[Effect of Erchen Decoction on liver mitochondrial function by inhibiting mTORC1/SREBP1/CAV1 pathway in mice with high-fat diet].

This study aims to investigate the effect of Erchen Decoction(ECD) on liver mitochondrial function in mice with a high-fat diet and its possible mechanism. A total of sixty C57BL/6J mice were randomly divided into a normal group, high-fat group, ECD group, mTORC1 activator(MHY) group, ECD+MHY group, and polyene phosphatidyl choline(PPC) group, with 10 rats in each group. The normal group was given a normal diet, and the other groups were fed a high-fat diet for 20 weeks. At the 17th week, the ECD group and ECD+MHY group were given ECD(8.7 g·kg~(-1)) daily, and the PPC group was given PPC(0.18 g·kg~(-1)) daily, while the remaining groups were given normal saline(0.01 mL·g~(-1)) daily for four weeks. In the 19th week, the MHY group and ECD+MHY group were injected intraperitoneally with MHY(5 mg·kg~(-1)) every other day for two weeks. During the experiment, the general conditions of the mice were observed. The contents of triglyceride(TG) and total cholesterol(TC) in serum were measured. Morphological changes in liver tissue were examined through HE and oil red O staining. The content of adenosine triphosphate(ATP) was determined using chemiluminescence, and mitochondrial membrane potential was assessed using a fluorescence probe(JC-1). Western blot was performed to detect the expression of rapamycin target protein complex 1(mTOR1), ribosomal protein S6 kinase B1(S6K), sterol regulatory element binding protein 1(SREBP1), and caveolin 1(CAV1). RESULTS:: revealed that compared with the normal group, the mice in the high-fat group exhibited significant increases in body weight and abdominal circumference(P<0.01). Additionally, there were significant increases in TG and TC levels(P<0.01). HE and oil red O staining showed that the boundaries of hepatic lobules were unclear; hepatocytes were enlarged, round, and irregularly arranged, with obvious lipid droplet deposition and inflammatory cell infiltration. The liver ATP content and mitochondrial membrane potential decreased significantly(P<0.01). The expression of p-mTOR, p-S6K, and n-SREBP1 increased significantly(P<0.01), while the expression of CAV1 decreased significantly(P<0.01). Compared with the high-fat group, the body weight and TG content of mice in the ECD group and PPC group decreased significantly(P<0.05). Improvements were observed in hepatocyte morphology, lipid deposition, and inflammatory cell infiltration. Furthermore, there were significant increases in ATP content and mitochondrial membrane potential(P<0.05 or P<0.01). The expression of p-mTOR, p-S6K, and n-SREBP1 decreased significantly in the ECD group(P<0.01), while CAV1 expression increased significantly(P<0.01). However, the indices mentioned above did not show improvement in the MHY group. When the ECD+MHY group was compared with the MHY group, there were significant reductions in body weight and TG contents(P<0.05). The morphological changes of hepatocytes, lipid deposition, and inflammatory cell infiltration were recovered. Moreover, there were significant increases in liver ATP content and mitochondrial membrane potential(P<0.05 or P<0.05). The expression of p-mTOR, p-S6K, and n-SREBP1 decreased significantly(P<0.01), while CAV1 expression increased significantly(P<0.01). In conclusion, ECD can improve mitochondrial function by regulating the mTORC1/SREBP1/CAV1 pathway. This mechanism may be involved in the resolution of phlegm syndrome and the regulation of lipid metabolism.

Application of exosome-derived noncoding RNAs in bone regeneration: Opportunities and challenges.

