Association between oxidative balance score and kidney stone in United States adults: analysis from NHANES 2007-2018.

Purpose: To investigate the relationship between the Oxidative Balance Score (OBS) and kidney stone risk using NHANES 2007-2018 data, and to explore potential mechanisms and population-specific effects. Materials and methods: Data from the NHANES 2007-2018 were analyzed. OBS was calculated based on 16 dietary components and 4 lifestyle components. Multivariate logistic regression was employed to investigate the relationship between OBS and kidney stone. Further stratified analyses were conducted to examine the associations across different subgroups. Results: A total of 19,799 participants were included in the study. There was a consistent inverse association between OBS and the risk of kidney stones (OR = 0.97; 95% CI: 0.96-0.99). After dividing the participants into quartiles based on OBS, compared to the lowest quartile of OBS, the risk of kidney stones in the highest quartile of OBS was reduced by 33% (95% CI 0.50-0.89; p = 0.002). This association was consistent across both dietary and lifestyle OBS scores. The protective effect of OBS was notably pronounced among Non-Hispanic white and Other race groups, and among individuals with a higher level of education. However, the association was not significant among individuals with diabetes. Conclusion: A higher OBS, indicating a balance skewed towards antioxidants, is associated with a reduced risk of kidney stones, especially among specific population subgroups. These findings underscore the potential role of oxidative balance in kidney stone pathogenesis and highlight the importance of considering individual and population-specific factors in future research and preventive strategies.

A potential biological signature of 7-methylguanosine-related lncRNA to predict the immunotherapy effects in bladder cancer.

Background: Bladder urothelial carcinoma (BLCA) is the second prevalent genitourinary carcinoma globally. N7-methylguanosine (m7G) is important for tumorigenesis and progression. This study aimed to build a predictive model for m7G-related long non-coding RNAs (lncRNAs), elucidate their role in the tumor immune microenvironment (TIME), and predict immunotherapy response in BLCA. Methods: We first used univariate Cox regression and coexpression analyses to identify m7G-related lncRNAs. Next, the prognostic model was built by utilizing LASSO regression analysis. Then, the prognostic significance of the model was examined utilizing Kaplan-Meier survival analysis, receiver operating characteristic (ROC) curves, nomogram, and univariate, multivariate Cox regression. We also analyzed Gene set enrichment analyses (GSEA), immune analysis and principal component analysis (PCA) in risk groups. To further predict immunotherapy effectiveness, we evaluated the predictive ability for immunotherapy in 2 risk groups and clusters using tumor immune dysfunction and exclusion (TIDE) score and Immunophenoscore (IPS). Results: Seven lncRNAs related to m7G were used to create a model. The calibration plots for the model suggested a strong fit with the prediction of overall survival (OS). The area under the curve (AUC) for first, second, and third years was respectively, 0.722, 0.711, and 0.686. In addition, the risk score had strong correlation with TIME features and genes linked to immune checkpoint blockade (ICB). TIDE scores were dramatically different between two risk groups (p < 0.05), and IPS scores were markedly different between two clusters (p < 0.05). Conclusion: Our research constructed a novel m7G-related lncRNAs that could be used to predict patient outcomes and the effectiveness of immunotherapy in BLCA. Immunotherapy may be more effective for the low-risk group and cluster 2.

Repetitive transcranial magnetic stimulation promotes neurological functional recovery in rats with traumatic brain injury by upregulating synaptic plasticity-related proteins.

Studies have shown that repetitive transcranial magnetic stimulation (rTMS) can enhance synaptic plasticity and improve neurological dysfunction. However, the mechanism through which rTMS can improve moderate traumatic brain injury remains poorly understood. In this study, we established rat models of moderate traumatic brain injury using Feeney's weight-dropping method and treated them using rTMS. To help determine the mechanism of action, we measured levels of several important brain activity-related proteins and their mRNA. On the injured side of the brain, we found that rTMS increased the protein levels and mRNA expression of brain-derived neurotrophic factor, tropomyosin receptor kinase B, N-methyl-D-aspartic acid receptor 1, and phosphorylated cAMP response element binding protein, which are closely associated with the occurrence of long-term potentiation. rTMS also partially reversed the loss of synaptophysin after injury and promoted the remodeling of synaptic ultrastructure. These findings suggest that upregulation of synaptic plasticity-related protein expression is the mechanism through which rTMS promotes neurological function recovery after moderate traumatic brain injury.

