LncRNA AGAP2 antisense RNA 1 stabilized by insulin-like growth factor 2 mRNA binding protein 3 promotes macrophage M2 polarization in clear cell renal cell carcinoma through regulation of the microRNA-9-5p/THBS2/PI3K-Akt pathway.

BACKGROUND: Increasing evidence highlights the potential role of long non-coding RNAs (lncRNAs) in the biological behaviors of renal cell carcinoma (RCC). Here, we explored the mechanism of AGAP2-AS1 in the occurrence and development of clear cell RCC (ccRCC) involving IGF2BP3/miR-9-5p/THBS2. METHODS: The expressions of AGAP2-AS1, IGF2BP3, miR-9-5p, and THBS2 and their relationship were analyzed by bioinformatics. The targeting relationship between AGAP2-AS1 and miR-9-5p and between miR-9-5p and THBS2 was evaluated with their effect on cell biological behaviors and macrophage polarization assayed. Finally, we tested the effect of AGAP2-AS1 on ccRCC tumor formation in xenograft tumors. RESULTS: IGF2BP3 could stabilize AGAP2-AS1 through m6A modification. AGAP2-AS1 was highly expressed in ccRCC tissues and cells. The lentivirus-mediated intervention of AGAP2-AS1 induced malignant behaviors of ccRCC cells and led to M2 polarization of macrophages. In addition, THBS2 promoted M2 polarization of macrophages by activating the PI3K/AKT signaling pathway. AGAP2-AS1 could directly bind with miR-9-5p and promote the expression of THBS2 downstream of miR-9-5p. These results were further verified by in vivo experiments. CONCLUSION: AGAP2-AS1 stabilized by IGF2BP3 competitively binds to miR-9-5p to up-regulate THBS2, activating the PI3K/AKT signaling pathway and inducing macrophage M2 polarization, thus facilitating the development of RCC.

KMT2B promotes the growth of renal cell carcinoma via upregulation of SNHG12 expression and promotion of CEP55 transcription.

BACKGROUND: This study aims to clarify the mechanistic action of long non-coding RNA (lncRNA) SNHG12 in the development of renal cell carcinoma (RCC), which may be associated with promoter methylation modification by KMT2B and the regulation of the E2F1/CEP55 axis. METHODS: TCGA and GEO databases were used to predict the involvement of SNHG12 in RCC. Knockdown of SNHG12/E2F1/CEP55 was performed. Next, SNHG12 expression and other mRNAs were quantified by RT-qPCR. Subsequently, CCK-8 was used to detect cell proliferation. Wound healing assay and Transwell assay were used to detect cell migration and invasion, respectively. The in vitro angiogenesis of human umbilical vein endothelial cells (HUVECs) was explored by matrigel-based capillary-like tube formation assay. ChIP assay was used to detect H3K4me3 in SNHG12 promoter region. The binding of E2F1 to CEP55 promoter region was analyzed with ChIP and dual luciferase reporter assays. RIP assay was used to detect the binding of SNHG12 to E2F1. Finally, the effect of SNHG12 on the tumor formation and angiogenesis of RCC was assessed in nude mouse xenograft model. RESULTS: SNHG12 was highly expressed in RCC tissues and cells, and it was related to the poor prognosis of RCC patients. SNHG12 knockdown significantly inhibited RCC cell proliferation, migration, and invasion and HUVEC angiogenesis. KMT2B up-regulated SNHG12 expression through modifying H3K4me3 in its promoter region. In addition, SNHG12 promoted CEP55 expression by recruiting the transcription factor E2F1. Knockdown of SNHG12 blocked E2F1 recruitment and down-regulated the expression of CEP55, thereby inhibiting tumor formation and angiogenesis in nude mice. CONCLUSION: The evidence provided by our study highlighted the involvement of KMT2B in up-regulation of lncRNA as well as the transcription of CEP55, resulting in the promotion of angiogenesis and growth of RCC.

[Clinical Significance of Serum ADA Combined with GLB, CREA, ß2-MG and HGB in Newly Diagnosed Multiple Myeloma].

