Construction of living-cell tissue engineered amniotic membrane for ocular surface disease.

BACKGROUND: Human amniotic membrane (AM) transplantation has been applied to treat ocular surface diseases, including corneal trauma. The focus of much deliberation is to balance the mechanical strength of the amniotic membrane, its resistance to biodegradation, and its therapeutic efficacy. It is commonly observed that the crosslinked human decellularized amniotic membranes lose the functional human amniotic epithelial cells (hAECs), which play a key role in curing the injured tissues. METHODS AND RESULTS: In this study, we crosslinked human decellularized amniotic membranes (dAM) with genipin and re-planted the hAECs onto the genipin crosslinked AM. The properties of the AM were evaluated based on optical clarity, biodegradation, cytotoxicity, and ultrastructure. The crosslinked AM maintained its transparency. The color of crosslinked AM deepened with increasing concentrations of genipin. And the extracts from low concentrations of genipin crosslinked AM had no toxic effect on human corneal epithelial cells (HCECs), while high concentrations of genipin exhibited cytotoxicity. The microscopic observation and H&E staining revealed that 2 mg/mL genipin-crosslinked dAM (2 mg/mL cl-dAM) was more favorable for the attachment, migration, and proliferation of hAECs. Moreover, the results of the CCK-8 assay and the transwell assay further indicated that the living hAECs' tissue-engineered amniotic membranes could facilitate the proliferation and migration of human corneal stromal cells (HCSCs) in vitro. CONCLUSIONS: In conclusion, the cl-dAM with living hAECs demonstrates superior biostability and holds significant promise as a material for ocular surface tissue repair in clinical applications.

Mindfulness therapy for patients with coronary heart disease: A systematic review and meta-analysis.

AIM: Coronary heart disease (CHD) is a prevalent cardiovascular disease with high mortality rates worldwide. Patients with CHD often experience adverse psychological stress related to the disease's diagnosis, treatment and recovery phases. This stress can hurt sleep quality and overall quality of life. Mindfulness-based interventions (MBIs) have been studied as a psychotherapeutic approach to alleviating the psychological stress associated with CHD. This study aimed to determine the effectives of MBIs for health outcomes in patients with CHD. METHODS: A total of eight English-language databases were searched, and eight relevant studies were included in the analysis. The included studies were assessed for literature quality, and data were extracted and analysed using Review Manager 5.3. RESULTS: A total of eight studies involving 802 participants were included in the analysis. Compared to control groups, MBIs significantly reduced anxiety, depression, perceived stress, and systolic blood pressure. However, there was no significant effect on diastolic blood pressure, quality of life or body mass index. One study reported that MBIs significantly improved sleep quality in patients with acute myocardial infarction after percutaneous coronary intervention but had no significant effect on body mass index. CONCLUSION: MBIs had significant effects on anxiety and depression in patients with CHD, reduced perceived stress and were associated with reductions in systolic blood pressure and improvements in sleep quality. However, they did not significantly affect diastolic blood pressure, quality of life or body mass index.

An Overview of Taste-Masking Technologies: Approaches, Application, and Assessment Methods.

It is well-known that plenty of active pharmaceutical ingredients (API) inherently possess an unpleasant taste, which influences the acceptance of patients, especially children. Therefore, manufacturing taste-masked dosage forms has attracted a lot of attention. This review describes in detail the taste-masking technologies based on the difference in the taste transmission mechanism which is currently available. In particular, the review highlights the application of various methods, with a special focus on how to screen the appropriate masking technology according to the properties of API. Subsequently, we overviewed how to assess taste-masking efficacy, guiding researchers to rationally design taste-masking formulations.

CHIR99021 balance TGFß1 induced human corneal endothelial-to-mesenchymal transition to favor corneal endothelial cell proliferation.

