Distinctive Lipid Characteristics of Colorectal Cancer Revealed through Non-targeted Lipidomics Analysis of Tongue Coating.

The metabolites and microbiota in tongue coating display distinct characteristics in certain digestive disorders, yet their relationship with colorectal cancer (CRC) remains unexplored. Here, we employed liquid chromatography coupled with tandem mass spectrometry to analyze the lipid composition of tongue coating using a nontargeted approach in 30 individuals with colorectal adenomas (CRA), 32 with CRC, and 30 healthy controls (HC). We identified 21 tongue coating lipids that effectively distinguished CRC from HC (AUC = 0.89), and 9 lipids that differentiated CRC from CRA (AUC = 0.9). Furthermore, we observed significant alterations in the tongue coating lipid composition in the CRC group compared to HC/CRA groups. As the adenoma-cancer sequence progressed, there was an increase in long-chain unsaturated triglycerides (TG) levels and a decrease in phosphatidylethanolamine plasmalogen (PE-P) levels. Furthermore, we noted a positive correlation between N-acyl ornithine (NAOrn), sphingomyelin (SM), and ceramide phosphoethanolamine (PE-Cer), potentially produced by members of the Bacteroidetes phylum. The levels of inflammatory lipid metabolite 12-HETE showed a decreasing trend with colorectal tumor progression, indicating the potential involvement of tongue coating microbiota and tumor immune regulation in early CRC development. Our findings highlight the potential utility of tongue coating lipid analysis as a noninvasive tool for CRC diagnosis.

Characterization of tongue coating microbiome from patients with colorectal cancer.

Background: Tongue coating microbiota has aroused particular interest in profiling oral and digestive system cancers. However, little is known on the relationship between tongue coating microbiome and colorectal cancer (CRC). Methods: Metagenomic shotgun sequencing was performed on tongue coating samples collected from 30 patients with CRC, 30 patients with colorectal polyps (CP), and 30 healthy controls (HC). We further validated the potential of the tongue coating microbiota to predict the CRC by a random forest model. Results: We found a greater species diversity in CRC samples, and the nucleoside and nucleotide biosynthesis pathway was more apparent in the CRC group. Importantly, various species across participants jointly shaped three distinguishable fur types.The tongue coating microbiome profiling data gave an area under the receiver operating characteristic curve (AUC) of 0.915 in discriminating CRC patients from control participants; species such as Atopobium rimae, Streptococcus sanguinis, and Prevotella oris aided differentiation of CRC patients from healthy participants. Conclusion: These results elucidate the use of tongue coating microbiome in CRC patients firstly, and the fur-types observed contribute to a better understanding of the microbial community in human. Furthermore, the tongue coating microbiota-based biomarkers provide a valuable reference for CRC prediction and diagnosis.

G/ ß- TCP composite scaffold material promotes osteogenic differentiation of bone marrow mesenchymal stem cells.

To explore self-made graphene/ß Graphene (G)/ß- tricalcium phosphate, G/ß- The effect of TCP composite scaffold material on osteogenic differentiation of BMSC. Preparation of G/ß- TCP composite material was used to investigate the effect of composite material on bone marrow mesenchymal stem cell ossification/ß- TCP material was used to treat primary BMSCs of rats. Cell morphology changes were observed under scanning electron microscopy, cell cycle and proliferation were detected by flow cytometry, and gene expression of chondrogenic genes Fibronectin, collagen I, collagen II, ICAM, and VCAM was detected by q-PCR. In addition, using osteogenic induction medium and G/ß- TCP composite materials were co treated with BMSCs, and ALP and alizarin red staining were used to observe the effect of the materials on osteogenic differentiation. q-PCR was used to detect the gene expression of osteogenic related genes Runx2, OCN, and OPN. G/ ß- After the TCP composite was co cultured with BMSC, the proportion of G0/G1 phase of BMSC cells was significantly increased, the cell proliferation ability was enhanced, and the gene expression of fibronectin, collagen I, collagen II, ICAM, and VCAM were significantly increased. The ALP staining results indicate that BMSC in G/ß- After treatment with TCP composite material, significant enhancement of osteogenic ability was observed at 7,14 and 21 days. In addition, BMSC in G/ß- A significant increase in calcium deposition was observed at 7,14 and 21 days after treatment with TCP composite materials. The effect of different time points on the expression of osteogenic related genes varies. At 7 and 14 days, the expression of RUNX2 was significantly reduced compared to the control, but significantly increased at 21 days; OCN significantly increased on the 21st day; OPN significantly increased at 14 days. G/ß- TCP materials significantly promote the osteogenic differentiation of BMSCs.

