A Versatile Platform to Generate Prodrugs with Rapid and Precise Albumin Hitchhiking and High Cargo Loading for Tumor-Targeted Chemotherapy.

Due to its tumor homing and long serum half-life, albumin is an ideal drug carrier for chemotherapy. For endogenous albumin hitchhiking with high cargo loading, a trimeric albumin-binding domain (ABD), i.e., ABD-Tri is designed by fusing an ABD with high specificity and affinity for albumin to a self-trimerizing domain (Tri) with an additional cysteine residue. ABD-Tri is highly (40 mg L-1) expressed as soluble and trimeric proteins in Escherichia coli (E. coli). Once mixed together, ABD-Tri rapidly and specifically forms a stable complex with albumin under physiological conditions without obviously changing its receptor- and cell-binding and tumor-homing properties. Maleimide-modified prodrugs are highly effectively conjugated to ABD-Tri to produce homogenous ABD-Tri-prodrugs with triple cargo loading under physiological conditions by thiol-maleimide click chemistry. Unlike the maleimide moiety, which can only mediate time- and concentration-dependent albumin binding, ABD-Tri mediated fast (within several minutes) albumin binding of drugs even at extremely low concentrations (µg mL-1). Compared to maleimide-modified prodrugs, ABD-Tri-prodrugs exhibit better tumor homing and greater in vivo antitumor effect, indicating that conjugation of chemical drug to ABD-Tri outperforms maleimide modification for endogenous albumin hitchhiking. The results demonstrate that ABD-Tri may serve as a novel platform to produce albumin-binding prodrugs with high cargo-loading capacity for tumor-targeted chemotherapy.

Suppressed Surface Reorganization in a High-Density Poly(methyl methacrylate) Brush.

A high-density poly(methyl methacrylate) (PMMA) brush (σ = 0.77 chain/nm2) with a lower molecular weight distribution was prepared onto a silicon wafer by surface-initiated atom transfer radical polymerization. The surface of the PMMA brush chains was characterized upon the process of the environmental change, from air to water, using contact angle measurements in conjunction with sum-frequency generation spectroscopy. The surface structure and properties altered less with the changing environment from air to water for the PMMA brush than for a spin-coated film; that is, the extent of surface reorganization could be suppressed by grafting densely-packed chains onto a substrate. Also, the water penetration into the brush surface was inhibited because of the densely packed chain structure.

Thermal damage width and hemostatic effect of bipolar electrocoagulation, LigaSure, and Ultracision techniques on goat mesenteric vessels and optimal power for bipolar electrocoagulation.

BACKGROUND: We aimed to determine the optimal bipolar electrocoagulation power for laparoscopic surgery and to investigate which method, bipolar electrocoagulation, advanced bipolar, or ultrasonic technique was more reliable. METHODS: Goat mesenteric vessels (210 in vivo samples) with diameters of 3.03-5.44 mm were selected. Bipolar electrocoagulation with 80 W, 75 W, 70 W, 65 W, 60 W, 55 W, and 50 W, and advanced bipolar and ultrasonic techniques were performed on mesenteric vessels. The thermal damage width, hemostatic effect, and burst pressure of these tissues were recorded. SPSS version 13.0 was used for all data analysis. RESULTS: The results showed that 60 W was the optimal for bipolar electrocoagulation based on the thermal damage width, hemostatic effect, and burst pressure. In contrast, the thermal damage width of advanced bipolar and ultrasonic techniques was smaller than that of bipolar electrocoagulation, and advanced bipolartechnique had the highest successful rate for hemostasis and highest burst pressure. CONCLUSIONS: Bipolar electrocoagulation was optimally performed with 60 W of power. Compared with ultrasonic and bipolar electrocoagulation techniques, advanced bipolar use was more reliable for mesenteric vessels in laparoscopic surgery; however, bipolar electrocoagulation with optimal power can be used for its simplicity of operation and low cost.

