Biomimetic delivery of emodin via macrophage membrane-coated UiO-66-NH2 nanoparticles for acute pancreatitis treatment.

Acute pancreatitis (AP) is a severe inflammatory condition with a rising incidence and high mortality rates, especially in severe cases. Emodin (ED), known for its potent anti-inflammatory properties, holds promise in addressing AP. However, its clinical application is hindered by limitations such as low bioavailability and insufficient target specificity. Herein, we developed a novel drug delivery system using macrophage membrane-coated UiO-66-NH2 nanoparticles loaded with ED (MVs-UiO-ED). UiO-66-NH2 was successfully synthesized and characterized, revealing an octahedral structure with a suitable size distribution. The successful loading of ED onto UiO-66-NH2 was confirmed by ultraviolet and infrared spectroscopy. Subsequently, MVs-UiO-ED was prepared by coating macrophage membrane-derived vesicles onto UiO-ED, resulting in a biomimetic delivery system. In vitro release studies demonstrated that MVs-UiO-ED exhibited a sustained-release profile, indicating its potential for prolonged drug circulation. An AP mouse model was established to evaluate the therapeutic efficacy of MVs-UiO-ED. Compared with the model group, MVs-UiO-ED significantly reduced serum levels of α-amylase and lipase, two indicators of pancreatitis severity. Furthermore, histopathological examinations revealed that MVs-UiO-ED ameliorated pancreatic tissue damage. This study underscores the potential of MVs-UiO-ED as an effective therapeutic approach for AP.

A novel p55PIK signaling peptide inhibitor alleviates neuroinflammation via the STAT3/NF-kB signaling pathway in experimental stroke.

BACKGROUND: Ischemic stroke remains the predominant contributor to mortality and disability globally. Microglia undergo rapid activation and initiate inflammatory cascade reactions by phenotypic polarization, participating in the regulation of inflammatory injury and tissue repair post-ischemic stroke. Regulating microglia-mediated neuroinflammation is a promising therapeutic strategy for ischemic stroke. Previously, we designed and synthesized a novel p55PIK inhibitor, TAT-N15 polypeptide, which presents inhibitive activity on NF-κB signaling-mediated inflammation in acute conjunctivitis and allergic rhinitis. The present study aimed to explore the therapeutic effect and mechanism of TAT-N15 on ischemia stroke. METHODS: The mouse model of transient cerebral ischemia was made using the intraluminal filament method. After being treated with daily intraperitoneal injections of TAT-N15 (10 mg/kg) for 7 d, the neurological outcomes and the cerebral infarction volume were evaluated. Histopathology of the ischemia cerebral hemisphere was observed by H&E and Nissl staining. Neuronal survival, astrogliosis, and co-labeling of CD86/Iba1 and CD206/Iba1 were detected by immunofluorescence. The cell apoptosis was estimated by TUNEL staining. The expression levels of apoptosis-associated proteins, proinflammatory cytokines, protein markers of M1 and M2 microglia, and the phosphorylation of NF-κB and STAT3 proteins in the ischemic penumbra were detected by Western blot. RESULTS: TAT-N15 treatment significantly decreased the infarct volume and alleviated neurological functional impairment, neuronal injury, and neuron apoptosis. Meanwhile, TAT-N15 treatment restrained the activation of microglia and astrocytes as well as the protein expression of proinflammatory cytokine in ischemic penumbra. Additionally, the administration of TAT-N15 treatment resulted in a significant reduction in the density of M1 phenotype microglia while concurrently increasing the density of M2 phenotype microglia within the ischemic penumbra. Finally, mechanical analysis unveiled that TAT-N15 exerted a substantial inhibitory effect on the protein expression of phosphorylated STAT3 and NF-κB. CONCLUSION: TAT-N15 may inhibit neuroinflammation via regulating microglia activation and polarization through the STAT3/NF-κB pathway, which exhibits the neuroprotection effect in ischemic stroke.

Tangeretin Mitigates Trimethylamine Oxide Induced Arterial Inflammation by Disrupting Choline-Trimethylamine Conversion through Specific Manipulation of Intestinal Microflora.