Bone marrow mesenchymal stem cell-derived exosomal microRNA-382 promotes osteogenesis in osteoblast via regulation of SLIT2.

BACKGROUND: Osteoporosis (OP) is a systemic skeletal disorder with increased bone fragility. Human bone marrow mesenchymal stem cells (hBMSCs) have multi-lineage differentiation ability, which may play important roles in osteoporosis. In this study, we aim to investigate the role of hBMSC-derived miR-382 in osteogenic differentiation. METHODS: The miRNA and mRNA expressions in peripheral blood monocytes between persons with high or low bone mineral density (BMD) were compared. Then we collected the hBMSC-secreted sEV and examined the dominant components. The over-expression of the miR-382 in MG63 cell and its progression of osteogenic differentiation were investigated by qRT-PCR, western blot and alizarin red staining. The interaction between miR-382 and SLIT2 was confirmed by dual-luciferase assay. The role of SLIT2 was also confirmed through up-regulation in MG63 cell, and the osteogenic differentiation-associated gene and protein were tested. RESULTS: According to bioinformatic analysis, a series of differential expressed genes between persons with high or low BMD were compared. After internalization of hBMSC-sEV in MG63 cells, we observed that the ability of osteogenic differentiation was significantly enhanced. Similarly, after up-regulation of miR-382 in MG63 cells, osteogenic differentiation was also promoted. According to the dual-luciferase assay, the targeting function of miR-382 in SLIT2 was demonstrated. Moreover, the benefits of hBMSC-sEV in osteogenesis were abrogated through up-regulation of SLIT2. CONCLUSION: Our study provided evidence that miR-382-contained hBMSC-sEV held great promise in osteogenic differentiation in MG63 cells after internalization by targeting SLIT2, which can be served as molecular targets to develop effective therapy.

Establishment of a lysosome-related prognostic signature in breast cancer to predict immune infiltration and therapy response.

Background: Lysosomes are instrumental in intracellular degradation and recycling, with their functional alterations holding significance in tumor growth. Nevertheless, the precise role of lysosome-related genes (LRGs) in breast cancer (BC) remains elucidated. This study aimed to establish a prognostic model for BC based on LRGs. Methods: Employing The Cancer Genome Atlas (TCGA) BC cohort as a training dataset, this study identified differentially expressed lysosome-related genes (DLRGs) through intersecting LRGs with differential expression genes (DEGs) between tumor and normal samples. A prognostic model of BC was subsequently developed using Cox regression analysis and validated within two Gene Expression Omnibus (GEO) external validation sets. Further analyses explored functional pathways, the immune microenvironment, immunotherapeutic responses, and sensitivity to chemotherapeutic drugs in different risk groups. Additionally, the mRNA and protein expression levels of genes within the risk model were examined by utilizing the Gene Expression Profiling Interactive Analysis (GEPIA) and Human Protein Atlas (HPA) databases. Clinical tissue specimens obtained from patients were gathered to validate the expression of the model genes via Real-Time Polymerase Chain Reaction (RT-PCR). Results: We developed a risk model of BC based on five specific genes (ATP6AP1, SLC7A5, EPDR1, SDC1, and PIGR). The model was validated for overall survival (OS) in two GEO validation sets (p=0.00034 for GSE20685 and p=0.0095 for GSE58812). In addition, the nomogram incorporating clinical factors showed better predictive performance. Compared to the low-risk group, the high-risk group had a higher level of certain immune cell infiltration, including regulatory T cells (Tregs) and type 2 T helper cells (Th2). The high-risk patients appeared to respond less well to general immunotherapy and chemotherapeutic drugs, according to the Tumor Immune Dysfunction and Exclusion (TIDE), Immunophenotype Score (IPS), and drug sensitivity scores. The RT-PCR results validated the expression trends of some prognostic-related genes in agreement with the previous differential expression analysis. Conclusion: Our innovative lysosome-associated signature can predict the prognosis for BC patients, offering insights for guiding subsequent immunotherapeutic and chemotherapeutic interventions. Furthermore, it has the potential to provide a scientific foundation for identifying prospective therapeutic targets.

Acupoint Injection for Alleviating Side Effects of Chemotherapy in People with Cancer: A Systematic Review and Meta-Analysis.

