Animals ; Disease Progression ; Kidney Diseases ; physiopathology ; Kidney Glomerulus ; drug effects ; pathology ; Rats ; Renal Agents ; pharmacology ; Renin-Angiotensin System ; drug effects ; Sclerosis

OBJECTIVETo investigate the effect of 6-gingerol, the main active component of ginger, on hair shaft elongation in vitro and hair growth in vivo.

METHODSFirstly, Hair follicles were co-cultured with 3 different concentration of 6-gingerol for 5 days and hair elongation in three groups was measured. Secondly, The proliferative effect of 6-gingerol on DPCs was measured using MTT assay. Thirdly, the expression of Bcl-2 and Bax in DPCs were measured using Western blotting. In vivo study, the influence of 6-gingerol on hair growth in C57BL/6 rats was measured through topical application of 6-gingerol on the dorsal skin of each animal.

RESULTSThe length of hair shaft in 20 microg/ml 6-Gingerol group (0.50 +/- 0.08 mm) is less than 0 microg/ml (0.66 +/- 0.19) mm and 10 microg/ml (0.64 +/- 0.03) mm 6-Gingerol group (P < 0.05). In cell culture, compared to 0 microg/ml and 5 microg/ml 6-Gingerol, 10 microg/ml 6-Gingerol can significantly inhibited the proliferation of DPCs (P < 0.05). Along with the growth inhibition of DPCs by 6-gingerol, the Bax/Bcl-2 ratio increased obviously. In vivo study, the hair length and density decreased a lot after using 1 mg/ml 6-gingerol.

CONCLUSIONS6-Gingerol can suppress human hair shaft elongation because it has pro-apoptotic effects on DPCs via increasing Bax/Bcl-2 ratio. It might inhibit hair growth by prolonging the telogen stage in vivo.

Animals ; Catechols ; pharmacology ; Cell Culture Techniques ; Cells, Cultured ; Fatty Alcohols ; pharmacology ; Hair ; drug effects ; growth & development ; Hair Follicle ; drug effects ; growth & development ; Humans ; Mice ; Mice, Inbred C57BL ; Plant Extracts ; pharmacology ; Rats ; bcl-2-Associated X Protein ; metabolism

More and more studies have shown that NOD-like receptor protein 3 (NLRP3) inflammasome has become the regulatory factor of inflammatory response and protective immunity, and the assembly and activation of NLRP3 inflammasomes are closely related to the anti-tumor immunity effect. Depending on the cell type and stimuli, activation of the NLRP3 inflammasome can induce immune cells to become polarized, hyperactive, or pyroptotic, releasing interleukin (IL)-1β and IL-18, which leads to cascade immune or inflammatory responses, and its role in tumor immunity has received extensive attention. Here, we review the mechanisms of the NLRP3 inflammasome enhancing CD8⁺ T cells-mediated anti-tumor immunity by inducing the pyroptosis of tumor cell, the pyroptosis or hyperactive state of dendritic cells (DCs), and the pyroptosis or polarization of the macrophages. Different anti-tumor immune roles of NLRP3 inflammasome activation in tumor cells and immune cells provide new directions for future research and may influence the development of next-generation immunotherapy.

BACKGROUNDDonor and recipient risk factors on graft function have been well characterized. The contribution of demographic factors, such as age, gender, and other potential factors of donor and recipient at the time of transplantation on the function of a graft is much less well understood. In this study, we analyzed the effects of factors such as age, gender, etc., on the short-term and long-term graft function in kidney transplant recipients from living donor.

METHODSA total of 335 living donors and their recipients, who had kidney transplantation in our center from May 2004 to December 2009, were included. Serum creatinine level was used as the assessment criterion (serum creatinine level lower than 115 mmol/L is normal). Factors related to graft function such as age, gender, blood relation by consanguinity, human leukocyte antigen (HLA) mismatch, ABO type, etc., were analyzed separately.

RESULTSDonor age is the key factor affecting both the short-term and long-term function of a grafted kidney from a living donor. The group with donors younger than 48 years showed the best kidney function post transplantation. Match of gender and age is another important factor that influences the function of grafted kidney from a living donor. The older donor to younger recipient group had the worst outcome after kidney transplantation. After 36 months post transplantation, female donor to male recipient group had worse kidney function compared to other groups. We also found that calcinerin inhibitor used in the maintenance period may influence the function of a grafted kidney. No significant statistical differences were found in consanguinity, blood type, and mismatch of HLA.

