Senescent fibroblast facilitates re-epithelization and collagen deposition in radiation-induced skin injury through IL-33-mediated macrophage polarization.

BACKGROUND: The need for radiotherapy among the elderly rises with increasing life expectancy and a corresponding increase of elderly cancer patients. Radiation-induced skin injury is one of the most frequent adverse effects in radiotherapy patients, severely limiting their life quality. Re-epithelialization and collagen deposition have essential roles in the recovery of skin injuries induced by high doses of ionizing radiation. At the same time, radiation-induced senescent cells accumulate in irradiated tissues. However, the effects and mechanisms of senescent cells on re-epithelialization and collagen deposition in radiation-induced skin injury have not been fully elucidated. RESULTS: Here, we identified a role for a population of senescent cells expressing p16 in promoting re-epithelialization and collagen deposition in radiation-induced skin injury. Targeted ablation of p16+ senescent cells or treatment with Senolytics resulted in the disruption of collagen structure and the retardation of epidermal coverage. By analyzing a publicly available single-cell sequencing dataset, we identified fibroblasts as a major contributor to the promotion of re-epithelialization and collagen deposition in senescent cells. Notably, our analysis of publicly available transcriptome sequencing data highlighted IL-33 as a key senescence-associated secretory phenotype produced by senescent fibroblasts. Neutralizing IL-33 significantly impedes the healing process. Finally, we found that the effect of IL-33 was partly due to the modulation of macrophage polarization. CONCLUSIONS: In conclusion, our data suggested that senescent fibroblasts accumulated in radiation-induced skin injury sites participated in wound healing mainly by secreting IL-33. This secretion regulated the local immune microenvironment and macrophage polarization, thus emphasizing the importance of precise regulation of senescent cells in a phased manner.

Urinary SIRT2 Reflects Kidney Injury in Type 2 Diabetes.

INTRODUCTION: The early diagnosis of kidney injury in type 2 diabetes (T2DM) is important to prevent the long-term damaging effects of kidney loss and is decisive for patient outcomes. While SIRT2 is implicated in diabetes pathogenesis, its correlation with diabetic nephropathy remains unexplored. This study was designed to evaluate the association of urine SIRT2 levels with diabetic kidney injury, as well as potential underlying mechanisms. METHODS: In T2DM patients, db/db mice, and high glucose plus palmitic acid treated HK2 cell models, ELISA, Immunoturbidimetry, Immunohistochemistry, Western blot, and Quantitative real-time polymerase chain reaction were used to detect SIRT2 levels and kidney damage. According to urinary albumin/creatinine ratio (UACR), 163 T2DM patients were divided into three groups. Spearman correlation analysis was used to investigate the relationship between urinary sirtuin2/creatinine ratio (USCR) and biomarkers of kidney injury. The influencing factors of albuminuria in T2DM patients were analyzed by logistic regression model. RESULTS: In our findings, the Macro group exhibited the highest USCR levels as UACR increased. There was a positive association between USCR and UACR, α1-microglobulin/creatinine ratio (UαCR), ß2-microglobulin/creatinine ratio (UßCR), and retinol-binding protein/creatinine ratio (URCR), with a negative correlation observed with eGFR. Logistic ordered multiclassification regression analysis, adjusting for confounding variables, confirmed that USCR remained a significant risk factor for the severity of albuminuria in T2DM patients. In the db/db mice kidney SIRT2 protein level increased significantly. Increased SIRT2 protein levels were also observed in renal tubular epithelial cells treated with high glucose plus palmitic acid. Moreover, SIRT2 promotes the expression of proinflammatory factors TNF-α and IL-6 by modulating the phosphorylation of p38 MAPK and p-JNK in renal tubular cells induced by high glucose and palmitic acid. CONCLUSION: Urinary SIRT2 is closely related to eGFR, renal tubule injury, and urinary albumin excretion in T2DM patients, which is expected to be an important indicator to comprehensively reflect renal injury.

Probiotics improve renal function, glucose, lipids, inflammation and oxidative stress in diabetic kidney disease: a systematic review and meta-analysis.

