Engineered probiotics introduced to improve intestinal microecology for the treatment of chronic diseases: present state and perspectives.

Purpose: Correcting intestinal microecological imbalance has become one of the core strategies to treat chronic diseases. Some traditional microecology-based therapies targeting intestine, such as prebiotic therapy, probiotic therapy and fecal microbiota transplantation therapy, have been used in the prevention and treatment of clinical chronic diseases, which still facing low safety and poor controllability problems. The development of synthetic biology technology has promoted the development of intestinal microecology-based therapeutics for chronic diseases, which exhibiting higher robustness and controllability, and become an important part of the next generation of microecological therapy. The purpose of this review is to summarize the application of synthetic biology in intestinal microecology-based therapeutics for chronic diseases. Methods: The available literatures were searched to find out experimental studies and relevant review articles on the application of synthetic biology in intestinal microecology-based therapeutics for chronic diseases from year 1990 to 2023. Results: Evidence proposed that synthetic biology has been applied in the intestinal microecology-based therapeutics for chronic diseases, covering metabolic diseases (e.g. diabetes, obesity, nonalcoholic fatty liver disease and phenylketonuria), digestive diseases (e.g. inflammatory bowel disease and colorectal cancer), and neurodegenerative diseases (e.g. Alzheimer's disease and Parkinson's disease). Conclusion: This review summarizes the application of synthetic biology in intestinal microecology-based therapeutics for major chronic diseases and discusses the opportunities and challenges in the above process, providing clinical possibilities of synthetic biology technology applied in microecological therapies.

Microplastics affect C, N, and P cycling in natural environments: Highlighting the driver of soil hydraulic properties.

As microplastics (MPs) are organic polymers with a carbon-based framework, they may affect nutrient cycling. Information regarding how MPs influence N, P, and C cycling and the underlying driving force remains lacking. N, P, and C cycling induced by soil hydraulic properties under MPs exposure (including polyethylene (PE), polyvinyl chloride (PVC), polystyrene (PS), polypropylene (PP)) in the natural environment were investigated in this study. MPs exposure increased the soil water content (11.2-84.5%) and reduced bulk density (11.4-42.8%); soil saturated hydraulic conductivity increased by 7.3-69.4% under PP and PE exposure. MPs exposure led to increases in available phosphorus, NO3--N, NH4+-N, and soil organic matter; the bacterial communities related to N and C cycling were significantly changed. Expression levels of soil N and C cycling-related genes were enhanced under low concentrations (0.5% and 2%) of MPs, except PVC; consequently, soil nitrogen storage and organic carbon storage increased by 12-75% and 6.7-93%, respectively. Correlation analyses among soil hydraulic properties, bacterial communities, and functional genes related to nutrient cycling revealed that soil hydraulic properties (including soil water content, saturated water capacity, and soil saturated hydraulic conductivity) were the dominant factors affecting soil N and C storage under MPs exposure.

Identification of exosomes-related lncRNAs in clear cell renal cell carcinoma based on Bayesian spike-and-slab lasso approach.

Exosomes-related long non-coding RNAs (lncRNAs) have been reported to play significant roles in clear cell renal cell carcinoma (ccRCC). However, there is little known about the relationship between exosomes-related lncRNAs and ccRCC. This study aimed to select optimal prognostic model based on exosomes-related lncRNAs to provide a methodological reference for high-dimensional data. Based on the Cancer Genome Atlas (TCGA) database of 515 ccRCC patients, two risk score models were generated underlying Bayesian spike-and-slab lasso and lasso regression. The optimal model was determined by calculating the area of time-dependent receiver-operating characteristic (ROC) curves in the TCGA and ArrayExpress databases. The immune patterns and sensitivity of immunotherapy between the high and low groups were further explored. Initially, we constructed two risk score models containing 11 and 7 exosomes-related lncRNAs according to Bayesian spike-and-slab lasso and lasso regression respectively. ROC curves revealed that the model constructed by Bayesian spike-and-slab lasso regression was more reliable in predicting survival at 1, 3, and 5 years, yielding an area under the curves (AUCs) of 0.796, 0.732, and 0.742, respectively. Kaplan-Meier (K-M) curves presented that prognosis was poorer in the high-risk score group (P < 0.001). Additionally, the high-risk score group patients were enriched in immune-activating phenotypes and more sensitive to immunotherapy. The exosomes-related lncRNAs model constructed with Bayesian spike-and-slab lasso regression has higher predictive power for ccRCC patients' prognosis, which provides methodological reference for the analysis of high-dimensional data in bioinformatics and guides the tailored treatment of ccRCC patients.