Snoopligase-catalyzed molecular glue enables efficient generation of hyperoligomerized TRAIL variant with enhanced antitumor effect.

Clinical application of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is predominantly limited by its inefficient apoptosis induction in tumor cells, which might be improved by using molecular superglue-mediated hyperoligomerization to increase its valency. Here, the minimal superglue peptide pairs, including Snoopligase-catalyzed SnoopTagJr/SnoopDogTag and SpyStapler-catalyzed SpyTag/SpyBDTag, were individually fused at the N- or C-terminus of the TRAIL promoter to produce superglue-fusion TRAIL variants. Similar to native trivalent TRAIL, these superglue-fusion TRAIL variants were highly expressed in Escherichia coli (E. coli) and spontaneously trimerized. In the presence of Snoopligase or SpyStapler, the trivalent superglue-fusion TRAIL variants were predominantly crosslinked into hexavalent TRAIL variants. Nevertheless, Snoopligase was more efficient than SpyStapler in the production of hexavalent TRAIL variants. In particular, Snoopligase-catalyzed trivalent TRAIL variants with N-terminal fusion of SnoopTagJr/SnoopDogTag produced hexavalent SnHexaTR with the highest yield (∼70%). The in vitro cytotoxicity of SnHexaTR was 10-40 times greater than that of TRAIL in several tumor cells. In addition, compared to trivalent TRAIL, hexavalent SnHexaTR showed a longer serum half-life and greater tumor uptake, which resulted in eradication of 50% of tumor xenografts of TRAIL-sensitive COLO 205. In mice bearing TRAIL-resistant HT-29 tumor xenografts, hexavalent SnHexaTR combined with bortezomib encapsulated in liposomes also showed robust tumor growth suppression, indicating that hyperoligomerization mediated by minimal molecular superglue significantly increased the cytotoxicity and antitumor effect of TRAIL. As a novel anticancer agent candidate, the hexavalent SnHexaTR has great potential for clinical application in cancer therapy.

Effect of Aerobic and Resistant Exercise Intervention on Inflammaging of Type 2 Diabetes Mellitus in Middle-Aged and Older Adults: A Systematic Review and Meta-Analysis.

OBJECTIVES: To examine the effect of aerobic and resistant exercise intervention on inflammaging in middle-aged and older adults with type 2 diabetes mellitus (T2DM) using inflammatory cytokines, such as interleukin (IL)-1 ß, IL-6, tumor necrosis factor-α (TNF-α), and C-reactive protein (CRP) as biomarkers. DESIGN: Systematic review and meta-analysis. SETTING AND PARTICIPANTS: Middle-aged and older adults with T2DM in the community. METHODS: Articles were searched from 8 electronic databases. Randomized control trials (RCTs) published in English, from inception to October 31, 2021, were included in this review. Two authors conducted data extraction and quality appraisal independently following guidelines in the Cochrane Handbook for Systematic Reviews of Interventions. Meta-analysis was conducted using Review Manager. Heterogeneity was investigated using subgroup and sensitivity analysis. RESULTS: This review included 14 RCTs. The meta-analysis showed significant improvement in IL-6 [Z = 3.05; 95% confidence interval (CI): -3.60 to -0.79; P = .002], CRP (Z = 2.44; 95% CI: -0.55 to -0.06; P = .01) and TNF-α levels (Z = 2.96; 95% CI: -2.21 to -0.45; P = .003) post-exercise programs. Subgroup analysis revealed that combined aerobic and resistance exercises and long-term exercises have more significant improvement to the outcomes than usual care. Based on the Grades of Recommendation, Assessment, Development and Evaluation system, considerable risk of bias and low level of certainty were revealed in all biomarker outcomes. CONCLUSIONS AND IMPLICATIONS: Exercise intervention is effective in improving inflammatory, metabolic, and lipid markers in middle-aged and older adults with T2DM. By modifying the levels of these markers with exercise, inflammation and insulin resistance can be improved. Long-term, combined aerobic and resistance exercise interventions have more significant effect on biomarkers. The small sample size of this meta-analysis limited the generalizability of the results. Future studies can consider adopting a more optimized exercise regimen to achieve effective T2DM management in middle-aged and older adults. Similar studies should expand to other populations and larger sample sizes to explore replicability of these effects.

