[Mechanism of tetramethylpyrazine combined with neural stem cells transplantation on cerebral ischemia-reperfusion rats].

This study aimed to investigate the intervention effect of tetramethylpyrazine(TMP) combined with transplantation of neural stem cells(NSCs) on middle cerebral artery occlusion(MCAO) rat model and to explore the mechanism of TMP combined with NSCs transplantation on ischemic stroke based on the regulation of stem cell biological behavior. MCAO rats were randomly divided into a model group, a TMP group, an NSCs transplantation group, and a TMP combined with NSCs transplantation group according to neurological function scores. A sham group was set up at the same time. The neurological function score was used to evaluate the improvement of neurological function in MCAO rats after TMP combined with NSCs transplantation. The proliferation, migration, and differentiation of NSCs were evaluated by BrdU, BrdU/DCX, BrdU/NeuN, and BrdU/GFAP immunofluorescence labeling. The protein expression of stromal cell-derived factor 1(SDF-1), C-X-C motif chemokine receptor 4(CXCR4), as well as oxidative stress pathway proteins nuclear factor erythroid 2-related factor 2(Nrf2), Kelch-like ECH-associated protein 1(KEAP1), heme oxygenase 1(HO-1), NAD(P)H quinone oxidoreductase 1(NQO1) was detected by Western blot to study the migration mechanism of TMP combined with NSCs. The results showed that TMP combined with NSCs transplantation significantly improved the neurological function score in MCAO rats. Immunofluorescence staining showed a significant increase in the number of BrdU~+, BrdU~+/DCX~+, BrdU~+/NeuN~+, and BrdU~+/GFAP~+ cells in the TMP, NSCs transplantation, and combined treatment groups, with the combined treatment group showing the most significant increase. Further Western blot analysis revealed significantly elevated expression of CXCR4 protein in the TMP, NSCs transplantation, and combined treatment groups, along with up-regulated protein expression of Nrf2, HO-1, and NQO1, and decreased KEAP1 protein expression. This study showed that both TMP and NSCs transplantation can promote the recovery of neurological function by promoting the proliferation, migration, and differentiation of NSCs, and the effect of TMP combined with NSCs transplantation is superior. The mechanism of action may be related to the activation of the Nrf2/HO-1/CXCR4 pathway.

Chlorogenic acid improves the development of porcine parthenogenetic embryos by regulating oxidative stress and ameliorating mitochondrial function.

Chlorogenic acid (CGA) is an effective phenolic antioxidant that can scavenge hydroxyl radicals and superoxide anions. Herein, the protective effects and mechanisms leading to CGA-induced porcine parthenogenetic activation (PA) in early-stage embryos were investigated. Our results showed that 50 µM CGA treatment during the in vitro culture (IVC) period significantly increased the cleavage and blastocyst formation rates and improved the blastocyst quality of porcine early-stage embryos derived from PAs. Then, genes related to zygotic genome activation (ZGA) were identified and investigated, revealing that CGA can promote ZGA in porcine PA early-stage embryos. Further analysis revealed that CGA treatment during the IVC period decreased the abundance of reactive oxygen species (ROS), increased the abundance of glutathione and enhanced the activity of catalase and superoxide dismutase in porcine PA early-stage embryos. Mitochondrial function analysis revealed that CGA increased mitochondrial membrane potential and ATP levels and upregulated the mitochondrial homeostasis-related gene NRF-1 in porcine PA early-stage embryos. In summary, our results suggest that CGA treatment during the IVC period helps porcine PA early-stage embryos by regulating oxidative stress and improving mitochondrial function.

Action Mechanism Underlying Improvement Effect of Fuzi Lizhong Decoction on Nonalcoholic Fatty Liver Disease: A Study Based on Network Pharmacology and Molecular Docking.

