Anti-inflammatory and immunoregulatory effects of colistin sulphate on human PBMCs.

In previous studies, CST has been identified as having an immunostimulatory effect on Caenorhabditis elegans and macrophage of rats. Here, we further investigated its immunomodulatory effects on human peripheral blood mononuclear cells (PBMCs). LPS-stimulated PBMCs inflammatory model was established. Flow cytometry was applied to measure phagocytosis of PBMCs. Cytokine mRNA and protein expression levels of LPS-stimulated PBMCs with or without CST were measured by qRT-PCR and ELISA. The transcriptomic profile of CST-treated PBMCs was investigated by RNA-sequencing. Gene Ontology (GO) and Kyoto Encylopedia of Genes and Genomes (KEGG) were applied to find potential signalling pathways. PBMCs showed a significant increase in phagocytic activity at 6 h after being incubated with CST at the concentration of 10 µg/mL. In the presence of LPS, CST maintained and promoted the expression of TNF-α and chemokine CCL24. The content of pro-inflammatory cytokines, such as IL-1ß, IL-6 and IFN-γ, which were released from LPS-stimulated PBMCs, was reduced by CST at 6 h. Anti-inflammatory cytokines, such as IL-4, IL-13 and TGF-ß1, were significantly increased by CST at 24 h. A total of 277 differentially expressed immune-related genes (DEIRGs) were detected and cytokine-cytokine receptor interaction was highly enriched. CST presented obvious anti-inflammatory and immunoregulatory effects in LPS-induced PBMCs inflammatory model not only by improving the ability of PBMCs to clear pathogens but also by decreasing pro-inflammatory cytokines and increasing anti-inflammatory cytokines. And the mechanism may be related to cytokine-cytokine receptor interaction.

Cell sheet formation enhances the therapeutic effects of adipose-derived stromal vascular fraction on urethral stricture.

Urethral stricture (US) is a common disease in urology, lacking effective treatment options. Although injecting a stem cells suspension into the affected area has shown therapeutic benefits, challenges such as low retention rate and limited efficacy hinder the clinical application of stem cells. This study evaluates the therapeutic impact and the mechanism of adipose-derived vascular fraction (SVF) combined with cell sheet engineering technique on urethral fibrosis in a rat model of US. The results showed that SVF-cell sheets exhibit positive expression of α-SMA, CD31, CD34, Stro-1, and eNOS. In vivo study showed less collagen deposition, low urethral fibrosis, and minimal tissue alteration in the group receiving cell sheet transplantation. Furthermore, the formation of a three-dimensional (3D) tissue-like structure by the cell sheets enhances the paracrine effect of SVF, facilitates the infiltration of M2 macrophages, and suppresses the TGF-ß/Smad2 pathway through HGF secretion, thereby exerting antifibrotic effects. Small animal in vivo imaging demonstrates improved retention of SVF cells at the damaged urethra site with cell sheet application. Our results suggest that SVF combined with cell sheet technology more efficiently inhibits the early stages of urethral fibrosis.

Negatively charged bladder acellular matrix loaded with positively charged adipose-derived mesenchymal stem cell-derived small extracellular vesicles for bladder tissue engineering.

Adipose-derived mesenchymal stem cell-derived small extracellular vesicles (Ad-MSC-sEVs/AMEs) combined with scaffold materials are used in tissue-engineered bladders; however, the lack of retention leads to limited distribution of AMEs in the scaffold areas and low bioavailability of AMEs after bladder reconstruction. To improve retention of AMEs, we developed a novel strategy that modifies the surface charge of the bladder acellular matrix (BAM) via oxidative self-polymerization of dopamine-reducing graphene oxide (GO) and AMEs using ε-polylysine-polyethylene-distearyl phosphatidylethanolamine (PPD). We evaluated two BAM surface modification methods and evaluated the biocompatibility of materials and PPD and electrostatic adherence effects between PPD-modified AMEs and rGO-PDA/BAM in vivo and in vitro. Surface modification increased retention of AMEs, enhanced regeneration of bladder structures, and increased electrical conductivity of rGO-PDA/BAM, thereby improving bladder function recovery. RNA-sequencing revealed 543 miRNAs in human AMEs and 514 miRNAs in rat AMEs. A Venn diagram was used to show target genes of miRNA with the highest proportion predicted by the four databases; related biological processes and pathways were predicted by KEGG and GO analyses. We report a strategy for improving bioavailability of AMEs for bladder reconstruction and reveal that enriched miR-21-5p targets PIK3R1 and activates the PI3K/Akt pathway to promote cell proliferation and migration.