OBJECTIVE: To investigate the role of serum adenosine deaminase (ADA) combined with globulin (GLB), creatinine (CREA), ß2-microglobulin (ß2-MG) and hemoglobin (HGB) in the initial screening of multiple myeloma (MM), in order to reduce missed diagnosis and misdiagnosis of MM. METHODS: A retrospective analysis was performed on 62 newly diagnosed multiple myeloma (NDMM) patients who were admitted to the Department of Hematology of the First Affiliated Hospital of Chengdu Medical College from April 2018 to December 2021, and 33 patients with benign hematologic diseases and 30 healthy subjects were selected as the control group. The expression of ADA in pan-cancer was analyzed using TCGA and GTEx databases. The general data and laboratory indicators of the subjects were collected, and the differences of ADA activity and other laboratory indicators in each group were compared. The relationship between serum ADA activity and clinical data of NDMM patients was analyzed. The changes of ADA activity before and after chemotherapy in NDMM patients and the differences of ADA activity in NDMM patients with different DS and ISS stages were compared. Multivariate logistic regression was used to analyze the risk factors of NDMM. The receiver operating characteristic(ROC) curve was used to evaluate the diagnostic efficacy of ADA and other laboratory indicators in MM. Bioinformatics method was used to analyze the co-expression networks and enrichment pathways of ADA. RESULTS: ADA level was significantly upregulated in tissues of 14 types of cancer in TCGA database, and ADA was highly expressed in 11 types of cancer in TCGA combined with GTEx databases. The serum levels of ADA, GLB, uric acid (UA), cystatin C (CysC) and ß2-MG in the NDMM group were significantly higher than those in benign hematologic disease group and healthy control group ( P < 0.05), while the levels of ALB and the value of albumin to globulin ratio (A∶G) in the NDMM group were significantly lower than those in the other two groups ( P < 0.001). There were significant differences in DS stage (P =0.036), ISS stage (P =0.019) and the levels of CREA (P =0.036), UA (P =0.034), ß2-MG (P =0.019) in NDMM patients with different ADA activity levels. After primary chemotherapy, ADA activity and ß2-MG concentration were decreased in NDMM patients ( P < 0.01). The comparison results of patients in different stages showed that ADA activity of patients in DS stage I+II was significantly lower than that of patients in DS stage III (P <0.05), and ADA activity of patiens in ISS stage I+II was significantly lower than that of patients in ISS stage III ( P < 0.01). Multivariate logistic regression analysis showed that increased GLB, increased ADA activity, increased CREA, increased ß2-MG and decreased HGB were independent risk factors for NDMM. The area under the curve (AUC) of ADA in the diagnosis of MM was 0.847, and the AUC of ADA combined with GLB, CREA, ß2-MG and HGB in the diagnosis of MM was 0.940. The results of co-expression network and enrichment pathway analysis showed that ADA bounded to 20 proteins and it was significantly associated with the metabolic pathways of purine, pyrimidine, nicotinate and nicotinamide. CONCLUSION: The detection of ADA activity in serum is of positive significance for the auxiliary diagnosis, therapeutic evaluation and monitoring the progress of NDMM patients. ADA combined with GLB, CREA, ß2-MG and HGB can improve the detection rate of MM, and reduce missed diagnosis and misdiagnosis to a certain extent.

Estimation of safe and effective dose of vancomycin in MRSA-infected patients using serum cystatin C concentrations.

OBJECTIVE: To utilize serum cystatin C (CysC) concentration to identify the daily dosage regimen of vancomycin (Van) for the treatment of patients with methicillin-resistant Staphylococcus aureus (MRSA) infections. METHODS: Serum Van, CysC, and serum and urine creatinine (Cr) concentrations were detected in 65 MRSA-infected patients. The estimated glomerular filtration rate (eGFR), Cr clearance (CLcr) and Van clearance (CLvan) were calculated and the correlation equation between CysC and CLvan was obtained using mathematical methods. Finally, the daily dosage equation of Van was derived according to pharmacokinetic theory. RESULTS: In the test sample, serum Cr was 183.27 ± 68.34 µmol/l, CLcr was 75.56 ± 30.02 ml/min, eGFR was 70.79 ± 40.79 ml/min, and serum CysC was 1.35 ± 0.61 mg/l. There was significant correlation between eGFR and CLcr (R2 = 0.8051, p = 0.000). Bland-Altman analysis showed an agreement of 96.9% (63/65) between eGFR and CLcr. eGFR was significantly correlated with CLvan (R2 = 0.8465, p = 0.000) and the correlation was significantly higher than that between CLvan and CLcr (R2 = 0.6367, p = 0.000). CysC fits a high correlated CLvan estimating equation (R2 = 0.9211, p = 0.000): CLvan(ml/min) = 64.4026 × (CysC)-1.1488. Accordingly, the predicted equation was created for calculation of the Van dosage to achieve the appropriate target steady-state serum concentration (Css): IR (the rate of continuous infusion, g/D) = 64.4026 × (CysC)-1.1488 × Css (mg/l) × (60/1,000) × 24. CONCLUSIONS: Serum CysC is a good marker of renal function in comparison with serum Cr for the dose determination of Van. CysC can estimate the daily dose of Van, and may improve therapeutic success rates of MRSA-infected patients.

