Trajectories of peripheral white blood cells count around the menopause: a prospective cohort study.

BACKGROUND: Menopause significantly impacts the immune system. Postmenopausal women are more susceptible to infection. Nonetheless, the pattern of change in peripheral white blood cell counts around the menopause remains poorly understood. METHODS: We conducted a prospective longitudinal cohort study with repeated measurements using Kailuan cohort study of 3632 Chinese women who participated in the first checkup (2006-2007) and reached their final menstrual period (FMP) by the end of the seventh checkup (2018-2020). Peripheral WBC count indicators included total white blood cells (TWBC), neutrophils (NEUT), lymphocytes (LYM), and monocytes (MON). Multivariable mixed effects regressions fitted piece-wise linear models to repeated measures of WBC count indicators as a function of time before or after the final menstrual period (FMP). Interaction and subgroup analysis were used to explore the effects of age and body mass index (BMI) on changes in WBC indicators around FMP. RESULTS: WBC count indicators decreased before the FMP, and the reduction in TWBC, NEUT, and MON continued for 2 years following the FMP. LYM and NEUT declined during < -1 years and - 4 ∼ + 2 years relative to FMP, respectively. A reduction in MON was observed pre-FMP, extending continuously through the two-year period post-FMP. TWBC declined from - 3 to + 2 years relative to FMP, but both MON and TWBC increased during > + 2 years. The baseline age had an interaction effect on changes in WBC indicators during specific menopausal stages, except for TWBC. Individuals in different age subgroups showed distinct trajectories for NEUT, LYM and MON around the FMP. High baseline BMI had a synergistic effect on changes in specific menopause segments for TWBC, LYM, and MON. The impact of menopause on TWBC and LYM was postponed or counterbalanced in high BMI individuals. Individuals in three BMI subgroups experienced similar MON changes around FMP, and there were slight variations during < -4 years. CONCLUSIONS: Menopause was associated with count changes of peripheral WBC. The trajectories of various WBC types differ around menopause. Age and BMI affected WBC trajectory around menopause. The menopause period may represent a window of opportunity to promote immune health in middle-aged women.

Intraoperative quantitative crystalline lens nuclear opacities analysis based on crystalline lenSx platform.

PURPOSE: The main objective is to quantify the lens nuclear opacity using spectral-domain optical coherence tomography (SD-OCT) and to evaluate its association with Lens Opacities Classification System III (LOCS-III) system, lens thickness (LT), and surgical parameters. The secondary objective is to assess the diagnostic model performance for hard nuclear cataract. METHODS: This study included 70 eyes of 57 adults with cataract, with 49 (70%) and 21 (30%) in training and validation cohort, respectively. Correlations of the average nuclear density (AND) /maximum nuclear density (MND) with LOCS-III scores, LT, and surgical parameters were analyzed. Univariate and multivariate logistic regression analysis, receiver operating characteristic curves and calibration curves were performed for the diagnostic of hard nuclear cataract. RESULTS: The pre-operative uncorrected distance visual acuity (UDVA), intraocular pressure (IOP), mean axial length (AL), and LT were 1.20 ± 0.47 log MAR, 15.50 ± 2.87 mmHg, 27.34 ± 3.77 mm and 4.32 ± 0.45 mm, respectively. The average nuclear opalescence (NO) and nuclear colour (NC) scores were 3.61 ± 0.94 and 3.50 ± 0.91 (ranging from 1.00 to 6.90), respectively. The average AND and MND were 137.94 ± 17.01 and 230.01 ± 8.91, respectively. NC and NO scores both significantly correlated with the AND (rNC = 0.733, p = 0.000; rNO = 0.755, p = 0.000) and MND (rNC = 0.643, p = 0.000; rNO = 0.634, p = 0.000). In the training cohort, the area under the curve (AUC) of the model was 0.769 (P < 0.001, 95%CI 0.620-0.919), which had a good degree of differentiation (Fig. 2a). The calibration curve showed good agreement between predicted and actual probability. CONCLUSION: The nuclear density measurement on SD-OCT images can serve as an objective and reliable indicator for quantifying nuclear density.

The role of social network embeddedness and collective efficacy in encouraging farmers' participation in water environmental management.

