Traditional Chinese medicine for post-viral olfactory dysfunction: A systematic review.

Background: Post-viral olfactory dysfunction (PVOD) is the common symptoms of long COVID, lacking of effective treatments. Traditional Chinese medicine (TCM) is claimed to be effective in treating olfactory dysfunction, but the evidence has not yet been critically appraised. We conducted a systematic review to evaluate the effectiveness and safety of TCM for PVOD. Methods: We searched eight databases to identified clinical controlled studies about TCM for PVOD. The Cochrane risk of bias tools and GRADE were used to evaluate the quality of evidence. Risk ratio (RR), mean differences (MD), and 95 % confidence interval (CI), were used for effect estimation and RevMan 5.4.1 was used for data analysis. Results: Six randomized controlled trials (RCTs) (545 participants), two non-randomized controlled trials (non-RCTs) (112 participants), and one retrospective cohort study (30 participants) were included. The overall quality of included studies was low. Acupuncture (n = 8) and acupoint injection (n = 3) were the mainly used TCM therapies. Five RCTs showed a better effect in TCM group. Four trials used acupuncture, and three trials used acupoint injection. The results of two non-RCTs and one cohort study were not statistically significant. Two trials reported mild to moderate adverse events (pain and brief syncope caused by acupuncture or acupoint injection). Conclusions: Limited evidence focus on acupuncture and acupoint injection for PVOD and suggests that acupuncture and acupoint injection may be effective in improving PVOD. More well-designed trials should focus on acupuncture to confirm the benefit. Protocol registration: The protocol of this review was registered at PROSPERO: CRD42022366776.

Oral administration of Lactobacillus delbrueckii subsp. lactis LDL557 attenuates airway inflammation and changes the gut microbiota in a Der p-sensitized mouse model of allergic asthma.

BACKGROUND: Lactic acid bacteria may be used as probiotics to prevent or treat various diseases, and Lactobacillus delbrueckii has an inhibitory effect on the development of atopic diseases. OBJECTIVE: This study explored the effects of L. delbrueckii subsp. lactis strain LDL557 administration on a mouse asthma model resulting from Dermatophoides pteronyssinus (Der p) sensitization and investigated the associated gut microbiota. METHODS: Der p-sensitized and challenged BALB/c mice were orally administered with three different doses of live (low, 107 colony-forming units (CFU); medium, 108 CFU; high, 109 CFU) and heat-killed (109 cells) LDL557 in 200 µL of PBS daily, starting 2 weeks before Der p sensitization and lasting 4 weeks. After the allergen challenge, airway responsiveness to methacholine and the influx of inflammatory cells to the lungs were assessed. The gut microbiome was obtained by sequencing the V3-V4 region of the 16S rRNA gene from mice stool samples. RESULTS: LDL557 in the live (109 CFU) and heat-killed (109 cells) conditions reduced the airway hyper-responsiveness after stimulation with methacholine, inflammatory cell infiltration, and mucus production. These effects were similar to those in groups treated with dexamethasone. No significant change in the gut microbiota was observed after LDL557 treatment, except for the tendency of heat-killed LDL557 to change the gut microbial profile to a greater extent than live LDL557. CONCLUSION: In summary, we found that live and heat-killed LDL557 had the beneficial effect of preventing Der p-induced allergic inflammation in a mouse model of asthma.

The etiology and differential diagnosis of "autoimmune hepatitis-like liver disease" in children: a single-center retrospective study.