[Comparative study of antitumor activity of cantharidin and cantharis peptides].

OBJECTIVE: To prepare cantharidin and cantharidin peptides from Mylabris and compare their antitumor activity. METHODS: Cantharis peptides was prepared by bionic enzymolysis approach and cantharidin was prepared by alkaline water supersonic extraction. The inhibitory effects of both compounds on BEL-7402 cells proliferation of human liver cancer were tested by Prestoblue method. The influence of both compounds on the grown of tumor, thymus, spleen of S180 tumor-bearing mice were detected. RESULTS: Cantharis peptides and cantharidin could inhibit the proliferation of BEL-7402 cells (P < 0.05) in vivo, and the inhibitory effect of cantharis peptide was 12.54% lower than that of cantharidin. At the same time, they could inhibit the grown of S180 sarcoma (P < 0.05), and the inhibitory effect of cantharidin was higher than that of cantharis peptides (5.93%). Furthermore, cantharis peptides could't inhibit the grown of thymus and spleen. CONCLUSION: Both cantharis peptides and cantharidin have antineoplastic activity, but cantharidin peptides have no immunosuppression.

Analysis of non-targeted serum metabolomics in patients with chronic kidney disease and hyperuricemia.

Hyperuricemia (HUA) is a common complication of chronic kidney disease (CKD). Conversely, HUA can promote the disease progression of CKD. However, the molecular mechanism of HUA in CKD development remains unclear. In the present study, we applied ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) to analyze the serum metabolite profiling of 47 HUA patients, 41 non-hyperuricemic CKD (NUA-CKD) patients, and 51 CKD and HUA (HUA-CKD) patients, and then subjected to multivariate statistical analysis, metabolic pathway analysis and diagnostic performance evaluation. Metabolic profiling of serums showed that 40 differential metabolites (fold-change threshold (FC) > 1.5 or<2/3, variable importance in projection (VIP) > 1, and p < 0.05) were screened in HUA-CKD and HUA patients, and 24 differential metabolites (FC > 1.2 or<0.83, VIP>1, and p < 0.05) were screened in HUA-CKD and NUA-CKD patients. According to the analysis of metabolic pathways, significant changes existed in three metabolic pathways (compared with the HUA group) and two metabolic pathways (compared with the HUA-CKD group) in HUA-CKD patients. Glycerophospholipid metabolism was a significant pathway in HUA-CKD. Our findings show that the metabolic disorder in HUA-CKD patients was more serious than that in NUA-CKD or HUA patients. A theoretical basis is provided for HUA to accelerate CKD progress.

Serum total oxidant/antioxidant status and trace element levels in breast cancer patients.

BACKGROUND: Oxidative stress and trace elements have been implicated in the development of breast cancer. However, how they contribute to the pathogenesis of the disease and the relationship between them remain unclear. In addition, most previous studies detecting one or a few oxidant/antioxidant markers failed to consider the overall oxidant/antioxidant status of the subjects. This study was designed to address this and to investigate the association between oxidative status and trace elements in the pathogenesis of breast cancer. METHODS: Fifty-six patients with breast carcinoma at different clinical stages, 32 patients with benign breast tumor, and 20 healthy subjects (controls) were recruited into this study. Their serum total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI), and levels of Cu, Zn, Fe, Se, Mg, and Mn were measured. RESULTS: Levels of TAS, TOS, OSI, and trace elements significantly differed between the study groups. Among subgroups of patients with different clinical stages of breast cancer, the levels of all the trace elements except Zn were similar, whereas TAS, TOS, and OSI levels were all significantly different. There were significant correlations between oxidative stress parameters and levels of trace elements in patients with breast carcinoma but not in patients with benign breast tumor or in the healthy controls. CONCLUSIONS: Disturbed oxidative stress status and trace element levels may contribute to the pathogenesis of breast tumors. TAS, TOS, and OSI may be useful biomarkers for monitoring the clinical status of breast cancer.

Re-understanding and focusing on normoalbuminuric diabetic kidney disease.