AIMS: The role of probiotics in the management of diabetic kidney disease (DKD) has been shown. Several current trials are investigating the effect of probiotics, which are widely used to modulate biomarkers of renal function, glucose, lipids, inflammation and oxidative stress in patients with DKD. However, their findings are controversial. This study aimed to systematically evaluate the impact of probiotics on patients with DKD via meta-analysis. METHODS: PubMed, The Cochrane Library, Web of Science, Scopus, Embase, China National Knowledge Infrastructure, Chinese Wanfang Database and Chinese VIP Database were searched for relevant studies from the establishment of these databases to September 2021. The pooled results evaluated the impact of probiotics on renal function, glucose, lipids, inflammation and oxidative stress indicators in patients with DKD. Additionally, subgroup analysis was performed based on intervention duration, probiotic dose and probiotic consumption patterns, respectively. RESULTS: Ten trials that included 552 participants were identified for analysis. Compared with the controls, probiotics significantly decreased serum creatinine (Scr) [WMD = -0.17 mg/dL; 95%CI = -0.29, -0.05; p = 0.004], blood urea nitrogen (BUN) [WMD = -1.36 mg/dL; 95%CI = -2.20, -0.52; p = 0.001], cystatin C (Cys C) [WMD = -29.50 ng/mL; 95%CI = -32.82, -26.18; p < 0.00001], urinary albumin/creatinine ratio (UACR) [WMD = -16.05 mg/g; 95%CI = -27.12, -4.99; p = 0.004] and natrium (Na) [WMD = -0.94 mmol/L; 95%CI = -1.82, -0.05; p = 0.04] in patients with DKD. Enhanced glycemic control was observed in patients with DKD receiving probiotics compared with controls, as demonstrated by reduced levels of fasting plasma glucose (FPG), hemoglobin A1c (HbA1c), homeostasis model of assessment-estimated insulin resistance (HOMA-IR), and increased quantitative insulin sensitivity check index (QUICKI). Probiotics affected lipid metabolism parameters with decreasing triglycerides (TG), total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-c) levels in patients with DKD. Probiotics could also could improve inflammation and oxidative stress by decreasing high-sensitivity C-reactive protein (hs-CRP), plasma malondialdehyde (MDA), total antioxidant capacity (TAC), glutathione (GSH) and nitric oxide (NO). Additionally, subgroup analysis showed that those who received multiple species probiotics had a statistically significant difference in BUN, FPG, HOMA-IR, high-density lipoprotein cholesterol (HDL-c), MDA, TAC, and NO. Meanwhile, Scr, LDL-c, HDL-c, MDA, and TAC were ameliorated when the intervention duration was more than eight weeks and BUN, FPG, HOMA-IR, and MDA were improved when the probiotic dose was greater than four billion CFU/day. CONCLUSIONS: Our analysis revealed that probiotics could delay the progression of renal function injury, improve glucose and lipid metabolism, and reduce inflammation and oxidative stress in patients with DKD. Subgroup analysis showed that intervention duration, probiotic dose and probiotic consumption patterns had an effect of probiotics on outcomes.

A Novel Selenium Polysaccharide Alleviates the Manganese (Mn)-Induced Toxicity in Hep G2 Cells and Caenorhabditis elegans.

Manganese (Mn) is now known to have a variety of toxicities, particularly when exposed to it in the workplace. However, there are still ineffective methods for reducing Mn's hazardous effects. In this study, a new selenium polysaccharide (Se-PCS) was developed from the shell of Camellia oleifera to reduce Mn toxicity in vitro and in vivo. The results revealed that Se-PCS may boost cell survival in Hep G2 cells exposed to Mn and activate antioxidant enzyme activity, lowering ROS and cell apoptosis. Furthermore, after being treated with Se-PCS, Caenorhabditis elegans survived longer under Mn stress. daf-16, a tolerant critical gene, was turned on. Moreover, the antioxidant system was enhanced as the increase in strong antioxidant enzyme activity and high expression of the sod-3, ctl-2, and gst-1 genes. A variety of mutations were also used to confirm that Se-PCS downregulated the insulin signaling pathway. These findings showed that Se-PCS protected Hep G2 cells and C. elegans via the insulin/IGF-1 signaling pathway and that it could be developed into a promising medication to treat Mn toxicity.

The pregnancy-related anxiety characteristics in women with gestational diabetes mellitus: why should we care?