An in-depth mechanistic study of the p-hydroxyphenylglycine synthetic process using in situ ATR-IR spectroscopy.

In this study, an in situ ATR-IR technique was used as a powerful tool to gain insight into the synthetic process of p-hydroxyphenylglycine (p-HPG) by the sulfamic acid-glyoxylic acid-phenol method. Combined with other chemical and instrumental analysis technologies, the reaction sequence and key intermediates of this one-pot reaction were determined, and two concomitant reaction paths have been put forward for the first time. The possible reaction mechanism has been suggested, and the reaction efficiency of each path is discussed in detail. Through the optimization of the experimental parameters, an approximately 40% increase in the final product yield was achieved compared with previous reports. We believe that this study will without a doubt trigger research interest in understanding the industrial production process of important chemicals and pharmaceuticals and as a result will promote the sustainable development and application of novel, efficient chemical reaction routes.

A trimeric immunoglobin G-binding domain outperforms recombinant protein G and protein L as a ligand for fragment antigen-binding purification.

Fragment antigen-binding (Fab) has several advantages in the treatment and diagnosis of some diseases. The lack of highly efficient affinity chromatography platform creates a purification bottleneck for the downstream processing of Fab-based products, which raises the urgent need for a novel immunoglobin G (IgG)-binding domain (IgBD) with both high affinity and broad specificity for Fab. SpGC3FabRR (designated CFab) was previously identified as a Fab-selective IgBD, which triggered our interest in evaluating the potential of CFab for Fab purification. However, we found that monomeric CFab showed weak Fab-binding. To increase its affinity, a self-trimerizing domain (tri) was fused to CFab to produce CFab-tri. It was found that CFab-tri existed as a trimer and showed promising binding to Fab derived from IgG of humans, rhesus monkeys, mice, rats, and rabbits. Affinity chromatography demonstrated that the recovery rates of Fab derived from IgG of humans, rats, mice, and rabbits by CFab-tri-HP column were 2- to 5-fold of those by protein G-HP column. Human Fab was effectively purified by both protein L- and CFab-tri-HP column. However, unlike CFab-tri-HP column, protein L-HP column was inefficient for purification of Fab derived from IgG of rats, mice, and rabbits. Notably, rat Fab spiked into the extract of Escherichia coli (E. coli) was effectively recovered by CFab-tri-HP column. These results indicate that CFab-tri outperforms protein G and protein L as a ligand for Fab purification, and CFab-tri-based affinity chromatography might be developed as a novel platform for Fab purification.

The prognostic utility of CSF neurogranin in predicting future cognitive decline in the Alzheimer's disease continuum: A systematic review and meta-analysis with narrative synthesis.

Core cerebrospinal fluid (CSF) biomarkers (Aß42, T-tau, P-tau) were included as supporting diagnostic criteria for Alzheimer's Disease (AD), but they lack the power to predict AD progression. On the other hand, a new biomarker CSF Neurogranin (Ng) has been shown to predict cognitive decline. This systematic review aims to synthesise the prognostic utility of CSF Ng in predicting cognitive decline in the AD continuum. Seven databases were searched systematically from inception to 30 September 2020. Participants were 55 years or older, who had baseline and at least one follow-up cognitive assessments. Risk of bias was assessed using the Quality in Prognosis Studies tool. Meta-analysis was conducted by pooling standardised beta coefficients and adjusted hazard ratios. Thirteen studies were included and high-quality evidence suggests that CSF Ng predicts Mini-Mental State Examination (MMSE) decline in Aß+ mild cognitive impairment (MCI). Moderate quality evidence showed that CSF Ng could predict the decline of memory and executive function in MCI. Narrative synthesis found that CSF Ng/Aß42 was also likely to predict cognitive decline. More studies are required to validate the use of CSF Ng as an AD prognostic marker and its application in future development of drug treatment and diagnosis.