Corneal endothelial cells (CECs) play a major role in the maintenance of stromal hydration via the barrier and pump function for clear vision. Adult CECs cannot regenerate after injury. CECs cultured in vitro can undergo mitosis but may undergo corneal endothelial-to-mesenchymal transition (EnMT) and lose their endothelial characteristics. In this study, we examined the effects of CHIR99021 on transforming growth factor beta-1(TGFß1)-induced EnMT in human CECs (hCECs) lines. CHIR99021 kept hCECs in the hexagonal shape and could downregulate the EnMT markers alpha-smooth muscle actin (α-SMA) and fibronectin (FN1), meanwhile maintained the hCECs function markers Na+/K+-ATPase and zonula occludens-1 (ZO-1) at levels comparable to those in the normal control. Interestingly, we found that the combination of CHIR99021 and TGFß1 at appropriate concentrations would significantly promote the proliferation and migration of hCECs. These effects may be related to the inhibition of RhoA or Rac1, as well as the activation of Wnt and Erk pathway, with a calcium homeostasis. Our findings indicate that CHIR99021 inhibit EnMT and that the combination of CHIR99021 and TGFß1 may provide new ideas for corneal endothelial regeneration and wound healing.

A novel long noncoding RNA AC125257.1 facilitates colorectal cancer progression by targeting miR-133a-3p/CASC5 axis.

Colorectal cancer (CRC) is a common malignant gastrointestinal tumor. Long noncoding RNAs (lncRNAs) are revealed to be critically involved in CRC progression, providing new direction for exploring the pathogenesis of CRC. This study aimed to explore the biological functions and regulatory mechanisms of lncRNA AC125257.1 in CRC. Western blotting and reverse-transcription quantitative polymerase chain reaction were used for the measurement of gene expression. Cell counting kit-8 assay and flow cytometry analysis were used to explore the effects of AC125257.1 on CRC cell viability and apoptosis. RNA pull-down and immunoprecipitation assays were performed for validating the binding between AC125257.1 and its potential downstream microRNA. Results showed that lncRNA AC125257.1 expression was upregulated in CRC cells and tumor tissues. AC125257.1 enhanced cell viability and suppressed apoptosis of CRC cells. Moreover, the knockdown of AC125257.1 suppressed CRC progression in vitro and inhibited tumor growth in vivo. miR-133a-3p was revealed to bind with AC125257.1 in CRC cells. CASC5 was proved to be targeted by miR-133a-3p. Moreover, rescue assays indicated that the knockdown of AC125257.1 suppressed the pathogenic overexpression of CASC5. To conclude, AC125257.1 aggravates CRC development via miR-873-5p/CASC5 axis. Our findings might suggest a novel perspective that AC125257.1 may become the target for CRC treatment.

Effects of traditional Chinese exercises on the rehabilitation of patients with chronic heart failure: A meta-analysis.

Background: With the development of rehabilitation medicine, exercise therapy has gradually become one of the methods to prevent and treat cardiovascular diseases. It is widely used in clinic because it can further reduce the mortality rate, improve clinical symptoms, restore the activity ability of the body, improve the quality of life of patients and reduce the hospitalization rate. Traditional Chinese exercises have developed rapidly in recent years, which mainly include Baduanjin, Tai Ji, etc. However, meta-analyses of all types of exercises are not well characterized. Objectives: To evaluate the effect of traditional Chinese exercises (TCEs) on the rehabilitation of patients with chronic heart failure (CHF) using a meta-analysis. Methods: A systematic search of randomized controlled trials (RCTs) on TCEs for patients with CHF in 13 databases (PubMed, China National Knowledge Infrastructure, etc.). Meta-analysis was performed using Review Manager software (version 5.3) after two investigators independently screened the studies, assessed the quality of the studies, and extracted the data. Results: Meta-analysis of 21 randomized controlled trials which involved 1,665 patients with chronic heart failure showed that practicing TCEs was effective in improving patients' physiological outcomes such as VO2max [MD = 2.14, 95% CI (1.02, 3.26), P < 0.001], AT [MD = 1.61, 95% CI (1.06, 2.16), P < 0.001], and left ventricular ejection fraction [MD = 2.60, 95% CI (1.17, 4.02), P < 0.001]. Non-physiological outcomes benefited from the application of TCEs: 6-min walking distance [MD = 38.55, 95% CI (36.67, 40.42), P < 0.001], quality of life [MD = 5.52, 95% CI (3.17, 7.88), P < 0.001], and single-item TCM symptom scores in CHF patients: tiredness and fatigue [MD = 0.78, 95% CI (0.03, 1.53), P = 0.04], shortness of breath [MD = 0.44,95% CI (0.26, 0.62), P < 0.0001], facial puffiness and limb swelling [MD = 0.44,95% CI (0.12, 0.76), P = 0.007], palpitations [MD = 0.68,95% CI (0.14, 1.21), P = 0.01] were improved. Conclusions: TCEs improved several recovery indicators, heart failure-related clinical symptoms, quality of life, and physiological indicators in patients with CHF. It is worthwhile to expand the participants for practical application in clinical practice, but the existing evidence is insufficient and the heterogeneity of outcome is large. Therefore, more high-quality clinical trials are needed to support these results. Systematic review registration: PROSPERO, identifier [CRD42022383246].