OBJECTIVE: This study aimed to investigate the efficacy of acupoint injection for alleviating side effects of chemotherapy in people with cancer. METHODS: PubMed, EMBASE, Cochrane library databases, CNKI, VIP, WanFang Date, and CBM were searched for randomized controlled trials (RCTs) from inception through December 28, 2020. This meta-analysis was performed using Review Manager 5.3. RESULTS: A total of 8 RCTs including 557 participants were eligible and included in the meta-analysis. The selected RCTs studied acupoint injection for alleviating side effects of chemotherapy in people with cancer. Statistically significant improvements were observed for the incidence of nausea and vomiting (RR = 0.39; 95% CI 0.26, 0.58; P < 0.00001), the number of leukocyte (MD = 1.89; 95%CI 0.74, 3.03; P = 0.001), and the number of platelet (MD = 28.82; 95%CI 19.33, 38.30; P < 0.00001). Two of these studies suggested that acupoint injection can also reduce some other adverse reactions, which showed a statistical difference (RR = 0.29; 95% CI 0.11, 0.75; P = 0.01). CONCLUSION: The analysis indicated that acupoint injection can alleviate side effects of chemotherapy in people with cancer. However, due to the high risk of bias and small sample size in the included studies, the results need to be further confirmed by further large, rigorously designed trials.

Risk Interval of Complete Blood Counts May be Closely Associated with Bone Mineral Density in the Elderly Chinese Population.

BACKGROUND: Accumulating research suggests that hematopoiesis and bone metabolism are interconnected. Several studies have investigated the partial indexes of peripheral blood counts related to bone mineral density (BMD). The aim of this study was to investigate the associations between all of the parameters, especially the risk interval of complete blood counts (CBC) and BMD in a sample of elderly subjects aged >70 years. METHODS: Three hundred and eighty-six subjects aged > 70 years in our hospital were enrolled in a cross-sectional study and underwent BMD measurement along with a CBC test. Patients were divided into two groups: "at least osteopenia" (T-score < -1) and a normal group (T-score ≥ -1). The clinicopathological characteristics, CBC parameters, and BMD were analyzed between the two groups. We performed a supervised discretization (using a conditional inference tree algorithm) to find the risk interval for the continuous variables, especially for CBC parameters, and bootstrap multivariable logistic regression to estimate the odds of CBC parameters associated with BMD. RESULTS: A total of 248 subjects were included in the study and divided into the normal (n = 43) and "at least osteopenia" groups (n = 205). Subjects in the "at least osteopenia" group had varying degrees of decreases in white blood cell (WBC) count, red blood cell (RBC) count, hemoglobin (Hb), mean corpuscular hemoglobin concentration (MCHC), hematocrit (HCT), platelet volume distribution width (PDW) mean platelet volume (MPV), eosinophils, and lymphocytes, and had increases in platelets (PLTs). MCHC, WBC, RBC, PDW, MPV, Hb, and lymphocytes were successfully divided into two (low and high) intervals. Bootstrap logistic regression showed that low levels of body mass index (BMI) [(11.88, 23.53); OR: 4.07; p < 0.0001], lymphocytes [(0.54, 2.3); OR: 3.95; p < 0.0001] and PDW [(8.5, 12.7); OR: 2.44; p < 0.0001] along with being female and older age [(72, 97); OR: 2.16; p < 0.0001] were significantly associated with BMD as risk factors. CONCLUSIONS: The elderly with BMD loss tended to show an abnormal sign in the CBC test. Low levels of lymphocytes and PDW may contribute to the evaluation of osteoporosis risk in the elderly. Bone remodeling and hematopoiesis may have stronger associations and interactions than has been previously recognized.

[Effects of Bushen Zhuanggu Granules on expressions of serum GH with IGF-1 and its receptors in bone tissue of ovariectomized rats].