Divergent C-H activation synthesis of chalcones, quinolones and indoles.

We here report a condition-controlled divergent synthesis strategy of chalcones, quinolones and indoles, which was achieved via a C-H activation reaction of N-nitrosoanilines and cyclopropenones. Variations of Ag salts are observed to be crucial for divergently constructing the three distinct chemical scaffolds. A Rh(i)- and Rh(iii)-cocatalyzed decarbonylation/C-H activation/[3+2] annulation cascade reaction was developed for the synthesis of indoles. These methodologies are characterized by mild reaction conditions, high functional group tolerance, and amenability to gram-scale synthesis, providing a reference for future derivation of new chemical scaffolds by C-H activation.

Evaluation of the effects of applying the ventricular care bundle (VCB) method for reducing ventilator-associated pneumonia (VAP) in the intensive care unit of a general Chinese tertiary hospital.

BACKGROUND: Ventilator-associated pneumonia (VAP) is a severe complication that occurs within patients who must use ventilators in the intensive care unit (ICU). Ventilator care bundles (VCB) have been applied across many developed regions and have produced positive results in controlling VAP. In this study, we report on the implementation and effects of using VCBs to manage VAP in a general tertiary hospital in the Inner Mongolia Autonomous Region of China. METHODS: A targeted surveillance method was used to survey all the patients (n=4,716) in the ICU from June 1, 2017 to May 31, 2019. Patients from June 1, 2017 to May 31, 2018, and June 1, 2018, to May 31, 2019, were respectively divided into 2 groups: the control group (2,029 patients) and intervention group (2,687 patients). These dates were selected because VCB was implemented from June 1, 2018, in our institution. The variables that were associated with VCB and observed were the head-of-bed elevation, oral care, maintenance of the pressure for the cuff of the endotracheal tube, aspiration of subglottic secretion, daily sedation vacation protocol, daily extubation assessment results, and hand hygiene. After collecting the data, the compliance of VCB, ventilator use ratio, and the incidence rate of VAP in these 2 groups were compared. RESULTS: We observed that compliance with all of the intervention measures for VCB improved results in the intervention group compared to the control. Furthermore, the compliance rate of hand hygiene increased from 71.99% to 91.97%, and the head-of-bed elevation of 30°-45° increased from 62.02% to 85.96%. All differences between these two groups were statistically significant, according to the χ 2 -test. The ventilator use ratio was statistically and significantly lower in the intervention group (34.86%) compared to the control group (40.29%) (χ 2 =95.513, P<0.001). The incidence rate of VAP was statistically and significantly lower in the intervention group (13.70‰) compared to the control group (18.85‰) (χ 2 =5.471, P=0.019). CONCLUSIONS: Our results show that VCB prevents VAP. Therefore, personnel training, clinical supervision, and surveillance feedback could promote a reduction in intervention measures.

Drug resistance of healthcare-associated pathogenic bacteria and carbapenem-resistant Acinetobacter baumannii homology in the general intensive care unit.

