There were significant increase in urine protein excretion,raised malondialdehyde(MDA) level and expressions of NF-?B,p22phox and p47phox in renal tissue,and significant decrease in reduced glutathione,superoxide dismutase,vitamin C and E levels in type 2 diabetic Goto-Kakisaki rats after 12 weeks. There was obvious histomorphologic change in the kidneys.All the above indices were improved by intraperitoneal injection of?-lipoic acid(35 mg/kg q.o.d).Besides,significant positive correlations were found of MDA level to p22phox,p47phox and NF-?B in the renal tissue,?-lipoic acid seems to protect the diabetic kidney in this diabetic rat model via antioxidative effects.

Adult ; Air Pollutants, Occupational ; adverse effects ; Chemical Industry ; Female ; Humans ; Insecticides ; adverse effects ; Male ; Maximum Allowable Concentration ; Middle Aged ; Occupational Diseases ; chemically induced ; diagnosis ; Organothiophosphorus Compounds ; adverse effects ; Phosphorus Compounds ; adverse effects ; Sulfides ; adverse effects

Adolescent ; Adult ; Anticoagulants ; therapeutic use ; Blood Coagulation Disorders ; diagnosis ; drug therapy ; Female ; Humans ; Male ; Middle Aged ; Vascular Malformations ; diagnosis ; drug therapy ; Veins ; pathology ; Young Adult

The dynamic expression of cytokines and phenotypes during the differentiation process of dendritic cell precursors (pre-DCs) to mature dendritic cells (DCs) was investigated,and the effects of inflammatory stimulation with lipopolysaccharide (LPS) on DCs differentiation were understood.The differentiation of bone marrow cells isolated from Balb/c mice was induced to DCs in an 8-day cell culture system with RPMI-1640 complete culture medium containing 10％ FBS,20 ng/mL recombinant mouse granulocyte-macrophage colony-stimulating factor (rmGM-CSF) and 10 ng/mL recombinant mouse interleukin-4 (rmIL-4).On the day 3,6 and 7 after culture,DCs were divided into non-LPS group and LPS group,given 500 ng/mL LPS for 24 h stimulation and no stimulation respectively.The expression levels of CD 1 l c+,MHC-Ⅱ +,CD40+,CD80+ and CD86+ were detected by flow cytometry,and those of IL-2,IL-4,IL-10,IL-12 p70 and IFN-γ in the supernatant by ELISA.On the day 3 and 6 after culture,the expression of IL-2,IL-4,IL-10 and IFN-γ in DCs showed no significant differences between non-LPS group and LPS group,whereas the differences were significant at day 7.The expression levels of cytokines (for IL-2,IL-4,IL-10,IFN-γ and IL-12 p70:152.86±6.91,778.33±8.35,44.55±2.54,5.8.26±1.09 and 2423.00±57.21 pg/mL respectively) in LPS group were higher than those in non-LPS group,especially IL-12 p70 increased obviously at day 7.It was concluded that during the differentiation process of pre-DCs to mature DCs,LPS stimulates DCs producing large amounts of IL-12 p70 and Thl-type cytokines as compared with Th2-type cytokines,and day 7 may be a key time-point for DCs polarization.

Alleles ; Amelogenin/genetics* ; Chromosomes, Human, Y ; Humans ; Male ; Sex Determination Analysis

The abnormality of ubiquitin proteasome pathway is an important factor leading to the imbalance of protein homeostasis. In this process, the deubiquitinase responsible for removing the ubiquitin chain of protein substrate is very important. Its abnormal activity or expression can cause the functional changes of key oncogenic/tumor suppressor proteins, which directly or indirectly lead to the occurrence, development and malignant evolution of tumors. Based on this, the discovery and research of small molecule inhibitors targeting deubiquitinases have become a hot field of anti-tumor candidate drugs. This review will focus on the regulatory effect and mechanism of ubiquitin proteasome pathway, especially deubiquitinase on tumor, introduce the application of deubiquitinase small molecule inhibitors in tumor treatment, and discuss the research status and latest progress of small molecule inhibitors, so as to provide ideas for the research of new anti-tumor strategies based on deubiquitinase.