Porous gelatin microspheres implanted with adipose mesenchymal stromal cells promote angiogenesis via protein kinase B/endothelial nitric oxide synthase signaling pathway in bladder reconstruction.

BACKGROUND AIMS: Cell failure and angiogenesis are the key to bladder wall regeneration. Three-dimensional (3D) culture using porous gelatin microspheres (GMs) as a vehicle promotes stem cell proliferation and improves the paracrine capacity of cells. This study aimed to evaluate the therapeutic potential of GMs constructed from adipose-derived mesenchymal stromal cells (ADSCs) (ADSC-GMs) combined with bladder acellular matrix (BAM) in tissue-engineered bladders. METHODS: Isolation of ADSCs, flow cytometry, scanning electron microscopy and cell counting kit-8, ß-galactosidase and enzyme-linked immunosorbent assays were performed in vitro to compare two-dimensional (2D) and 3D cultures. In the in vivo study, male Sprague-Dawley rats were randomly divided into three groups: the BAM replacement alone (BAM) group, ADSCs grown on BAM in replacement (ADSC) group and ADSC-GMs combined with BAM followed by replacement (ADSC-GM) group. Bladder function assessed by urodynamics after 12 weeks of bladder replacement, and the rats were sacrificed at 4 and 12 weeks for further experiments. RESULTS: The in vitro results showed that GM culture promoted ADSC proliferation, inhibited apoptosis and delayed senescence compared with those in the 2D culture. In addition, ADSC-GMs increased the secretion of the angiogenic factors vascular endothelial growth factor, platelet-derived growth factor-BB, and basal fibroblast growth factor. In vivo experiments revealed that ADSC-GMs adhered to the BAM for longer than ADSCs. Moreover, ADSC-GMs significantly promoted the regeneration of bladder vessels and smooth muscle, thereby facilitating the recovery of bladder function. The expression of phosphorylated protein kinase B (AKT) and phosphorylated endothelial nitric oxide synthase (eNOS) was significantly greater in the ADSC-GMs group compared with the BAM and ADSCs groups. CONCLUSIONS: ADSC-GMs increased retention of ADSCs on the BAM, thereby promoting the regeneration and functional recovery of the bladder tissue. ADSC-GMs promoted angiogenesis by activating the AKT/eNOS pathway.

Efficacy and safety of vancomycin for the treatment of Staphylococcus aureus bacteraemia: a systematic review and meta-analysis.

OBJECTIVES: To evaluate the safety and efficacy of vancomycin with the other anti-Gram-positive bacteria antibiotics in the treatment of Staphylococcus aureus bacteraemia. METHODS: We searched the PubMed, MEDLINE, Embase and Cochrane Library databases until August 2022 for studies that compared vancomycin with other antibiotic regimens for treating Staphylococcus aureus bacteraemia. Clinical and microbiological responses, adverse events, relapse rate and mortality were considered. RESULTS: Fifteen randomized controlled trials and nine retrospective studies were included. The efficacy and safety data of vancomycin differed from those of the comparators group. After subgroup analysis, the differences came mainly from the trials compared with daptomycin. Compared to daptomycin, vancomycin showed a lower microbiological cure rate (OR = 0.58, 95% CI = 0.41∼0.82, I2 = 0%, P = 0.002) and clinical cure rate (OR = 0.53, 95% CI = 0.42∼0.68, I2 = 3%, P < 0.00001), as well as more adverse events (OR = 3.21, 95% CI = 1.43∼7.19, I2 = 59%, P = 0.005). CONCLUSION: The efficacy of vancomycin in treating Staphylococcus aureus bacteraemia is still excellent but slightly inferior in adverse events. However, this does not affect its use as a first-line drug. Daptomycin is expected to be a better antimicrobial drug.

Construction of tissue-engineered bladders using an artificial acellular nanocomposite scaffold loaded with stromal vascular fraction secretome.