BACKGROUND: The objective of this study was to understand the distribution and drug resistance of healthcare-associated infection (HAI) pathogens in an intensive care unit (ICU) of a general tertiary hospital in Inner Mongolia, and to classify carbapenem-resistant Acinetobacter baumannii (CR-AB) in ICU patients and environmental samples. Additionally, this study aimed to provide scientific evidence for the use of clinical antibiotics and effective prevention and control measures for CR-AB outbreak. METHODS: The distribution and drug resistance of pathogens isolated from patient's samples in the ICU of 12 Hospitals from January to May 2019 were retrospectively analyzed. Meanwhile, CR-AB isolated from patients and environmental samples were collected and classified by pulsed-field gel electrophoresis (PFGE). RESULTS: The pathogens isolated from ICU samples, mainly Gram-negative bacteria (63.07%), were CR-AB, Klebsiella pneumoniae, and Pseudomonas aeruginosa; the main Gram-positive bacteria (22.13%) were Enterococcus faecium and Staphylococcus aureus; and fungi accounted for the remaining (14.80%). The samples mainly came from sputum (41.09%). Among non-fermenting bacteria, the resistance rates of CRAB to piperacillin, piperacillin/tazobactam, and other treatments were higher than those of Pseudomonas aeruginosa (P<0.05). Meanwhile, the resistance rates to ampicillin/sulbactam and compound sulfamethoxazole were lower than those of Pseudomonas aeruginosa (P<0.05). The resistance rates of Klebsiella pneumoniae to piperacillin/tazobactam, ceftazidime, and others were higher than those of Escherichia coli (P<0.05). Among Gram-positive bacteria, the resistance rates of Enterococcus faecium to erythromycin, clindamycin, and other treatment were higher than those of Staphylococcus aureus (P<0.05). A total of 62 bands were obtained from 63 strains of CR-AB by electrophoresis. Also, 16 clusters (A-P) were obtained with a 74% similarity coefficient, among which K, L, and N types (more than 9 strains) were more common. CONCLUSIONS: Gram-negative bacteria were the primary pathogens of HAI in the ICU, and their drug resistance was serious. There is homology in the PFGE typing of CR-AB. Therefore, hospitals should strengthen the surveillance of drug-resistant pathogenic bacteria. Additionally, further cleaning and disinfection measures are needed to improve environmental hygiene and prevent outbreaks of HAI.

Healthcare-associated infection prevention and control management in a tertiary hospital and an overall evaluation.

BACKGROUND: Healthcare-associated infection (HAI) is a crucial factor influencing medical quality. Studies about HAI management situations are rare, especially for the Inner Mongolia region of China. Therefore, this study aimed to investigate management procedures and the overall evaluation of HAI in order to inform HAI management improvement more scientifically. METHODS: A questionnaire was used to investigate HAI-related prevention and control indicators in tertiary hospitals in the Inner Mongolia region from July 2018 to June 2019. RESULTS: The survey showed that the mean incidence rate of HAI was 3.79%. The mean rate of hand hygiene compliance of healthcare workers (HCWs), inpatient's antibiotics-use rate, and the detection of the antibiotic ratio before therapy was 54.34%, 34.33%, and 25.40%, respectively. The mean of the surgical site infection (SSI) rate of the level I incision and the preventive antibiotics-use ratio of the level I incision was 1.31% and 28.89%, respectively. The mean of the multi-drug resistant organism (MDRO) infection rate was 0.40% and the mean of the MDRO detection rate was 18.55%. The mean of the central line-associated bloodstream infection rate was 2.24%, the ventilator-associated pneumonia (VAP) rate was 11.17%, and the catheter-associated urinary tract infection (CAUTI) rate was 1.95‰. As for the overall evaluation, 19 (35.85%) hospitals had a bad grade, 18 (33.96%) hospitals had a medium grade, and 16 (30.19%) hospitals had a good grade. CONCLUSIONS: The incidence rate of HAI in tertiary hospitals in the Inner Mongolia region is higher than the national level. Also, the overall evaluation of bad-grade hospitals and their deficiencies should be used as an example to improve the HAI management level.

[Role of ovarian tumor stem-like cells sorted from human epithelial ovarian cancer SKOV3 cells in vasculogenic mimicry formation].