Prognostic Model for Clear-cell Renal Cell Carcinoma Based on Natural Killer Cell-related Genes.

BACKGROUND: Natural killer (NK) cells are a key factor affecting progression and immune surveillance of clear-cell renal cell carcinoma (ccRCC). This study sought to construct a natural killer cell-related prognostic signature (NKRPS) to predict the outcome of ccRCC patients and to furnish guidance for finding appropriate treatment strategies. METHODS: From the TCGA and ArrayExpress databases, transcriptomic profiles and relevant clinical information of ccRCC patients were downloaded for the TCGA cohort (n = 515) and the E-MTAB-1980 cohort (n = 101). With the univariate Cox analysis and LASSO-Cox regression algorithm, a NKRPS was built to evaluate patients' prognosis. Receiver operating characteristic (ROC) curves and calibration curves were drawn to estimate the predictive power of the prognostic model. Then, tumor microenvironment (TME), tumor mutational burden (TMB), sensitization to immune checkpoint inhibitors (ICIs) therapy and targeted drug treatment were analyzed in ccRCC patients. RESULTS: Nine genes (BID, CCL7, CSF2, IL23A, KNSTRN, RHBDD3, PIK3R3, RNF19B and VAV3) were identified to construct a NKRPS. High-risk group displayed undesirable survival compared to low-risk group (P < .05). Moreover, the area under the curve (AUC) of ROC at 1-, 3- and 5-year were 0.766, 0.755, and 0.757, respectively. High-risk group was characterized by superior immune infiltration, higher TMB, and higher expression of 5 ICI-related genes. Additionally, this model enabled to predict the sensitivity of patients to chemotherapy drugs. CONCLUSION: NKRPS had a strong predictive power on prognosis of ccRCC patients, which may facilitate individualized treatment and medical decision making.

Frequency-dependent white-matter functional network changes associated with cognitive deficits in subcortical vascular cognitive impairment.

Vascular cognitive impairment (VCI) refers to all forms of cognitive decline associated with cerebrovascular diseases, in which white matter (WM) is highly vulnerable. Although previous studies have shown that blood oxygen level-dependent (BOLD) signals inside WM can effectively reflect neural activities, whether WM BOLD signal alterations are present and their roles underlying cognitive impairment in VCI remain largely unknown. In this study, 36 subcortical VCI (SVCI) patients and 36 healthy controls were enrolled to evaluate WM dysfunction. Specifically, fourteen distinct WM networks were identified from resting-state functional MRI using K-means clustering analysis. Subsequently, between-network functional connectivity (FC) and within-network BOLD signal amplitude of WM networks were calculated in three frequency bands (band A: 0.01-0.15 Hz, band B: 0.08-0.15 Hz, and band C: 0.01-0.08 Hz). Patients with SVCI manifested decreased FC mainly in bilateral parietal WM regions, forceps major, superior and inferior longitudinal fasciculi. These connections extensively linked with distinct WM networks and with gray-matter networks such as frontoparietal control, dorsal and ventral attention networks, which exhibited frequency-specific alterations in SVCI. Additionally, extensive amplitude reductions were found in SVCI, showing frequency-dependent properties in parietal, anterior corona radiate, pre/post central, superior and inferior longitudinal fasciculus networks. Furthermore, these decreased FC and amplitudes showed significant positive correlations with cognitive performances in SVCI, and high diagnostic performances for SVCI especially combining all bands. Our study indicated that VCI-related cognitive deficits were characterized by frequency-dependent WM functional abnormalities, which offered novel applicable neuromarkers for VCI.

Associations between psycho-behavioral risk factors and diabetic retinopathy: NHANES (2005-2018).