Tissue engineering approaches offer promising alternative strategies for reconstructing bladder tissue; however, the low retention of transplanted cells and the possible risk of rejection limit their therapeutic efficacy. Clinical applicability is further limited by the lack of suitable scaffold materials to support the needs of various cell types. In the present study, we developed an artificial nanoscaffold system consisting of stromal vascular fraction (SVF) secretome (Sec) loaded onto zeolitic imidazolate framework-8 (ZIF-8) nanoparticles, which were then incorporated into bladder acellular matrix. This artificial acellular nanocomposite scaffold (ANS) can achieve gradient degradation and slowly release SVF-Sec to promote tissue regeneration. Furthermore, even after long-term cryopreservation, this completely acellular bladder nanoscaffold material still maintains its efficacy. In a rat bladder replacement model, ANS transplantation demonstrated potent proangiogenic ability and induced M2 macrophage polarization to promote tissue regeneration and restore bladder function. Our study demonstrates the safety and efficacy of the ANS, which can play a stem cell-like role while avoiding the disadvantages of cell therapy. Furthermore, the ANS can replace the bladder regeneration model based on cell-binding scaffold materials and has the potential for clinical application. STATEMENT OF SIGNIFICANCE: This study aimed to develop a gradient-degradable artificial acellular nanocomposite scaffold (ANS) loaded with stromal vascular fraction (SVF) secretome for rehabilitating bladders. Using various in vitro methods as well as rat- and zebrafish-based in vivo models, the developed ANS was assessed for efficacy and safety. Results indicated that the ANS achieved gradient degradation and slowly released the SVF secretome to promote tissue regeneration, even after long-term cryopreservation. Furthermore, ANS transplantation demonstrated a potent pro-angiogenic ability and induced M2 macrophage polarization to promote tissue regeneration and restore bladder function in a bladder replacement model. Our study demonstrates that ANS may replace bladder regeneration models based on cell-binding scaffold materials and have potential clinical application.

Overexpression of PsAMT1.2 in poplar enhances nitrogen utilization and resistance to drought stress.

Ammonium is an important form of inorganic nitrogen, which is essential for plant growth and development, and the uptake of ammonium is mediated by different members of ammonium transporters (AMTs). It is reported that PsAMT1.2 is specially expressed in the root of poplar, and the overexpression of PsAMT1.2 could improve plant growth and the salt tolerance of poplar. However, the role of AMTs in plant drought and low nitrogen (LN) resistance remains unclear. To understand the role of PsAMT1.2 in drought and LN tolerance, the response of PsAMT1.2-overexpression poplar to polyethylene glycol (PEG)-simulated drought stress (5% PEG) under LN (0.001 mM NH4NO3) and moderate nitrogen (0.5 mM NH4NO3) conditions was investigated. The PsAMT1.2-overexpression poplar showed better growth with increased stem increment, net photosynthetic rate, chlorophyll content, root length, root area, average root diameter and root volume under drought and/or LN stress compared with the wild type (WT). Meanwhile, the content of malondialdehyde significantly decreased, and the activities of superoxide dismutase and catalase significantly increased in the roots and leaves of PsAMT1.2-overexpression poplar compared with WT. The content of NH4+ and NO2- in the roots and leaves of PsAMT1.2-overexpression poplar was increased, and nitrogen metabolism-related genes, such as GS1.3, GS2, Fd-GOGAT and NADH-GOGAT, were significantly upregulated in the roots and/or leaves of PsAMT1.2-overexpression poplar compared with WT under drought and LN stress. The result of this study would be helpful for understanding the function of PsAMT1.2 in plant drought and LN tolerance and also provides a new insight into improving the drought and LN tolerance of Populus at the molecular level.

Sig1R activates extracellular matrix-induced bladder cancer cell proliferation and angiogenesis by combing ß-integrin.

The extracellular matrix (ECM) regulates many biological functions involved in tumorigenesis and tumor development; however, the underlying mechanism remains unknown. Sigma 1 receptor (Sig1R), a stress-activated chaperone, regulates the crosstalk between the ECM and tumor cells and is related to the malignant characteristics of several tumors. However, the link between Sig1R overexpression and ECM during malignancy has not been established in bladder cancer (BC). Here, we analyzed the interaction of Sig1R and ß-integrin in BC cells and its role in ECM-mediated cell proliferation and angiogenesis. We found that Sig1R forms a complex with ß-integrin to promote ECM-mediated BC cell proliferation and angiogenesis, which enhances the aggressiveness of the tumor cells. This leads to poor survival. Our research revealed that Sig1R mediates the cross-talk between BC cells and their ECM microenvironment, thereby driving the progression of BC. Promisingly, targeting an ion channel function through Sig1R inhibition may serve as a potential approach for BC treatment.