BACKGROUND: Gestational diabetes mellitus (GDM) is very commonly-seen in clinical settings, and GDM patients may have higher levels of anxiety. It's necessary to evaluate the anxiety level and potentially influencing factors in patients with GDM, to provide insights for the management of anxiety of GDM patients. METHODS: Patients with GDM treated in our hospital from May, 2018 to May, 2020 were included. We evaluated the characteristics of patients and the scores of pregnancy-related anxiety scale for anxiety level, vulnerable personality style questionnaire (VPSQ) for personality, general self-efficacy scale (GSES) for self-efficacy, social support rating scale (SSRS) for social support level. Logistic regression analyses were conducted to identify the potential influencing factors of anxiety in GDM patients. RESULTS: A total of 386 GDM patients were included, the incidence of anxiety in patients with GDM was 59.07%. Anxiety was positively correlated with the susceptible personality (r = 0.604, p = 0.023), and it was negatively correlated with self-efficacy and social support (r = -0.586 and -0.598 respectively, all p < 0.05). The education level, monthly income, abnormal pregnancy (miscarriage, premature rupture of membranes) and cesarean section history and first pregnancy were the independent influencing factors for the anxiety in the patients with GDM (all p < 0.05). CONCLUSIONS: The anxiety of GDM patients is very common, early care and interventions are warranted for those patients with abnormal pregnancy and cesarean section history, first pregnancy, lower education level, and less monthly income.

Urine Haptoglobin/Creatinine Ratio Correlates with Tubular Injury Biomarkers and Severity of Albuminuria in Type 2 Diabetes Patients.

This aim of this study was to investigate the correlation between urine haptoglobin/creatinine ratio(UHCR) and tubular injury biomarkers or severity of albuminuria in type 2 diabetes. Recruited T2DM patients (n=120) were divided into three groups based on urine albumin/creatinine ratio (UACR): normal albuminuria (Normo group, UACR<30 mg/g, n=40), microalbuminuria (Micro group, 30 mg/g ≤UACR<300 mg/g, n=38), and macroalbuminuria (Macro group, UACR ≥300 mg/g, n=42), with matched healthy individuals (NC group, n=30) as controls. ELISA assay was used to detect the levels of urine haptoglobin, NGAL and KIM-1. Automated biochemical analyzer was applied to detect the concentrations of urine creatinine and retinol binding protein (RBP). To eliminate concentration errors, urine NGAL, KIM-1, and RBP were normalized by creatinine and expressed as UHCR, UNCR, UKCR, and URCR, respectively. We found UHCR was significantly increased in T2DM patients as compared with NC group. Among the three diabetic groups, the Macro group had the highest level of UHCR, whereas the Normo group had the lowest level. T2DM patients with higher UHCR levels also had higher levels of UNCR, UKCR, and URCR. Spearman's correlation analysis indicated that UHCR was positively correlated with UACR, UNCR, UKCR, or URCR levels, and negatively correlated with eGFR. ROC curve analysis showed that UHCR was a sensitive and specific indicator for early diagnosis of DN. Stepwise multiple regression analysis showed that UHCR and UNCR were independent variables for UACR. Our research demonstrated that UHCR correlates with tubular injury biomarkers, including UNCR, UKCR, and URCR, and is independently associated with the severity of albuminuria in T2DM.

A metagenome-wide association study of gut microbiota in type 2 diabetes.

Assessment and characterization of gut microbiota has become a major research area in human disease, including type 2 diabetes, the most prevalent endocrine disease worldwide. To carry out analysis on gut microbial content in patients with type 2 diabetes, we developed a protocol for a metagenome-wide association study (MGWAS) and undertook a two-stage MGWAS based on deep shotgun sequencing of the gut microbial DNA from 345 Chinese individuals. We identified and validated approximately 60,000 type-2-diabetes-associated markers and established the concept of a metagenomic linkage group, enabling taxonomic species-level analyses. MGWAS analysis showed that patients with type 2 diabetes were characterized by a moderate degree of gut microbial dysbiosis, a decrease in the abundance of some universal butyrate-producing bacteria and an increase in various opportunistic pathogens, as well as an enrichment of other microbial functions conferring sulphate reduction and oxidative stress resistance. An analysis of 23 additional individuals demonstrated that these gut microbial markers might be useful for classifying type 2 diabetes.