Background: Children with autoimmune hepatitis (AIH) often present with symptoms similar to those of other liver diseases. This study consists of a comparison between the clinical and histological characteristics of AIH and those of other four AIH-like liver diseases [i.e., drug-induced liver injury (DILI), gene deficiency, infectious liver disease and other etiology of liver disease], as well as an evaluation of the AIH scoring system's diagnostic performance. Methods: All children with AIH-like liver disease at our center from January 2013 to December 2022 were included. The clinical and histological characteristics of the AIH group were retrospectively analyzed and compared with those of the other four groups. Results: A total of 208 children were included and divided into AIH group (18 patients), DILI group (38 patients), gene deficiency group (44 patients), infectious liver disease group (74 patients), and other etiology group (34 patients). The antinuclear antibodies (ANA) ≥ 1:320 rate was significantly higher in the AIH compared to the other four groups after multiple testing correction (p < 0.0125), while patients with positive antibodies to liver-kidney microsomal-1 (anti-LKM1, n = 3) and smooth muscle antibodies (SMA, n = 2) were only observed in the AIH group. The positive rates of antibodies to liver cytosol type1 (anti-LC1) and Ro52 were higher than those in the other four groups. The serum immunoglobulin G (IgG) and globulin levels, as well as the proportions of portal lymphoplasmacytic infiltration, lobular hepatitis with more than moderate interface hepatitis, and lobular hepatitis with lymphoplasmacytic infiltration, were significantly higher in the AIH group than in the other four groups after multiple testing correction (p < 0.0125). The cirrhosis rate in the AIH group was higher than that in the DILI and infectious liver disease groups (p < 0.0125). Both the simplified (AUC > 0.73) and the revised systems (AUC > 0.93) for AIH have good diagnostic performance, with the latter being superior (p < 0.05). Conclusion: Positive autoantibodies (ANA ≥ 1:320 or anti-LKM1 positive, or accompanied by SMA, anti-LC1 or Ro-52 positive) and elevated serum IgG or globulin levels contribute to early recognition of AIH. The presence of lobular hepatitis with more than moderate interface hepatitis and lymphoplasmacytic infiltration contribute to the diagnosis of AIH.

[Retracted] Silencing of RTKN2 by siRNA suppresses proliferation, and induces G1 arrest and apoptosis in human bladder cancer cells.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that certain of the Transwell migration assay data shown in Fig. 4D on p. 4876 were strikingly similar to data that had already been published in different form in another article written by different authors at a different research institute. In addition, a pair of the data panels in Fig. 4D were overlapping, indicating that data derived from the same original source had been used to represent what were intended to be the results obtained from differently performed experiments.  Owing to the fact that the contentious data in the above article had already been published prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 13: 4872­4878, 2016; DOI: 10.3892/mmr.2016.5127].

From trade-off to synergy: microbial insights into enhancing plant growth and immunity.

The reduction in crop yield caused by pathogens and pests presents a significant challenge to global food security. Genetic engineering, which aims to bolster plant defence mechanisms, emerges as a cost-effective solution for disease control. However, this approach often incurs a growth penalty, known as the growth-defence trade-off. The precise molecular mechanisms governing this phenomenon are still not completely understood, but they generally fall under two main hypotheses: a "passive" redistribution of metabolic resources, or an "active" regulatory choice to optimize plant fitness. Despite the knowledge gaps, considerable practical endeavours are in the process of disentangling growth from defence. The plant microbiome, encompassing both above- and below-ground components, plays a pivotal role in fostering plant growth and resilience to stresses. There is increasing evidence which indicates that plants maintain intimate associations with diverse, specifically selected microbial communities. Meta-analyses have unveiled well-coordinated, two-way communications between plant shoots and roots, showcasing the capacity of plants to actively manage their microbiota for balancing growth with immunity, especially in response to pathogen incursions. This review centers on successes in making use of specific root-associated microbes to mitigate the growth-defence trade-off, emphasizing pivotal advancements in unravelling the mechanisms behind plant growth and defence. These findings illuminate promising avenues for future research and practical applications.

10 weeks low intensity treadmill exercise intervention ameliorates motor deficits and sustains muscle mass via decreasing oxidative damage and increasing mitochondria function in a rat model of Parkinson's disease.

AIMS: Parkinson's disease (PD) is characterized by loss of dopamine neurons in the brain, which leads to motor dysfunction; excessive inflammation induces neuronal death. This study aimed to determine the most effective exercise modality to improve motor dysfunction in PD by comparing three different exercise regimens (low-intensity treadmill, high-intensity treadmill, and swimming). MATERIALS AND METHODS: The rat model for PD was established through stereotaxic surgery, inducing unilateral 6-OHDA (6-hydroxydopamine) lesions. The low-intensity treadmill regimen exerted better protective effects on neurological and motor functions in a rat model of unilateral 6-OHDA-induced PD compared to high-intensity treadmill and swimming. The most suitable exercise regimen and the optimal duration of daily exercise (15 or 30 min) on motor activity and oxidative stress parameters were evaluated. KEY FINDINGS: Comparison of 15 and 30 min low-intensity treadmill regimens (10 m/min) revealed 30 min daily exercise was the optimal duration and had more favorable impacts on neurological and motor function. Furthermore, we assessed the neuroprotective effects of exercising for 15 and 30 min per day for either four or ten weeks; 30 min of daily exercise for ten weeks improved mitochondrial function, the antioxidant defense system, neurotrophic factors, and muscle mass, and thereby provided protection against dopaminergic neuron loss, and motor dysfunction in rats with 6-OHDA-induced PD. SIGNIFICANCE: 30 min of daily low-intensity treadmill exercise over 10 weeks resulted in heightened mitochondrial function in both muscle and brain tissues, therefore, yielded a neuroprotective effect against the loss of dopaminergic neurons and motor dysfunction in PD rats.