Diabetes mellitus (DM) has grown up to be an important issue of global public health because of its high incidence rate. About 25% of DM patients can develop diabetic foot/ulcers (DF/DFU). Diabetic kidney disease (DKD) is the main cause of end-stage kidney disease (ESKD). DF/DFU and DKD are serious complications of DM. Therefore, early diagnosis and timely prevention and treatment of DF/DFU and DKD are essential for the progress of DM. The clinical diagnosis and staging of DKD are mostly based on the urinary albumin excretion rate (UAER) and EGFR. However, clinically, DKD patients show normoalbuminuric diabetic kidney disease (NADKD) instead of clinical proteinuria. The old NADKD concept is no longer suitable and should be updated accordingly with the redefinition of normal proteinuria by NKF/FDA. Based on the relevant guidelines of DM and CKD and combined with the current situation of clinical research, the review described NADKD from the aspects of epidemiology, pathological mechanism, clinical characteristics, biomarkers, disease diagnosis, and the relationship with DF/DFU to arouse the new understanding of NADKD in the medical profession and pay attention to it.

Study on potential markers for diagnosis of renal cell carcinoma by serum untargeted metabolomics based on UPLC-MS/MS.

Objective: Renal cell carcinoma (RCC) is the most common malignancy of the kidney. However, there is no reliable biomarker with high sensitivity and specificity for diagnosis and differential diagnosis. This study aims to analyze serum metabolite profile of patients with RCC and screen for potential diagnostic biomarkers. Methods: Forty-five healthy controls (HC), 40 patients with benign kidney tumor (BKT) and 46 patients with RCC were enrolled in this study. Serum metabolites were detected by ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), and then subjected to multivariate statistical analysis, metabolic pathway analysis and diagnostic performance evaluation. Results: The changes of glycerophospholipid metabolism, phosphatidylinositol signaling system, glycerolipid metabolism, d-glutamine and d-glutamate metabolism, galactose metabolism, and folate biosynthesis were observed in RCC group. Two hundred and forty differential metabolites were screened between RCC and HC groups, and 64 differential metabolites were screened between RCC and BKT groups. Among them, 4 differential metabolites, including 3-ß-D-Galactosyl-sn-glycerol, 7,8-Dihydroneopterin, lysophosphatidylcholine (LPC) 19:2, and γ-Aminobutyryl-lysine (an amino acid metabolite), were of high clinical value not only in the diagnosis of RCC (RCC group vs. HC group; AUC = 0.990, 0.916, 0.909, and 0.962; Sensitivity = 97.73%, 97.73%, 93.18%, and 86.36%; Specificity = 100.00%, 73.33%, 80.00%, and 95.56%), but also in the differential diagnosis of benign and malignant kidney tumors (RCC group vs. BKT group; AUC = 0.989, 0.941, 0.845 and 0.981; Sensitivity = 93.33%, 93.33%, 77.27% and 93.33%; Specificity = 100.00%, 84.21%, 78.38% and 92.11%). Conclusion: The occurrence of RCC may involve changes in multiple metabolic pathways. The 3-ß-D-Galactosyl-sn-glycerol, 7,8-Dihydroneopterin, LPC 19:2 and γ-Aminobutyryl-lysine may be potential biomarkers for the diagnosis or differential diagnosis of RCC.

Circ_000829 Plays an Anticancer Role in Renal Cell Carcinoma by Suppressing SRSF1-Mediated Alternative Splicing of SLC39A14.

Background: Covalently closed circular RNAs (circRNAs) play critical oncogenic or anticancer roles in various cancers including renal cell carcinoma (RCC), pointing to their regulation as a promising strategy against development of RCC. We, thus, studied the tumor-suppressive role of circ_000829 in RCC through in vitro and in vivo experiments. Methods: The expression of circ_000829 was validated in clinical RCC tissues and RCC cell lines. Based on ectopic expression and knockdown experiments, we examined the interactions among circ_000829, serine and arginine rich splicing factor 1 (SRSF1), and solute carrier family 39 member 14 (SLC39A14, zinc transporter). Then, the effects of circ_000829, SRSF1, and SLC39A14 on cell cycle distribution and proliferation in vitro and on tumor growth in vivo were evaluated in RCC cells. Results: Circ_000829 was poorly expressed in RCC tissues and cells, while SRSF1 was highly expressed. Restoration of circ_000829 reduced the levels of SRSF1 and SLC39A14B, thereby repressing the RCC cell proliferation in vitro and tumor growth in vivo. Meanwhile, overexpression of SRSF1 and SLC39A14B promoted the proliferation and cell cycle entry of RCC cells. Mechanistically, circ_000829 directly bound to SRSF1, and SRSF1 enhanced the expression of SLC39A14B by mediating the alternative splicing of SLC39A14. SLC39A14B upregulation negated the effect of SLC39A14 knockdown on RCC cell proliferation. Conclusion: Hence, this study suggests the antiproliferative role of circ_000829 in RCC growth and further elucidates the underlying mechanism involving the inhibited SRSF1-mediated alternative splicing of SLC39A14 mRNA.