Serum TNF-α, GTH and MDA of high-fat diet-induced obesity and obesity resistant rats.

OBJECTIVE: Mechanism of high fat diet-induced obesity is analyzed and serum tumor necrosis factor, malondialdehyde and glutathione levels of obesity resistant rats are effectively analyzed. METHODS: 120 male SD rats were grouped into obesity group and control group, each group with 60 rats. Obese rats were fed with high fat diet, while control rats were fed with ordinary fodder. After six months of feeding, growth degree of two groups of rats is observed , and the rats are divided into obesity group and obesity resistant group based on extent of growth. Then glutathione, tumor necrosis factor-α and MDA content in bat serum are detected with enzyme-linked immunosorbent assay. RESULTS: The content of tumor necrosis factor α in obese rats and obesity resistant rats is far higher than that in control group (P < 0.05), there exists no statistical significance (P > 0.05) in tumor necrosis factor α in obesity group and obesity resistant group, glutathione level of obesity group rats and obesity resistant group rats is significantly increased (P < 0.05) compared with that of control group, and also serum MDA level of the two groups has statistical significance compared with that of normal control group (P < 0.05). CONCLUSION: Among rats fed with high fat diet, in comparison with weight of obesity resistant rats and control group rats, there is no statistically significant difference, (P > 0.05). However, high fat diet will impact mechanisms in vivo in rats, which then induces oxidative stress response and inflammatory response in rats.

Recent progress in atomically precise metal nanoclusters for photocatalytic application.

Photocatalysis is a widely recognized green and sustainable technology that can harness inexhaustible solar energy to carry out chemical reactions, offering the opportunity to mitigate environmental issues and the energy crisis. Photocatalysts with wide spectral response and rapid charge transfer capability are crucial for highly efficient photocatalytic activity. Atomically precise metal nanoclusters (NCs), an emerging atomic-level material, have attracted great interests owing to their ultrasmall size, unique atomic stacking, abundant surface active sites, and quantum confinement effect. In particular, the molecule-like discrete electronic energy level endows them with small-band-gap semiconductor behavior, which allows for photoexcitation in order to generate electrons and holes to participate in the photoredox reaction. In addition, metal NCs exhibit strong light-harvesting ability in the wide spectral UV-near IR region, and the diversity of optical absorption properties can be precisely regulated by the composition and structure. These merits make metal NCs ideal candidates for photocatalysis. In this review, the recent advances in atomically-precise metal NCs for photocatalytic application are summarized, including photocatalytic water splitting, CO2 reduction, organic transformation, photoelectrocatalytic reactions, N2 fixation and H2O2 production. In addition, the strategy for promoting photostability, charge transfer and separation efficiency of metal NCs is highlighted. Finally, a perspective on the challenges and opportunities for NCs-based photocatalysts is provided.

Inflammasome: structure, biological functions, and therapeutic targets.

Inflammasomes are a group of protein complex located in cytoplasm and assemble in response to a wide variety of pathogen-associated molecule patterns, damage-associated molecule patterns, and cellular stress. Generally, the activation of inflammasomes will lead to maturation of proinflammatory cytokines and pyroptotic cell death, both associated with inflammatory cascade amplification. A sensor protein, an adaptor, and a procaspase protein interact through their functional domains and compose one subunit of inflammasome complex. Under physiological conditions, inflammasome functions against pathogen infection and endogenous dangers including mtROS, mtDNA, and so on, while dysregulation of its activation can lead to unwanted results. In recent years, advances have been made to clarify the mechanisms of inflammasome activation, the structural details of them and their functions (negative/positive) in multiple disease models in both animal models and human. The wide range of the stimuli makes the function of inflammasome diverse and complex. Here, we review the structure, biological functions, and therapeutic targets of inflammasomes, while highlight NLRP3, NLRC4, and AIM2 inflammasomes, which are the most well studied. In conclusion, this review focuses on the activation process, biological functions, and structure of the most well-studied inflammasomes, summarizing and predicting approaches for disease treatment and prevention with inflammasome as a target. We aim to provide fresh insight into new solutions to the challenges in this field.

Polyphenols from Blumea laciniata Extended the Lifespan and Enhanced Resistance to Stress in Caenorhabditis elegans via the Insulin Signaling Pathway.