Angular-resolved Rabi oscillations of orthorhombic spins in a Co(II) molecular qubit.

Magnetic molecules are promising candidates for quantum information processing (QIP) due to their tunable electron structures and quantum properties. A high spin Co(II) complex, CoH2dota, is studied for its potential to be used as a quantum bit (qubit) utilizing continuous wave (CW) and pulsed electron paramagnetic resonance (EPR) spectroscopy at low temperature. On the X-band microwave energy scale, the system can be treated as an effective spin 1/2 with a strongly anisotropic g-tensor resulting from the significant spin-orbital coupling. An experimental and theoretical study is conducted to investigate the anisotropic Rabi oscillations of the two magnetically equivalent spin centres with different orientations in a single crystal sample, which aims to verify the relationship between the Rabi frequency and the orientation of the g-tensor. The findings of this study show that an effective quantum manipulation method is developed for orthorhombic spin systems.

Neuronal intranuclear inclusion disease in New Zealand: A novel discovery.

Neuronal intranuclear inclusion disease, caused by a GGC repeat expansion in the 5'-untranslated region of NOTCH2NLC, is a rare neurodegenerative condition with highly variable clinical manifestations. In recent years, the number of reported cases have increased dramatically in East Asia. We report the first four genetically confirmed cases of neuronal intranuclear inclusion disease in New Zealand, all having Polynesian ancestry (three New Zealand Maori and one Cook Island Maori). Phenotypically, they resemble cases reported from recent large East Asian cohorts.

Neuropsychiatric Symptoms Predict Faster Cognitive Decline in Dementia Collaborative Care Than Antipsychotic Use.

Background: To compare short-term cognitive outcomes among groups with and without neuropsychiatric symptoms (NPSs) or antipsychotic prescription and to determine which disease status or treatment modality is associated with relatively faster cognitive decline. Methods: We retrospectively analyzed a prospective cohort of patients diagnosed with dementia and mild cognitive impairment. All participants were evaluated using the Cognitive Abilities Screening Instrument (CASI) during their initial clinical assessments and at the annual follow-up. The dependent variable was annual delta CASI. Multivariate linear regression analysis was used to assess the degree of association between NPS, antipsychotic use, and cognitive decline after adjusting for confounding factors. Neuropsychiatric symptoms were examined individually to determine their predictive value for cognitive decline. Results: A total of 407 (N = 407) patients were included in the study. NPSs, rather than antipsychotic use, led to faster cognitive decline. A higher baseline NPI total score predicted a significantly faster decline in CASI scores (1-year delta CASI = -0.22, 95% CI = -0.38~ -0.05, p = 0.010). Specific items (delusions, agitation, depression, anxiety, euphoria, and apathy) in the NPS significantly increased cognitive decline. Conclusion: Certain neuropsychiatric symptoms, rather than antipsychotic use, lead to faster cognitive decline in a dementia collaborative care model. Checking for and providing appropriate interventions for NPS in people with dementia and their caregivers are highlighted.

The effects of symbolic gestural training on enhancing recovery of spoken naming in people with aphasia: A systematic review and meta-analysis.

PURPOSE: This study aimed to evaluate the effects of symbolic gestural training on enhancing recovery of spoken naming in people with aphasia (PWA) using a systematic review and meta-analysis. METHOD: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, article search was conducted from four databases: Web of Science Core Collection, Medline, PsycINFO, and EBSCO. A total of 45 participants from four studies investigating the symbolic gestural training effects on PWA and outcome measures of spoken naming were included. RESULT: The meta-analysis showed a medium overall effect of symbolic gestural training on enhancing recovery of spoken naming in PWA. Subgroup analysis also revealed that the training effect was more remarkable in the gesture + verbal training paradigm than in the gesture-only training paradigm. However, the differences in the training effects between short and long duration, and training supplied with and without feedback, were nonsignificant. CONCLUSION: This study illustrates the current state of the literature on symbolic gestural training in PWA, and serves as a reference for clinicians, patients, and health policy-makers regarding the application of symbolic gestural training in clinical or rehabilitation programs.