Evaluation of vitamin D storage in patients with chronic kidney disease: Detection of serum vitamin D metabolites using high performance liquid chromatography-tandem mass spectrometry.

BACKGROUND: Vitamin D (VitD) deficiency is extremely common in chronic kidney disease (CKD). However, the current clinical testing of vitamin D is based on the recommended serum 25-hydroxyvitamin D [25(OH)D]. The levels of VitD components in CKD patients are rarely reported. In this study, we tested various VitD components, and used different methods to evaluate the VitD status of CKD patients in vivo. METHODS: Totally 173 CKD patients and 111 control individuals were enrolled. Serum levels of 25(OH)D2, 25(OH)D3, C3-epimers (C3-epi) and free 25(OH)D [f-25(OH)D] were measured. The 25(OH)D2/25(OH)D3 ratio, C3-epi/25(OH)D3 ratio, total 25(OH)D [t-25(OH)D], and bioavailable vitamin D (BAVD) were calculated, respectively. RESULTS: The ratios of 25(OH)D2/25(OH)D3, C3-epi/25(OH)D3, and the level of C3-epi in CKD patients were significantly higher than those in the control group (all P < 0.05). The levels of t-25(OH)D, 25(OH)D3, C3-epi, f-25(OH)D and BAVD in patients with CKD stage 5 were significantly lower than those in stages 2, 3, and 4 (all P < 0.05). The calculated VitD storage according to Method 3 [25(OH)D2/3 + 25(OH)D3] was only 32.95 %, which was lower than the results of 53.76 % by Method 1 [25(OH)D2+ 25(OH)D3+C3-epi] and 48.56 % by Method 2 [25(OH)D2/3 + 25(OH)D3+C3-epi]. In addition, the VitD results calculated by three methods were positively correlated with f-25(OH)D and BAVD, while C3-epi levels were also positively correlated with f-25(OH)D and BAVD. CONCLUSION: Serum levels of t-25(OH)D, 25(OH)D3, C3-epi, f-25(OH)D and BAVD in CKD patients gradually decrease with the progression of CKD stages. Though the results of VitD storage in CKD patients evaluated by different methods are different, simultaneous detection of 25(OH)D2, 25(OH)D3, C3-epi and f-25(OH)D levels and fully estimation of their respective biological activities could accurately evaluate the VitD storage in vivo.

The Relationship between Serum Trace Elements and Oxidative Stress of Patients with Different Types of Cancer.

OBJECTIVE: Many studies have identified causal and promotive roles of oxidative stress (OxS) and oxidative damage caused by OxS in the occurrence and progression of cancer. Many biomarkers in the blood circulation of patients may change correspondingly with the development of tumors. This study is aimed at investigating the correlation between OxS and serum trace element (TE) levels of patients with different types of cancer. METHODS: 1143 different types of cancer patients and 178 healthy controls from Mar. 2018 to Aug. 2020 in Mianyang Central Hospital were involved in this study. Their levels of OxS parameters (including total oxidant status (TOS), total antioxidant status (TAS), and oxidant stress index (OSI)) and the concentrations of serum TEs (including Cu, Zn, Fe, and Se) were determined. RESULTS: Compared with healthy controls, all types of cancer patients had higher TOS level (all P adj < 0.001) and OSI level (z = 6.228 ~ 9.909, all P adj < 0.001) and lower TAS level (all P adj < 0.001). Compared with healthy controls, the changes of four TE levels in serum were different in different types of cancer patients, among which Cu increased in all groups, but there was no statistical difference in gastric and brain cancer; Se decreased in all groups, but there was no statistical difference in gastric, colorectal, esophageal, and other cancer; Zn was significantly decreased in breast cancer patients (P adj < 0.001); there was no statistical difference in the change of Fe in liver, kidney, and other cancer. Spearman correlation showed that the change of Cu concentration was most closely related to the three OxS parameters and was strongly correlated in the observed several types of tumors (r s > 0.6). Multinomial logistic regression showed that the risks of different tumors are related to the level change of multiple TEs and OxS parameters (ORTOS = 1.19 ~ 2.82, OROSI = 2.56 ~ 4.70, ORTAS = 0.20 ~ 0.46, ORCu = 0.73 ~ 1.44, ORZn = 0.81 ~ 0.91, ORFe = 0.68 ~ 1.18, and ORSe = 0.22 ~ 0.45, all P < 0.006). CONCLUSIONS: The OxS exists in the occurrence and development of cancer, which may be related to the changes of certain trace elements. In order to evaluate OxS correctly, it is necessary to detect TAS and TOS and at the same time, their ratio OSI should be detected. Assessment of markers representing the overall level of OxS and TEs may guarantee improved the monitoring of disease occurrence and development risk in cancer patients.

