulating the gut microbiota and suppressing hyperactivation of NLRP3 inflammasome in the colon. Microbiota-gut-brain axis may be an effective target pathway for acupuncture treatment of PSD.