Previous studies have revealed the microbial metabolism of dietary choline in the gut, leading to its conversion into trimethylamine (TMA). Polymethoxyflavones (PMFs), exemplified by tangeretin, have shown efficacy in mitigating choline-induced cardiovascular inflammation. However, the specific mechanism by which these compounds exert their effects, particularly in modulating the gut microbiota, remains uncertain. This investigation focused on tangeretin, a representative PMFs, to explore its influence on the gut microbiota and the choline-TMA conversion process. Experimental results showed that tangeretin treatment significantly attenuated the population of CutC-active bacteria, particularly Clostridiaceae and Lactobacillus, induced by choline chloride in rat models. This inhibition led to a decreased efficiency in choline conversion to TMA, thereby ameliorating cardiovascular inflammation resulting from prolonged choline consumption. In conclusion, tangeretin's preventive effect against cardiovascular inflammation is intricately linked to its targeted modulation of TMA-producing bacterial activity.

Clinical application and detection techniques of liquid biopsy in gastric cancer.

Gastric cancer (GC) is one of the most common tumors worldwide and the leading cause of tumor-related mortality. Endoscopy and serological tumor marker testing are currently the main methods of GC screening, and treatment relies on surgical resection or chemotherapy. However, traditional examination and treatment methods are more harmful to patients and less sensitive and accurate. A minimally invasive method to respond to GC early screening, prognosis monitoring, treatment efficacy, and drug resistance situations is urgently needed. As a result, liquid biopsy techniques have received much attention in the clinical application of GC. The non-invasive liquid biopsy technique requires fewer samples, is reproducible, and can guide individualized patient treatment by monitoring patients' molecular-level changes in real-time. In this review, we introduced the clinical applications of circulating tumor cells, circulating free DNA, circulating tumor DNA, non-coding RNAs, exosomes, and proteins, which are the primary markers in liquid biopsy technology in GC. We also discuss the current limitations and future trends of liquid biopsy technology as applied to early clinical biopsy technology.

Characterization of the angular memory effect of dynamic turbid media.

The optical angular memory effect (AME) is a basic feature of turbid media and defines the correlation of speckles when the incident light is tilted. AME based imaging through solid scattering media such as ground glass and biomedical tissue has been recently developed. However, in the case of liquid media such as turbid water or blood, the speckle pattern exhibits dynamic time-varying characteristics, which introduces several challenges. The AME of the thick volume dynamic media is particularly different from the layer scatterers. In practice, there are more parameters, e.g., scattering particle size, shape, density, or even the illuminating beam aperture that can influence the AME range. Experimental demonstration of AME phenomenon in liquid dynamic media and confirm the distinctions will contribution to complete the AME theory. In this paper, a dual-polarization speckle detection setup was developed to characterize the AME of dynamic turbid media, where two orthogonal polarized beams were employed for simultaneous detection by a single CCD. The AME of turbid water, milk and blood were measured. The influence of thickness, concentration, particle size and shape, and beam diameter were analyzed. The AME increasement of upon the decrease of beam diameter was tested and verified. The results demonstrate the feasibility of this method for investigating the AME phenomenon and provide guidance for AME based imaging through scattering media.

Inhibition of A1 Astrocytes and Activation of A2 Astrocytes for the Treatment of Spinal Cord Injury.

Spinal cord injury (SCI) is a serious injury to the central nervous system that causes significant physical and psychological trauma to the patient. SCI includes primary spinal cord injuries and secondary spinal cord injuries. The secondary injury refers to the pathological process or reaction after the primary injury. Although SCI has always been thought to be an incurable injury, the human nerve has the ability to repair itself after an injury. However, the reparability is limited because glial scar formation impedes functional recovery. There is a type of astrocyte that can differentiate into two forms of reactive astrocytes known as 'A1' and 'A2' astrocytes. A1 astrocytes release cytotoxic chemicals that cause neurons and oligodendrocytes to die and perform a harmful role. A2 astrocytes can produce neurotrophic factors and act as neuroprotectors. This article discusses ways to block A1 astrocytes while stimulating A2 astrocytes to formulate a new treatment for spinal cord injury.

Application value of structured psychological nursing combined group health education in blood purification patients: Assisted by the purification of a nanofiber composite.

