Cells, Cultured ; Enzyme-Linked Immunosorbent Assay ; Female ; Fetal Blood ; Humans ; Infant, Newborn ; Lipopolysaccharides ; Lymphocytes ; metabolism ; Male ; RNA, Messenger ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Suppressor of Cytokine Signaling 1 Protein ; Suppressor of Cytokine Signaling 3 Protein ; Suppressor of Cytokine Signaling Proteins ; genetics ; metabolism ; Time Factors ; Toll-Like Receptor 2 ; genetics ; metabolism ; Toll-Like Receptor 4 ; genetics ; metabolism ; Tumor Necrosis Factor-alpha ; metabolism

Adolescent ; Female ; Humans ; Mucocele ; Nose Diseases ; pathology ; Turbinates ; pathology

Objective To study the effects of curcumin mediated photodynamic therapy (PDT)on the growth and proliferation in human cervical cancer cell line H8 in vitro and in vivo,and to investigate its antitumor mechanisms.Methods The effects of curcumin mediated PDT on proliferation of human cervical cancer H8 cell by MTT assay was used to screen the optimal parameter.Changes in cell morphology were observed by May-Gr ünwald-Farbstoff Giemsa staining.The apoptosis rate was estimated by flow cytometry.The effect of PDT by curcumin on the expressions of Bcl-2,P53 and survivin in H8 cells was detected by fluorescence real-time reverse transcription-polymerase chain reaction (RT-PCR).Forty BALB/C nude mice underwent subcutaneous injection of H8 cell line so as to establish animal models,and then were randomly divided into four equal groups:control group,irradiation alone group,curcumin alone group,curcumin PDT group.HE staining and pathological examination were performed.Immunohistochemical study was conducted to detect the protein expression of the apoptosis inhibiting genes of Bcl-2.Results The proliferation inhibition of H8 cells was obvious after PDT when curcumin 5μmol/L with irradiation 100 J/cm2,and with dose dependent manner.Typical morphologic features of apoptosis appeared characterizedly by marked chromatin condensation,nuclear pyknosis and fragmentation,and the appearance of apoptotic bodies.The total apoptosis rate was higher in PDT group [(47.21 ± 4.11)％]than in control group(1.71 ±0.16) ％ (P＜0.01).The mRNA expression of Bcl-2,P53 and survivin in H8 cells were suppressed significantly.HE staining showed remarkable subcutaneous necrosis in the PDT group.Immunohistochemistry showed remarkable down-regulation of protein expression of Bcl-2(P＜0.01).Conclusions Curcumin-mediated photodynamic therapy has a significant killing effect on H8 cells in vivo and in vitro.Its antitumor effect might be related to induction of Tumor cell apoptosis and suppression of Bcl-2 mRNA and protein expression.

Forensic Psychiatry ; Homicide ; Humans

Objective:To investigate the correlation between amide proton transfer-weighted (APTw) values and Ki-67 labeling index of cervical squamous cell carcinoma.Methods:From October 2017 to December 2018, 24 patients with cervical squamous cell carcinoma [International Federation of Gynecology and Obstetrics (FIGO) stage Ⅰ-Ⅲ] were prospectively enrolled in Peking Union Medical College Hospital and underwent pelvic morphological MRI on a 3.0 T MR scanner, including three-dimensional turbo-spin-echo APTw imaging and DWI. The maximum diameters of the lesions, APTw values and ADC values on the slice with the maximum diameter of the lesion were independently measured by two radiologists. The ICC was computed to evaluate the inter-observer consistency. Ki-67 immunohistochemical expression status was assessed by one pathologist. The Pearson correlation analysis was performed between the APTw values, maximum diameters, ADC values and Ki-67 labeling index.Results:The APTw values of cervical squamous cell carcinoma were (2.9±0.5)%. Inter-observer ICC was 0.972 (95%CI 0.937-0.988). The APTw values were positively moderately correlated with Ki-67 labeling index [(61.9±18.7)%, r=0.532, P=0.008]. The maximum diameters of the lesions were (28.7±10.6) mm. The mean ADC values were (0.998±0.217)×10 -3 mm 2/s. No correlations were found between maximum diameters, ADC values and Ki-67 labeling index ( r=0.038, P=0.859; r=0.238, P=0.263). Conclusion:APTw values can partially reveal the proliferation status of cervical squamous cell carcinoma.

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.

Adult ; Aged ; Animals ; Female ; Humans ; Kidney Calculi ; surgery ; Male ; Middle Aged ; Nephrostomy, Percutaneous ; instrumentation ; methods ; Pyonephrosis ; surgery ; Swine ; Swine, Miniature ; Ultrasonography, Interventional