Can biomarkers identified from the uterine fluid transcriptome be used to establish a noninvasive endometrial receptivity prediction tool? A proof-of-concept study.

BACKGROUND: Embryo implantation in a receptive endometrium is crucial for successful pregnancy. Endometrial receptivity (ER) prediction tools based on endometrial transcriptome biomarkers by endometrial biopsy have been used to guide successful embryo implantation in in vitro fertilization (IVF) patients. However, no reliable noninvasive ER prediction method has been established, and one is greatly needed. We aimed to identify biomarkers from uterine fluid transcriptomic sequencing data for establishing noninvasive ER prediction tool and to evaluate its clinical application potential in patients undergoing IVF. METHODS: The non-invasive RNA-seq based endometrial receptivity test (nirsERT) was established by analyzing transcriptomic profile of 144 uterine fluid specimens (LH + 5, LH + 7, and LH + 9) at three different receptive status from 48 IVF patients with normal ER in combination with random forest algorithm. Subsequently, 22 IVF patients who underwent frozen-thaw blastocyst transfer were recruited and analyzed the correlation between the predicted results of nirsERT and pregnancy outcomes. RESULTS: A total of 864 ER-associated differentially expressed genes (DEGs) involved in biological processes associated with endometrium-embryo crosstalk, including protein binding, signal reception and transduction, biomacromolecule transport and cell-cell adherens junctions, were selected. Subsequently, a nirsERT model consisting of 87 markers and 3 hub genes was established using a random forest algorithm. 10-fold cross-validation resulted in a mean accuracy of 93.0%. A small cohort (n = 22) retrospective observation shows that 77.8% (14/18) of IVF patients predicted with a normal WOI had successful intrauterine pregnancies, while none of the 3 patients with a displaced WOI had successful pregnancies. One patient failed due to poor sequencing data quality. CONCLUSIONS: NirsERT based on uterine fluid transcriptome biomarkers can predict the WOI period relatively accurately and may serve as a noninvasive, reliable and same cycle test for ER in reproductive clinics. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR-DDD-17013375. Registered 14 November 2017, http://www.chictr.org.cn/index.aspx .

The impact of parental migration on left-behind children's vision health in rural China.

BACKGROUND: Parental migration is an important factor affecting left-behind children's health. However, few studies have addressed the effect of parental migration on children's vision health in China. To fill the gap, this study aimed to assess the impact of parental migration on left-behind children's vision health and to explore the possible mechanisms of the effect. METHODS: Data were obtained from the baseline survey of the China Education Panel Survey (CEPS), which included over 10,000 junior high school students. This study used myopia, the most common vision problem among junior high school students, and tried to analyze whether myopia was corrected with eyeglasses as indicator variables of vision health. The impact of parental migration on vision health was assessed using an instrumental variables approach. RESULTS: The results show that parental migration reduced the likelihood of myopia in left-behind children and decreased the possibility of myopic left-behind children being corrected. This result passed a series of robustness tests. The mechanism analysis indicated that compared to non-left-behind children, left-behind children spent more time on outdoor activities and less time on after-school classes, reducing their risk of being myopic. Further, because left-behind children live apart from their parents, their myopia problem is more difficult for parents to notice, and left-behind children are less likely to inform their parents of their myopia than non-left-behind children actively. This helps to explain why left-behind children have a lower correction rate with eyeglasses. CONCLUSIONS: Our findings suggest that parental migration, while not increasing the prevalence of myopia in left-behind children, has led to inequity in myopic left-behind children's correction. Given the severe consequences of uncorrected myopia, action is required to enhance the correction rate of myopic left-behind children.

Synergistic effect of low-frequency ultrasound and antibiotics on the treatment of Klebsiella pneumoniae pneumonia in mice.

