The association between hemoglobin level and sarcopenia in Chinese patients with Crohn's disease.

Sarcopenia and anemia are common complications in patients with Crohn's Disease (CD). However, few studies have shown the association between sarcopenia and hemoglobin levels in CD patients. This retrospective study aimed to explore such association in Chinese patients with CD. Two hundred and twelve adult CD inpatients who underwent computed tomography (CT) or magnetic resonance imaging (MRI) examinations from July 2019 to December 2021 were included in the study. Sarcopenia was defined according to the cutoff value of skeletal muscle index of lumbar spine 3 (SMI-L3) (< 44.77cm2/m2 for males and < 32.5cm2/m2 for females). The CD patients were divided into two groups based on the presence or absence of sarcopenia. Clinical data, hemoglobin levels, and other laboratory data were retrospectively collected. The association between hemoglobin levels and sarcopenia was analyzed by univariable and multivariable logistic regression analysis. Sarcopenia occurred in 114 CD patients (53.8%). Compared to patients without sarcopenia, patients with sarcopenia had a lower proportion of L1 (30.7% vs. 45.8%, p = 0.032) and B1 classification (58.8% vs. 72.4%, p = 0.037). Patients with sarcopenia had significantly lower levels of hemoglobin (Hb) (116.5 ± 22.8 vs. 128.1 ± 21.0, p < 0.001). The prevalence of sarcopenia increased with the decrease in hemoglobin level (p for trend < 0.05). Linear regression analysis showed that hemoglobin levels were associated with SMI-L3 (ß = 0.091, p = 0.001). Multivariable logistic regression analysis found that higher hemoglobin levels (OR:0.944; 95% CI: 0.947,0.998; p = 0.036) were independent protective factors for sarcopenia. Lower hemoglobin levels are independently associated factors of sarcopenia in adult Chinese patients with CD.

Surface functionalization of calcium magnesium phosphate cements with alginate sodium for enhanced bone regeneration via TRPM7/PI3K/Akt signaling pathway.

Although calcium­magnesium phosphate cements (CMPCs) have been widely applied to treating critical-size bone defects, their repair efficiency is unsatisfactory owing to their weak surface bioactivity and uncontrolled ion release. In this study, we lyophilized alginate sodium (AS) as a coating onto HAp/K-struvite (H@KSv) to develop AS/HAp/K-struvite (AH@KSv), which promotes bone regeneration. The compressive strength and hydrophilicity of AH@KSv significantly improved, leading to enhanced cell adhesion in vitro. Importantly, the SA coating enables continuous ions release of Mg2+ and Ca2+, finally leading to enhanced osteogenesis in vitro/vivo and different patterns of new bone ingrowth in vivo. Furthermore, these composites increased the expression levels of biomarkers of the TRPM7/PI3K/Akt signaling pathway via an equilibrium effect of Mg2+ to Ca2+. In conclusion, our study provides novel insights into the mechanisms of Mg-based biomaterials for bone regeneration.

The Association Between Environmental Cadmium Exposure and Parathyroid Hormone Levels.

Cadmium exposure is associated with renal dysfunction and bone damage. Chronic kidney disease and bone loss are also related to parathyroid hormone (PTH). However, whether cadmium exposure affect PTH level is not completely understood. In this study, we observed the association between environmental cadmium exposure and PTH levels in a Chinese population. A ChinaCd study was performed in China in 1990s which included 790 subjects living in heavily, moderately and low cadmium polluted area. 354 of them (121 men and 233 women) also had the data of serum PTH. The cadmium levels in blood (BCd) and urine (UCd) were determined by flame atomic absorption spectrometry. Serum PTH was detected by immunoradiometric assay. Renal function was assessed based on urinary N-acetyl-ß-d-glucosaminidase (UNAG), ß2-microglobulin (UBMG) and urinary albumin (UALB). The median BCd and UCd levels were 4.69 µg/L and 5.50 µg/g creatinine. The BCd, UCd, UNAG, UBMG and UALB levels in subjects with low PTH (< 5.0 ng/L) were significantly higher than those with PTH ≥ 5.0 ng/L (p < 0.05 or p < 0.01). Spearman correlation analysis also showed that UCd level was negatively correlated to PTH levels (r = -0.17, p = 0.008) in women. A weak correlation was also observed between PTH level and BCd in women (r = -0.11, p = 0.09) and UBMG in total population (r = -0.114, p = 0.07). Univariable and mutivariable logistic regression analysis both demonstrated that high BCd (> 10 µg/L) (odds ratio (OR) = 2.26, 95% confidence interval (CI):1.10-4.63; OR = 2.36, 95%CI: 1.11-5.05) and UCd level (> 20 µg/g cr) (OR = 2.84, 95% CI:1.32-6.10; OR = 2.97, 95%CI: 1.25-7.05) were associated with high risk of low PTH. Our data showed that environmental cadmium exposure was associated with low PTH level.