To explore the research value of structured psychological nursing combined with group health education in patients with blood purification. From May 2020 to March 2022, 96 pure-blood patients in the hospital were selected and divided into research group and control group according to simple random classification, with 48 patients in each group. The control group received routine nursing, and the study group conducted health education combined with structured psychological nursing on the basis of usual care. The disease cognitive ability, negative emotions, blood purification adequacy rate, nutritional status qualification rate and complication rate of the two groups before and after intervention were counted. (1) The number of disease points with unclear status in the study group after intervention was 10.39 ± 1.87, complications were 13.88 ± 2.27, lack of disease information was 12.36 ± 2.16, and unpredictability was 9.58 ± 1.38, which were lower than 13.12 ± 2.53, 17.56 ± 2.53, 15.83 ± 3.0411.67 ± 1.71; (2) After the intervention, the values of SDS of 40.77 ± 3.69 and SAS of 41.52 ± 4.06 were lower than those of 45.82 ± 5.01 and 46.35 ± 4.81 in the control group. (3) The blood adequacy rate of the study group was 91.67%, and the nutritional qualification rate was 93.75%, and the data of both groups were higher than that of 77.08% and 79.17% of the control group. (4) The incidence of complications in the study group was 4.17%, and the control group was 16.67%. Group health education and structured psychological care can effectively alleviate patients' negative emotions and deepen their awareness of diseases, thereby improving blood purification rate and nutrient absorption.

Quercetin-loaded PLGA nanoparticles coating with macrophage membranes for targeted delivery in acute liver injury.

Quercetin (QU), a natural flavonoid with potent anti-inflammatory and antioxidant properties, holds promise in treating acute liver injury (ALI). Nonetheless, its limited solubility hampers its efficacy, and its systemic distribution lacks targeting, leading to off-target effects. To address these challenges, we developed macrophage membrane-coated quercetin-loaded PLGA nanoparticles (MVs-QU-NPs) for active ALI targeting. The resulting MVs-QU-NPs exhibited a spherical morphology with a clear core-shell structure. The average size and zeta potential were assessed as 141.70 ± 0.89 nm and -31.83 ± 0.76 mV, respectively. Further studies revealed sustained drug release characteristics from MVs-QU-NPs over a continuous period of 24 h. Moreover, these MVs-QU-NPs demonstrated excellent biocompatibility when tested on normal liver cells. The results of biodistribution analysis in ALI mice displayed the remarkable ALI-targeting ability of MVs-DiD-NPs, with the highest fluorescence intensity observed in liver tissue. This biomimetic approach combining macrophage membranes with nanoparticle delivery, holds great potential for targeted ALI treatment.

Dead Cas(t) light on new life: CRISPRa-mediated reprogramming of somatic cells into neurons.

Overexpression of exogenous lineage-specific transcription factors could directly induce terminally differentiated somatic cells into target cell types. However, the low conversion efficiency and the concern about introducing exogenous genes limit the clinical application. With the rapid progress in genome editing, the application of CRISPR/dCas9 has been expanding rapidly, including converting somatic cells into other types of cells in vivo and in vitro. Using the CRISPR/dCas9 system, direct neuronal reprogramming could be achieved by activating endogenous genes. Here, we will discuss the latest progress, new insights, and future challenges of the application of the dCas9 system in direct neuronal reprogramming.

Analysis of bleeding after ultrasound-guided needle biopsy of benign cervical lymph nodes.

AIM: Summarized the incidence of bleeding after ultrasound-guided coarse needle biopsy (US-CNB) of benign cervical lymph nodes. METHODS: We retrospectively examined the clinical and follow-up records of 590 patients with benign cervical lymph node disease who underwent US-CNB at our hospital during February 2015-July 2022 and were confirmed to have the disease by CNB and surgical pathology. The number of cases, types of diseases, and degree of bleeding of all patients with bleeding after US-CNB were statistically analyzed. RESULTS: Of the 590 patients, bleeding was noted in 44 cases(7.46%), and the infectious lymph node bleeding rate was 9.48%. Infectious lymph nodes were more likely to bleed than noninfectious lymph nodes after CNB, ,x2 = 8.771; P = 0.003, Lymph nodes with pus were more likely to bleed than solid lymph nodes after CNB, x2 = 4.414; P = 0.036,. CONCLUSION: The bleeding of all patients after CNB was minor bleeding. Infected lymph nodes bleed more frequently than noninfected lymph nodes. Lymph nodes with mobility and a large pus cavity, are more likely to bleed after CNB.

High expression of CLEC10A in head and neck squamous cell carcinoma indicates favorable prognosis and high-level immune infiltration status.