Metagenomic surveillance and comparative genomic analysis of Chlamydia psittaci in patients with pneumonia.

Chlamydia psittaci, a strictly intracellular bacterium, is an underestimated etiologic agent leading to infections in a broad range of animals and mild illness or pneumonia in humans. In this study, the metagenomes of bronchoalveolar lavage fluids from the patients with pneumonia were sequenced and highly abundant C. psittaci was found. The target-enriched metagenomic reads were recruited to reconstruct draft genomes with more than 99% completeness. Two C. psittaci strains from novel sequence types were detected and these were closely related to the animal-borne isolates derived from the lineages of ST43 and ST28, indicating the zoonotic transmissions of C. psittaci would benefit its prevalence worldwide. Comparative genomic analysis combined with public isolate genomes revealed that the pan-genome of C. psittaci possessed a more stable gene repertoire than those of other extracellular bacteria, with ~90% of the genes per genome being conserved core genes. Furthermore, the evidence for significantly positive selection was identified in 20 virulence-associated gene products, particularly bacterial membrane-embedded proteins and type three secretion machines, which may play important roles in the pathogen-host interactions. This survey uncovered novel strains of C. psittaci causing pneumonia and the evolutionary analysis characterized prominent gene candidates involved in bacterial adaptation to immune pressures. The metagenomic approach is of significance to the surveillance of difficult-to-culture intracellular pathogens and the research into molecular epidemiology and evolutionary biology of C. psittaci.

Incidence and risk factors of asymptomatic bacteriuria in patients with type 2 diabetes mellitus: a meta-analysis.