Water environmental management (WEM) has a significant influence on the global ecological balance. As an institutional innovation, the River Chief System (RCS) in China has achieved a positive short-term impact on addressing water environmental problems. However, its effects are limited in rural China. As a type of public good, the rural WEM demands the active participation not only of government but also of farmers. Based on the social cognitive and social network theory, this study empirically investigates how rural social networks promote farmers' participation in WEM. Using the survey of 860 farmers in the Yellow and Yangtze River Basin, we employ the double-hurdle model (D-H-M) to craft the primary assessment. The results show that the social network embeddedness facilitates farmers' participation in WEM directly. Collective efficacy plays a full mediation role in the relationship between social network embeddedness and farmers' participation. Moreover, the perceived role of village leaders affects the relationship between social networks and farmers' participation. Our research enriches the application of social network theory in the rural social context and offers an innovative approach to solving farmers' participation problems in WEM.

Merbromin is a mixed-type inhibitor of 3-chyomotrypsin like protease of SARS-CoV-2.

3-chyomotrypsin like protease (3CLpro) has been considered as a promising target for developing anti-SARS-CoV-2 drugs. Herein, about 6000 compounds were analyzed by high-throughput screening using enzyme activity model, and Merbromin, an antibacterial agent, was identified as a potent inhibitor of 3CLpro. Merbromin strongly inhibited the proteolytic activity of 3CLpro but not the other three proteases Proteinase K, Trypsin and Papain. Michaelis-Menten kinetic analysis showed that Merbromin was a mixed-type inhibitor of 3CLpro, due to its ability of increasing the KM and decreasing the Kcat of 3CLpro. The binding assays and molecular docking suggested that 3CLpro possessed two binding sites for Merbromin. Consistently, Merbromin showed a weak binding to the other three proteases. Together, these findings demonstrated that Merbromin is a selective inhibitor of 3CLpro and provided a scaffold to design effective inhibitors of SARS-CoV-2.

Variations in the toxicity and condition index of five bivalve species throughout a red tide event caused by Alexandrium catenella: A field study.

Harmful red tides in China have caused paralytic shellfish toxins (PSTs) pollution and led to severe socioeconomic effects in shellfish aquaculture. Although shellfish can survive harmful algal blooms, the effects on their Condition Index (CI) have been underestimated. This study sought to evaluate the effects of the profiles and levels of paralytic shellfish toxins on variations in the CI in bivalves under natural blooming conditions. We observed clear soft tissue lesions to varying degrees except in Mytilus galloprovincialis after toxin exposure. Among the five species of shellfish exposed in situ, only M. galloprovincialis accumulated PSTs content above the maximum permitted level (800 µg STX di-HCl eq./kg). The highest toxin content in all sample tissues was observed in Patinopecten yessoensis. Significant interspecies differences in PSTs accumulation among the five bivalve species were observed in the hepatopancreas. A total of nine PSTs components and four new C-11 hydroxyl metabolites (so-called M-toxins) toxins were detected, and detoxification diversity was observed among bivalves. We observed a higher proportion of M-toxin in early stages, and the proportions changed only slightly over time in M. galloprovincialis and Magallana gigas, thus accounting for the significantly higher metabolism rate. Notably, the CI in M. gigas and Argopecten irradians was positively correlated with lowest toxin accumulation of PSTs content, but significantly inhibited. In conclusion, our results revealed a significant inhibitory effect on the CI in shellfish, in a species specific manner, with distinct levels of inhibition correlated with different toxin metabolites. Our study revealed the toxin content of different bivalves exposed to a natural red tide environment and the consequent effects on growth, thus building a foundation for research on the mechanisms underlying the effects of PSTs on growth. These data establish the ecological and economic significance of the effects of harmful algal blooms on bivalves.

Transport of intensity equation-based terahertz lensless full-field phase imaging.

Terahertz (THz) phase imaging is widely spreading in various scenarios, among which full-field phase distributions are commonly retrieved by digital holography or ptychography. In this Letter, the transport of the intensity equation reconstruction method is applied into the THz band. An algorithm named the lensless US-transport of intensity equation (TIE) is proposed to accommodate to an in-line configuration. The object phase is retrieved by primarily conducting iterations between the axial intensity derivative and the phase distribution at the recording plane and subsequent backward diffraction propagation. This method is applicable to both isolated and extended weakly absorbing samples with higher reconstruction quality and remarkably less time cost than holographic phase retrieval algorithms. It can also be attempted in other non-interferometric geometries or using low-cost partially coherent THz sources, which significantly broaden the application scope of THz phase imaging.

Association between chronic periodontitis and the risk of Alzheimer's disease: combination of text mining and GEO dataset.