A score of DNA damage repair pathway with the predictive ability for chemotherapy and immunotherapy is strongly associated with immune signaling pathway in pan-cancer.

DNA damage repair (DDR) is critical in maintaining normal cellular function and genome integrity and is associated with cancer risk, progression, and therapeutic response. However, there is still a lack of a thorough understanding of the effects of DDR genes' expression level in cancer progression and therapeutic resistance. Therefore, we defined a tumor-related DDR score (TR-DDR score), utilizing the expression levels of 20 genes, to quantify the tumor signature of DNA damage repair pathways in tumors and explore the possible function and mechanism for the score among different cancers. The TR-DDR score has remarkably predictive power for tumor tissues. It is a more accurate indicator for the response of chemotherapy or immunotherapy combined with the tumor-infiltrating lymphocyte (TIL) and G2M checkpoint score than the pre-existing predictors (CD8 or PD-L1). This study points out that the TR-DDR score generally has positive correlations with patients of advanced-stage, genome-instability, and cell proliferation signature, while negative correlations with inflammatory response, apoptosis, and p53 pathway signature. In the context of tumor immune response, the TR-DDR score strongly positively correlates with the number of T cells (CD4+ activated memory cells, CD8+ cells, T regs, Tfh) and macrophages M1 polarization. In addition, by difference analysis and correlation analysis, COL2A1, MAGEA4, FCRL4, and ZIC1 are screened out as the potential modulating factors for the TR-DDR score. In summary, we light on a new biomarker for DNA damage repair pathways and explore its possible mechanism to guide therapeutic strategies and drug response prediction.

Ononin induces cell apoptosis and reduces inflammation in rheumatoid arthritis fibroblast-like synoviocytes by alleviating MAPK and NF-κB signaling pathways.

As a kind of chronic inflammatory diseases, Rheumatoid arthritis (RA) has a low cure rate and easy recurrence. It has widely reported that abnormal activation of mitogen-activated protein kinase (MAPK) and nuclear factor kappa-B (NF-κB) signaling pathways are associated with the development of RA inflammation. Blocking the inflammatory signaling pathways of rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) can delay the development of RA. Ononin is a natural isoflavone glycoside and plays a key role in modulating inflammation related signaling pathways. However, whether Ononin exerts anti-inflammatory effects on RA inflammation remains unknown. In this study, we evaluated the therapeutic effect of Ononin on RA by establishing a tumor necrosis factor α (TNF-α)-induced RA-FLS cell model. Our data confirmed that Ononin could alleviate TNF-α-induced RA-FLS and MH7A cells viability, increase cell apoptosis, decrease the production of pro-inflammatory cytokines like interleukin-1ß (IL-1ß) and interleukin 6 (IL-6), and further inhibit the abnormal activation of NF-κB and MAPK pathways. Our results suggested that Ononin could be a potential therapeutic agent for RA.

SPOP promotes ubiquitination and degradation of LATS1 to enhance kidney cancer progression.

BACKGROUND: Emerging evidence has demonstrated that SPOP functions as an oncoprotein in kidney cancer to promote tumorigenesis by ubiquitination-mediated degradation of multiple regulators of cellular proliferation and apoptosis. However, the detailed molecular mechanism underlying the oncogenic role of SPOP in kidney tumorigenesis remains elusive. METHODS: Multiple approaches such as Co-IP, Transfection, RT-PCR, Western blotting, and animal studies were utilized to explore the role of SPOP in kidney cancer. FINDINGS: Here we identified LATS1, a critical component of the Hippo tumour suppressor pathway, as a novel ubiquitin substrate of SPOP. We found that LATS1 interacted with Cullin3, and depletion of Cullin 3 upregulated the abundance of LATS1 largely via prolonging LATS1 protein half-life. Mechanistically, SPOP specifically interacted with LATS1, and promoted the poly-ubiquitination and subsequent degradation of LATS1 in a degron-dependent manner. As such, over-expression of SPOP promoted cell proliferation partly through regulating cell cycle distribution in kidney cancer cells. Furthermore, SPOP also promoted kidney cancer cell invasion via degrading LATS1. INTERPRETATION: Our study provides evidence for a novel mechanism of SPOP in kidney cancer progression in part through promoting degradation of the LATS1 tumour suppressor.