A novel mutation in hERG gene associated with azithromycin-induced acquired long QT syndrome.

BACKGROUND: Mutations in human ether-à-go-go-related gene (hERG) potassium channels are closely associated with long QT syndrome (LQTS). Previous studies have demonstrated that macrolide antibiotics increase the risk of cardiovascular diseases. To date, the mechanisms underlying acquired LQTS remain elusive. METHODS: A novel hERG mutation I1025N was identified in an azithromycin-treated patient with acquired long QT syndrome via Sanger sequencing. The mutant I1025N plasmid was transfected into HEK-293 cells, which were subsequently incubated with azithromycin. The effect of azithromycin and mutant I1025N on the hERG channel was evaluated via western blot, immunofluorescence, and electrophysiology techniques. RESULTS: The protein expression of the mature hERG protein was down-regulated, whereas that of the immature hERG protein was up-regulated in mutant I1025N HEK-293 cells. Azithromycin administration resulted in a negative effect on the maturation of the hERG protein. Additionally, the I1025N mutation exerted an inhibitory effect on hERG channel current. Moreover, azithromycin inhibited hERG channel current in a concentration-dependent manner. The I1025N mutation and azithromycin synergistically decreased hERG channel expression and hERG current. However, the I1025N mutation and azithromycin did not alter channel gating dynamics. CONCLUSIONS: These findings suggest that hERG gene mutations might be involved in the genetic susceptibility mechanism underlying acquired LQTS induced by azithromycin.

Resveratrol inhibits arecoline-induced fibrotic properties of buccal mucosal fibroblasts via miR-200a activation.

Background/purpose: Oral submucous fibrosis (OSF) is a precancerous lesion in the oral cavity, commonly results from the Areca nut chewing habit. Arecoline, the main component of Areca nut, is known to stimulate the activation of myofibroblasts, which can lead to abnormal collagen I deposition. Meanwhile, Resveratrol is a non-flavonoid phenolic substance that can be naturally obtained from various berries and foods. Given that resveratrol has significant anti-fibrosis traits in other organs, but little is known about its effect on OSF, this study aimed to investigate the therapeutic impact of resveratrol on OSF and its underlying mechanism. Materials and methods: The cytotoxicity of resveratrol was tested using normal buccal mucosal fibroblasts (BMFs). Myofibroblast phenotypes such as collagen contractile, enhanced migration, and wound healing capacities in dose-dependently resveratrol-treated fBMFs were examined. Results: Current results showed that arecoline induced cell migration and contractile activity in BMFs as well as upregulated the expressions of α-SMA, type I collagen, and ZEB1 markers. Resveratrol intervention, on the other hand, was shown to inhibit arecoline-induced myofibroblast activation and reduce myofibroblast hallmarks and EMT markers. Additionally, resveratrol was also demonstrated to restore the downregulated miR-200a in the arecoline-stimulated cells. Conclusion: In a nutshell, these findings implicate that resveratrol may have an inhibitory influence on arecoline-induced fibrosis via the regulation of miR-200a. Hence, resveratrol may be used as a therapeutic strategy for OSF intervention.

Er:YAG laser suppresses pro-inflammatory cytokines expression and inflammasome in human periodontal ligament fibroblasts with Porphyromonas gingivalis-lipopolysaccharide stimulation.

Background/purpose: Periodontitis is an inflammatory condition of the tooth-supporting structures triggered by the host's immune response towards the bacterial deposits around the teeth. It is well acknowledged that pro-inflammatory interleukin (IL)-6, IL-8, MCP-1 as well as the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome, are the key modulators in the activation of this response. Erbium-doped yttrium-aluminium-garnet (Er:YAG) laser, a solid-state crystal laser have been commonly used in the treatment of periodontal diseases. However, little is understood about the molecular mechanism of the Er:YAG laser, especially in targeting the host immune response brought on by periodontal pathogens. Hence, the current study focused on the protective effects of Er:YAG laser on periodontitis in-vitro in terms of pro-inflammatory cytokines, chemokines and NLRP3 inflammasome expressions. Materials and methods: Human periodontal ligament fibroblast (PDLFs) were first stimulated with lipopolysaccharides (LPS) from P. gingivalis (Pg-LPS) to simulate periodontitis. Cells were then irradiated with Er:YAG laser of ascending energy densities (3.6-6.3 J/cm2), followed by cell proliferation and wound healing assay. Next, the effects of Er:YAG laser on the expressions of IL-6, IL-8, MCP-1, NLRP3, and cleaved GSDMD were examined. Results: Pg-LPS was found to reduce cell's proliferation rate and wound healing ability in PDLFs and these were rescued by Er:YAG laser irradiation. In addition, LPS stimuli resulted in a marked upregulation in the secretion of IL-6, IL-8 and MCP-1 as well as the mRNA and protein expression of NLRP3 and cleaved-GSDMD protein whereas Er:YAG laser suppressed the elicited phenomena. Conclusion: To our knowledge, this is the first study to look into the laser's implication on the NLRP3 inflammasome in periodontitis models. Our study reveals a crucial role of Er:YAG laser in ameliorating periodontitis in-vitro through the modulation of IL-6, IL-8, MCP-1 and the NLRP3 inflammasome and highlights that the control of the NLRP3 inflammasome may become a potential approach for periodontitis.