BACKGROUND: Although chronic periodontitis has previously been reported to be linked with Alzheimer's disease (AD), the pathogenesis between the two is unclear. The purpose of this study is to analyze and screen the relevant and promising molecular markers between chronic periodontitis and Alzheimer's disease (AD). METHODS: In this paper, we analyzed three AD expression datasets and extracted differentially expressed genes (DEGs), then intersected them with chronic periodontitis genes obtained from text mining, and finally obtained integrated DEGs. We followed that by enriching the matching the matching cell signal cascade through DAVID analysis. Moreover, the MCODE of Cytoscape software was employed to uncover the protein-protein interaction (PPI) network and the matching hub gene. Finally, we verified our data using a different independent AD cohort. RESULTS: The chronic periodontitis gene set acquired from text abstracting was intersected with the previously obtained three AD groups, and 12 common genes were obtained. Functional enrichment assessment uncovered 12 cross-genes, which were mainly linked to cell morphogenesis involved in neuron differentiation, leading edge membrane, and receptor ligand activity. After PPI network creation, the ten hub genes linked to AD were retrieved, consisting of SPP1, THY1, CD44, ITGB1, HSPB3, CREB1, SST, UCHL1, CCL5 and BMP7. Finally, the function terms in the new independent dataset were used to verify the previous dataset, and we found 22 GO terms and one pathway, "ECM-receptor interaction pathways", in the overlapping functional terms. CONCLUSIONS: The establishment of the above-mentioned candidate key genes, as well as the enriched signaling cascades, provides promising molecular markers for chronic periodontitis-related AD, which may help the diagnosis and treatment of AD patients in the future.

Continuous-wave terahertz self-referencing digital holography based on Fresnel's mirrors.

Continuous-wave terahertz digital holography (TDH) is a booming full-field phase-contrast imaging method validated in both in-line and Mach-Zehnder off-axis geometries. In this Letter, a self-referencing TDH approach is proposed based on the Fresnel's mirrors, by which the object wavefront is partitioned and reflected. Two beams interfere with each other to form an off-axis hologram. The proposed recording configuration is immune from a superposed twin image and has higher temporal stability than Mach-Zehnder interferometers. To evaluate the phase-contrast imaging performance, different types of samples are measured.

Benzoquinone induces ROS-dependent mitochondria-mediated apoptosis in HL-60 cells.

Benzene exposure affects the hematopoietic system and leads to the occurrence of various types of leukemia and hematotoxicity. It has been confirmed that active metabolites of benzene, including 1,4-benzoquinone (1,4-BQ), can induce reactive oxygen species (ROS) and apoptosis in the bone marrow, and recent studies have also suggested that benzene exposure can affect mitochondrial function in both experimental animals and cell lines. However, the potential relationship among ROS production, mitochondrial damages, and subsequent apoptosis following benzene exposure has not been well studied in detail. In the present study, we utilized HL-60 cells, a well-characterized human myeloid cell line, as an in vitro model and examined the effects of 1,4-BQ on intracellular ROS formation, mitochondria damage, and the occurrence of apoptotic events with or without using the ROS scavenger N-acetyl-l-cysteine (NAC). The results demonstrated that 1,4-BQ could dose-dependently induce production of ROS and mitochondrial damage as characterized by mitochondrial membrane potential disruption, mitochondrial ultrastructure alteration, and induced apoptosis and activated caspase-3 and caspase-9. Preincubation of HL-60 cells with NAC prior to 1,4-BQ treatment could block 1,4-BQ-induced production of ROS and the occurrence of apoptosis. These results demonstrated that 1,4-BQ induced apoptosis in HL-60 cells through a ROS-dependent mitochondrial-mediated pathway.

[NIR Fingerprints of Different Medicinal Parts of Angelicae Sinensis Radix].

OBJECTIVE: To investigate the spectrum characteristics of near-intrared dittuse retlectance spectroscopy (NIR) fingerprint of different medicinal parts of Angelicae Sinensis Radix. METHODS: 96 batches of samples were collected from 14 counties of Gansu Province and Yunnan Province. The NIR fingerprints were collected by integrated sphere. Similarity analysis and partial least square discriminant analysis(PLS-DA) were used to analyze the fingerprint. RESULTS: The average spectrum of NIR fingerprint of different medicinal parts of Angelicae Sinensis Radix showed some differences; the absorbance in characteristic absorption was in a decreasing order of body > tail > head > whole. Most NIR fingerprint similarities of different medicinal parts of Angelicae Sinensis Radix exceeded 0. 95. The established model of PLS-DA could be used to accurately classify the medicinal parts of Angelicae Sinensis Radix. The differences of NIR fingerprints of different medicinal parts of Angelicae Sinensis Radix were mainly existing in the wave number ranges of 8,443 - 8,284 cm -1, 7,003 - 6,896 cm-1, 6,102 - 5,864 cm-1, 4,847 - 4,674 cm-1, and 4,386 - 4,208 cm-1. CONCLUSION: The different medicinal parts of Angelicae Sinensis Radix have some differences in chemical components.