Analysis of Vitamin D Components in Serum of Minors by UHPLC-MS/MS.

Serum 25-hydroxyvitamin D [25(OH)D] concentration represents the body's reserves of vitamin D, which is mostly used by clinicians to evaluate the storage status of vitamin D in the body. The present study aimed to investigate the serum vitamin D components in different health status of minors to correctly evaluate the vitamin D storage in vivo. A total of 2,270 minors were included in the study, which was divided into healthy group (1,204 cases) and disease group (1,066 cases, including 270 short stature, 433 respiratory infections, 175 malnutrition and 188 tic disorder subjects). The levels of 25-hydroxyvitamin D2 [25(OH)D2] and 25-hydroxyvitamin D3 [25(OH)D3] were measured by UHPLC-MS/MS in all subjects, and the 25(OH)D3 activity equivalents [25(OH)D3-AE] and 25(OH)D were calculated. In addition, the 3-epi-25-hydroxyvitamin D3 [3-epi-25(OH)D3] concentrations of 278 subjects (including 147 healthy and 131 disease subjects) were measured by random sampling. 25(OH)D2, 25(OH)D3, 25(OH)D and 25(OH)D3-AE levels in disease group were significantly lower than those in healthy group (p<0.001). According to the level of 25(OH)D, the sufficiency of vitamin D [25(OH)D≥30 ng/mL] was 65.4% in healthy group and 50.5% in disease group. When the 25(OH)D2 activity was converted into 25(OH)D3-AE, 53.2% of the patients in the healthy group had sufficiency vitamin D, and 39.1% in the disease group. The 3-epi-25(OH)D3 level in the disease group was significantly lower than that in the healthy group (p<0.001). Not only the 25(OH)D, but also the both of 25(OH)D2 and 25(OH)D3 levels may overestimate the vitamin D status in subjects. For accurate evaluation, at least the serum levels of 25(OH)D2, 25(OH)D3 and 3-epi-25(OH)D3 should be determined simultaneously.

Serum copper and zinc levels in breast cancer: A meta-analysis.

BACKGROUND: More and more studies have investigated the relationship between serum copper (Cu) and/or zinc (Zn) levels and breast cancer (BC). However, the results are inconsistent. It is unclear whether the serum Cu to Zn ratio (Cu/Zn) is associated with BC risk. Therefore, we evaluated serum Cu and Zn concentrations, and Cu/Zn in BC through meta-analysis. MATERIALS AND METHODS: Studies reporting serum Cu and/or Zn concentrations in BC patients and controls from 1991 to 2020 were identified from PubMed, CNKI, and Wanfang databases online. Based on a random effects model, summary standard mean differences (SMDs) and the corresponding 95 % confidence intervals (95 % CIs) were applied to compare the serum levels of Cu, Zn and Cu/Zn between BC patients and controls. RESULTS: Thirty-six eligible studies involving 5747 female subjects were included. The present study illustrated that the BC patients had significantly higher serum Cu levels than healthy controls (HC) (SMD (95 % CI): 1.99(1.48, 2.49)) and patients with benign breast diseases (BD) (SMD (95 % CI): 0.99(0.38, 1.61)). However, Zn concentrations were statistically decreased in BC patients than HC (SMD (95 % CI): -1.20(-1.74, -0.66)) and BD (SMD (95 % CI): -1.13 (-1.73, -0.54)). Cu/Zn concentrations were remarkably increased in BC patients than HC (SMD (95 % CI): 2.75(1.79, 3.60)) and BD (SMD (95 % CI): 2.98(1.91, 4.05)) in some studies. CONCLUSION: The results show that elevated serum levels of Cu and Cu/Zn, as well as decreased Zn might be associated with increased risk of breast cancer. These three parameters have the potential to distinguish breast cancer from benign breast diseases.

Diagnostic performance of serum cystatin C and complement component 1q in lupus nephritis.