The antibiotic-resistant Klebsiella pneumoniae (Kp) has become a significant crisis in treating pneumonia. Low-frequency ultrasound (LFU) is promising to overcome the obstacles. Mice were infected with bioluminescent Kp Xen39 by intratracheal injection to study the therapeutic effect of LFU in combination with antibiotics. The counts per second (CPS) were assessed with an animal biophoton imaging system. Bacterial clearance, histopathology, and the concentrations of cytokines were determined to evaluate the therapeutic effect. LC-MS/MS was used to detect the distribution of antibiotics in the lung and plasma. LFU in combination with meropenem (MEM) or amikacin (AMK) significantly improved the behavioural state of mice. The CPS of the LFU combination group were more significantly decreased compared with those of the antibiotic alone groups. The average colony-forming units of lung tissue in the LFU combination groups were also lower than those of the antibiotic groups. Although no significant changes of cytokines (IL-6 and TNF-α) in plasma and bronchoalveolar lavage fluid were observed, LFU in combination with antibiotics showed less inflammatory damage from histopathological results compared with the antibiotic-alone groups. Moreover, 10 min of LFU treatment promoted the distribution of MEM and AMK in mouse lung tissue at 60 and 30 min, respectively, after dosage. LFU could enhance the effectiveness of MEM and AMK in the treatment of Kp-induced pneumonia, which might be attributed to the fact that LFU could promote the distribution of antibiotics in lung tissue and reduce inflammatory injury.

Homeostatic Model Assessment for Insulin Resistance Is Associated With Late Miscarriage in Non-Dyslipidemic Women Undergoing Fresh IVF/ICSI Embryo Transfer.

Objective: To evaluate the associations between homeostatic model assessment for insulin resistance (HOMA-IR) and pregnancy outcomes in non-dyslipidemic infertile women undergoing in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET). Materials and Methods: This is a retrospective study involving 3,615 non-dyslipidemic infertile women who attend to the Reproductive Medicine Center of Xiangya Hospital, Central South University (CSU) between January 2014 and October 2021. Eligible participants were divided into three groups according to the quartiles of HOMA-IR: Group 1 (HOMA-IR <1.46), Group 2 (1.46 to <2.71) and Group 3 (HOMA-IR ≥2.71). Baseline data, clinical characteristics during the assisted reproductive technology (ART) procedure, pregnancy, and neonatal outcomes were compared among the three groups. Subgroup analysis based on presence or absence of the polycystic ovary syndrome (PCOS) status was also performed to analyze the effects of HOMA-IR among non-PCOS populations. Results: The late miscarriage rate and percentage of macrosomia increased with the HOMA-IR group (for late miscarriage rate: 2.23% vs. 3.04% vs. 7.35%, P<0.001; for macrosomia: 0.21% vs. 1.70% vs. 3.23%, P=0.002). Increased HOMA-IR (HOMA-IR≥2.71) was positively associated with late miscarriage (crude OR 3.50, 95% CI 1.64-7.47, P=0.001; adjusted OR 3.56, 95% CI 1.56-8.15, P=0.003). In the subgroup analysis, there were 3,165 participants in the non-PCOS group and 450 were assigned to the PCOS group. Late miscarriage rate increased with the HOMA-IR group among non-PCOS populations (2.20% vs. 3.03% vs. 7.67%, P<0.001). Late miscarriage rate of PCOS women were comparable among the three HOMA-IR groups (2.50% vs. 3.06% vs. 5.71%, P=0.634). Among non-PCOS women, increased HOMA-IR (HOMA-IR≥2.71) was positively associated with late miscarriage (crude OR 3.71, 95% CI 1.66-8.30, P=0.001; adjusted OR 3.82, 95% CI 1.59-9.17, P=0.003). Conclusions: Late miscarriage rate and prevalence of macrosomia increased with the HOMA-IR index. Preconception HOMA-IR is an independent risk factor for late miscarriage in normolipidemic women undergoing IVF/ICSI-ET. Controlling insulin resistance before ART might prevent the occurrence of late miscarriage and macrosomia.

Lipid metabolism and endometrial receptivity.