With advances in the fields of regenerative medicine, cell-free therapy has received increased attention. Exosomes have a variety of endogenous properties that provide stability for molecular transport across biological barriers to cells, as a form of cell-to-cell communication that regulates function and phenotype. In addition, exosomes are an important component of paracrine signaling in stem-cell-based therapy and can be used as a stand-alone therapy or as a drug delivery system. The remarkable potential of exosomes has paved the pathway for cell-free treatment in bone regeneration. Exosomes are enriched in distinct noncoding RNAs (ncRNAs), including microRNAs, long ncRNAs and circular RNAs. Different ncRNAs have multiple functions. Altered expression of ncRNA in exosomes is associated with the regenerative potential and development of various diseases, such as femoral head osteonecrosis, myocardial infarction, and cancer. Although there is increasing evidence that exosome-derived ncRNAs (exo-ncRNAs) have the potential for bone regeneration, the detailed mechanisms are not fully understood. Here, we review the biogenesis of exo-ncRNA and the effects of ncRNAs on angiogenesis and osteoblast- and osteoclast-related pathways in different diseases. However, there are still many unsolved problems and challenges in the clinical application of ncRNA; for instance, production, storage, targeted delivery and therapeutic potency assessment. Advancements in exo-ncRNA methods and design will promote the development of therapeutics, revolutionizing the present landscape.

Genome-wide analysis and expression profiling of Cation/H+ exchanger (CAX) family genes reveal likely functions in cadmium stress responses in poplar.

Cadmium, a toxic heavy metal, seriously affects human health and ecological security. The cation/H+ exchanger (CAX) family is a unique metal transporter that plays a crucial role in Cd acquisition, transfer, and remission in plants. Although there are many studies related to the genome-wide analysis of Populus trichocarpa, little research has been done on the CAX family genes, especially concerning Cd stress. In this study, genome-wide analysis of the Populus CAX family identified seven stress-related CAX genes. The evolutionary tree indicated that the CaCA family genes were grouped into four clusters. Moreover, seven pairs of genes were derived by segmental duplication in poplars. Cis-acting element analysis identified numerous stress-related elements in the promoters of diverse PtrCAXs. Furthermore, some PtrCAXs were up-regulated by drought, beetle, and mechanical damage, indicating their possible function in regulating stress response. Under cadmium stress, all CAX genes in the roots were up-regulated. Our findings suggest that plants may regulate their response to Cd stress through the TF-CAXs module. Comprehensively investigating the CAX family provides a scientific basis for the phytoremediation of heavy metal pollution by Populus.

Impact of the Activation Status of the Akt/mTOR Signalling Pathway on the Clinical Behaviour of Synovial Sarcoma: Retrospective Analysis of 174 Patients at a Single Institution.

PURPOSE: Phosphoinositide 3-kinase (PI3K) and the downstream Akt/mammalian target of rapamycin (mTOR) pathway are central to the control of cell proliferation and survival. Although abnormal activation of this pathway has been well established in a variety of tumours, limited studies are available on synovial sarcoma. The aim of this study was to investigate the expression of several key proteins of those pathways in synovial sarcomas and to correlate the expression of these proteins with clinicopathologic features and prognosis. PATIENTS AND METHODS: A total of 174 patients with synovial sarcomas were recruited for this study. The phosphorylation status of Akt, mTOR, and eukaryotic translation initiation factor 4E binding protein (4E-BP1) was measured by immunohistochemistry assays in formalin-fixed, paraffin-embedded samples. Correlations between the expression levels of these proteins and clinicopathologic features and prognosis were analysed. RESULTS: The positive rates of phosphorylated (p)Akt, pmTOR, p4E-BP1, and CyclinD1 were 62.7%, 55.6%, 47.1%, and 52.6%, respectively. The positive results of pmTOR, pAkt, and downstream p4E-BP1 were correlated with each other. The positive pAkt, pmTOR, p4E-BP1, and CyclinD1 results were more highly expressed in head and neck and visceral tumours, and positive p4E-BP1 results were correlated with larger size and larger areas of necrosis. In multivariate analysis of clinicopathologic factors, head and neck and visceral location, large tumour size, larger areas of necrosis and frequent mitosis were confirmed as risk factors for shorter overall survival. Positive pAkt, pmTOR and p4E-BP1 results were correlated significantly with shorter overall survival, and CyclinD1 was not in the univariate analysis. The positive pmTOR, pAkt, p4E-BP1, and CyclinD1 results were significantly poor prognostic factors for overall survival, and only positive p4E-BP1 results were significantly associated with shorter event-free survival in multivariate analysis. CONCLUSION: This study demonstrated the high expression of pAkt, pmTOR, and p4E-BP1 associated with aggressive clinical behaviour in synovial sarcomas and provided evidence for prognostic evaluation and targeted therapy.