BACKGROUND: The information concerning non-invasive, easily obtainable, and accurate biomarkers for diagnosis of lupus nephritis (LN) is extremely limited. The aim of this study was to evaluate the diagnostic performance of cystatin C (CysC) and complement component 1q (C1q) for LN. METHODS: A case-control study that included 905 patients with systemic lupus erythematosus (SLE) without LN (group SLE), 334 patients with active lupus nephritis (group LNA), 255 patients with inactive lupus nephritis (group LNI), and 497 healthy individuals (group HC) was performed in Mianyang Central Hospital from March 2017 to December 2018. The serum levels of CysC, C1q, urea (Urea), and creatinine (Creat) were measured, and 2 estimated glomerular filtration rates (eGFRCysC and eGFRCreat) were calculated by equations which were based on serum CysC established by our group and the modification of diet in renal disease (MDRD), respectively. ANOVA analysis or Kruskal-Wallis test was used for comparing the differences among the groups, and receiver operating characteristic (ROC) curve was applied to identify the diagnostic efficiencies of individual or combined multiple indicators. RESULTS: Significantly elevated CysC and decreased C1q were observed in the LNA and LNI groups, which was in contrast to their levels in the SLE and HC groups. CysC (AUC = 0.906) or eGFRCysC (AUC = 0.907) assessed the highest diagnostic performance on LNA when detected individually, followed by C1q (AUC = 0.753). Joint utilization of C1q and CysC achieved very good performance (AUC = 0.933) which approximated to the best one observed in the combinations of C1q, Urea, CysC, eGFRCreat, and Creat (AUC = 0.975). CONCLUSION: The separately detected CysC (eGFRCysC) and C1q were superior to the conventional biomarkers Urea, Creat, and eGFRCreat in the diagnosis of LNA. Moreover, although the combined detection of Urea, Creat, C1q, CysC, and eGFRCreat had the greatest diagnostic performance, the joint utilization of CysC and C1q could be prioritized for rapid discrimination of LNA if the economic burden is taken into consideration.

[Determination of serum argininosuccinate lyase in diagnosing liver diseases].

OBJECTIVE: To investigate the value of the determination of the levels of serum argininosuccinate lyase (ASL) in diagnosing various liver diseases. METHODS: Two hundred and ninety-one patients with various liver diseases, 257 patients with non-liver disease, and 32 healthy controls were recruited for this study and their serum ASL, ALT, AST, GGT, LDH, ALP, and total bilirubin (TBil) levels were determined. Liver biopsies were performed on 31 patients with hepatopathy. RESULTS: Receiver operating characteristic (ROC) curve analysis showed that the sensitivity and specificity of ASL in assessing liver diseases were 100% and 91.1% (at cut-off values of 8 U/L), those of ALT were 97.6% and 24.7% and those of AST were 83.8% and 28.3% (both at cut-off values = 40.0 U/L), respectively. The levels of ASL in various liver disease patients were: in liver cancer - acute hepatitis - liver cirrhosis - chronic hepatitis. A positive correlation (r = 0.417) was observed between serum ASL levels (86.9+/-26.5) and scores of histopathological inflammation grading (9.83+/-3.36). CONCLUSION: ASL is of higher sensitivity and specificity than those of ALT and AST for diagnosing liver diseases. ASL may be used as a useful marker in estimating hepatopathy.

Biotransformation of Dioscorea nipponica by Rat Intestinal Microflora and Cardioprotective Effects of Diosgenin.

Studying the biotransformation of natural products by intestinal microflora is an important approach to understanding how and why some medicines-particularly natural medicines-work. In many cases, the active components are generated by metabolic activation. This is critical for drug research and development. As a means to explore the therapeutic mechanism of Dioscorea nipponica (DN), a medicinal plant used to treat myocardial ischemia (MI), metabolites generated by intestinal microflora from DN were identified, and the cardioprotective efficacy of these metabolites was evaluated. Our results demonstrate that diosgenin is the main metabolite produced by rat intestinal microflora from DN. Further, our results show that diosgenin protects the myocardium against ischemic insult through increasing enzymatic and nonenzymatic antioxidant levels in vivo and by decreasing oxidative stress damage. These mechanisms explain the clinical efficacy of DN as an anti-MI drug.

Role of Cystatin C and glomerular filtration rate in diagnosis of kidney impairment in hepatic cirrhosis patients.