OBJECTIVE: To isolate tumor stem-like cells from human epithelial ovarian cancer SKOV3 cells and explore their role in the formation of vascularization mimicry (VM). METHODS: SKOV3 cells were passaged to the 7th generation by suspension culture in serum-free medium, and the percentages of CD133- and CD117-positive cells in the 1st, 3rd, 5th and 7th generations were analyzed using flow cytometry. The proliferative activity of the cells sorted from the 7th generation SKOV3 cells was assessed with colony formation assay. A three-dimensional cell culture model was established to compare the ability of VM formation between the sorted cells and the parental SKOV3 cells. The expression levels of matrix metalloproteinases-2 (MMP-2) and MMP-9 in the two groups were detected using real-time PCR and Western blotting. RESULTS: Some SKOV3 cells formed typical cell spheres with suspension growth in serum-free medium and were passaged to the 7th generation. Flow cytometry revealed that the percentage of CD133-positive cells increased with cell passaging. The cloning efficiency of the sorted cells was significantly higher than that of the parental SKOV3 cells (50.33% vs 5.33%, P < 0.001). The VM formation ability of the sorted cells was stronger than that of the parental SKOV3 cells in the three-dimensional cell culture system. RT-PCR and Western blotting showed that the expression levels of MMP-2 and MMP-9 were significantly higher in the 7th passage cells than in the parental cells (P < 0.05). CONCLUSIONS: The sorted cells from SKOV3 cells cultured in serum-free medium exhibit biological properties of tumor stem cells with strong VM formation ability, suggesting their role in VM formation.

Active surveillance of ventilator-associated pneumonia in the intensive care unit and establishment of the risk grading system and effect evaluation.

BACKGROUND: To discuss ventilator-associated pneumonia (VAP) patient's clinical characteristic and related factors in the intensive care unit (ICU), and to establish a risk grading system for VAP patients in the ICU in order to provide a reference for VAP prevention. METHODS: A total of 1,513 patients in eight ICUs who received mechanical ventilation between June 2015 and June 2018 were randomized and into two groups, with 908 patients in the model group and 605 patients in the verification group. The model group was used to analyze the influencing factors of VAP and establish a risk grading system, while the verification group was used to verify the risk grading system. A receiver operating characteristic (ROC) curve was used to evaluate the predictive effect of the grading system. RESULTS: During the 3-year study period, of the 1,513 total patients, 188 patients were infected with VAP, leading to an incidence rate of 12.43% (188/1,513) and an infection rate of 15.23‰ (188/12,347). ICU length of stay, mechanical ventilation days, frequency of oral care, unused subglottic secretion drainage, tracheotomy, APACHE II score, and combined antibiotics use were risk factors of VAP infection for patients who received mechanical ventilation in the modeling group (P<0.05). In a VAP risk-grading system established based on risk factors, the high, medium and low-grade patients had a statistically significantly different VAP infection rate in the model group, and patients with a high grade had a higher risk of VAP infection. Patients' data in the model and verification groups were used to draw a ROC curve which showed a good predictive effect. CONCLUSIONS: This study establishes and verifies the VAP risk grading system for patients who receive mechanical ventilation. It is helpful in high-risk patient surveillance and in reducing and preventing VAP infection.

E-cadherin gene polymorphisms and haplotype associated with the occurrence of epithelial ovarian cancer in Chinese.