Identification of potential crucial genes associated with the pathogenesis and prognosis of prostate cancer.

Aim: Prostate cancer (PCa) is the sixth leading cause of cancer-related deaths in men throughout the world. This study aimed to investigate genes associated with the pathogenesis and prognosis of PCa. Materials & methods: Data of PCa cases were obtained from public datasets and were analyzed using an integrated bioinformatics strategy. Results: A total of 969 differential expression genes were identified. Moreover, GSE16560 and The Cancer Genome Atlas (TCGA) data showed a prognostic prompt function of the nine-gene signature, as well as in PCa with Gleason 7. Finally, majority of the nine hub genes were associated with drug sensitivity, mutational landscape, immune infiltrates and clinical characteristics of PCa. Conclusion: The nine-gene signature was correlated with drug sensitivity, mutational landscape, immune infiltrates, clinical characteristics and survival from PCa.

hPTH(3-34)(29-34) selectively activated PKC and mimicked osteoanabolic effects of hPTH(1-34).

Teriparatide (hPTH(1-34)) exhibits both osteoanabolic and osteocatabolic effects. We generated a novel PTH analog by duplicating the PTH(29-34) domain to hPTH(3-34) (named MY-1), which was identified to activate PKC but not PLC and cAMP/PKA signaling. It increased osteo-differentiation but did not affect osteoclastogenesis and RANKL expression in primary osteoblasts or bone marrow cells. MY-1 and hPTH(1-34) increased the synthesis and decreased the degradation οf ß-catenin protein in osteoblasts, while PKC inhibitor blunted such effects. In vivo results indicated that intermittent MY-1 and hPTH(1-34) prevented bone loss in ovariectomized mice, and that MY-1 infusion increased bone volume in normal mice. Histological analysis observed more osteoclasts surrounding the cancellous bone surface in hPTH(1-34), but not MY-1 treated mice. We conclude that MY-1 mimicked the osteoanabolic but not the osteocatabolic effects of hPTH(1-34), which is related to PKC and ß-catenin signaling. Such anabolic-only analog provides a new strategy to study PTH's versatile functions and design new medicines to treat osteoporosis and bone defects.

USP7 stabilizes EZH2 and enhances cancer malignant progression.

EZH2, a histone methylase, plays a critical role in the tumor progression via regulation of progenitor genes. However, the detailed molecular mechanism of EZH2 in cancer malignant progression remains unknown. Therefore, we aimed to investigate how EZH2 is regulated in human cancer. We used numerous approaches, including Co-immunoprecipitation (Co-IP), Transfection, RT-PCR, Western blotting, Transwell assays, and animal studies, to determine the deubiquitination mechanism of EZH2 in cancer cells. We demonstrated that USP7 regulated EZH2 in human cancer cells and in vivo in mouse models. Overexpression of USP7 promoted the expression of EZH2 protein, but overexpression of a USP7 mutant did not change the EZH2 level. Consistently, knockdown of USP7 resulted in a striking decrease in EZH2 protein levels in human cancer cells. Functionally, USP7 overexpression promoted cell growth and invasion via deubiquitination of EZH2. Consistently, downregulation of USP7 inhibited cell migration and invasion in cancer. More importantly, knockdown of USP7 inhibited tumor growth, while USP7 overexpression exhibited opposed effect in mice. Our results indicate that USP7 regulates EZH2 via its deubiquitination and stabilization. The USP7/EZH2 axis could present a new promising therapeutic target for cancer patients.

[Prolonged continuous infusion of teriparatide promotes bone metabolism in normal but not in castrated mice].