BACKGROUND: Obesity has now been recognized as a high-risk factor for reproductive health. Although remarkable advancements have been made in ART, a considerable number of infertile obese women still suffer from serial implantation failure, despite the high quality of embryos transferred. Although obesity has long been known to exert various deleterious effects on female fertility, the underlying mechanisms, especially the roles of lipid metabolism in endometrial receptivity, remain largely elusive. OBJECTIVE AND RATIONALE: This review summarizes current evidence on the impacts of several major lipids and lipid-derived mediators on the embryonic implantation process. Emerging methods for evaluating endometrial receptivity, for example transcriptomic and lipidomic analysis, are also discussed. SEARCH METHODS: The PubMed and Embase databases were searched using the following keywords: (lipid or fatty acid or prostaglandin or phospholipid or sphingolipid or endocannabinoid or lysophosphatidic acid or cholesterol or progesterone or estrogen or transcriptomic or lipidomic or obesity or dyslipidemia or polycystic ovary syndrome) AND (endometrial receptivity or uterine receptivity or embryo implantation or assisted reproductive technology or in vitro fertilization or embryo transfer). A comprehensive literature search was performed on the roles of lipid-related metabolic pathways in embryo implantation published between January 1970 and March 2022. Only studies with original data and reviews published in English were included in this review. Additional information was obtained from references cited in the articles resulting from the literature search. OUTCOMES: Recent studies have shown that a fatty acids-related pro-inflammatory response in the embryo-endometrium boundary facilitates pregnancy via mediation of prostaglandin signaling. Phospholipid-derived mediators, for example endocannabinoids, lysophosphatidic acid and sphingosine-1-phosphate, are associated with endometrial receptivity, embryo spacing and decidualization based on evidence from both animal and human studies. Progesterone and estrogen are two cholesterol-derived steroid hormones that synergistically mediate the structural and functional alterations in the uterus ready for blastocyst implantation. Variations in serum cholesterol profiles throughout the menstrual cycle imply a demand for steroidogenesis at the time of window of implantation (WOI). Since 2002, endometrial transcriptomic analysis has been serving as a diagnostic tool for WOI dating. Numerous genes that govern lipid homeostasis have been identified and, based on specific alterations of lipidomic signatures differentially expressed in WOI, lipidomic analysis of endometrial fluid provides a possibility for non-invasive diagnosis of lipids alterations during the WOI. WIDER IMPLICATIONS: Given that lipid metabolic dysregulation potentially plays a role in infertility, a better understanding of lipid metabolism could have significant clinical implications for the diagnosis and treatment of female reproductive disorders.

Effect of uncultured adipose-derived stromal vascular fraction on preventing urethral stricture formation in rats.

Urethral stricture (US) remains a challenging disease without effective treatment options due to the high recurrence rate. This study aims to evaluate the preventive effect of uncultured adipose derived stromal vascular fraction (SVF) on urethral fibrosis in a rat model of US. Results demonstrated that US rats displayed hyperechogenic urethral wall with a narrowed lumen compared with sham rats, while SVF rats exhibited less extensive urethral changes. By histology, US rats showed obvious submucosal fibrosis in the urethral specimens, while SVF rats exhibited mild submucosal fibrosis with less extensive tissue changes. Furthermore, US rats showed increased gene and protein expression of collagen I (2.0 ± 0.2, 2.2 ± 0.2, all were normalized against GAPDH, including the following), collagen III (2.5 ± 0.3, 1.2 ± 0.1), and TGFß1R (2.8 ± 0.3, 1.9 ± 0.2), while SVF cells administration contributed to decreased gene and protein expression of collagen I (1.6 ± 0.2, 1.6 ± 0.2), collagen III (1.8 ± 0.4, 0.9 ± 0.1), and TGFß1R (1.8 ± 0.3, 1.3 ± 0.2), in parallel with the improvement of vascularization and increased expression of VEGF (1.7 ± 0.1) and bFGF (3.1 ± 0.3). Additionally, SVF served anti-inflammatory effect through regulation of inflammatory cytokines and cells, accompanied with conversion of the macrophage phenotype. Our findings suggested that uncultured SVF presented an inhibitory effect on stricture formation at an early stage of urethral fibrosis.

Therapeutic effect of adipose stromal vascular fraction spheroids for partial bladder outlet obstruction induced underactive bladder.