[Correlation Analysis Between Common Peaks of Angelica sinensis HPLC Fingerprint and Mineral Elements in Its Growing Soil].

OBJECTIVE: To investigate the correlation between common peaks of Angelica sinensis HPLC fingerprint and mineral elements in its growing soil. METHODS: The fingerprints of 120 batches of Angelica sinensis from 12 habitats were determined by HPLC. The contents of Pb, As, Cr, Sb, Hg, Cu, Cd, Ni, Zn, Mg, Mn, Ca, Fe, Na and K in corresponding soil were determined by ICP-MS and AAS. Bivariate and multiple linear regression were used to analyze the correlation. RESULTS: There were significant ( P < 0. 01 or P < 0.05) positive and negative correlation between many common peaks in HPLC fingerprint of Angelica sinensis and mineral elements in its growing soil. The contribution of mineral elements in soil on peak 1 were Zn > K > Sb > Fe > Na; on peak 6 (3-butylphthalide) were Mn > Mg > Ca; on peak 7 were Cr > Zn; on peak 8 were Mn > Na; on peak 11 were As > K > Fe > Cd; on peak 12 were Zn > Mn > K; on peak 13 (Z-butylidenephthalide) were Mn > Zn > Cd; on peak 15 were Zn > K; on peak 16 were Fe > Ni; on peak 17 were Zn > Mn > Ni > Fe > K; on peak 18 were Zn > Na; peaks 2,3 (ferulic acid), 4 and 14 (Z-ligustilide) was mainly affected by As, Zn, Sb and Cu, respectively. CONCLUSION: The relationship between HPLC fingerprint peak of Angelica sinensis and mineral elements in its growing soil shows complexity, multiplicity and interactivity, which should be selectively examined during manuring micronutrient fertilizer and Angelica sinensis cultivation.

[Study on mineral elements distribution in soil of Angelica sinensis producing regions and its relationship with altitude and soil types].

OBJECTIVE: To investigate the distribution characteristics of mineral elements in the soil of Angelica sinensis producing regions and its relationship with altitude and soil types. METHODS: The contents of 15 mineral elements in 103 batches of soil from 13 counties were determined by ICP-MS or AAS. Pearson correlation analysis, partial correlation analysis and systematical cluster analysis were used to analyze the data. RESULTS: Pearson correlation analysis showed that the content of Mg in soil and altitude showed significant positive correlation(P <0. 01), the content of Cd in soil and altitude showed significant negative correlation(P <0. 05), and the con- tents of Pb, Cd, As, Cu, Cr as well as Ni in soil and altitude showed negative correlation. The result of systematic cluster analysis showed that 103 batches of soil were clustered into 5 groups. The main soil types of group I were black soil, haplic kastanozems and black sandy-soil, group II was loess, group III was cinnamon soil, group IV were red soil and grey cinnamon soil, and group V were black soil, haplic kastanozems, grey cinnamon soil and cinnamon soil. CONCLUSION: The distribution of mineral elements in soil is closely related to altitude and soil types.

Reversal of atherosclerosis by restoration of vascular copper homeostasis.

Atherosclerosis has traditionally been considered as a disorder characterized by the accumulation of cholesterol and thrombotic materials within the arterial wall. However, it is now understood to be a complex inflammatory disease involving multiple factors. Central to the pathogenesis of atherosclerosis are the interactions among monocytes, macrophages, and neutrophils, which play pivotal roles in the initiation, progression, and destabilization of atherosclerotic lesions. Recent advances in our understanding of atherosclerosis pathogenesis, coupled with results obtained from experimental interventions, lead us to propose the hypothesis that atherosclerosis may be reversible. This paper outlines the evolution of this hypothesis and presents corroborating evidence that supports the potential for atherosclerosis regression through the restoration of vascular copper homeostasis. We posit that these insights may pave the way for innovative therapeutic approaches aimed at the reversal of atherosclerosis.

Energy strategy alteration, rather than toxicity itself, interferes with the population fluctuation of Brachionus plicatilis exposed to water-accommodated fractions (WAFs) of crude oil.