Biological effects of ubiquitin-specific peptidase 22 on thyroid papillary cancer cells and its mechanism of action.

BACKGROUND: In this study, ubiquitin-specific peptidase 22 (USP22) was detected in both thyroid papillary cancer-1 (TPC-1) and normal thyroid epithelial cell lines (HT-ori3), and its biological function was analyzed. METHOD: Cell culture, resuscitation, and passage, Western blot, and real-time polymerase chain reaction were used. RESULTS: The expression of USP22 was found to be significantly higher in TPC-1 cancer cells than in normal cells. After silencing of the USP22 gene in TPC-1 cells, the levels of USP22 gene and protein expression were significantly decreased. After 6 h with silencing of the USP22 gene, the migration rate was lower and the cells had become smaller than in the control group (P<0.05). At 24 h, the number of invasive cells was significantly lower than in the control group (P<0.05). A cell viability test showed that the differences between the groups increased on days 4 and 5 (P<0.05). The number of colony-forming cells had also decreased significantly after 10 days (P<0.05) in the USP22-siRNA1 group. Compared with the control group, the protein levels of USP22, cyclin D2, and Bmi-1 were significantly decreased (P<0.05). The decrease of USP22 was positively correlated with the decrease of Bmi-1 and cyclin D2. After silencing of the USP22 gene in normal HT-ori3 cells, the USP22 gene and protein expressions decreased significantly (P<0.05). A cell viability test showed that the difference had increased (P<0.01), and the number of cloned cells had significantly decreased than that in negative group (P<0.01). CONCLUSIONS: In conclusion, the USP22 gene plays a key role in the growth, proliferation, invasion, and migration of papillary thyroid cancer cells. USP22 possibly exerts its effect in TPC through the Bmi-1 and cyclin D2 pathways. USP22 also plays a crucial role in the growth of normal thyroid cells.

Overexpression of Forkhead box Q1 correlates with poor prognosis in papillary thyroid carcinoma.

OBJECTIVE: Forkhead box Q1 (FOXQ1), a member of the forkhead transcription factor family, plays important parts in cell cycle, apoptosis, metabolism, immunology and tumour genesis. Its expression has been associated with poor clinical prognosis in various tumours. However, the clinical significance of FOXQ1 in papillary thyroid carcinoma (PTC) has not been fully studied. The purpose of this study was to investigate whether FOXQ1 is correlated with poor prognosis in PTC. DESIGN/METHODS: We performed a retrospective study of 136 PTCs. Immunohistochemistry (IHC) was used to examine the expression of FOXQ1 in 136 PTCs and 47 nodular goitre specimens. Rank-sum test, chi-square test, Kaplan-Meier survival analysis, univariate and multivariate Cox analyses were used to investigate the clinical and prognostic significance of FOXQ1 expression in PTC. RESULTS: The comparison of PTC specimens with nodular goitre with papillary hyperplasia specimens revealed an upregulation of FOXQ1 in PTC. Overexpression of FOXQ1 was observed in 63.24% of PTC and correlated with classic variant, tall variant, distant metastasis, AJCC stage and recurrence. FOXQ1-positive expression was associated with shorter disease-free survival: median disease-free survival of FOXQ1-positive patients was 23 months compared with 128 months for FOXQ1-negative patients (Log-rank χ2  = 12.31, P = 0.00045). Additional independent risk factors in this study were multifocality (recurrence-free survival [RFS]: hazard ratio [HR] = 2.391, P < 0.05), extrathyroidal extension (RFS: HR = 3.906, P < 0.05) and positive expression of FOXQ1 (RFS: HR = 6.385, P < 0.01). CONCLUSIONS: Our results indicated that FOXQ1 may be a useful additional biomarker to evaluate the progression of PTC and to predict likely relapse of disease.