CONCLUSIONSDonor age is an important factor affecting the function of a grafted kidney from a living donor. We also recommend taking nephron, immunology factor, infection, and demographic information all into consideration when assessing the outcome of kidney transplantation.

Adolescent ; Adult ; Aging ; Child ; Female ; Histocompatibility Testing ; Humans ; Kidney ; physiopathology ; Kidney Transplantation ; Living Donors ; Logistic Models ; Male ; Middle Aged

Carnosol has been proved to have anti-breast cancer effect in previous research. But its ER subtype's specific regulation and mediation mechanisms remain unclear. The aim of this study is to observe the effect of carnosol on cell proliferation and its estrogen receptor α and β's specific regulation and mediation mechanisms with ER positive breast cancer T47D cell. With estrogen receptor α and β antagonists MPP and PHTPP as tools, the MTT cell proliferation assay was performed to observe the effect of carnosol on T47D cell proliferation. The changes in the T47D cell proliferation cycle were detected by flow cytometry. The effect of carnosol on ERα and ERβ expressions of T47D cells was measured by Western blot. The findings showed that 1 x 10(-5)-1 x 10(-7) mol x L(-1) carnosol could significantly inhibit the T47D cell proliferation, which could be enhanced by MPP or weakened by PHTPP. Meanwhile, 1 x 10(-5) mol x L(-1) or 1 x 10(-6) mol x L(-1) carnosol could significantly increase ERα and ERβ expressions of T47D cells, and remarkably increase ERα/ERβ ratio. The results showed that carnosol showed the inhibitory effect on the proliferation of ER positive breast cancer cells through target cell ER, especially ERβ pathway. In the meantime, carnosol could regulate expressions and proportions of target cell ER subtype ERα and ERβ.
Blotting, Western ; Breast Neoplasms ; metabolism ; pathology ; Cell Cycle ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Diterpenes, Abietane ; chemistry ; pharmacology ; Dose-Response Relationship, Drug ; Estrogen Receptor Modulators ; pharmacology ; Estrogen Receptor alpha ; antagonists & inhibitors ; metabolism ; Estrogen Receptor beta ; antagonists & inhibitors ; metabolism ; Female ; Flow Cytometry ; Humans ; Molecular Structure ; Pyrazoles ; pharmacology ; Pyrimidines ; pharmacology

Allogeneic hematopoietic stem cell transplantation is the only curative therapy for severe beta-thalassemia. This time, the experience of utilizing HLA 2-loci mismatched sibling cord blood transplantation (CBT) in a child with severe beta-thalassemia was firstly reported in our country. A 3-year-male patient had been diagnosed with severe beta-thalassemia at 6 months of age (HbF 86.6%, HbA1 1.7%, HbA2 1.7%, beta globin gene mutation CD17, A-->T/IVS-II-654, C-->T). The patient's HLA typing was A 24,11, B 58,35 and DRB1 03,15. During a subsequent maternal pregnancy. The prenatal diagnosis for thalassemia and prenatal HLA typing analysis were performed on 18 weeks of pregnancy. The results indicated that the male fetus was a heterozygote (beta globin gene mutation N/CD17, A-->T), HLA typing was A 24,11, B 58,51 and DRB1 03,12. 120 ml cord blood was collected at time of delivery, the total numbers of nucleated cells, CFU-GM and CD34(+) cells were 1.830 x 10(9), 16.653 x 10(5) and 3.11 x 10(6), respectively. A new conditioning regimen including: hypertransfusion, continuous i.v. desferrioxamine, busulfan, cyclophosphamide, antithymocyte globulin plus hydroxyurea and fludarabine. GVHD prophylaxis comprised cyclosporin A and mycophenolate mofetil. The viability of cord blood at the time infusion was 92%, The total numbers of nucleated cells, CFU-GM and CD34(+) cells in the transfused cord blood were 12.06 x 10(7)/kg, 1.098 x 10(5)/kg, and 2.04 x 10(6)/kg, respectively. Results showed that the patient's clinical course after cord blood transplantation was unremarkable. Acute GVHD grade I developed on day 15, methylprednisolone 2 mg/kg was given to cure. Neutrophil engraftment (ANC > 0.5 x 10(9)/L) on day 17, platelet engraftment (> 50 x 10(9)/L) on day 50. The patients became independent from red blood cell transfusion since day 80 (when his hemoglobin level kept > 12.5 g/L). His beta globin gene mutation and HLA typing were all the same as the donor's analyzed on day 60 and 200. There was also a switch in blood group from A pre-transplant to O post-transplant. It is concluded that the new conditioning and GVHD prophylaxis regimens allow a successful engraftment in this case. This observation may contribute in developing UCBT as an alternative when matched sibling donors are not available.
Child, Preschool ; Cord Blood Stem Cell Transplantation ; adverse effects ; Globins ; genetics ; Graft vs Host Disease ; etiology ; HLA Antigens ; immunology ; Histocompatibility ; genetics ; immunology ; Histocompatibility Testing ; methods ; Humans ; Male ; Mutation ; Siblings ; Transplantation Tolerance ; immunology ; Transplantation, Homologous ; beta-Thalassemia ; therapy