KRAS is one of the most frequently mutated human oncogenes. In spite of mounting efforts on the development of direct or indirect inhibition targeting KRAS, little has been achieved because of insurmountable difficulties, titling KRAS "undruggable". Recently, subtype-specific inhibitors have shown great hope. Some KRAS^G12C inhibitors have entered clinical trials, including adagrasib and sotorasib, and have shown preliminary clinical effectiveness. Experiences from the inhibitors targeting the downstream factors of RAS pathways show that the anticancer activity of these drugs will be limited due to the development of drug resistance. Preclinical studies of KRAS^G12C inhibitors have revealed that the application of these agents might be hampered by the drug resistance issue. The current review aims to describe the current status of KRAS^G12C inhibitors, and discuss the mechanisms underlying KRAS^G12C inhibitor resistance, so as to provide the clues for the combat of drug resistance.

Objective To investigate a more perfect method for a nice outward appearance of the thumb(finger) reconstructed.Methods An artery pedicle composite flap from fibular side of the great toe is inlaid in the tibial(ventral) side of the free second toe for thumb reconstruction and the same free second toe with a distal part of metatarsal bone with a double-wings flap for finger reconstruction before transplantation. Results The reconstructed thumb(finger) gets a nice looking and normal function while no blight to the great toe occurred.Conclusion It is an effective new procedure in ameliorating outward appearance of the recon- structed thumb(finger) by transferring the free moulded second toe.

AIMTo evaluate the antiproliferative activity of contragestazol (DL111-IT) on the human prostate cancer cell line PC3 in vitro and in vivo and to elucidate its potential molecular mechanisms.

METHODSThe cell killing ability of DL111-IT was measured by the 3-(4,5-dimethylthia-zol,2-yl)-2,5-diphenyltetrazolium bromide (MTT) reagent assay method and the tumor xenograft model. The cell cycle was analyzed by flow cytometry and protein expression, including retinoblastoma (pRb), cyclin-dependent kinase 4 (CDK4) and cyclin D1, was detected by Western blotting.

RESULTSDL111-IT exhibited high efficiency on cell growth inhibition of the human androgen-independent prostate cancer cell line PC3. The drug concentration that yielded 50% cell inhibition (IC50 value) was 9.9 mg/mL. In the PC3 tumor xenograft study, DL111-IT (1.25 mg/kg-20.0 mg/kg) given once a day for 10 days significantly inhibited tumor growth, with the inhibition rate ranging from 21% to 50%. Flow cytometric analysis indicated that DL111-IT could cause G1 arrest in the PC3 cell line, but not apoptosis. DL111-IT enhanced pRb expression and down-regulated CDK4 and cyclin D1 expression, suggesting that cell cycle regulation might contribute to the anticancer property of DL111-IT.

CONCLUSIONDL111-IT inhibits the proliferation of human androgen-independent prostate cancer cell line PC3 in vitro and in vivo by a cell cycle regulation pathway.

Androgens ; pharmacology ; Animals ; Cell Division ; drug effects ; Cell Line, Tumor ; Cyclin D1 ; metabolism ; Cyclin-Dependent Kinase 4 ; metabolism ; Dose-Response Relationship, Drug ; Female ; G1 Phase ; drug effects ; Humans ; Immunosuppressive Agents ; pharmacology ; In Vitro Techniques ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasm Transplantation ; Prostatic Neoplasms ; drug therapy ; pathology ; Resting Phase, Cell Cycle ; drug effects ; Retinoblastoma Protein ; metabolism ; Transplantation, Heterologous ; Triazoles ; pharmacology

OBJECTIVETo discuss the treatment of the scrotal vein malformation in teenagers and clinical efficacy.

METHODS32 cases with the local and diffuse scrotal vein malformation were retrospectively analyzed. 31 cases underwent local injection with 40% urea before resection. The urea was injected locally into tumor through multi-points within 30 seconds, 2-6 ml every time, one time a day. The injection was performed for 5-12 days. The treatment was refused in one case. The therapeutic effect and cosmetic result were recorded.

RESULTSThe tumors were removed radically in 28 cases including one operation in 25 cases and secondary operation in 3 cases. The patients were followed up for 1-3 years with no recurrence. Cosmetic result with bilaterally symmetric scrotum was satisfactory. The tumors in 3 severe cases were partially resected with improvement.

CONCLUSIONSCombined treatment with urea injection and surgical procedure can effectively treat the scrotal vein malformation with satisfactory result.

Adolescent ; Humans ; Injections, Intralesional ; Male ; Retrospective Studies ; Scrotum ; blood supply ; Urea ; administration & dosage ; therapeutic use ; Vascular Malformations ; therapy ; Young Adult