BACKGROUND: The prevalence of type 2 diabetes mellitus (T2DM) is increasing each year and has become one of the most prominent health concerns worldwide. Patients with T2DM are prone to infectious diseases, and urinary tract infections are also widespread. Despite a comprehensive understanding of urinary tract infection (UTI), there is a lack of research regarding primary prevention strategies for asymptomatic bacteriuria (ASB). OBJECTIVE: To clarify the incidence and risk factors of asymptomatic urinary tract infection in patients with T2DM by meta-analysis to provide evidence for preventing UTI. Help patients, their families, and caregivers to identify the risk factors of patients in time and intervene to reduce the incidence of ASB in patients with T2DM. Fill in the gaps in existing research. STUDY DESIGN: Meta-analyses were conducted in line with PRISMA guidelines. METHODS: Eleven databases were systematically searched for articles about ASB in T2DM, and the retrieval time was selected from the establishment of the database to February 5, 2023. Literature screening, quality evaluation, and meta-analysis were independently performed by two researchers according to the inclusion and exclusion criteria, and a meta-analysis was performed using Stata 17.0. RESULTS: Fourteen articles were included, including cohort and case-control studies. A meta-analysis of 4044 patients with T2DM was included. The incidence of ASB in patients with T2DM was 23.7%(95% CI (0.183, 0.291); P < 0.001). After controlling for confounding variables, the following risk factors were associated with ASB in patients with T2DM: age (WMD = 3.18, 95% CI (1.91, 4.45), I2 = 75.5%, P < 0.001), female sex (OR = 1.07, 95% CI(1.02, 1.12), I2 = 79.3%, P = 0.002), duration of type 2 diabetes (WMD = 2.54, 95% CI (1.53, 5.43), I2 = 80.7%, P < 0.001), HbA1c (WMD = 0.63, 95% CI (0.43, 0.84), I2 = 62.6,%. P < 0.001), hypertension (OR = 1.59, 95% CI (1.24, 2.04), I2 = 0%, <0.001), hyperlipidemia (OR = 1.66, 95% CI (1.27, 2.18), I2 = 0%, P < 0.001), Neuropathy (OR = 1.81, 95% CI (1.38, 2.37), I2 = 0%, P < 0.001), proteinuria (OR = 3.00, 95% CI (1.82, 4.95), I2 = 62.7%, P < 0.001). CONCLUSION: The overall prevalence of ASB in T2DM is 23.7%. Age, female sex, course of T2DM, HbA1C, hypertension, hyperlipidemia, neuropathy, and proteinuria were identified as related risk factors for ASB in T2DM. These findings can provide a robust theoretical basis for preventing and managing ASB in T2DM.

Effects of Nursing Intervention Based on Health Belief Model on Self-Perceived Burden, Drug Compliance, and Quality of Life of Renal Transplant Recipients.

Objective: To explore the effects of nursing intervention based on health belief model (HBM) on self-perceived burden, drug compliance, and quality of life of renal transplant recipients. Methods: Sixty patients with renal transplantation treated in our hospital from February 2019 to July 2021 were enrolled. The patients were randomly assigned to control group and study group. The former received routine nursing and the latter received nursing intervention based on HBM. Results: The nursing satisfaction in the study group was higher compared to the control group (P < 0.05). Secondly, we compared the scores of self-burdens. Before nursing, they exhibited no significant difference (P > 0.05); after nursing, they decreased. Moreover, the physical burden, economic burden, and emotional burden of the study group were lower compared to the control group (P < 0.05). In terms of drug compliance, the rates of no missed medication, noncontinuous missed medication, timely medication, dose-by-dose medication, and non-self-stopping medication in the study group were higher compared to the control group (P < 0.05). The scores of SAS and SDS exhibited no significant difference before nursing (P > 0.05). After nursing, they decreased. Furthermore, the scores of SAS and SDS of the study group were lower compared to the control group (P < 0.05). The self-management ability exhibited no significant difference before nursing (P > 0.05); after nursing, it increased. Moreover, the self-management ability of the study group at discharge and 1 month, 3 months, and 6 months after discharge was higher compared to the control group (P < 0.05). Finally, we compared the scores of quality of life. Before nursing, there was no significant difference (P > 0.05). The scores of physiological function, psychological function, social function, and health self-cognition in the study group were lower compared to the control group (P < 0.05). Conclusion: The nursing intervention based on HBM can enhance the medication compliance of renal transplant recipients, and the intervention effect is long-lasting. Meanwhile, it can effectively enhance the negative emotion of patients, reduce the burden of self-feeling, promote the quality of life, strengthen the self-management of patients, and facilitate the prognosis.

Human amniotic epithelial cell-derived extracellular vesicles provide an extracellular matrix-based microenvironment for corneal injury repair.