Unveiling the applications of membrane proteins from oil bodies: leading the way in artificial oil body technology and other biotechnological advancements.

Oil bodies (OBs) function as organelles that store lipids in plant seeds. An oil body (OB) is encased by a membrane composed of proteins (e.g., oleosins, caleosins, and steroleosins) and a phospholipid monolayer. The distinctive protein-phospholipid membrane architecture of OBs imparts exceptional stability even in extreme environments, thereby sparking increasing interest in their structure and properties. However, a comprehensive understanding of the structure-activity relationships determining the stability and properties of oil bodies requires a more profound exploration of the associated membrane proteins, an aspect that remains relatively unexplored. In this review, we aim to summarize and discuss the structural attributes, biological functions, and properties of OB membrane proteins. From a commercial perspective, an in-depth understanding of the structural and functional properties of OBs is important for the expansion of their applications by producing artificial oil bodies (AOB). Besides exploring their structural intricacies, we describe various methods that are used for purifying and isolating OB membrane proteins. These insights may provide a foundational framework for the practical utilization of OB membrane proteins in diverse applications within the realm of AOB technology, including biological and probiotic delivery, protein purification, enzyme immobilization, astringency detection, and antibody production.

Microbiome signatures associated with clinical stages of gastric Cancer: whole metagenome shotgun sequencing study.

BACKGROUND: Gastric cancer is one of the global health concerns. A series of studies on the stomach have confirmed the role of the microbiome in shaping gastrointestinal diseases. Delineation of microbiome signatures to distinguish chronic gastritis from gastric cancer will provide a non-invasive preventative and treatment strategy. In this study, we performed whole metagenome shotgun sequencing of fecal samples to enhance the detection of rare bacterial species and increase genome sequence coverage. Additionally, we employed multiple bioinformatics approaches to investigate the potential targets of the microbiome as an indicator of differentiating gastric cancer from chronic gastritis. RESULTS: A total of 65 patients were enrolled, comprising 33 individuals with chronic gastritis and 32 with gastric cancer. Within each group, the chronic gastritis group was sub-grouped into intestinal metaplasia (n = 15) and non-intestinal metaplasia (n = 18); the gastric cancer group, early stage (stages 1 and 2, n = 13) and late stage (stages 3 and 4, n = 19) cancer. No significant differences in alpha and beta diversities were detected among the patient groups. However, in a two-group univariate comparison, higher Fusobacteria abundance was identified in phylum; Fusobacteria presented higher abundance in gastric cancer (LDA scored 4.27, q = 0.041 in LEfSe). Age and sex-adjusted MaAsLin and Random Forest variable of importance (VIMP) analysis in species provided meaningful features; Bacteria_caccae was the most contributing species toward gastric cancer and late-stage cancer (beta:2.43, se:0.891, p:0.008, VIMP score:2.543). In contrast, Bifidobacterium_longum significantly contributed to chronic gastritis (beta:-1.8, se:0.699, p:0.009, VIMP score:1.988). Age, sex, and BMI-adjusted MasAsLin on metabolic pathway analysis showed that GLCMANNANAUT-PWY degradation was higher in gastric cancer and one of the contributing species was Fusobacterium_varium. CONCLUSION: Microbiomes belonging to the pathogenic phylum Fusobacteria and species Bacteroides_caccae and Streptococcus_anginosus can be significant targets for monitoring the progression of gastric cancer. Whereas Bifidobacterium_longum and Lachnospiraceae_bacterium_5_1_63FAA might be protection biomarkers against gastric cancer.