Introduction: Diabetes mellitus (DM) and diabetic retinopathy (DR) increase the global burden. Since their pathogenesis is complex, it is necessary to use the biopsychosocial model to discover the most effective strategies. The study is aimed to investigate the psycho-behavioral factors of DR and confirm the discrepancies from previous studies. Research design and methods: The study comprised seven cycles of cross-sectional data of the National Health and Nutrition Examination Survey (NHANES) from 2005-2006 to 2017-2018. Samples of DM were selected from this complex multi-stage probability sample and divided into the non-DR and DR groups, where 4,426 samples represented 18,990,825 individuals after weighting. This study comprehensively explored the biological, social, and psychological risk factors of DR, among which the biological factors included blood pressure, blood routine, HbA1c%, blood glucose, the duration of DM, family history, comorbidities, and treatment methods. Social aspects include gender, education, income, insurance, smoking, drinking, sleep habits, and recreational activities. The Patient Health Questionnaire-9 (PHQ-9) was used to assess the psychological state. Taylor series regression was used to examine the connection between factors and DR. Results: Men accounted for 55.5% of the DR group (P = 0.0174). Lymphocyte count, insulin treatment, heart failure, stroke, liver condition, and renal failure showed significant differences in DR (P < 0.05). The incidence of depression in DR was 40.5%. Mild to moderate depression [odds ratio was associated with DR [(OR) = 1.37, 95% confidence interval (CI): 1.06-1.79], but there was no statistical difference in severe depression (OR = 1.34, 95% CI: 0.83-2.17). Although ≤ 6 h of sleep was associated with DR (OR = 1.38, 95% CI: 1.01-1.88), we found no statistical differences in alcohol consumption, recreational activities, or sedentary time between the two groups in our current study (P > 0.05). Conclusions: The biological risk factors of DR are significant. It showed that stroke is associated with DR, and retinal exams have the potential value as a screening tool for the brain. Besides, psycho-behavioral risk factors of DR should also be paid attention. Our study highlights that mild and moderate depression and ≤6 h of sleep are distinguishably associated with DM complicated with DR. It indicates that psycho-behavioral risk factors confer a vital influence on diabetic health care and DR.

Identification of a Prognostic Model Based on Immune Cell Signatures in Clear Cell Renal Cell Carcinoma.

Background: Accumulating evidence substantiated that the immune cells were intricately intertwined with the prognosis and therapy of clear cell renal cell carcinoma (ccRCC). We aimed to construct an immune cell signatures (ICS) score model to predict the prognosis of ccRCC patients and furnish guidance for finding appropriate treatment strategies. Methods: Based on The Cancer Genome Atlas (TCGA) database, the normalized enrichment score (NES) of 184 ICSf was calculated using single-sample gene set enrichment analysis (ssGSEA). An ICS score model was generated in light of univariate Cox regression and Least absolute shrinkage and selection operator (Lasso)-Cox regression, which was independently validated in ArrayExpress database. In addition, we appraised the predictive power of the model via Kaplan-Meier (K-M) curves and time-dependent receiver operating characteristic (ROC) curves. Eventually, immune infiltration, genomic alterations and immunotherapy were analyzed between high and low ICS score groups. Results: Initially, we screened 11 ICS with prognostic impact based on 515 ccRCC patients. K-M curves presented that the high ICS score group experienced a poorer prognosis (P < 0.001). In parallel, ROC curves revealed a satisfactory reliability of model to predict individual survival at 1, 3, and 5 years, with area under the curves (AUCs) of 0.744, 0.713, and 0.742, respectively. In addition, we revealed that the high ICS score group was characterized by increased infiltration of immune cells, strengthened BAP1 mutation frequency, and enhanced expression of immune checkpoint genes. Conclusion: The ICS score model has higher predictive power for patients' prognosis and can instruct ccRCC patients in seeking suitable treatment.

MicroRNA-181a/b-1-encapsulated PEG/PLGA nanofibrous scaffold promotes osteogenesis of human mesenchymal stem cells.

Bioactive nanofibres play a useful role in increasing the efficiency of tissue engineering scaffolds. MicroRNAs (miRs) alone, and in combination with tissue engineering scaffolds, can be effective in treating bone fractures and osteoporosis by regulating many post-transcriptional cellular pathways. Herein, miR-181a/b-1 was incorporated in the electrospun poly (lactic-co-glycolic acid) (PLGA) nanofibres (PLGA-miR). After characterization scaffolds, the osteoinductive capacity of the nanofibres was investigated when adipose-derived mesenchymal stem cells (AT-MSCs) were cultured on the PLGA and PLGA-miR nanofibres. miR incorporating in the nanofibres has not any significant effect on the size and morphology of the nanofibres, but its biocompatibility was increased significantly compared to the empty nanofibres. Alkaline phosphatase (ALP) activity and calcium measures were evaluated as two important osteogenic markers, and the results revealed that the highest measures were observed in the AT-MSCs cultured on PLGA-miR nanofibres. Detected ALP activity and calcium measures in miR-transduced AT-MSCs cultured on TCPS were also significantly higher than AT-MSCs cultured on PLGA and TCPS groups. The highest expression levels of bone-related genes were observed in the AT-MSCs cultured on PLGA-miR nanofibres. This improvement in the osteogenic differentiation potential of the AT-MSCs was also confirmed by evaluating osteopontin protein in the cells cultured on PLGA-miR. It can be concluded that miR-181a/b-1 has a significant impact on the AT-MSC osteogenic differentiation, and this impact synergistically increased when incorporated in the PLGA nanofibres.