To study the biological functions and applications of human amniotic epithelial cell-derived extracellular vesicles (hAEC-EVs), the cargos of hAEC-EVs were analyzed using miRNA sequencing and proteomics analysis. The hAECs and hAEC-EVs in this study had specific characteristics. Multi-omics analyses showed that extracellular matrix (ECM) reorganization, inhibition of excessive myofibroblasts, and promotion of target cell adhesion to the ECM were their primary functions. We evaluated the application of hAEC-EVs for corneal alkali burn healing in rabbits and elucidated the fundamental mechanisms. Slit-lamp images revealed that corneal alkali burns induced central epithelial loss, stromal haze, iris, and pupil obscurity in rabbits. Slit-lamp examination and histological findings indicated that hAEC-EVs facilitated re-epithelialization of the cornea after alkali burns, reduced scar formation and promoted the restoration of corneal tissue transparency. Significantly fewer α-SMA-positive myofibroblasts were observed in the hAEC-EV-treated group than the PBS group. HAEC-EVs effectively promoted the proliferation and migration of hCECs and hCSCs in vitro and activated the focal adhesion signaling pathway. We demonstrated that hAEC-EVs were excellent cell-free candidates for the treatment of ECM lesion-based diseases, including corneal alkali burns. HAEC-EVs promoted ECM reorganization and cell adhesion of target tissues or cells via orderly activation of the focal adhesion signaling pathway.

Evaluating the effectiveness of crosswalk tactile paving on street-crossing behavior: A field trial study for people with visual impairment.

People with visual impairment cannot easily obtain external information through vision and thus they face more challenges when traveling than sighted people. The travel environment for people with visual impairment includes pedestrian safety concerns, especially when crossing roads at intersections. Tactile paving can be used as a guidance cue for street-crossing purposes but its use is not yet widespread globally (except at some test sites in Japan). This study investigated the effectiveness of tactile paving on crosswalks based on a field trial conducted in China. A drone and three-axis accelerometer were used to collect participants' behavioral data. Several quantitative indices for street-crossing behavior, including trajectory, maximum distance of the directional deviation, crossing speed, crossing time, and gait regularity and symmetry, were investigated to measure the participants' street-crossing performance. Before-after comparative analysis of the quantitative index results was conducted to compare the participants' use of crosswalks with and without tactile paving. The results reveal that tactile paving helps people with visual impairment to maintain a straight crossing path, avoid directional deviation, reduce their crossing time, and improve their gait regularity and symmetry. Study participants reported positive impressions of the effectiveness of crosswalk tactile paving based on one-to-one interviews conducted after the crosswalk tests. The results also indicate that crosswalk tactile paving is more effective for people with blindness than for those with low vision. This study's findings could serve as a theoretical basis for the deployment of various barrier-free traffic facilities (especially street-crossing facilities) for people with visual impairment.

BMSC-derived extracellular vesicles intervened the pathogenic changes of scleroderma in mice through miRNAs.

BACKGROUND: Systemic sclerosis (SSc) is a disease that features severe fibrosis of the skin and lacks effective therapy. Bone marrow mesenchymal stem cell (BMSC)-derived extracellular vesicles (EVs) are potential stem cell-based tools for the treatment of SSc. METHODS: BMSCs were isolated from the bone marrow of mice and identified with surface markers according to multilineage differentiation. EVs were isolated from the BMSC culture medium by ultracentrifugation and identified with a Nanosight NS300 particle size analyzer, transmission electron microscopy (TEM), and western blot. The microRNAs (miRNAs) of BMSC-derived EVs (BMSC-EVs) were studied via miRNA sequencing (miRNA-seq) and bioinformatic analysis. An SSc mouse model was established via subcutaneous bleomycin (BLM) injection, and the mice were treated with BMSCs or BMSC-derived EVs. Skin tissues were dissociated and analyzed with H&E staining, RNA sequencing (RNA-seq), western blot, and immunohistochemical staining. RESULTS: Evident pathological changes, like fibrosis and inflammation, were induced in the skin of BLM-treated mice. BMSCs and BMSC-EVs effectively intervened such pathological manifestations and disease processes in a very similar way. The effects of the BMSC-EVs were found to be caused by the miRNAs they carried, which were proven to be involved in regulating the proliferation and differentiation of multiple cell types and in multiple EV-related biological processes. Furthermore, TGF-ß1-positive cells and α-SMA-positive myofibroblasts were significantly increased in the scleroderma skin of BLM-treated mice but evidently reduced in the scleroderma skin of the EV-treated SSc group. In addition, the numbers of mast cells and infiltrating macrophages and lymphocytes were evidently increased in the skin of BLM-treated mice but significantly reduced by EV treatment. In line with these observations, there were significantly higher mRNA levels of the inflammatory cytokines Il6, Il10, and Tnf-α in SSc mice than in control mice, but the levels decreased following EV treatment. Through bioinformatics analysis, the TGFß and WNT signaling pathways were revealed to be closely involved in the pathogenic changes seen in mouse SSc, and these pathways could be therapeutic targets for treating the disease. CONCLUSIONS: BMSC-derived EVs could be developed as a potential therapy for treating skin dysfunction in SSc, especially considering that they show similar efficacy to BMSCs but have fewer developmental regulatory requirements than cell therapy. The effects of EVs are generated by the miRNAs they carry, which alleviate SSc pathogenic changes by regulating the WNT and TGFß signaling pathways.