Blumea laciniata is widely used as a folk medicine in Asia, but relevant literature on it is rarely reported. We confirmed that polyphenol extract (containing chlorogenic acid, rutin, and luteolin-4-O-glucoside) from B. laciniata (EBL) showed strong antioxidant ability in vitro. Hence, in this work, we applied Caenorhabditis elegans to further investigate the antioxidant and anti-ageing abilities of EBL in vivo. The results showed that EBL enhanced the survival of C. elegans under thermal stress by 12.62% and sharply reduced the reactive oxygen species level as well as the content of malonaldehyde. Moreover, EBL increased the activities of antioxidant enzymes such as catalase and superoxide dismutase. Additionally, EBL promoted DAF-16, a transcription factor, into the nucleus. Besides, EBL extended the lifespan of C. elegans by 17.39%, showing an anti-ageing effect. Different mutants indicated that the insulin/IGF-1 signaling pathway participated in the antioxidant and anti-ageing effect of EBL on C. elegans.

PC4 serves as a negative regulator of skin wound healing in mice.

BACKGROUND: Human positive cofactor 4 (PC4) was initially characterized as a multifunctional transcriptional cofactor, but its role in skin wound healing is still unclear. The purpose of this study was to explore the role of PC4 in skin wound healing through PC4 knock-in mouse model. METHODS: A PC4 knock-in mouse model (PC4+/+) with a dorsal full-thickness wound was used to investigate the biological functions of PC4 in skin wound healing. Quantitative PCR, Western blot analysis and immunohistochemistry were performed to evaluate the expression of PC4; Sirius red staining and immunofluorescence were performed to explore the change of collagen deposition and angiogenesis. Proliferation and apoptosis were detected using Ki67 staining and TUNEL assay. Primary dermal fibroblasts were isolated from mouse skin to perform cell scratch experiments, cck-8 assay and colony formation assay. RESULTS: The PC4+/+ mice were fertile and did not display overt abnormalities but showed an obvious delay in cutaneous healing of dorsal skin. Histological staining showed insufficient re-epithelialization, decreased angiogenesis and collagen deposition, increased apoptosis and decreased cell proliferation in PC4+/+ skin. Our data also showed decreased migration rate and proliferation ability in cultured primary fibroblasts from PC4+/+ mice in vitro. CONCLUSIONS: This study suggests that PC4 might serve as a negative regulator of skin wound healing in mice.

ESTs analyses of Lampetra japonica liver and comparation transcriptome with the jawed vertebrates.

A cDNA library was constructed from the liver of Lampetra japonica. 10077 ESTs were obtained by random selecting clones for sequencing. The results demonstrated that 8515 ESTs were assembled into 648 consensus sequences, represented 2210 unique transcripts, 47.06% of which were predicted as full length cDNAs. In addition, 1562 ESTs were singlets. Using the BLAST to align the assembled ESTs, we found that 93.9% (2053) transcripts shared similarity to sequences published in GenBank databases. The functional annotations to assembled ESTs showed that the genes, involved in immunology, blood coagulation and metabolism of jawed vertebrates, were highly expressed in the liver of L. japonica. Furthermore, 8 potential novel genes were identified. Further comparing liver transcriptome of L. japonica with Fundulus heteroclitus, Mus musculus, Bos Taurus, and Homo sapiens revealed that the genes of Chitinase and Polysaccharides metabolism were more highly expressed in L. japonica than the others, which implied that they may play an important role in immunity of L. japonica. In addition, using the TargetScan, we marked microRNA target within 3' UTR of L. japonica liver transcriptome. The data indicated that some microRNA targets were homology with the targets embeded in human cancer genes. The result seems to provide a useful clue to the treatment of human cancer. Therefore, the present work will be an important resource for investigating the functional genomics and proteomics of L. japonica as well as evolution of vertebrates.

Correlation analysis between work-related musculoskeletal disorders and the nursing practice environment, quality of life, and social support in the nursing professionals.