The effect of hormonal levels and oxidative stress on bisphenol A and soy isoflavone reproductive toxicity in murine offspring.

Previous studies have suggested that human exposure to bisphenol A (BPA) and soy isoflavones (SIFs) can occur during pregnancy. The combination of these chemicals is hypothesized to have a toxic impact on the fetus. While BPA is an industrial chemical used widely in the manufacture of polycarbonate plastics and epoxy resins, SIFs are naturally occurring estrogen­like phytoestrogens. To determine the impact of the combination of BPA and SIFs on fetal development, the body weight, organ weight, anogenital distance and histopathological changes in the testes of F1 offspring were assessed in mice. Hormonal effects were determined by measuring serum levels of estrogen receptor (ESR), follicle­stimulating hormone (FSH), luteinizing hormone (LH) and testosterone (T). Additionally, mitochondrial DNA copy numbers, and the serum levels of malondialdehyde and superoxide dismutase, were determined to evaluate alterations in oxidative stress and potential toxicity. Exposure to BPA increased the body weight of the pups and reduced the ratio of anogenital distance to body weight, as well as testes weight. Moreover, BPA exposure also induced testicular lesions. The seminiferous tubules of testis were denatured in varying degrees and the lumen wall structure was disordered. The levels of ESR in all offspring and the T levels in male offspring significantly increased, compared with controls. Co­exposure to BPA and SIFs exacerbated these changes in body weight, testicular lesions and hormonal levels, relative to BPA exposure alone. Additionally, oxidative damage was only induced by high­dose BPA. Collectively, these findings suggested that BPA and SIFs could have synergistic effect on the reproductive system, which could be mediated by the regulation of ESR expression and testosterone release.

Knockdown of lncRNA TUG1 inhibits hippocampal neuronal apoptosis and participates in aerobic exercise-alleviated vascular cognitive impairment

OBJECTIVES: Our previous study indicated that aerobic exercise relieves cognitive impairment in patients with vascular cognitive impairment (VCI) via regulating brain-derived neurotrophic factor (BDNF), but the mechanism is not yet clear. This study aimed to explore whether lncRNA taurine upregulated gene 1 (TUG1) participates in the process of VCI by regulating BDNF. METHODS: The expressions of TUG1 and BDNF in the serum of VCI patients were detected. The potential molecular mechanisms of TUG1 in regulating hippocampal neuronal apoptosis were explored in oxygen and glucose deprivation-induced (OGD-induced) hippocampal cell line HT22. The VCI mouse model was established, and TUG1 and BDNF were overexpressed via lentivirus injection. The cognitive impairment of mice was detected by the Morris water maze experiment after the aerobic exercise. RESULTS: The level of TUG1 was elevated in the serum of VCI patients compared with the control group. The knockdown of TUG1 in OGD-induced HT22 cells increased BDNF level and decreased cell apoptosis, and the downregulation of BDNF restored the decreased cell apoptosis. RNA immunoprecipitation and RNA pull-down assays showed that TUG1 could bind to BDNF protein. The aerobic exercise alleviated cognitive impairment and inhibited hippocampal apoptosis in VCI mice. Meanwhile, the overexpression of TUG1 reversed the therapeutic effects of aerobic exercise on cognitive impairment. CONCLUSIONS: The knockdown of TUG1 reduced hippocampal neuronal apoptosis and participates in the aerobic exercise-alleviated VCI, which was partly through regulating BDNF.

Neonatal Weight and Prenatal Exposure to Polychlorinated Biphenyls: A Meta-Analysis.

BACKGROUND: This research studied the relationship between maternal exposure to polychlorinated biphenyls and neonatal birth weight through systematic review and meta-analysis of existing literature. METHODS: We searched for all the studies published in MEDLINE / PUBMEDN / EMBASE (Medical Abstract Database) by June 2018, and seven studies had been selected. RESULTS: The results showed that there was significant correlation between birth weight reduction and PCBS exposure throughout pregnancy (ß=-0.586g, 95%CI:-0.629,-0.543). There was a negative correlation between birth weight and PCBs exposure and umbilical cord serum (ß=-0.833g) and maternal serum (ß= -0.504g).Subgroup analyses showed significantly different effects of PCBs exposure on birth weight in different regions, stages of pregnancy and study designs. It was thought the heterogeneity was mainly caused by geographical regions, stages of pregnancy, and the assessment methods. CONCLUSION: The meta analysis revealed a negative correlation between PCBs exposure and birth weight but there was significant difference in the correlation between birth weight loss.