The association between jaundice and poorly differentiated pancreatic neuroendocrine neoplasms (Ki67 index > 55.0%).

BACKGROUND: Jaundice occurs in some pancreatic disease. However, its occurrences and role in pancreatic neuroendocrine neoplasms (PNENs) has not been well studied. In this study we showed the association between jaundice and the risk of high grade and poorly differentiated PNENs. METHODS: Ninety-three patients with head-neck PNENs were included. Poorly differentiated pancreatic neuroendocrine neoplasms were defined by a ki67 index > 55.0%. Logistic regression was used to show the association between demographic information, clinical signs and symptoms and the risk of poorly differentiated tumors. A nomogram model was developed to predict poorly differentiated tumor. RESULTS: Eight of 93 PNEN patients (8.6%) had jaundice. The age and ki67 index in patients with jaundice were significantly higher than those patients without jaundice. All jaundice occurred in patients with grade 3 PNENs. Mutivariable regression analysis showed that age (odds ratio(OR) = 1.10, 95% confidence interval (CI):1.02-1.19), tumor size (OR = 1.42, 95%CI:1.01-2.00) and jaundice (OR = 14.98, 95%CI: 1.22-184.09) were associated with the risk of poorly differentiated PNENs. The age and size combination showed a good performance in predicting poorly differentiated PNENs (area under the curve (AUC) = 0.81, 95% CI: 0.71-0.90). The addition of jaundice further improved the age- and size-based model (AUC = 0.86, 95% CI: 0.78-0.91). A nomogram was developed based on age, tumor size and jaundice. CONCLUSION: Our data showed that jaundice was associated with the risk of high grade PNENs and poorly differentiated PNENs.

Construction of a prognostic risk score model based on the ARHGAP family to predict the survival of osteosarcoma.

BACKGROUND: Osteosarcoma (OS) is the most common primary malignancy of bone tumors. More and more ARHGAP family genes have been confirmed are to the occurrence, development, and invasion of tumors. However, its significance in osteosarcoma remains unclear. In this study, we aimed to identify the relationship between ARHGAP family genes and prognosis in patients with OS. METHODS: OS samples were retrieved from the TCGA and GEO databases. We then performed LASSO regression analysis and multivariate COX regression analysis to select ARHGAP family genes to construct a risk prognosis model. We then validated this prognostic model. We utilized ESTIMATE and CIBERSORT algorithms to calculate the stroma and immune scores of samples, as well as the proportions of tumor infiltrating immune cells (TICs). Finally, we conducted in vivo and in vitro experiments to investigate the effect of ARHGAP28 on osteosarcoma. RESULTS: We selected five genes to construct a risk prognosis model. Patients were divided into high- and low-risk groups and the survival time of the high-risk group was lower than that of the low-risk group. The high-risk group in the prognosis model constructed had relatively poor immune function. GSEA and ssGSEA showed that the low-risk group had abundant immune pathway infiltration. The overexpression of ARHGAP28 can inhibit the proliferation, migration, and invasion of osteosarcoma cells and tumor growth in mice, and IHC showed that overexpression of ARHGAP28 could inhibit the proliferation of tumor cells. CONCLUSION: We constructed a risk prognostic model based on five ARHGAP family genes, which can predict the overall survival of patients with osteosarcoma, to better assist us in clinical decision-making and individualized treatment.

Identification of a novel gene signature with regard to ferroptosis, prognosis prediction, and immune microenvironment in osteosarcoma.