OBJECTIVE: To investigate the effects of continuous pumping of teriparatide (TPTD) on bone metabolism in ovariectomized and normal mice and provide experimental evidence for the selection of animal models for studying the effects of TPTD and its related peptides on osteoclasts. METHODS: Twenty-four female C57BL mice (6-weeks old) were subjected to ovariectomy (OVX) or sham operation followed 7 days later by continuous pumping of TPTD or the solvent vehicle (VEH) via a micropump (SHAM-VEH, SHAM-TPTD, OVX-VEH, and OVX-TPTD groups; n=6). Two weeks later, the tibial and femoral bones were harvested for micro-CT scanning to measure the parameters of the tibia and the femoral cortical bone. Histopathological examinations of the tibial tissue were conducted using HE staining and TRAP staining and the number of osteoclasts and the growth plate thickness were determined. The serum Ca2 + levels of the mice were measured. The primary osteoblasts from the cranial bone were treated with estradiol (E2) and TPTD for 48 h, and the expressions of ß-catenin and RANKL protein in the cells were analyzed. RESULTS: The trabecular bone mass of OVX mice was significantly lower than that of sham-operated mice (P < 0.05). Continuous TPTD pumping significantly reduced tibial cancellous bone mass and femoral cortical bone area in the sham-operated mice, while in the castrated mice, TPTD pumping increased the cancellous bone mass without changing the cortical bone area. TRAP staining showed that cancellous osteoblasts in the tibia increased significantly in the castrated mice as compared with the sham-operated mice, and TPTD pumping significantly increased the number of cancellous osteoblasts in the sham-operated mice (P < 0.05). In the primary cultured osteoblasts, treatment with both E2 and TPTD obviously lowered the expression of ß-catenin and increased the expression of RANKL as compared with TPTD treatment alone. CONCLUSIONS: Continuous pumping of TPTD promotes bone resorption in normal mice but does not produce obvious bone resorption effect in the ovariectomized mice, suggesting that castrated mice are not suitable models for studying the effect of TPTD and the related peptides on the osteoclasts.

An Adrenal Hepatoid Adenocarcinoma with Left Renal Vein Thrombosis Extending into the Inferior Vena Cava.

Hepatoid adenocarcinoma (HAC) is an uncommon tumor with morphological resemblance to hepatocellular car-cinoma. HAC of the adrenal glands is extremely rare. Here, we report the case of an 83-year-old man with adrenal HAC who presented with a greatly increased preoperative serum alpha-fetoprotein level (> 24,200 ng/mL). The findings of magnetic resonance imaging and contrast-enhanced abdominal computed tomography revealed a large mass occupying the left adrenal gland region as well as thrombosis of the renal vein extending into the inferior vena cava. Subsequently, the adrenal HAC was treated by surgical resection and targeted sorafenib therapy. How-ever, the patient died 9 months later because of systemic metastasis of the tumor. In conclusion, adrenal HAC with inferior vena cava tumor thrombosis is extremely rare and challenging to diagnose and treat. Pathological and immunohistochemical examination are helpful for diagnosis and surgical excision is the main strategy for treating the tumor.

Loss of FOXP3 and TSC1 Accelerates Prostate Cancer Progression through Synergistic Transcriptional and Posttranslational Regulation of c-MYC.

Although c-MYC and mTOR are frequently activated proteins in prostate cancer, any interaction between the two is largely untested. Here, we characterize the functional cross-talk between FOXP3-c-MYC and TSC1-mTOR signaling during tumor progression. Deletion of Tsc1 in mouse embryonic fibroblasts (MEF) decreased phosphorylation of c-MYC at threonine 58 (pT58) and increased phosphorylation at serine 62 (pS62), an observation validated in prostate cancer cells. Conversely, inhibition of mTOR increased pT58 but decreased pS62. Loss of both FOXP3 and TSC1 in prostate cancer cells synergistically enhanced c-MYC expression via regulation of c-Myc transcription and protein phosphorylation. This crosstalk between FOXP3 and TSC1 appeared to be mediated by both the mTOR-4EBP1-c-MYC and FOXP3-c-MYC pathways. In mice, Tsc1 and Foxp3 double deletions in the prostate led to prostate carcinomas at an early age; this did not occur in these mice with an added c-Myc deletion. In addition, we observed synergistic antitumor effects of cotreating mice with inhibitors of mTOR and c-MYC in prostate cancer cells and in Foxp3 and Tsc1 double-mutant mice. In human prostate cancer, loss of nuclear FOXP3 is often accompanied by low expression of TSC1. Because loss of FOXP3 transcriptionally induces c-Myc expression and loss of TSC1 activates mTOR signaling, these data suggest cross-talk between FOXP3-c-MYC and TSC1-mTOR signaling that converges on c-MYC to regulate tumor progression. Coadministration of c-MYC and mTOR inhibitors may overcome the resistance to mTOR inhibition commonly observed in prostate cancer cells. SIGNIFICANCE: These results establish the principle of a synergistic action of TSC1 and FOXP3 during prostate cancer progression and provide new therapeutic targets for patients who have prostate cancer with two signaling defects.Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/79/7/1413/F1.large.jpg.