We aim to analyze the correlated influential factors between work-related musculoskeletal disorders (WMSDs) and nursing practice environment and quality of life and social support.From January 2015 to October 2015, cluster sampling was performed on the nurses from 12 hospitals in the 6 areas in Xinjiang. The questionnaires including the modified Nordic Musculoskeletal Questionnaire, Practice Environment Scale (PES), the Mos 36-item Short Form Health Survey, and Social Support Rating Scale were used to investigate. Multivariate logistic regression analysis was used to explore the influential factors of WMSDs.The total prevalence of WMSDs was 79.52% in the nurses ever since the working occupation, which was mainly involved waist (64.83%), neck (61.83%), and shoulder (52.36%). Multivariate logistic regression analysis indicated age (≥26 years), working in the Department of Surgery, Department of Critical Care, Outpatient Department, and Department of Anesthesia, working duration of >40 hours per week were the risk factors of WMSDs in the nurses. The physiological function (PF), body pain, total healthy condition, adequate working force and financial support, and social support were the protective factors of WMSDs.The prevalence of WMSDs in the nurses in Xinjiang Autonomous Region was high. PF, bodily pain, total healthy condition, having adequate staff and support resources to provide quality patient care, and social support were the protective factors of WMSDs in the nurses.

Cross-Cultural Validation of the High Blood Pressure Health Literacy Scale in a Chinese Community.

BACKGROUND: Considering the importance of health literacy (HL) for the maximum yield from the hypertension control programs, development of a reliable and valid instrument of hypertension-related HL is critical. This study aimed to translate and validate the High Blood Pressure-Health Literacy Scale (HBP-HLS) into Chinese (C-HBP-HLS) and evaluate its psychometric properties in Chinese context. METHOD: Between June 2013 and January 2014, a cross-sectional study was conducted among recruited hypertensive patients belonging to the Han and Kazakh-Chinese communities in Urumqi, Xinjiang, China. RESULTS: A pilot sample (n = 242) was selected for the exploratory factor analysis of the translated and modified instrument. Another sample (n = 308) was recruited for the confirmatory factor analysis. C-HBP-HLS consisted of five dimensions (Print Health Literacy, Medication Label, Understanding Ability, Newest Vital Sign Test, and Avoiding Food Allergy) containing 15 items, accounting for 77.7% of the total variance. The 5-factor model demonstrated a good overall fit. The scale-level content validity index was 0.85. Cronbach's alpha of the overall scale was 0.78 and test-retest reliability was 0.96. Education level had a strong positive correlation with the scores for items Q1, Q2, and Q3(r = 0.481, 0.492, 0.475, respectively). Health Literacy scores among Kazakh patients were significantly lower than Han (7.13±7.90 vs. 30.10±13.42, Z = -14.573, P<0.001). CONCLUSION: C-HBP-HLS demonstrated suitable factor structure and robust psychometric properties for measuring health literacy level among hypertensive patients in China.

[Transcription and promoter hypermethylation of thyroid stimulating hormone receptor gene in human papillary thyroid carcinoma].

OBJECTIVE: To study the mRNA expression of the tumor suppressor gene thyroid stimulating hormone receptor (TSHR) gene in papillary thyroid carcinoma (PTC) and the correlation between aberrant promoter methylation of TSHR gene and the tumorigenesis of PTC. METHODS: RT-PCR was used to detect the mRNA expression of TSHR gene in 50 PTC cases, 20 cases of nodular goiter and 12 cases of thyroid adenoma tissue. The status of TSHR gene promoter methylation was determined using methylation-specific PCR technique. RESULTS: Of the 50 PTC patients, 34 (68%) were found to have hypermethylation of TSHR gene promoter region, as compared to 7 out of the 32 control patients (21.9%) positive for TSHR gene promoter hypermethylation, suggesting a significantly higher rate of TSHR promoter methylation of in PTC patients than in the control patients (chi(2) = 16.61, P<0.05). Of the 34 PTC patients with TSHR promoter methylation, 14 (41.2%) showed the absence of TSHR mRNA expression; in the 16 PTC patients without TSHR promoter methylation, only 2 (12.5%) were negative for TSHR mRNA expression, showing a significant difference in the rate of negative TSHR mRNA expression with regard to TSHR promoter methylation. The PTC patients had a significantly lower TSHR mRNA expression than the control patients (chi(2) = 4.02, P<0.05). CONCLUSION: Methylation of TSHR gene in the promoter region is a common molecular event, which might be associated with the tumorigenesis and progression of human PTC.