AIMTo observe the dynamic expression of ERK1 in fibrotic rat liver.

METHODSThe rat hepatic fibrosis was induced by bile duct ligation (BDL). Histopathological changes were evaluated by hematoxylin and eosin staining, and by Masson's trichrome method. ERK1 mRNA in liver was determined by reverse transcription-polymerase chain reaction (RT-PCR), while the distribution of ERK1 was assessed by immunohistochemistry. ERK1 protein was detected by using Western blotting analysis.

RESULTSWith the development of hepatic fibrosis, the positive cells of ERK1 increased a lot, they were mainly distributed at portal ducts, fiber septa and around the bile ducts, vascular endothelial cells and perisinusoidal cells. Western blotting analysis results displayed that the expression of ERK1 protein were up-regulated with model course, and its levels were the highest at week 4 after operation, achieving to 3.9-fold of that in normal rat liver. ERK1 mRNA expressed in normal rat livers as well, they were up-regulated at day 2 after BDL and its level was the highest at week 4 after BDL.

CONCLUSIONThese data suggest that the expression of ERK1 and its mRNA can be increase greatly in fibrotic rat liver.

Animals ; Liver ; metabolism ; pathology ; Liver Cirrhosis, Biliary ; metabolism ; pathology ; Male ; Mitogen-Activated Protein Kinase 3 ; metabolism ; RNA, Messenger ; genetics ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo investigate the expression of B cell specific MLV integration site-1 (Bmi-1) in colorectal cancer (CRC) and its correlation to the clinicopathological features and prognosis of CRC.

METHODSSixty CRC, 30 adenomas and 20 normal colorectal mucosal tissues were collected to detect the expression of Bmi-1 protein using immunohistochemistry, and the results were analyzed in comparison with the clinicopathological features and survival rate of patients.

RESULTSThe positivity rate of Bmi-1 expression in CRC tissue was 51.7%. In CRC, the rate of Bmi-1 overexpression was 25.0%, significantly higher than that in the adenomas and normal colorectal mucosal tissues (6.67% and 0%, respectively, P<0.05). The overexpression of Bmi-1 protein in CRC was obviously associated with distant metastasis and the TNM stage (P<0.05), but not with gender, age, tumor size, tumor site, histological type, differentiation degree and lymph node metastasis (P>0.05). But logistic regression analysis showed that Bmi-1 protein overexpression in CRC was associated only with distant metastasis (P<0.01,OR>1); Kaplan-Meier survival analysis showed that the survival rate of the patients with high Bmi-1 expression was significantly lower than that in patients with low expression (P<0.05).

CONCLUSIONThe overexpression of Bmi-1 protein was significantly correlated to the tumorigenesis, metastasis and prognosis of CRC, and may serve as an indicator for evaluating the prognosis of CRC.