Rottlerin inhibits cell growth and invasion via down-regulation of EZH2 in prostate cancer.

Rottlerin as a natural agent, which is isolated from Mallotus philippinensis, has been identified to play a critical role in tumor inhibition. However, the molecular mechanism of rottlerin-mediated anti-tumor activity is still ambiguous. It has been reported that EZH2 exhibits oncogenic functions in a variety of human cancers. Therefore, inhibition of EZH2 could be a promising strategy for the treatment of human cancers. In this study, we aim to explore whether rottlerin could inhibit tumorigenesis via suppression of EZH2 in prostate cancer cells. Multiple approaches such as FACS, Transwell invasion assay, RT-PCR, Western blotting, and transfection were performed to determine our aim. We found that rottlerin treatment led to inhibition of cell growth, migration and invasion, but induction of apoptosis in prostate cancer cells. Importantly, we defined that rottlerin decreased the expression of EZH2 and H3K27me3 in prostate cancer cells. Moreover, overexpression of EZH2 abrogated the rottlerin-induced inhibition of cell growth, migration, and invasion in prostate cancer cells. Consistently, down-regulation of EZH2 enhanced rottlerin-triggered anti-tumor function. Collectively, our work demonstrated that rottlerin exerted its tumor suppressive function via inhibition of EZH2 expression in prostate cancer cells. Our findings indicated that rottlerin might be a potential therapeutic compound for treating patients with prostate cancer.

Expression of Androgen Receptor Variant 7 (AR-V7) in Circulated Tumor Cells and Correlation with Drug Resistance of Prostate Cancer Cells.

BACKGROUND Prostate cancer is a common type of malignant tumor invading the male reproductive-urinary system, which has increasing incidence worldwide. Androgen receptor variant 7 (AR-V7) participates in regulating prostate cancer cell proliferation and gene expression. This study aimed to investigate the expression of AR-V7 in circulated tumor cells (CTCs) in patients with prostate cancer and to assess its correlation with drug sensitivity against enzalutamide or abiraterone. MATERIAL AND METHODS Blood samples of prostate cancer patients were collected for separating CTCs, in which mRNA expression level of full-length AR and AR-V7 was measured to analyze their correlation with enzalutamide or abiraterone resistance. Progression-free survival (PFS) of patients with different AR-V7 expression levels was compared. AR-V7 was overexpressed in transfected prostate cancer cells, and its effects on proliferation were analyzed by clonal formation assay. RESULTS qRT-PCR showed AR-V7 overexpression in a total of 13 patients; 76.92% of these patients developed drug resistance, the distal metastasis of which was significantly higher than that in the group with AR-V7 downregulation, with lower PFS (p<0.01). In cultured prostate cancer cells, AR-V7 upregulation resulted in a significantly higher clonal formation rate than in the control group with enzalutamide-containing medium (p<0.05). CONCLUSIONS In prostate cancer cells, AR-V7 expression is correlated with drug resistance, as AR-V7 upregulation leads to enhanced proliferation potency of cancer cells, indicating unfavorable prognosis of patients.

Phospholipase C signaling activated by parathyroid hormone mediates the rapid osteoclastogenesis in the fracture healing of orchiectomized mice.