Objective: To investigate the effects of Bushen Zhuanggu granule on the expressions of serum growth hormone (GH) and insulin-like growth factor-1(IGF-1) and their receptors in bone tissues of ovariectomized rats. Methods: Forty-eight SD female rats (weight 273±21.3 g) were divided into 4 four groups: the dosage of Bushen Zhuanggu granule group (BSZG) was 2.5 g/(kg·d),the do -sage of estradiol group(E2) was 0.071mg/(kg·d),sham group (SHAM) and ovariectomized model group (OVX group) were given the same amount of saline by oral administration.Each group included 12 rats,the treatments were conducted once a day. After 3 and 6 months of treatment,bone mineral density (B -MD) was measured by bone density instrument;the serum levels of GH and IGF-1 were detected by EL-ISA;the expressions of GHR and IGF-1R of bone tissue were detected by qPCR;the optical density(OD)value and positive cell count of pituitary GH immunohistochemical tablets were analyzed by Image J software,respectively. Results: ①After 3 months intervention,compared with the SHAM, the BMD of the spine in E2 group was increased(P＜0.05),and the BMD of both parts in BSZG group were increased(P＜0.05).After two stage intervention,BMD of both part in the two drug groups was higher than that in the OVX group(P＜0.05).②After two-stage intervention,the expression levels of serum GH and IGF-1,GHR and IGF-1R in BSZG group were higher than those in OVX group (P＜0.05).The levels of serum GH and it's receptors in the E2 group were increased (P＜0.05), but the serum IGF-1 level remained unchanged (P＞0.05) or even was decreased (P＜0.05).③After two stage in -tervention,the OD values and the positive cells count in the two drug intervention groups were increased (P＞0.05).④Pearson correlation analysis showed that serum GH,IGF-1 concentration and it's receptors in bone tissue were positively related with BMD. Serum GH concentration was positively correlated with OD values and number of positive cells. Conclusion: Bushen Zhuanggu granule can be used to improve the expressions of GH,IGF-1 in serum and its receptors in bone tissues of ovariectomized osteoporosis rats to prevent further loss of bone mass and increase bone mineral density.

Relation of Age, Sex and Bone Mineral Density to Serum 25-Hydroxyvitamin D Levels in Chinese Women and Men.

OBJECTIVE: To investigate the relation of circulating 25-hydroxyvitamin D (25[OH]D) levels to age, sex, and bone mineral density (BMD) in adults living in Guangzhou Province. METHODS: This cross-sectional study comprised 188 women and 122 men aged 17-88 years who were randomly sampled among community-dwelling Guangzhou residents. BMD at the lumbar spine and femoral neck was measured by dual energy X-ray absorptiometry, and serum concentrations of 25(OH)D, parathyroid hormone (PTH), procollagen I N-terminal peptide, and beta C-telopeptide of collagen were assayed by electrochemiluminescence immunoassay. Serum 25(OH)D concentrations were divided into four subgroups: severe deficiency (<10 ng/mL), deficiency (10-20 ng/mL), insufficiency (20-30 ng/mL), and sufficiency (≥30 ng/mL). RESULTS: The mean age of participants was 47.39 ± 19.32 years. Serum 25(OH)D levels were significantly lower in women than men (25.35 ± 6.59 ng/mL vs 27.25 ± 7.94 ng/mL, P < 0.05). The prevalence of 25(OH)D severe deficiency (<10 ng/mL) was 1.6% in men, zero in women; 25(OH)D deficiency (10-20 ng/mL) was 22.9% in women and 20.5% in men; and 25(OH)D insufficiency (20-30 ng/mL) was 73.4% in women and 65.6% in men. An inverse relationship between serum 25(OH)D levels and age (r = -0.249, P < 0.01) was observed in men, but no correlation was found in women (r = 0.130, P > 0.05). Serum 25(OH)D levels were positively associated with lumbar spine and femoral neck BMD (r = 0.382, P < 0.01; r = 0.384, P < 0.01, respectively) in elderly women and (r = 0.332, P < 0.05; r = 0.260, P < 0.05, respectively) and in young men. When adjustments were made for age, correlations between serum 25(OH)D levels and lumbar spine and femoral neck BMD persisted (r = 0.325, P < 0.05; r = 0.323, P < 0.05, respectively) in elderly women. However, age-adjusted serum 25(OH)D levels were positively correlated with BMD at lumbar spine (r = 0.278, P < 0.05) but not at femoral neck (r = 0.165, P > 0.05) in young men. No association between unadjusted or age-adjusted serum 25(OH)D levels and lumbar spine and femoral neck BMD was found in young and middle-aged women and in middle-aged and elderly men. Neither serum PTH levels nor bone turnover markers were related to unadjusted and age-adjusted serum 25(OH)D levels in our participants. CONCLUSION: More than two-third of participants residing in Guangzhou had vitamin D insufficiency. Serum 25(OH)D level is an important biomarker for BMD in elderly women and young men.