Hepatic cirrhosis is often accompanied by functional kidney impairment, which may be reversed if early treatment is promptly administered. This study aimed to investigate the role of Cystatin C and Cystatin C estimated glomerular filtration rate in the diagnosis of kidney impairment in patients with hepatic cirrhosis.Four hundred sixty five patients with hepatic cirrhosis were recruited. Serum creatinine and Cystatin C were determined, and their estimated glomerular filtration rates were calculated.The area under the receiver-operating characteristic curve (area under curve [AUC]) of Cystatin C and Cystatin C estimated glomerular filtration rate was significantly larger than that of serum creatinine and serum creatinine estimated glomerular filtration rate, respectively (P = .000). When the optimal cut-off value and upper reference limit were used, similar sensitivity, misdiagnosis rate, and diagnostic consistency were only observed in Cystatin C estimated glomerular filtration rate (P > .05).Cystatin C and Cystatin C estimated glomerular filtration rate are superior to serum creatinine and serum creatinine estimated glomerular filtration rate in diagnosis of secondary kidney impairment, and Cystatin C estimated glomerular filtration rate has a better performance as compared with Cystatin C. However, it is not a measured parameter, and thus the lab should determine its own optimal cut-off value.

Association between chromosomal aberration of exfoliated bladder cells in the urine and oxidative stress in patients with bladder transitional cell carcinoma.

The aim of the current study was to investigate the chromosomal aberrations of exfoliated bladder cells in the urine and blood oxidative stress in patients with bladder transitional cell carcinoma (BTCC). A total of 40 healthy controls and 246 patients with BTCC were recruited. Abnormal levels of CSP3, CSP7, CSP17 and GLPp16 were detected by fluorescence in situ hybridization (FISH) in exfoliated bladder cells in the urine of patients with BTCC. Serum total oxidant status (TOS), total antioxidant status (TAS) and oxidative stress index (OSI) were measured. Significant differences were observed in the abnormal CSP3, CSP7, CSP17, GLPp16 signals and FISH positive rate between patients with BTCC and healthy controls (P<0.001). Serum TOS, TAS and OSI were also significantly different between the two groups (P<0.001). The clinical stage of BTCC was not associated with abnormal CSP3, CSP7, CSP17, GLPp16 or FISH positive rate and oxidative stress (P>0.05). A Gamma rank correlation analysis revealed an association between the pathological grade of BTCC with abnormal CSP3, CSP7 and CSP17 as well as FISH positive rate (P<0.001). In addition, the clinical stage of BTCC was associated with serum TOS, TAS and OSI (P<0.001). Evaluation of the association between chromosomal aberrations and oxidative stress revealed that abnormal CSP3, CSP7 and CSP17 were positively associated with serum TOS and OSI (P<0.001), abnormal CSP7 and CSP17 were negatively associated with serum TAS (P<0.001), but abnormal GLPp16 was not associated with serum TOS, TAS or OSI (P>0.05). Therefore, the chromosomal aberrations of exfoliated bladder cells in the urine are associated with blood oxidative stress in patients with BTCC, and these factors may contribute to the occurrence and development of BTCC.

Analysis of the diagnostic efficiency of serum oxidative stress parameters in patients with breast cancer at various clinical stages.

BACKGROUND: Reactive oxygen species (ROS) are balanced through enzymatic mechanisms and exogenous antioxidants; imbalance results in oxidative stress (OxS). It is known that OxS plays an important role in the occurrence, development, and metastasis of breast cancer. The present study aimed to assess serum total oxidant status (TOS), total antioxidant status (TAS), and oxidant stress index (OSI) in patients at different clinical stages of breast cancer and to evaluate their diagnostic accuracy. METHODS: Serum TOS, TAS, and OSI were determined in 91 patients with breast cancer at different stages, 51 patients with benign breast tumors, and 35 healthy adults. RESULTS: Significant differences in serum TOS (F=104.384, p=0.000), TAS (F=18.247, p=0.000), and OSI (F=62.598, p=0.000) were observed among the 3 groups (benign breast tumor patients, breast cancer patients, and healthy women). Of the enrolled breast cancer patients, significant differences were also observed among different tumor stages, with TOS and OSI gradually increasing as the disease progressed, while TAS diminished. Receiver operating characteristic curve analysis revealed that the area under the ROC curve for OSI (AUCOSI) was significantly higher than AUCTAS (z=2.344, p=0.019) in distinguishing breast cancer from control groups (including disease control and the healthy control). The AUCOSI (z=4.700, p=0.001) or AUCTOS (z=4.700, p=0.001) was significantly higher than AUCTAS in distinguishing breast cancer from the healthy control. The AUCOSI (z=5.907, p=0.000) or AUCTOS (z=5.667, p=0.000) was significantly higher than AUCTAS in distinguishing benign breast tumors from the healthy control. CONCLUSION: Oxidative stress parameters might serve as important indexes for monitoring breast cancer occurrence and progression. The combined evaluation of TOS, TAS, and OSI could be more beneficial for clinical assessment.