Ferroptosis is a novel form of non-apoptotic cell death that mainly results from the iron-dependent lethal accumulation of lipid peroxidation products. Here, we defined differentially expressed genes between control and RSL3-treated osteosarcoma cells as ferroptosis-associated genes (FAGs). These FAGs were then subjected to weighted gene correlation network analysis (WGCNA), and we found that the turquoise module, containing 71 FAGs, was markedly related to the patient's vital status. After that, FAGs in the turquoise module were utilized to construct a prognostic multigene (COL5A2, HOXB4, and UNC5B) signature for risk stratification in osteosarcoma. Validation in internal and external cohorts indicated the accuracy and clinical applicability of this signature in predicting the prognosis of patients with osteosarcoma. Univariate and multivariate Cox regression analyses suggested that the signature-derived risk score is an independent indicator of patient prognosis. Immunological analysis indicated that significant variations in stromal and ESTIMATE scores, as well as tumor purity, were found when the high- and low-risk groups were compared. Regarding immune cell infiltration, the proportion of activated CD4 memory T cells was significantly lower in the high-risk group than that in the low-risk group. The ssGSEA results suggested that CD8+ T, Tfh, and Th1 cell scores were consistently lower in the high-risk group than those in the low-risk group. In terms of immune-related activities, the high-risk group had considerably lower scores for promoting inflammation, T-cell co-inhibition, and T-cell co-stimulation than the low-risk group, indicating the differential immunological state of the high- and low-risk groups. Of the three FAGs included in the signature, the expression of COL5A2, HOXB4, and UNC5B was higher in the high-risk groups, and the expression of COL5A2 and UNC5B was negatively associated with patient prognosis. Additionally, the mRNA levels of COL5A2 and HOXB4 were lower and those of UNC5B were higher in RSL3-treated cells than in control cells. In all, we systematically analyzed the transcriptional changes of osteosarcoma cells induced by RSL3 and constructed a novel three-gene signature with regard to ferroptosis, prognosis prediction, and immune microenvironment. We also identified COL5A2, HOXB4, and UNC5B as potential therapeutic targets and important regulators of ferroptosis in osteosarcoma.

Mir-5100 Mediates Proliferation, Migration and Invasion of Oral Squamous Cell Carcinoma Cells Via Targeting SCAI.

PURPOSE: We aimed to investigate the role of microRNA-5100 (miRNA-5100) in oral squamous cell carcinoma (OSCC) and its underlying mechanisms.Material/Methods: The expression of miR-5100 and suppressor of cancer cell invasion (SCAI) in OSCC cell lines were examined. A luciferase reporter assay was applied to confirm the combination between miR-5100 and SCAI. Then, miR-5100 inhibitor or small hairpin RNA (shRNA)-SCAI were transfected into cells. Cell Counting Kit-8 assay was executed for testing cell proliferation ability. Flow cytometry assay was exploited for measuring cell cycle. Invasion and migration of OSCC cells were assessed using Transwell assay and wound healing assay. The expression of proteins were detected using western blotting. RESULTS: The results demonstrated that the level of miR-5100 was upregulated while SCAI was downregulated in OSCC cells. SCAI was verified as a direct target of miR-5100. MiR-5100 silencing suppressed proliferation of OSCC cells, increased cells in the G1 and G2 phases, and reduced those in the S phase, which was reversed after transfection with shRNA-SCAI. Moreover, miR-5100 inhibitor downregulated the expression of cyclin-dependent kinase-2 (CDK-2) and cyclinD1, accompanied by upregulation in p27 expression, whereas SCAI silencing had the opposite results. The invasion and migration abilities of OSCC cells were reduced after treatment with miR-5100 inhibitor, whereas SCAI silencing suppressed the effects of miR-5100 inhibitor on OSCC cell behaviors. CONCLUSION: These findings suggested that miR-5100 silencing inhibit proliferation, invasion and migration of OSCC cells via upregulating the expression of SCAI, which provides theoretical basis and treatment strategies for the treatment of OSCC.

Decreasing Microtubule Actin Cross-Linking Factor 1 Inhibits Melanoma Metastasis by Decreasing Epithelial to Mesenchymal Transition.