BACKGROUND: The age-related osteoporosis is an increasing risk severely threatening the live quality of aged people. Human parathyroid hormone (hPTH) is applied to the therapy of osteoporosis successfully, however, the mechanism, especially the signaling pathway activated in the healing fracture by PTH is still unknown. METHODS: The once daily injections of hPTH(1-34) and GR (1-34) (the PLC deficient analog) into the orchiectomized male mice with bone fracture, were started at the second day after fracture and lasted for 4 weeks. To explore the role of phospholipase C signaling in the androgen-deficient fracture healing, the fracture healing were evaluated via radiography, micro-CT, biomechanics testing, serum biochemistry, bone marrow cell culture and gene expression quantification. RESULTS: After two weeks of fracture, both peptides significantly increased bone mineral density (BMD), bone mass content (BMC) and bone volume (BV/TV) in the healing area. However, compared to hPTH(1-34), GR(1-34) induced more woven bones, the higher BMC and BMD, as well as the less serum TRAP and osteoclasts. After four weeks of treatment, the effects of hPTH(1-34) on fracture healing showed no difference to those of GR(1-34). Consistently, GR(1-34) induced the similar osteogenesis but less osteoclastogenesis under the ex vivo condition immediately after administration compared to hPTH(1-34), which was verified by the weaker activation of RANKL, NFATC1, TRAP and Cathepsin K in GR(1-34) treatment. CONCLUSION: These results indicated that the PLC signaling activated by the intermittent injection of hPTH(1-34) leads to the bone resorption by rapidly activating the osteoclastogenesis in the fracture healing zone.

Percutaneous nephrostomy via the central venous catheter in combination with selective ureteroscopic lithotripsy for the treatment of ureteral stones in the middle-upper segment.

OBJECTIVE: To explore the therapeutic outcome and significance of preoperative percutaneous nephrolithotomy (PCNL) via the central venous catheter in combination with two-step hard ureteroscopic lithotripsy for the treatment of ureteral stones in the middle-upper segment. METHODS: The success rate and the occurrence of severe infection and perirenal hematoma were analyzed retrospectively in 37 patients who received preoperative PCNL via the central venous catheter in combination with two-step hard ureteroscopic lithotripsy for the treatment of ureteral stones in the middle-upper segment in our hospital between July 2012 and November 2014. RESULTS: The operation duration was 12-38 min with a mean of 18.5 min. The procedure was performed successfully in all patients without the postoperative occurrence of perirenal hematoma in any patient. No severe infection occurred in any patient according to the Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis (2012). CONCLUSION: Preoperative PCNL via the central venous catheter can significantly improve the success rate of ureteroscopic lithotripsy for the treatment of ureteral stones in the middle-upper segment, and reduce postoperative occurrences of severe infection and perirenal hematoma.

Parathyroid Hormone Activates Phospholipase C (PLC)-Independent Protein Kinase C Signaling Pathway via Protein Kinase A (PKA)-Dependent Mechanism: A New Defined Signaling Route Would Induce Alternative Consideration to Previous Conceptions.

BACKGROUND Parathyroid hormone (PTH) is an effective anti-osteoporosis agent, after binding to its receptor PTHR1, several signaling pathways, including cAMP/protein kinase A (PKA) and phospholipase C (PLC)/protein kinase C (PKC), are initiated through G proteins; with the cAMP/PKA pathway as the major pathway. Earlier studies have reported that PTHR1 might also activate PKC via a PLC-independent mechanism, but this pathway remains unclear. MATERIAL AND METHODS In HEK293 cells, cAMP accumulation was measured with ELISA and PKC was measured with fluorescence resonance energy transfer (FRET) analysis using CKAR plasmid. In MC3T3-E1 cells, real-time PCR was performed to examine gene expressions. Then assays for cell apoptosis, cell differentiation, alkaline phosphatase activity, and mineralization were performed. RESULTS The FRET analysis found that PTH(1-34), [G1,R19]PTH(1-34) (GR(1-34), and [G1,R19]PTH(1-28) (GR(1-28) were all activated by PKC. The PKC activation ability of GR(1-28) was blocked by cAMP inhibitor (Rp-cAMP) and rescued with the addition of active PKA-α and PKA-ß. The PKC activation ability of GR(1-34) was partially inhibited by Rp-cAMP. In MC3T3-E1 cells, gene expressions of ALP, CITED1, NR4a2, and OSX that was regulated by GR(1-28) were significantly changed by the pan-PKC inhibitor Go6983. After pretreatment with Rp-cAMP, the gene expressions of ALP, CITED1, and OPG were differentially regulated by GR(1-28) or GR(1-34), and the difference was blunted by Go6983. PTH(1-34), GR(1-28), and GR(1-34) significantly decreased early apoptosis and augmented osteoblastic differentiation in accordance with the activities of PKA and PKC. CONCLUSIONS PLC-independent PKC activation induced by PTH could be divided into two potential mechanisms: one was PKA-dependent and associated with PTH(1-28); the other was PKA-independent and associated with PTH(29-34). We also found that PTH could activate PLC-independent PKC via PKA-dependent mechanisms.