Small-Molecule Induction Promotes Corneal Endothelial Cell Differentiation From Human iPS Cells.

Purpose: Corneal endothelial cells (CECs) serve as a barrier and foothold for the corneal stroma to maintain the function and transparency of the cornea. Loss of CECs during aging or disease states leads to blindness, and cell replacement therapy using either donated or artificially differentiated CECs remains the only curative approach. Methods: Human induced pluripotent stem cells (hiPSCs) that were cultured in chemically defined medium were induced with dual-SMAD inhibition to differentiate into neural crest cells (NCCs). A small-molecule library was screened to differentiate the NCCs into corneal endothelial-like cells. The characteristics of these cells were identified with real-time PCR and immunofluorescence. Western blotting was applied to detect the signaling pathways and key factors regulated by the small molecules. Results: We developed an effective protocol to differentiate hiPSCs into CECs with defined small molecules. The hiPSC-CECs were characterized by ZO-1, AQP1, Vimentin and Na+/K+-ATPase. Based on our small-molecule screen, we identified a small-molecule combination, A769662 and AT13148, that enabled the most efficient production of CECs. The combination of A769662 and AT13148 upregulated the PKA/AKT signaling pathway, FOXO1 and PITX2 to promote the conversion of NCCs to CECs. Conclusion: We established an efficient small molecule-based method to differentiate hiPSCs into corneal endothelial-like cells, which might facilitate drug discovery and the development of cell-based therapies for corneal diseases.

Contribution of interaction between genetic variants of interleukin-11 and Helicobacter pylori infection to the susceptibility of gastric cancer.

BACKGROUND: Gastric cancer (GC) ranks the second leading cause of cancer-related mortality worldwide. We aimed to clarify the relevance of genetic variants of IL-11, a hub of various carcinogenic pathways, as well as their interactions with Helicobacter pylori (H. pylori) infection in the development of GC. METHODS: A case-control study with 880 GC cases and 900 healthy controls was conducted in a Chinese population. Six tagSNPs were detected by Taqman Allelic Discrimination assay, while H. pylori status was detected by Typing Detection Kit for Antibody to H. pylori and serum IL-11 level was measured using ELISA method. RESULTS: We found that rs1126760 (C vs T: OR=1.39, 95% CIs=1.13-1.70, P=0.002) and rs1126757 (C vs T: OR=0.82, 95% CIs=0.72-0.93, P=0.002) were significantly associated with susceptibility of GC. Even adjusted for Bonferroni correction, the results were still significant (P=0.002×6=0.012). IL-11 rs1126760 was significantly associated with higher serum and expression level of IL-11, while rs1126757 was significantly associated with lower serum IL-11 level (P<0.001). Significant interaction with H. pylori infection was identified for rs1126760 (P for interaction =0.005). Higher expression of the IL-11 gene was significant with development and poor prognosis of GC. CONCLUSION: Our study provides strong evidence that genetic variants of the IL-11 gene may interact with H. pylori infection and contribute to the development of GC. Further studies with larger sample size and functional experiments are needed to validate our findings.