BACKGROUNDS AND AIMS: E-cadherin plays an important role in the origin of epithelial ovarian cancer. However, the exact molecular mechanism by which this occurs is unknown. The polymorphisms located at the E-cadherin may contribute to an increased risk for certain cancers. In this paper, we studied the association between polymorphisms of E-cadherin and the risk of epithelial ovarian cancer. METHODS: We assessed the -160C/A, -347G/GA polymorphism within the promoter region and 3'-UTR +54C/T polymorphism of E-cadherin in epithelial ovarian cancer and control women. We also tested the expression of E-cadherin protein in ovarian cancer tissue among three genotype (3'-UTR +54C/T polymorphism) carriers. RESULTS: There was no significant difference in genotype distribution of the -160C/A and -347G/GA SNPs in the E-cadherin gene promoter region between ovarian cancer patients and controls, but haplotype -160A/-347GA relative to haplotype -160C/-347G was 48.6 (95% CI=2.9-806.2) for epithelial ovarian cancer risk. The C/C genotype of the 3'-UTR +54C/T polymorphism relative to the C/T+T/T genotype was 1.85 (95% CI=1.27-2.69) for epithelial ovarian cancer risk. E-cadherin protein expression in was lower in C/C genotype carriers than T allele carriers in ovarian cancer tissue (P=0.02). CONCLUSIONS: The C/C genotype of 3'-UTR C/T SNP and -160C/-374GA haplotype in E-cadherin gene may be a potential susceptibility factor for risk of epithelial ovarian cancer in Chinese, which indicated that the lower expression of E-cadherin might play an important role in the pathogenesis of epithelial ovarian cancer.

Polymorphisms in the matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-2 and the risk of human adenomyosis.

The matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) may contribute to the development of adenomyosis. The aim of the present study was to investigate whether three single nucleotide polymorphisms (SNPs) in the promoter regions of MMP-2 (-1306C/T and -735C/T) and TIMP-2 (-418G/C) genes were related to the risk of adenomyosis development. Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay in 180 adenomyosis patients and 324 frequency-matched control women in a Chinese population. There were significant differences in allele frequencies and genotype distributions of the MMP-2 -1306C/T polymorphism between patients and control women (P = 0.01 and 0.04, respectively). The frequency of C allele in patients (92.2%) was significantly higher than in the controls (87.0%) (P = 0.01). Compared with the C/T+T/T genotypes, the C/C genotype could significantly increase the risk of adenomyosis development, with an odds ratio of 1.83 (95% CI = 1.13-2.96). However, no statistically significant difference was found in allele frequencies and genotype distributions of MMP-2 -735C/T and TIMP-2 -418G/C SNPs between the two groups (all P values > 0.05). Two polymorphisms of MMP-2 displayed linkage disequilibrium (D' = 0.74). The haplotype analysis suggested no significant association of four haplotypes with the risk of adenomyosis development. Our results indicated an association of MMP-2 -1306C/T polymorphism with the risk of adenomyosis, suggesting a potential role in adenomyosis development in North Chinese women.

Small extracellular vesicles derived from human induced pluripotent stem cell-differentiated neural progenitor cells mitigate retinal ganglion cell degeneration in a mouse model of optic nerve injury.

JOURNAL/nrgr/04.03/01300535-202502000-00034/figure1/v/2024-05-28T214302Z/r/image-tiff Several studies have found that transplantation of neural progenitor cells (NPCs) promotes the survival of injured neurons. However, a poor integration rate and high risk of tumorigenicity after cell transplantation limits their clinical application. Small extracellular vesicles (sEVs) contain bioactive molecules for neuronal protection and regeneration. Previous studies have shown that stem/progenitor cell-derived sEVs can promote neuronal survival and recovery of neurological function in neurodegenerative eye diseases and other eye diseases. In this study, we intravitreally transplanted sEVs derived from human induced pluripotent stem cells (hiPSCs) and hiPSCs-differentiated NPCs (hiPSC-NPC) in a mouse model of optic nerve crush. Our results show that these intravitreally injected sEVs were ingested by retinal cells, especially those localized in the ganglion cell layer. Treatment with hiPSC-NPC-derived sEVs mitigated optic nerve crush-induced retinal ganglion cell degeneration, and regulated the retinal microenvironment by inhibiting excessive activation of microglia. Component analysis further revealed that hiPSC-NPC derived sEVs transported neuroprotective and anti-inflammatory miRNA cargos to target cells, which had protective effects on RGCs after optic nerve injury. These findings suggest that sEVs derived from hiPSC-NPC are a promising cell-free therapeutic strategy for optic neuropathy.