Immunotherapy has emerged as a promising treatment modality for HNSCC. However, only a small proportion of HNSCC patients experience clinical benefits from immunotherapy and identifying molecular markers that can serve as effective prognostic signatures and predictive indicators for immunotherapy response in patients with HNSCC is critical. CLEC10A has attracted attention because of its important role in improving the antitumor activity of immune cells. However, to our knowledge, no study has evaluated the role of CLEC10A in HNSCC prognosis, progression, and immune microenvironment. In the present study, we comprehensively analyzed expression profiles of CLEC10A and its association with tumor progression, HPV status, and survival of patients. Moreover, we explored the association between CLEC10A expression relative to immune infiltration and the response to immunotherapy. We explored the association between the timing of the receipt of palliative care relative to cancer diagnosis and survival. Our results revealed that CLEC10A has decreased expression in HNSCC compared with normal tissues, and that low expression of CLEC10A was associated with an advanced clinical stage and poor prognosis. Furthermore, a higher level of CLEC10A expression correlated with immune infiltration presence and response to immunotherapy in HNSCC. Thus, we demonstrated that CLEC10A could be a potential prognostic marker in patients with HNSCC, and a potential target for immunotherapy.

Spirally rotating particles with structured beams generated by phase-shifted zone plates.

The emerging field of structured beams has led to optical manipulation with tremendous progress. Beyond various methods for structured beams, we use phase-shifted zone plates known as beam-shaping diffractive optical elements to generate beams whose phase exclusively or both phase and intensity are twisted along a curve. These beams can trap and guide particles on open curved trajectories for continuous motion, not necessarily requiring a closed symmetric intensity distribution. We show the feasibility and versatility of the proposed method as a promising technique in optical manipulation in which the trajectory of the spiral rotation and the rate of rotation of trapped particles can be controlled.

CAQK modification enhances the targeted accumulation of metformin-loaded nanoparticles in rats with spinal cord injury.

Spinal cord injury (SCI) often causes neuronal membrane rupture and immediate death of neurons, followed by complicated secondary injuries. Treatment of SCI still remains a major challenge in clinical practice; thus, a great advance is urgently needed in this field. Metformin (MET) has anti-oxidant, anti-inflammatory, anti-apoptotic and neuroprotective properties, which may exert a potential therapeutic effect on SCI. In this study, we established a zein-based MET-loaded nanodrug system (CAQK-MET-NPs) for the targeted drug delivery for SCI. The results showed that MET could be effectively encapsulated into zein to obtain the zein-based spherical nanoparticles. Pharmacokinetic analysis indicated that CAQK-MET-NPs exhibited sustained-release and long-term therapeutic effects. The fluorescence imaging and tissue distribution experiments showed that CAQK-MET-NPs could efficiently accumulate at the lesion site of SCI rats. In conclusion, CAQK-MET-NPs may be a promising nanodrug for the treatment of SCI.

Association of urinary arsenic with insulin resistance: Cross-sectional analysis of the National Health and Nutrition Examination Survey, 2015-2016.

BACKGROUND: Long-term arsenic exposure is associated with diabetes in adults, the mechanism of which involves insulin resistance. The relationship between arsenic and insulin resistance in adults is unclear. We analyzed the relationship between urinary arsenic and insulin resistance in US adults. RESULTS: We identified 815 adults aged 20-79 years who participated in the 2015-2016 National Health and Nutrition Examination Survey (NHANES). Urinary arsenic, fasting glucose, serum insulin, and other key covariates were obtained from the NHANES data. The association between urinary arsenic and insulin resistance was evaluated by analyzing the urinary arsenic level and homeostasis model assessment-insulin resistance. The median total urinary arsenic level was 6.82 µg/L. After adjusting for possible confounding factors (gender, age, and body mass index), the 80th and 20th percentile odds ratio (OR) was 1.41 (95% confidence interval [CI] 1.07, 1.87); the OR of the 70th and 30th percentiles was 1.41 (95% CI 1.08, 1.84). CONCLUSIONS: In most subgroups, after similar adjustment, the relationship between urine total arsenic and insulin resistance remained. Total arsenic exposure in urine may be associated with insulin resistance. Evidence from larger and more adequately powered cohort studies is needed to confirm our results.

Acupoint catgut embedding improves senescence in a rat model of ageing by regulating mitophagy via the PINK1 pathway.