OBJECTIVE: This study aimed to decipher the bioactive compounds and potential mechanism of traditional Chinese medicine (TCM) formula Fuzi Lizhong Decoction (FLD) for nonalcoholic fatty liver disease (NAFLD) treatment via an integrative network pharmacology approach. METHODS: The candidate compounds of FLD and its relative targets were obtained from the TCMSP and PharmMapper web server, and the intersection genes for NAFLD were discerned using OMIM, GeneCards, and DisGeNET. Then, the PPI and component-target-pathway networks were constructed. Moreover, GO enrichment and KEGG pathway analysis were performed to investigate the potential signaling pathways associated with FLD's effect on NAFLD. Eventually, molecular docking simulation was carried out to validate the binding affinity between potential core components and key targets. RESULTS: A total of 143 candidate active compounds and 129 relative drug targets were obtained, in which 61 targets were overlapped with NAFLD. The PPI network analysis identified ALB, MAPK1, CASP3, MARK8, and AR as key targets, mainly focusing on cellular response to organic cyclic compound, steroid metabolic process, and response to steroid hormone in the biological processes. The KEGG pathway analysis demonstrated that 16 signaling pathways were closely correlated with FLD's effect on NALFD with cancer pathways, Th17 cell differentiation, and IL-17 signaling pathways as the most significant ones. In addition, the molecular docking analysis revealed that the core active compounds of FLD, such as 3'-methoxyglabridin, chrysanthemaxanthin, and Gancaonin H, had a high binding activity with such key targets as ALB, MAPK1, and CASP3. CONCLUSIONS: This study suggested that FLD exerted its effect on NAFLD via modulating multitargets with multicompounds through multipathways. It also demonstrated that the network pharmacology-based approach might provide insights for understanding the interrelationship between complex diseases and interventions of the TCM formula.

Antioxidant Activities of Quercetin and Its Complexes for Medicinal Application.

Quercetin is a bioactive compound that is widely used in botanical medicine and traditional Chinese medicine due to its potent antioxidant activity. In recent years, antioxidant activities of quercetin have been studied extensively, including its effects on glutathione (GSH), enzymatic activity, signal transduction pathways, and reactive oxygen species (ROS) caused by environmental and toxicological factors. Chemical studies on quercetin have mainly focused on the antioxidant activity of its metal ion complexes and complex ions. In this review, we highlight the recent advances in the antioxidant activities, chemical research, and medicinal application of quercetin.

Primary small cell neuroendocrine carcinoma of the Bartholin's gland: A case report.

Primary carcinoma of the Bartholin's gland (BG) is a rare malignancy. There are extremely rare cases of small cell neuroendocrine carcinoma (SCNC) of the BG reported in the English literature. A postmenopausal female presented with a 1-month history of increasing pain and swelling on the left vulva consistent with spontaneously bleeding. Pathology identified SCNC that arose in BG. The patient was treated with a radical wide local excision and bilateral inguinal lymph node dissection followed by six courses of chemotherapy. One month after primary treatment, without any pelvic recurrence or abnormal tumor markers indications, distant metastasis of the liver was diagnosed and VI hepatic lobectomy was performed. The patient maintained regular adjuvant chemotherapy every month under outpatient surveillance and has no local recurrence or distant metastasis.

Solid pseudopapillary tumor of the pancreas and concomitant urogenital malformations in a young woman.

Solid pseudopapillary tumor (SPT) of the pancreas is a rare pancreatic tumor with low malignant potential. It occurs characteristically more often in young women. SPT associated with extra- and pancreatic anomalies are occasionally reported. Here we report a case of pancreatic SPT with concomitant urogenital malformations including solitary kidney and uterus didelphys in a 25-year-old woman. The patient underwent central pancreatectomy, and SPT was confirmed with pathological results. Recurrence or metastasis was not found after 14 months of follow-up.

The role of CD44-hyaluronic acid interaction in exogenous mesenchymal stem cells homing to rat remnant kidney.

BACKGROUND/AIMS: The aim of our study was to reveal the role of CD44-Hyaluronic acid (HA) in the homing and improving renal function of systemically transplanted MSCs in chronic renal failure. METHODS: First, a remnant kidney model was established in rats and the expression of HA was determined using immunohistochemistry (IHC) and western blotting. Next, chemotaxis assay using flow cytometry, and cell migration assay of MSCs were performed in vitro. Then, MSCs were transplanted into rats, thus, sprague-Dawley (SD) rats were randomly divided into sham group, 5/6 nephrectomy (5/6 Nx) group, MSC group and MSC/Anti-CD44 group (n = 8 for all groups). Migration of MSCs to the kidney in these rats was assessed by using cell tracking experiments, and tissue damage was evaluated by morphological analysis using Masson's trichrome staining and periodic acid Schiff staining. RESULTS: HA was significantly observed in 5/6 Nx group, but not in sham group. Meanwhile, HA was discovered induced MSCs migration remarkably (p < 0.05) and anti-CD44 antibody inhibited the migration significantly (p < 0.05) in vitro. In vivo, the GFP-MSCs were observed in MSC group and the cells reduced in MSC/Anti-CD44 groups, especially, in the tubulointerstitium. CONCLUSION: Our findings reveal that CD44-HA has the potential to induce MSCs homing to injured tissue, while its effect on the ability of MSCs, improving tissue function, is not significant.