[Parathyroid hormone inhibits the apoptosis of osteoblast MC-3T3E1 cells through a non-PLC-dependent protein kinase C pathway].

OBJECTIVE: To investigate the effect of the non-PLC-dependent protein kinase C (PKC) pathway of parathyroid hormone (PTH) on the apoptosis and proliferation of osteoblast MC-3T3E1 cells. METHODS: MC-3T3E1 cells were seeded in 96-well plates at the density of 1.5×10(4) cells/mL and incubated for 3 day. The cells were then exposed to 100 nmol/L of [Gly(1), Arg(19)]hPTH(1-28), 100 nmol/L of [Gly(1), Arg(19)]hPTH(1-34), 100 nmol/L of [Gly(1), Arg(19)]hPTH(1-34)+1 µmol/L Go6983, 1 µmol/L Go6983, or deionized water (control) for 1, 24 or 48 h. After the treatments, cell counting kit-8 (CCK-8) and Caspase-Glo® 3/7 Assay (Caspase-3) were used to examine the proliferation and apoptosis of MC3T3-E1 cells. RESULTS: CCK-8 results showed that hPTH(1-34) increased the number of MC3T3-E1 cells compared with hPTH(1-34)+Go6983 at 1 h and 24 h, but this difference was not statistically different. At 48 h, treatment with hPTH(1-34), as compared with hPTH(1-28), significantly increased the number of MC3T3-E1 cells (P<0.05), and this effect was blocked by the PKC inhibitor Go6983 (P<0.05). hPTH(1-34) did not result in significant inhibition of MC3T3-E1 cell apoptosis at 1 h and 24 h as compared with hPTH(1-34)+Go6983, but significantly inhibited the cell apoptosis as compared with hPTH(1-28) (P<0.05); this inhibitory effect was blocked by Go6983 (P<0.05). CONCLUSION: s A relatively long time (for 48 h) of exposure to PTH can inhibit apoptosis and promote the proliferation of MC3T3-E1cells through a non-PLC-dependent PKC pathway.

[Transabdominal ultrasound measurement of intravesical prostatic protrusion helps diagnosis of benign prostatic obstruction].

OBJECTIVE: To evaluate the measurement of intravesical prostatic protrusion (IPP) by transabdominal ultrasonography (TAUS) in the diagnosis of benign prostatic obstruction (BPO). METHODS: We studied the clinical data of 109 BPH patients referred for lower urinary tract symptoms (LUTS) from April 2005 to December 2006. IPP was measured by TAUS, urodynamic parameters such as Qmax and PdetQmax obtained by urodynamic studies and AG values calculated. The patients were divided into an obstruction and a non-obstruction group according to their AG values. RESULTS: IPP was found statistically different between the obstruction and non-obstruction groups (P<0.001) and positively correlated with the AG value (r=0.729, P=0.001). With the cutoff at IPP > or = 10 mm for the diagnosis of BPO, the sensitivity, specificity and accuracy of the diagnosis were 89.9%, 97.5% and 92.7%, respectively. CONCLUSION: The measurement of IPP by TAUS offers a valuable help for the diagnosis of BPO.