Combining brief recall and ketamine treatment prevents stress-primed methamphetamine memory reinstatement via heightening mPFC GABA activity.

This study aimed to assess whether brief recall of methamphetamine (MA) memory, when combined with ketamine (KE) treatment, may prevent stress-primed MA memory reinstatement. Combining 3-min recall and KE facilitated MA memory extinction and resistance to subsequent stress-primed reinstatement. Such combination also produced glutamate metabotropic receptor 5 (mGluR5) upregulation in animals' medial prefrontal cortex (mPFC) γ-amino-butyric acid (GABA) neuron. Accordingly, chemogenetic methods were employed to bi-directionally modulate mPFC GABA activity. Following brief recall and KE-produced MA memory extinction, intra-mPFC mDlx-Gi-coupled-human-muscarinic-receptor 4 (hM4Di)-infused mice receiving compound 21 (C21) treatment showed eminent stress-primed reinstatement, while their GABA mGluR5 expression seemed to be unaltered. Intra-mPFC mDlx-Gq-coupled-human-muscarinic-receptor 3 (hM3Dq)-infused mice undergoing C21 treatment displayed MA memory extinction and resistance to stress-provoked reinstatement. These results suggest that combining a brief recall and KE treatment and exciting mPFC GABA neuron may facilitate MA memory extinction and resistance to stress-primed recall. mPFC GABA neuronal activity plays a role in mediating brief recall/KE-produced effects on curbing the stress-provoked MA seeking.

A missense mutation in human INSC causes peripheral neuropathy.

PAR3/INSC/LGN form an evolutionarily conserved complex required for asymmetric cell division in the developing brain, but its post-developmental function and disease relevance in the peripheral nervous system (PNS) remains unknown. We mapped a new locus for axonal Charcot-Marie-Tooth disease (CMT2) and identified a missense mutation c.209 T > G (p.Met70Arg) in the INSC gene. Modeling the INSCM70R variant in Drosophila, we showed that it caused proprioceptive defects in adult flies, leading to gait defects resembling those in CMT2 patients. Cellularly, PAR3/INSC/LGN dysfunction caused tubulin aggregation and necrotic neurodegeneration, with microtubule-stabilizing agents rescuing both morphological and functional defects of the INSCM70R mutation in the PNS. Our findings underscore the critical role of the PAR3/INSC/LGN machinery in the adult PNS and highlight a potential therapeutic target for INSC-associated CMT2.

MSC-derived exosomes deliver ZBTB4 to mediate transcriptional repression of ITIH3 in astrocytes in spinal cord injury.

BACKGROUND: BMSC-secreted exosomes (BMSC-Exos) have shown potential for promoting behavioral recovery following spinal cord injury (SCI). However, its role in blocking astrocyte activation remains unclear. Thus, this study aimed to determine whether BMSC-Exos impair the function of astrocytes following SCI in mice and to seek the mechanism. METHODS: BMSC-Exos were collected by ultracentrifugation and identified. The SCI mice were developed by laminectomy combined with spinal cord shock, followed by BMSC-Exos or nerve growth factor (positive control) treatment. HE staining, Nissl staining, and TUNEL were conducted to analyze the pathological structural damage and neuronal damage in the mouse spinal cord. Bioinformatics was used to screen altered molecules under the BMSC-Exos treatment. Effects of BMSC-Exos and changes in ZBTB4 and ITIH3 expression on neuronal damage induced by activated astrocytes in the co-culture system were analyzed by CCK-8 and flow cytometry. RESULTS: Nerve growth factor and BMSC-Exos promoted motor function recovery, alleviated nerve injury, and reduced apoptosis in mice with SCI. ZBTB4 was enriched in BMSC-Exos and lowly expressed in SCI. Downregulation of ZBTB4 diminished the therapeutic effects of BMSC-Exos against SCI. ITIH3 was a downstream target of ZBTB4. Neurotoxic activation of astrocytes induced neuronal injury, which was alleviated by BMSC-Exos. However, ZBTB4 knockdown overturned the effects of BMSC-Exos in vitro and combined ITIH3 knockdown alleviated the accentuating effects of ZBTB4 knockdown on neuronal injury. CONCLUSION: BMSC-Exos protected against astrocyte-induced neuronal injury by delivering ZBTB4 to repress ITIH3, ultimately improving motor function in mice with SCI.