BACKGROUND: Underactive bladder (UAB) is a common clinical problem but related research is rarely explored. As there are currently no effective therapies, the administration of adipose stromal vascular fraction (ad-SVF) provides a new potential method to treat underactive bladder. METHODS: Male Sprague-Dawley rats were induced by partial bladder outlet obstruction (PBOO) for four weeks and randomly divided into three groups: rats treated with PBS (Sham group); rats administrated with ad-SVF (ad-SVF group) and rats performed with ad-SVF spheroids (ad-SVFsp group). After four weeks, urodynamic studies were performed to evaluate bladder functions and all rats were sacrificed for further studies. RESULTS: We observed that the bladder functions and symptoms of UAB were significantly improved in the ad-SVFsp group than that in the Sham group and ad-SVF group. Meanwhile, our data showed that ad-SVF spheroids could remarkably promote angiogenesis, suppress cell apoptosis and stimulate cell proliferation in bladder tissue than that in the other two groups. Moreover, ad-SVF spheroids increased the expression levels of bFGF, HGF and VEGF-A than ad-SVF. IVIS Spectrum small-animal in vivo imaging system revealed that ad-SVF spheroids could increase the retention rate of transplanted cells in bladder tissue. CONCLUSIONS: Ad-SVF spheroids improved functions and symptoms of bladder induced by PBOO, which contributes to promote angiogenesis, suppress cell apoptosis and stimulate cell proliferation. Ad-SVF spheroids provide a potential treatment for the future patients with UAB.

Factors influencing post-screening visits of students to local vision centres in rural northwest China.

CLINICAL RELEVANCE: Children with uncorrected visual impairment have lower scores on a variety of motor and cognitive tests. Exploring the influencing factors of low-income groups seeking vision care services is helpful for identifying relevant barriers and necessary measures to improve the utilization rate of vision care services. BACKGROUND: The community-based vision center (VC) is a popular model for solving vision problem of students in rural China. Compliance is the key factor to the success of the VC model. Factors determining compliance with visitations to VC among primary school students after screening were explored. METHODS: A cross-sectional study was conducted with 15,763 students from 228 primary schools. Information was collected through questionnaires and vision examinations. The determinants that affect visits of students to the VC were analyzed using logistic regression. RESULTS: Among the 15,763 sample, 5,361 (34%) students had a visual impairment. At baseline, only 962 (18%) of students with visual impairment sought vision care services. After a local VC was established, among the 5,163 students who needed to be referred, only 2,237 (43.33%) students visited the VC. Multivariate logistic regression models for predicting students visit the VC revealed that the following characteristics were significant predictors: poor uncorrected visual acuity (P < 0.001), a higher grade level (P = 0.008; P = 0.010), 'left-behind' children (P < 0.001), short living distance between home and the VC (P < 0.001), and the fact that these students lived in Gansu province (P < 0.001). CONCLUSIONS: Establishing a VC that provides students with vision screening and free vision care services can increase the rate of seeking vision health services for students in rural areas, but the compliance rate still needs to be improved. The influencing factors for student compliance have been identified.

Administration of adipose stromal vascular fraction attenuates acute rejection in donation after circulatory death rat renal transplantation.

OBJECTIVE: Stem cell therapy represents a new approach to induce immune tolerance in solid organ transplantation. However, the time-consuming process of stem cell expending limits the range of stem cell treatment. Uncultured adipose stromal vascular fraction is considered an attractive cell source for cell-based therapy. This study aimed to evaluate the effect of stromal vascular fraction on the immune system in donation after circulatory death rat renal transplantation. METHODS: Stromal vascular fraction cells and splenocytes were co-cultured to evaluate the effect of stromal vascular fraction on splenocyte proliferation and viability. Sprague-Dawley rats were used as donors. and Wistar rats as recipients to establish a donation after a circulatory death rat renal transplantation model. Warm ischemia time was 5 min. Stromal vascular fraction was administered in the rat model following the intra-arterial route. The spleens and grafts of recipients were harvested on days 1, 3 and 7 post-transplantation for assessing acute rejection, infiltration of inflammatory cells, indoleamine 2, 3-dioxygenase expression and T-cell frequency in the spleen. RESULTS: Stromal vascular fraction could inhibit proliferation and induce apoptosis of splenocytes in vitro (P < 0.05). The administration of stromal vascular fraction could significantly reduce acute rejection and infiltration of CD8+ T cells and mononuclear macrophages in grafts, and increase indoleamine 2, 3-dioxygenase expression (P < 0.05). The frequency of CD8+ T cells decreased, and the frequency of CD25+ Foxp3+ regulatory T cells increased in the spleen of the acute rejection + stromal vascular fraction group on day 7 post-transplantation (P < 0.05). CONCLUSION: Administration of the adipose stromal vascular fraction could attenuate acute rejection in donation after circulatory death renal transplantation by increasing the ratio of regulatory T cells and enhancing indoleamine 2, 3-dioxygenase expression.