Oil spills are reported to have conflicting impacts of either injury or resilience on zooplankton communities, and physiological plasticity is speculated to be the possible causative factor. But how? An explanation was sought by exposing the marine rotifer Brachionus plicatilis to a series of water-accommodated fractions (WAFs) of crude oil under controlled laboratory conditions, and population dynamics, which is the core issue for zooplankton facing external stress, were analyzed. The total hydrocarbon concentration of WAFs was quickly degraded from a concentration of 5.0 mg L-1 to half within 24 h and then remained stable. No acute lethality was observed; only motion inhibition was observed in the group treated with 10 %, 50 % and 100 % WAFs, which occurred simultaneously with inhibition of feeding and filtration. However, sublethal exposure to the WAFs concentration series presented stimulation impacts on reproduction and even the population of B. plicatilis. The negative correlation between motion and reproduction seemed to indicate that a shift in the distribution of individual energy toward reproduction rather than motion resulted in increased reproduction after exposure to WAFs. More evidence from transmission electron microscopy (TEM) revealed ultrastructural impairment in both the ovaries and cilia in each treated group, and imbalance in mitochondrial numbers was one of the distinct features of alteration. WAFs stress may alter the energy utilization and storage paradigm, as indicated by the significant elevation in glycogen and the significant decrease in lipid content after WAFs exposure. Further evidence from metabolomics analysis showed that WAFs stress increased the level of lipid metabolism and inhibited some of the pathways in glucose metabolism. Sublethal acute toxicity was observed only in the first 24 h with WAFs exposure, and an energy strategy consisting of changes in the utilization and storage paradigm and reallocation is responsible for the population resilience of B. plicatilis during oil spills.

The Impact of Frailty on the Toxic Reaction of Chemotherapy in Patients With Cervical Cancer: A Longitudinal Study.

BACKGROUND: Longitudinal research on the impact of frailty on chemotherapy toxicity in patients with cervical cancer is limited. OBJECTIVES: To explore the impact of frailty on chemotherapy toxicity in patients with cervical cancer. METHODS: Two hundred fifty-nine postoperative cervical cancer patients from a hospital located in Northwest China were enrolled between July 2020 and December 2021. Participating patients were followed up for 4 chemotherapy cycles after surgery. Frailty was measured using the Tilburg Frailty Indicator. Chemotherapy toxic reactions were evaluated using the Common Terminology Criteria for Adverse Events 4.0. Repeated-measures analysis of variance and Cox regression analysis were used to analyze the effect of frailty on chemotherapy toxicity. RESULTS: Cox regression analysis showed that frailty could serve as an independent risk factor for total toxicity (hazard ratio [HR], 5.423; 95% confidence interval [CI], 3.260-9.023; P < .001), nausea (HR, 3.967; 95% CI, 2.446-6.433; P < .001), and vomiting (HR, 3.081; 95% CI, 1.921-4.942; P < .001). Repeated-measures analysis of variance showed that the white blood cell values of the frail group were lower than those of the nonfrail group (Fgroup effect = 4.172, P = .043), and the hemoglobin values of the frail group were lower than those of the nonfrail group (Fgroup effect = 6.589, P = .012). CONCLUSIONS: Frailty can increase the risk of total chemotherapy toxicity, nausea, and vomiting. Frailty can reduce the white blood cell and hemoglobin values of postoperative adjuvant chemotherapy cervical cancer patients. IMPLICATIONS FOR PRACTICE: Findings may assist healthcare providers in taking effective measures to reduce the toxicity of chemotherapy.

Is dancing an effective intervention for fat loss? A systematic review and meta-analysis of dance interventions on body composition.

OBJECTIVE: The systematic review aimed to review the research on the effects of dance interventions, relative to normal lifestyles, on body composition in people with overweight and obesity. METHODS: 7 databases were searched from their inception to 3 July 2023 for studies with dance interventions and normal lifestyles groups. Only studies investigating dance interventions in people with overweight and obesity(body mass index (BMI)>24kg/m2 and percent fat mass (Fat(%)) abnormal(male>20%, female>25%)) were included in the meta-analysis. There were no restrictions on dance forms. RESULTS: 654 studies were identified from the databases, and 10 studies were evaluated to be eligible. The meta-analysis revealed that compared to normal lifestyles dance had meaningful improvements in body mass(BM), BMI, waist circumference(WC), Fat(%), and fat mass(Fat(kg)). No significant differences were found in the waist-to-hip ratio(WHR). CONCLUSIONS: Dance is effective on fat loss in people with overweight and obesity, and has a significant improvement on body composition and morphology. For its high efficiency and greater sense of enjoyment, dance can be a beneficial exercise intervention for fat loss.