BACKGROUND: The microtubule actin cross-linking factor 1 (MACF1) is involved in cellular migration, adhesion, and invasion processes. Its abnormal expression initiates tumor cell proliferation and metastasis in numerous cancer types. METHODS: In this study, we utilized short hair-pin RNA interference of MACF1 to assess the inhibitory effects on the metastatic potential of B16F10 melanoma cells both in vitro and in vivo a mouse model. RESULTS: The MACF1 expression was increased in B16F10 cells-induced tumor tissues; while the down-regulation of MACF1 impacted the B16F10 melanoma cell metastatic behavior by decreasing the ability of colony formation and invasion in vitro as well as inhibiting B16F10 cells-induced tumor growth and lung metastasis in vivo. The results of Western blot and immunohistochemistry indicated that the expression of E-cadherin and Smad-7 was significantly increased whereas the expression of N-cadherin and TGF-ß1 was significantly decreased in tumor tissue of mice challenged with the B16F10/MACF1-RNAi cells when compared with the B16F10 cells challenged mice. CONCLUSION: The data presented in this study demonstrated that down-regulated MACF1 expression decreased B16F10 melanoma metastasis in mice by inhibiting the epithelial to mesenchymal transition program. Thus, MACF1 may be a novel target for melanoma therapy.

Development and validation of a seven-immune-feature-based prognostic score for oral squamous cell carcinoma after curative resection.

Immune infiltrates have been increasingly recognized as robust prognostic factors for human cancer. Here, we developed and validated a seven-immune-feature-based prognostic score (7IFBPS) for patients with oral squamous cell carcinoma (OSCC) after curative resection. Fourteen immune features regarding detailed locations and densities of seven types of tumor-infiltrating immune cells (TIIs) were characterized in clinical samples from 269 eligible patients in three independent cohorts by immunohistochemistry coupled with digital quantitation. Optimal cutoff values for individual immune features were yielded using X-tile software. The 7IFBPS was constructed by Kaplan-Meier and Cox regression model in training cohort and verified in testing, validation and combined cohorts. Concordance index (C-index), receiver operating characteristics and calibration curves were employed to define the performance of 7IFBPS in prognostic prediction. High CD3 IM (invasive margin), CD3 CT (center of tumor), CD8 CT, CD45RO IM, CD45RO CT, FOXP3 IM and FOXP3 CT significantly associated with improved survival. The 7IFBPS score was calculated using the formula: 1.041 × CD3 IM + 1.24 × CD3 CT + 1.701 × CD8 CT + 1.127 × CD45RO IM + 1.348 × CD45RO CT + 1.089 × FOXP3 IM + 1.483 FOXP3 CT. High 7IFBPS significantly associated with improved survival in all cohorts and served as an independent prognostic predictor. The C-index of 7IFBPS for predicting survival was 0.668 (95% CI, 0.609-0.726). Calibration curves for survival probability showed good agreement between prediction by 7IFBPS and actual observation. Collectively, our findings established the 7IFBPS as a novel powerful prognostic classifier for resectable OSCC. It holds potentials to be incorporated into current prognostic regime to better patient stratification.

Overexpression of Hippo pathway effector TAZ in tongue squamous cell carcinoma: correlation with clinicopathological features and patients' prognosis.

BACKGROUND: Transcriptional coactivator with PDZ-binding motif (TAZ) is a key downstream effector of Hippo signaling pathway involved in stem cell differentiation and organ development. Recently, its deregulation has been linked to initiation and progression of various cancers. The purpose of this study was to investigate the expression of TAZ in tongue squamous cell carcinoma (TSCC) and its prognostic value in predicting patients' outcomes. METHODS: TAZ expression and localization in a panel of TSCC cell lines and human immortalized oral epithelial cell (HIOEC) were determined by real-time RT-PCR, western blotting, and immunofluorescence. In 52 TSCC tumor specimens with detailed clinical and follow-up data, TAZ abundance was examined by immunohistochemistry and its associations with clinicopathological parameters, Ki-67 expression and patients' survival were further assessed. RESULTS: TAZ mRNA and protein levels were significantly higher in TSCC cells and specimens than those in non-cancerous cells and normal tongue mucosa. Overexpression of TAZ in TSCC was significantly associated with tumor size (P = 0.033), pathological grade (P = 0.026), clinical stage (P = 0.013), Ki-67 expression (P = 0.0485), and reduced overall and disease-free survival (Kaplan-Meier analysis, log-rank test, P = 0.020, 0.019, respectively). Multivariate Cox regression analysis identified TAZ as an important independent predictor for survival of patients with TSCC [HR (hazard ratio), 4.351; 95% CI (95% confidence interval), 1.477-12.819; P = 0.008]. CONCLUSION: Our data indicate that aberrant TAZ overexpression is associated with key clinicopathological features and poor survival in TSCC. These results suggest that TAZ might play critical roles in tumorigenesis of TSCC and become a novel prognostic biomarker and potential therapeutic target for this malignancy.