Associations between dyslipidaemia and pregnancy outcomes in the first complete cycle of IVF/ICSI: a real-world analysis.

RESEARCH QUESTION: Are there associations between dyslipidaemia and pregnancy outcomes in the first complete cycle of IVF/intracytoplasmic sperm injection (ICSI)? DESIGN: This long-term, retrospective real-world analysis involved 5030 infertile women who underwent a first complete IVF/ICSI cycle between January 2015 and October 2020. They were categorized into dyslipidaemia (n = 1903) and control (n = 3127) groups according to serum lipid concentrations before ovarian stimulation. Propensity score matching and multivariable logistic regression were used to control for confounding variables. RESULTS: In the raw cohort, women with dyslipidaemia had a significantly increased late miscarriage rate (P = 0.039), decreased term birth rate (P = 0.002) and decreased live birth rate (P = 0.005) compared with non-dyslipidaemic women. In the propensity score-matched cohort, the term birth rate (P = 0.038) and live birth rate (P = 0.044) were significantly lower in the dyslipidaemia group (n = 1686) than the controls (n = 1686). Multivariable logistic regression indicated that infertile women with dyslipidaemia (P = 0.026) and elevated serum total cholesterol concentrations (total cholesterol ≥5.20 mmol/l; P = 0.028) were significantly less likely to have a live birth. Rates of late miscarriage (P = 0.027), term birth (P = 0.003) and live birth (P = 0.010) differed significantly among women with normal, borderline increased and increased serum lipid concentrations. Compared with controls, women with increased serum lipid concentrations had a significantly higher late miscarriage rate, lower term birth rate and lower live birth rate. Women with increased serum lipid concentrations were significantly less likely than controls to have a live birth. CONCLUSIONS: Dyslipidaemia, total cholesterol ≥5.20 mmol/l and degrees of elevated serum lipid concentrations are negatively associated with live birth rate in the first complete IVF/ICSI cycle in infertile women.

circ-ZNF609: A potent circRNA in human cancers.

Circular RNAs (circRNAs) are a novel group of endogenous RNAs with a circular structure. Growing evidence indicates that circRNAs are involved in a variety of human diseases including malignancies. CircRNA ZNF609 (circ-ZNF609), derived from the ZNF609 gene sequence, has been demonstrated to be involved in the development and progression of many diseases. circ-ZNF609 is thought to be a viable diagnostic and prognostic biomarker for several diseases and might be a new therapeutic target, but further research is needed to accelerate clinical application. Here, we review the biogenesis and function of circRNAs and the functional roles and molecular mechanism related to circ-ZNF609 in neoplasms and other diseases.

Administration of Donor-Derived Nonexpanded Adipose Stromal Vascular Fraction Attenuates Ischemia-Reperfusion Injury in Donation After Cardiac Death Rat Renal Transplantation.

Donation after cardiac death (DCD) has become a potential source for transplantation organs. However, ischemia/reperfusion injury (IRI) induced by cardiac arrest has limited the use of DCD organs. Stromal vascular fraction (SVF) without the culturing step has been proposed as a safer and easier source for stem cell therapy, which has emerged as an attractive technology that could facilitate the recovery of renal function and structure from acute kidney injury induced by IRI after DCD renal transplantation. In this study, freshly isolated donor-derived SVF was identified and then delivered intra-arterially into the grafts in DCD rat renal transplantation. Administration of freshly isolated donor-derived SVF could significantly alleviate the IRI of renal grafts and enhance graft reparation by promoting graft cell proliferation and microvascularization in DCD renal transplantation. Moreover, results revealed that the oxidative stress in grafts was significantly alleviated with SVF treatment, and this might be attributed to the overexpression of antioxidative molecules including nuclear factor erythroid-related factor 2, superoxide dismutase-1, and heme oxygenase-1. In conclusion, our study demonstrated that the administration of freshly isolated donor-derived nonexpanded adipose SVF could attenuate IRI and protect the grafts after DCD rat renal transplantation.