Hexabromocyclododecane-induced reproductive toxicity in Brachionus plicatilis: Impacts and assessment.

Hexabromocyclododecane (HBCD), third-generation brominated flame retardants (BRFs), has aroused worldwide concern because of its wide application and potentially negative impacts on marine ecosystems, but an information gap still exists regarding marine low-trophic organisms. Brachionus plicatilis, the model marine zooplankton, was used in the present study, and its reproductive responses were used as the endpoint to indicate HBCD-induced toxicity. HBCD was suggested to be extremely highly toxic compounds regarding the 96 h-LC50 of 0.58 mg L-1. The sublethal exposure of HBCD injured the reproduction of B. plicatilis: The total number of offspring per female and the key population index calculated from the life table, including the intrinsic rate of population increase (rm) and net reproductive rate (R0), were significantly influenced in a concentration-dependent manner. The reproductive process was also altered, as indicated by the first spawning time, first hatching time and oocyst development time. At the same time, individual survival and growth (body length) were also negatively affected by HBCD. Reactive oxygen species (ROS) were suggested to be responsible for reproductive toxicity mainly because the total ROS contents as well as the main components of •OH and H2O2 greatly increased and resulted in the oxidative imbalance that presented as malondialdehyde (MDA) elevation. Simultaneous activation of the glutathione antioxidant system was accompanied by the apoptosis marker enzymes Caspase-3 and 9, as well as the correlation between ROS content, physiological alteration and cell apoptosis, providing further evidence for this. The integrated biomarker response (IBR) and adverse outcome pathway (AOP) showed that HBCD had a significant toxic effect on B. plicatilis near the concentration range of 96 h-LC50. The establishment of this concentration range will provide a reliable reference for future environmental concentration warning of HBCD in marine.

Correction: Sugarcane stem node identification algorithm based on improved YOLOv5.

[This corrects the article DOI: 10.1371/journal.pone.0295565.].

The combination of temozolomide and perifosine synergistically inhibit glioblastoma by impeding DNA repair and inducing apoptosis.

Temozolomide (TMZ) is widely utilized as the primary chemotherapeutic intervention for glioblastoma. However, the clinical use of TMZ is limited by its various side effects and resistance to chemotherapy. The present study revealed the synergistic inhibition of glioblastoma through the combined administration of TMZ and perifosine. This combination therapy markedly diminished BRCA1 expression, resulting in the suppression of DNA repair mechanisms. Furthermore, the combination of TMZ and perifosine elicited caspase-dependent apoptosis, decreasing glioblastoma cell viability and proliferation. The observed synergistic effect of this combination therapy on glioblastoma was validated in vivo, as evidenced by the substantial reduction in glioblastoma xenograft growth following combined treatment with TMZ and perifosine. In recurrent glioma patients, higher BRCA1 expression is associated with worse prognosis, especially the ones that received TMZ-treated. These findings underscore the potent antitumor activity of the AKT inhibitor perifosine when combined with TMZ and suggest that this approach is a promising strategy for clinical glioblastoma treatment.

Implantation of Adipose-Derived Mesenchymal Stromal Cells (ADSCs)-Lining Prosthetic Graft Promotes Vascular Regeneration in Monkeys and Pigs.

BACKGROUND: Current replacement procedures for stenosis or occluded arteries using prosthetic grafts have serious limitations in clinical applications, particularly, endothelialization of the luminal surface is a long-standing unresolved problem. METHOD: We produced a cell-based hybrid vascular graft using a bioink engulfing adipose-derived mesenchymal stromal cells (ADSCs) and a 3D bioprinting process lining the ADSCs on the luminal surface of GORE-Tex grafts. The hybrid graft was implanted as an interposition conduit to replace a 3-cm-long segment of the infrarenal abdominal aorta in Rhesus monkeys. RESULTS: Complete endothelium layer and smooth muscle layer were fully developed within 21 days post-implantation, along with normalized collagen deposition and crosslinking in the regenerated vasculature in all monkeys. The regenerated blood vessels showed normal functionality for the longest observation of more than 1650 days. The same procedure was also conducted in miniature pigs for the interposition replacement of a 10-cm-long right iliac artery and showed the same long-term effective and safe outcome. CONCLUSION: This cell-based vascular graft is ready to undergo clinical trials for human patients.