Ageing population is a tough task worldwide, and the aggravating trend of ageing population in China brings enormous pressure to healthcare system. Chinese acupuncture has shown definite anti-ageing effect as arthralgia relief, movement improvement, energy increase and immunity enhancement; however, the mechanisms underlying are far away from illumination. Increasing literature has highlighted the role of alterations in mitochondrial function as a potential central regulator in ageing biology; mitophagy plays a critical role in mitochondrial quality control. In the present study, we demonstrated that acupoint catgut embedding treatment ameliorated ageing-related alterations in appearance, muscle function and spatial memory in rats, reduced degenerated cells in hippocampus, and maintained relatively normal structures in the hippocampus tissue and neurons. These changes were proved to be associated with the regulation of mitochondrial function and autophagic activity. Furthermore, we investigated part of the molecular mechanisms and demonstrated that the PINK1 other than PINK1-Parkin signalling pathway involved in the effects of acupoint catgut embedding, and the imbalancement between mitochondrial fusion and fission and stimulation of mitochondrial biogenesis may aggravate or compensate for impaired mitochondria. The factors act downstream PINK, and the interaction between them for mitochondrial homeostasis in this process remains to be identified.

Identification of the downstream molecules of agrin/Dok-7 signaling in muscle.

The development of the neuromuscular junction depends on signaling processes that involve protein phosphorylation. Motor neuron releases agrin to activate muscle protein Dok-7, a key tyrosine kinase essential for the formation of a mature and functional neuromuscular junction. However, the signaling cascade downstream of Dok-7 remains poorly understood. In this study, we combined the clustered regularly interspaced short palindromic repeats/Cas9 technique and quantitative phosphoproteomics analysis to study the tyrosine phosphorylation events triggered by agrin/Dok-7. We found tyrosine phosphorylation level of 36 proteins increased specifically by agrin stimulation. In Dok-7 mutant myotubes, however, 13 of the 36 proteins failed to be enhanced by agrin stimulation, suggesting that these 13 proteins are Dok-7-dependent tyrosine-phosphorylated proteins, could work as downstream molecules of agrin/Dok-7 signaling. We validated one of the proteins, Anxa3, by in vitro and in vivo assays. Knocking down of Anxa3 in the cultured myotubes inhibited agrin-induced AChR clustering, whereas reduction of Anxa3 in mouse muscles induced abnormal postsynaptic development. Collectively, our phosphoproteomics analysis provides novel insights into the complicated signaling network downstream of agrin/Dok-7.

Potential liver damage due to co-exposure to As, Cd, and Pb in mining areas: Association analysis and research trends from a Chinese perspective.

There is global concern regarding the public health hazards of environmental exposure to multiple toxic heavy metals. The effects of toxic heavy metals on liver function have been suggested in previous reports, but the association between exposure to multiple toxic heavy metals and liver function has not been elucidated. The aim of this study was to investigate the effects of exposure to multiple toxic heavy metals, arsenic(As), lead(Pb), and cadmium(Cd), on liver function through population-based and animal studies. A total of 3590 participants were enrolled from the mining areas in Western Hunan Province. The concentrations of As, Pb, and Cd in the urine and plasma samples were determined using quadrupole inductively coupled plasma mass spectrometry (ICP-MS). Bayesian kernel machine regression (BKMR) was employed for the joint association assay. An animal study was conducted to further verify the cumulative effects of metals on liver damage-related parameters such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) levels. Research trends regarding toxic metals were also explored to obtain in-depth understanding of the current knowledge in this field. Typically, for single-exposure analysis, in most mines, Pb exhibited a significantly negative association with ALT levels, whereas for cumulative effects analysis, when As, Pb, and Cd concentrations were at the 50thpercentile, a significantly negative effect on liver ALT levels was observed. Furthermore, animal studies have shown that co-exposure to As, Pb, and Cd could aggravate liver dysfunction in mice compared to that in the single-metal treated group (p < 0.05). From 1990 to 2019, 1965 projects relating to As, Pb, and Cd research have been initiated, and the total RMB(RenMingBi) funded was approximately 800 million in China, as opposed to 2500 projects in the US with an approximate amount of US$ 1 billion, which is substantially greater than that of China. Finally, from a global viewpoint, scientists should continue to substantially contribute to the field of heavy metal contamination through more extensive academic investigation, global cooperation, and the development of novel control methods. Overall, this study identified that elevated combined concentrations of As, Pb, and Cd were significantly negatively associated with liver function.

TAT-modified serum albumin nanoparticles for sustained-release of tetramethylpyrazine and improved targeting to spinal cord injury.