Objective To evaluate the safety and efficiency of combined finasteride and metformin on benign prostatic hyperplasia (BPH) with type 2 diabetes mellitus(T2DM).Methods Totally 106 patients with BPH plus T2DM received finasteride and metformin treatment for over 12months.Before and after treatment,the side effects and following parameters were measured:prostatic volume (PV),prostate-specific antigen(PSA),international prostate symptom score (IPSS),quality of life (QOL),the maximum flow rate of urinary (Qmax),residual urine(RU),body mass index (BMI),cholesterol (TG).Results There were obvious changes in the following:PV decreased from (56.40±18.75)ml to(42.40± 19.68) ml,PSA decreased from(3.65± 1.08) μg/L to (1.76±0.66)μg/L,IPSS decreased from(22.58±9.45)to(16.67±7.56),QOL decreased from(4.22± ±0.87) to (2.36 ± 0.74),Qmax increased from(8.32±2.42)ml/s to(15.48±3.61)ml/s,RU decreased form(68.36±19.25)ml to(36.42±13.91)ml,BMI decreased from(28.52±3.73)kg/m2 to (19.76± 1.88)kg/m2,TG decreased from (2.52 ± 0.43) mmol/L to (1.38 ± 0.52) mmol/L.The changes of PV,PSA,IPSS,QOL,Qmax,RU,BMI and TG were statistically significant (all P＜0.05).Conclusions Long term combined finasteride and metformin treatment for BPH plus T2DM is effective and safe.And the two drugs may be improve the efficacy each other.

BACKGROUNDRecent studies have demonstrated that dexamethasone (DEX) interferes with immune responses by targeting key functions of dendritic cells (DCs) at the earliest stage. However, the cellular and molecular mechanisms are still incompletely understood. This study aimed to explore the possible mechanisms by investigating the roles of DEX on differentiation, maturation & function of murine DCs and the effects of DEX on DCs via Toll-like receptor 4 (TLR4)-nuclear factor (NF)-kappaB mediated signal pathway.

METHODSImmature DCs (imDCs) were cultured from murine bone marrow (BM) cells. We added DEX into culture medium at different time. The expression of CD11c, CD86 and I-A(b) (mouse MHC class II molecule) was determined by flow cytometry. We determined the expression of NF-kappaB and its inhibitory protein I-kappaBalpha by electrophoretic mobility shift assay (EMSA) and Western blotting, respectively. The productions of interleukin (IL)-12p70 and IL-10 in cell culture supernatants were determined by enzyme-linked immunosorbent assay (ELISA).

RESULTSDEX impaired differentiation of DCs from murine bone marrow progenitors, and inhibited lipopolysaccharide (LPS) induced maturation of DCs. DEX significantly inhibited NF-kappaB expression of normal DCs, the higher the DEX concentration or the longer the DEX treatment time, the more obvious the effect. However, DEX had little effect on LPS-induced NF-kappaB activation, and partially impaired LPS-induced I-kappaBalpha degradation. DEX significantly decreased LPS induced IL-12p70 production by DCs. Interestingly, our results showed a synergistic effect between DEX and LPS on the production of IL-10 by DCs.

CONCLUSIONSDEX inhibits the differentiation and maturation of murine DCs involved in TLR4-I-kappaB-NF-kappaB pathway, and also indirectly impairs Th1 development and interferes with the Th1-Th2 balance through IL-12 and/or IL-10 secretion by DCs.

Animals ; Blotting, Western ; Bone Marrow Cells ; cytology ; Cell Differentiation ; drug effects ; Cells, Cultured ; Dendritic Cells ; cytology ; metabolism ; Dexamethasone ; pharmacology ; Electrophoretic Mobility Shift Assay ; Enzyme-Linked Immunosorbent Assay ; Flow Cytometry ; Male ; Mice ; NF-kappa B ; metabolism ; Signal Transduction ; drug effects ; Toll-Like Receptor 4 ; metabolism

OBJECTIVETo investigate the protective role of brain-derived neurotrophic factor (BDNF) gene transfected bone-marrow mesenchymal stem cells (BMSC) on cochlear spiral ganglion cells (SGC) impaired by aminoglycoside antibiotics (AmAn).

METHODSThe differentiation of BMSC transfected by BDNF gene (BDNF-BMSC) were detected with immunohistochemical examination of Nestin, neuron-specific enolase (NSE), and glial fibrillary acid protein (GFAP) antibody in vitro. BDNF gene transfected BMSC were transplanted into the cochleae of guinea pigs deafened by amikacin, while the control groups were designed in which artificial perilymphatic fluid (APF), BMSC or BDNF gene was injected into cochleae alone. The cochleae were obtained on the week 1, 2 and 4 after injection, respectively, paraffin-embedded, and cut in a paramodiolar plane subsequently. The histopathological changes of cochleae were observed, the density of SGC was calculated by staining with HE, and the corresponding optical density (COD) was calculated with immunohistochemical staining using NSE antibody. And the protective role of various groups on the cochlear SGC were compared.

RESULTSThe positive staining rate of BDNF gene transfected BMSC with Nestin, NSE and GFAP antibody were all higher than that of BMSC in vitro (P < 0.01). After transplantation into cochleae, the differences of SGC density and COD among various groups were all significant on the same time points (P < 0.05). The SGC density and COD of the BDNF gene transfected BMSC group were the highest. The SGC density and COD of various groups on week 4 were all obviously decreased than those on week 1 and 2 (P < 0.05).

CONCLUSIONAmAn-induced SGC damage could be depressed by BMSC, BDNF gene or BDNF gene transfected BMSC transplantation into cochleae, while BDNF gene transfected BMSC showed the best protective role.

Animals ; Brain-Derived Neurotrophic Factor ; genetics ; Cells, Cultured ; Cochlea ; cytology ; Guinea Pigs ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stromal Cells ; Spiral Ganglion ; cytology ; Transfection