Adult ; Aged ; Case-Control Studies ; Colorectal Neoplasms ; metabolism ; pathology ; Female ; Humans ; Male ; Middle Aged ; Neoplasm Metastasis ; Nuclear Proteins ; genetics ; metabolism ; Polycomb Repressive Complex 1 ; Prognosis ; Proto-Oncogene Proteins ; genetics ; metabolism ; Repressor Proteins ; genetics ; metabolism ; Young Adult

Objective To investigate the clinical efficacy and safety of the Camrelizumab combined with Shenqi Fuzheng injection of advanced non-squamous non-small cell lung cancer(NSCLC).Methods Patients with advanced squamous NSCLC diagnosed and treated in the department of medical oncology of The First Affiliated Hospital of Xi'an Jiaotong University from January 2018 to January 2023 were selected as the study subjects,and all patients were treated with pemetrexed combined with carboplatin chemotherapy.On the basis of the chemotherapy regimen,patients were divided into the Camrelizumab group(treated with Carelizumab)and the Camrelizumab+SFI group(treated with Camrelizumab+SFI).The short-term and long-term efficacy were evaluated using objective response rate(ORR),disease control rate(DCR),progression free survival(PFS),and overall survival(OS).Survival data were analyzed using Kaplan-Meier method.The occurrence of side effects the adverse drug reactions was evaluated according to the common terminology standard for adverse events(CTCAE 4.03).Results A total of 95 patients with advanced NSCLC were included in this study.Among them,48 patients were in the Camrelizumab group,and 47 patients were in the Camrelizumab+SFI group.The ORR of advanced non-squamous NSCLC patients in the Camrelizumab+SFI group and Carolizumab group were 59.57％and 45.83％,respectively(x2=1.799,P=0.180),with DCR of 78.72％and 58.33％,respectively(x2=4.569,P=0.033).The median PFS(8.87 months vs.6.30 months,P=0.001 7)and median OS(9.13 months vs.7.73 months,P=0.037)of patients in the Camrelizumab+SFI group were significantly higher than those in the Camrelizumab group.In addition,there was no significant difference in the incidence of adverse reactions between two groups(P＞0.05).Conclusion Camrelizumab combined with Shenqi Fuzheng injection can improve the disease control rate and prolong the PFS and OS of patients with advanced non-squamous NSCLC.

Previous studies proposed that the synergistic effect of fibroblast growth factor-21 (FGF-21) and insulin may be due to the improvement of insulin sensitivity by FGF-21. However, there is no experimental evidence to support this. This study was designed to elucidate the mechanism of synergistic effect of FGF-21 and insulin in the regulation of glucose metabolism. The synergistic effect of FGF-21 and insulin on regulating glucose metabolism was demonstrated by investigating the glucose absorption rate by insulin resistance HepG2 cell model and the blood glucose chances in type 2 diabetic db/db mice after treatments with different concentrations of FGF-21 or/and insulin; The synergistic metabolism was revealed through detecting GLUT1 and GLUT4 transcription levels in the liver by real-time PCR method. The experimental results showed that FGF-21 and insulin have a synergistic effect on the regulation of glucose metabolism. The results of real-time PCR showed that the effective dose of FGF-21 could up-regulate the transcription level of GLUT1 in a dose-dependent manner, but had no effect on the transcription level of GLUT4. Insulin (4 u) alone could up-regulate the transcription level of GLUT4, yet had no effect on that of GLUT1. Ineffective dose 0.1 mg kg(-1) FGF-21 alone could not change the transcription level of GLUT1 or GLUT4. However, when the ineffective dose 0.1 mg x kg(-1) FGF-21 was used in combination with insulin (4 u) significantly increased the transcription levels of both GLUT1 and GLUT4, the transcription level of GLUT1 was similar to that treated with 5 time concentration of FGF-21 alone; the transcription level of GLUT4 is higher than that treated with insulin (4 u) alone. In summary, in the presence of FGF-21, insulin increases the sensitivity of FGF-21 through enhancing GLUT1 transcription. Vice versa, FGF-21 increases the sensitivity of insulin by stimulating GLUT4 transcription in the presence of insulin. FGF-21 and insulin exert a synergistic effect on glucose metabolism through mutual sensitization.
Animals ; Blood Glucose ; Diabetes Mellitus, Experimental ; metabolism ; Drug Synergism ; Fibroblast Growth Factors ; pharmacology ; Glucose ; metabolism ; Glucose Transporter Type 1 ; metabolism ; Glucose Transporter Type 4 ; metabolism ; Hep G2 Cells ; Humans ; Insulin ; pharmacology ; Insulin Resistance ; Liver ; metabolism ; Mice