BACKGROUND: Spinal Cord injury (SCI) is a kind of severe traumatic disease. The inflammatory response is a significant feature after SCI. Tetramethylpyrazine (TMP), a perennial herb of umbelliferae, is an alkaloid extracted from ligustici. TMP can inhibit the production of nitric oxide and reduce the inflammatory response in peripheral tissues. It can be seen that the therapeutic effect of TMP on SCI is worthy of affirmation. TMP has defects such as short half-life and poor water-solubility. In addition, the commonly used dosage forms of TMP include tablets, dropping pills, injections, etc., and its tissue and organ targeting is still a difficult problem to solve. To improve the solubility and targeting of TMP, here, we developed a nanotechnology-based drug delivery system, TMP-loaded nanoparticles modified with HIV trans-activator of transcription (TAT-TMP-NPs). RESULTS: The nanoparticles prepared in this study has integrated structure. The hemolysis rate of each group is less than 5%, indicating that the target drug delivery system has good safety. The results of in vivo pharmacokinetic studies show that TAT-TMP-NPs improves the bioavailability of TMP. The quantitative results of drug distribution in vivo show that TAT-TMP-NPs is more distributed in spinal cord tissue and had higher tissue targeting ability compared with other treatment groups. CONCLUSIONS: The target drug delivery system can overcome the defect of low solubility of TMP, achieve the targeting ability, and show the further clinical application prospect.

A novel dual-prodrug carried by cyclodextrin inclusion complex for the targeting treatment of colon cancer.

BACKGROUND: There is an obvious correlation between ulcerative colitis and colorectal cancer, and the risk of colorectal cancer in patients with ulcerative colitis is increasing. Therefore, the combination therapy of anti-inflammatory and anti-tumor drugs may show promising to inhibit colon cancer. 5-aminosalicylic acid (5-ASA) with anti-inflammatory function is effective for maintaining remission in patients with ulcerative colitis and may also reduce colorectal cancer risk. Histone deacetylase (HDAC) plays an essential role in the progression of colon cancer. Butyric acid (BA) is a kind of HDAC inhibitor and thus shows tumor suppression to colon cancer. However, the volatile and corrosive nature of BA presents challenges in practical application. In addition, its clinical application is limited due to its non-targeting ability and low bioavailability. We aimed to synthesize a novel dual-prodrug of 5-ASA and BA, referred as BBA, to synergistically inhibit colon cancer. Further, based on the fact that folate receptor (FR) is over-expressed in most solid tumors and it has been identified to be a cancer stem cell surface marker in colon cancer, we took folate as the targeting ligand and used carboxymethyl-ß-cyclodextrin (CM-ß-CD) to carry BBA and thus prepared a novel inclusion complex of BBA/FA-PEG-CM-ß-CD. RESULTS: It was found that BBA/FA-PEG-CM-ß-CD showed significant inhibition in cell proliferation against colon cancer cells SW620. It showed a pro-longed in vivo circulation and mainly accumulated in tumor tissue. More importantly, BBA/FA-PEG-CM-ß-CD gave great tumor suppression effect against nude mice bearing SW620 xenografts. CONCLUSIONS: Therefore, BBA/FA-PEG-CM-ß-CD may have clinical potential in colon cancer therapy.

Thrombospondin-4 (TSP4) gene-modified bone marrow stromal cells (BMSCs) promote the effect of therapeutic angiogenesis in critical limb ischemia (CLI) of diabetic rats.

Critical limb ischemia (CLI) is the leading cause of lower limb amputation. Traditional treatments for CLI have limitations. Studies have shown that thrombospondin-4 (TSP4) can promote the growth of neovascularization. In this study, we observed the angiogenesis efficiency of TSP4-overexpressing BMSC transplantation in CLI treatment. The recombinant FT106-tsp4-gfp lentiviral vector plasmid was constructed and transfected into 293FT cells. Primary BMSCs were successfully infected with the tsp4 virus, and TSP4 overexpression was confirmed before TSP4-BMSCs infusion. A rat CLI model was established, and 60 CLI rats were randomly divided into the CLI, BMSC + CLI and TSP4-BMSC + CLI groups. The effect of TSP4-BMSC on angiogenesis was detected by the motor function, immunohistochemistry and immunofluorescence staining assays. Neovascular density was detected by digital subtraction angiography (DSA). Our results demonstrated that TSP4-BMSCs improved the motor function score of the CLI rats and increased MMP2, MMP9, Ang-1, VEGF and vWF protein expression in tissue of the ischaemic area. Meanwhile, new blood vessels can be observed around the ischemic area after TSP4-BMSCs treatment. Our data illustrate that TSP4-BMSCs can promote the recovery of motor function in diabetic hind limb ischaemic rats. TSP4-BMSCs have better therapeutic effects than BMSCs.