New Nano-Film Single-Rivet Patent Ductus Arteriosus Occluders: A Prospective, Randomized and Double-blind Study.

Nitinol alloy occluders are widely used in the transcatheter intervention treatment of congenital heart diseases like patent ductus arteriosus (PDA). However, nitinol alloy contains high levels of nickel, which can lead to toxic effects in the immune and hematopoietic systems if released in sufficient quantities. A new type of single-rivet occluder coated with nano-film has been developed to limit the release of nickel. In total, 23 patients were recruited and randomly assigned to the experimental group (n=12) with the new nano-film single-rivet occluders or the control group (n=11) with the traditional occluders. One case in the control group was lost to follow-up. The remaining 22 cases were followed up at 24 h, 7 days, 1 month, 3 months, and 6 months after the procedure. There were no statistically significant differences in routine blood test, alanine aminotransferase, creatinine, and troponin between the experimental and control groups. Serum nickel concentration in both two groups increased at 24 h after the procedure, peaked at 1 month, and returned to preoperative levels at 6 months. Serum nickel levels in the experimental group were significantly lower than in the control group at 24 h, 7 days, 1 month, and 3 months after the procedure. These data suggested that the nano-film coating effectively prevented nickel release from the new occluders, and therefore has a preferable safety profile.

Efficacy of rituximab combined with CHOP for treating patients with diffuse large B-cell lymphoma.

BACKGROUND: This study aimed to evaluate the efficacy and safety of rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) for treating patients with diffuse large B-cell lymphoma (DLBCL). METHODS: A total of 144 patients with DLBCL were randomly divided into intervention group and control group, 72 patients in each group. The patients in the control group received cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy, while the participants in the intervention group received R-CHOP. The primary endpoint was relapse-free survival (RFS) and the secondary endpoints were overall survival rate (OSR) and adverse events (AEs). RESULTS: One hundred thirty-four patients completed the study. The intervention with R-CHOP did not show greater efficacy than CHOP in the estimated median follow-up time (intervention group 33 months vs control group 29 months, P = .15). In addition, no significant differences in the 5-year RFS (intervention group 81% vs placebo group 76%, P = .28) or the 5-year OSR (intervention group 93% vs placebo group 91%, P = .53) were found between the 2 groups. The AEs were also similar between the 2 groups. CONCLUSION: This study demonstrated that R-CHOP, when compared with CHOP alone, could not improve the RFS and OS of patients with DLBCL. Additionally, both groups had similar safety profiles.

Systematic evaluation of bevacizumab in recurrent ovarian cancer treatment.

PURPOSE: This study aimed to evaluate the efficacy and safety of bevacizumab in the treatment of recurrent ovarian cancer. METHODS: The Cochrane Library, MEDLINE, and EMBASE were searched. Data regarding the use of bevacizumab in recurrent ovarian cancer were collected from randomized controlled trials (RCTs). Data were evaluated with the Cochrane systematic method, and statistical analysis was performed with the RevMan 5.2 software. Two RCTs comprising a total of 845 patients were included. RESULTS: Bevacizumab combined with conventional chemotherapy prolonged the progression-free survival (PFS) (hazard ratio [HR] 0.48; 95% confidence interval [CI], 0.41-0.56), without significantly altering the overall survival (OS) (HR 1.03; 95% CI 0.79-1.33). Adverse events (NCI-CTCAE v.4.0) associated with bevacizumab were ≥ grade 3 hypertension (relative risk [RR] 2.30; 95% CI 1.39-3.83) and bleeding (RR 4.76; 95% CI 1.38-16.37). CONCLUSIONS: Bevacizumab prolonged the PFS of patients with recurrent ovarian cancer. Additional high-quality randomized controlled trials are needed to verify these results.