Epigenetic inactivation of BRCA1 through promoter hypermethylation in ovarian cancer progression.

AIM: The BRCA1 promoter is hypermethylated in ovarian cancer patients. We postulated that this hypermethylation might be involved in ovarian cancer progression. METHODS: To confirm our hypothesis, tissue and serum samples were collected from ovarian carcinoma patients and categorized according to tumor stage. Healthy or benign ovarian disease tissue samples and corresponding serum samples were used as controls. Breast and ovarian cancer susceptibility gene 1 (BRCA1) promoter methylation levels were detected by real-time polymerase chain reaction (PCR). Real-time PCR was also used to evaluate BRCA1 gene expression, and Western blot was performed to assay the expression of BRCA1 protein. RESULTS: BRCA1 showed hypomethylation in 30 normal ovarian and 30 benign ovarian tumors, but showed hypermethylation or methylation in ovarian cancer patients. There was also a significant difference in the BRCA1 promoter methylation levels between different ovarian cancer stages. Compared to stage I and the control groups, there were higher BRCA1 promoter methylation frequencies in stage II and III ovarian cancers. BRCA1 methylation correlated with the loss of BRCA1 expression. BRCA1 promoter in stage I tumors showed hypomethylated. CONCLUSION: Promoter hypermethylation may act as a biomarker for sporadic ovarian cancer progression, but is unlikely to be helpful in the early diagnosis of ovarian cancer.

Aberrant methylation of breast and ovarian cancer susceptibility gene 1 in chemosensitive human ovarian cancer cells does not involve the phosphatidylinositol 3'-kinase-Akt pathway.

Methylation is an important silencing mechanism of breast and ovarian cancer susceptibility gene 1 (BRCA1) expression in sporadic ovarian cancer. However, the role of BRCA1 methylation in chemotherapy in sporadic ovarian cancer and the related pathways have not been understood completely. This study has determined the roles of BRCA1 hypermethylation in chemotherapy of sporadic ovarian cancer and its related signaling pathways. We used bisulfite sequencing, real-time polymerase chain reaction, and western blotting to check the methylation state and expression levels of BRCA1 of the following cell lines: platinum-sensitive human ovarian cancer cell line COC1, platinum-resistant cell line COC1/DDP, SKOV-3, and 5-Aza-dC treated COC1. The cisplatin sensitivity of ovarian cancer cells was examined by MTS (methyl-thiazol tetrazolium) assay. Tumorigenicity in vivo and DDP-based chemosensitivity were compared among the above cells. Phosphatidylinositol 3'-kinase (PI3K)-Akt pathway activation in ovarian cancer cells was studied by western blotting. The frequency of BRCA1 methylation in the COC1 cell line was higher than in COC1/DDP and SKOV-3 cell lines, whereas the mRNA and protein expression of BRCA1 were lower than in the COC1/DDP and SKOV-3 cell lines. DNA demethylation decreased the chemosensitivity of COC1 cells and partially increased the expression levels of BRCA1. The activation of the PI3K-Akt pathway was low in ovarian cancer cells. Our results indicate that hypermethylation of BRCA1 might play an important role in the chemosensitivity of ovarian cancer, and that the PI3K-Akt pathway is not involved in this response.

The role of microRNAs in ovarian cancer initiation and progression.

Epithelial ovarian cancer (EOC) has the highest mortality rate of all gynaecological cancers. One of the greatest impediments to improving outcome is an incomplete understanding of the molecular underpinnings of EOC pathogenesis and progression. Recent studies suggest that microRNAs (miRNAs) are involved in ovarian tumorigenesis and cancer development. Several miRNA profiling studies have identified some consensus aberrantly expressed miRNAs in EOC tissues, and these EOC-related miRNAs may play critical roles in the pathogenesis and progression of EOC. Moreover, some of the miRNAs may have diagnostic or prognostic significance. In this review, recent progress to reveal the role of miRNAs in EOC will be addressed, and a model for miRNA functions in ovarian cancer initiation and progression will be proposed.