Objective To study the mechanism of RING finger protein 34 ( RNF34 ) involved in innate immunity . Methods Recombinant PCR was used and transient expression of the plasmid was achieved in HEK 293T cells.The cells were stimulated with Sendai virus ( SeV) or N-RIG-Ⅰfor the indicated time while luciferase activity was observed using the dual-luciferase reporter assay kit .Results We constructed the plasmid pcDNA 3-Flag-RNF34 and its three mutations .The study found that when stimulated by SeV , RNF34 could inhibit the activity of NF-κB and IFN-βmore significantly than RNF34-ΔFYVE, RNF34-ΔCID and RNF34-ΔRING.We also found that RNF 34 and its three mutants had similar inhibitory effect when the activation of NF-κB and IFN-βwas stimulated by the N-RIG-Ⅰ.Conclusion RNF34 negatively regulates innate immunity by acting on the RIG-Ⅰ-MAVS signaling pathway .

Mitogen-activated protein (MAP) kinases comprise a family of protein-serine/threonine kinases, which are highly conserved in protein structures from unicellular eukaryotic organisms to multicellular organisms, including mammals. These kinases, including ERKs, JNKs and p38s, are regulated by a phosphorelay cascade, with a prototype of three protein kinases that sequentially phosphorylate one another. MAPKs transduce extracellular signals into a variety of cellular processes, such as cell proliferation, survival, death, and differentiation. Consistent with their essential cellular functions, MAPKs have been shown to play critical roles in embryonic development, adult tissue homeostasis and various pathologies. In this review, we discuss recent findings that reveal the profound impact of these pathways on chronic inflammation and, particularly, inflammation-associated cancer development.
Animals ; Extracellular Signal-Regulated MAP Kinases ; metabolism ; Humans ; Inflammation ; complications ; enzymology ; JNK Mitogen-Activated Protein Kinases ; metabolism ; MAP Kinase Signaling System ; Mice ; Neoplasms ; enzymology ; etiology ; p38 Mitogen-Activated Protein Kinases ; metabolism

Objective:To observe the effect of disposable flexible ureteroscopy and laser lithotripsy combined with flexible ureteroscope sheath implantation in the treatment of patients with renal calculi.Methods:Sixty patients with kidney calculi treated by disposable flexible ureteroscopy and laser lithotripsy combined with flexible ureteroscope sheath implantation in the Second Affiliated Hospital of Xi′an Medical College from February 2021 to January 2024 were retrospectively selected as the observation group, matched according to age (±5 years) and gender factors, according to the random number table method, 60 patients with kidney calculi who were treated with disposable ureteroscopy combined with laser lithotripsy at the same time were selected as the control group. The amount of intraoperative blood loss, operation time and hospital stay were recorded and compared between the two groups. Serum renal function parameters urea nitrogen and creatinine levels were measured by automatic biochemical analyzer before and 3 days after surgery, and serum inflammatory factor C-reactive protein (CRP) and interleukin-6 (IL-6) levels were measured by enzyme-linked immunosorbent assay (ELISA). The incidence of complications was recorded and compared between the two groups. Measurement data were expressed as mean±standard deviation ( ± s), and independent sample t-test was used for comparison between groups. The count data were expressed as the number of cases and percentage, and the Chi-square test was used for comparison between groups. Results:The intraoperative blood loss, operation time and hospital stay in the observation group [(23.2±5.9) mL, (98.8±8.5) min, (4.2±1.0) d, respectively] were all lower than those in the control group [(27.3±6.5) mL, (112.5±9.8) min, (4.7±1.3) d, respectively], the differences were statistically significant ( P<0.05). The success rate of stone removal in the observation group was 100.00% (60/60), higher than that in the control group (81.67%, 49/60), and the difference was statistically significant ( χ2=10.01, P=0.002). 3 days after surgery, the levels of serum urea nitrogen, creatinine, CRP and IL-6 in the observation group [(7.04±1.24) mmol/L, (73.21±6.87) μmol/L, (15.83±2.57) mg/L, (10.52±1.02) ng/L] were lower than those in the control group [(7.63±1.32) mmol/L, (78.59±7.52) μmol/L, (21.32±3.22) mg/L, (15.47±1.35) ng/L], the difference were statistically significant ( P<0.05). The incidence of postoperative complications in the observation group (3.33%) was lower than that in the control group (13.33%), and the difference was statistically significant ( χ2=3.93, P=0.048). Conclusion:Disposable flexible ureteroscopy and laser lithotripsy combined with flexible ureteroscope sheath implantation in the treatment of patients with renal calculi can improve the protection of renal function, improve the stone removal rate of patients, reduce postoperative blood loss and complications, shorten the operation time and hospital stay, improve inflammatory response, and have good clinical efficacy.

Objective To investigate the therapeutic mechanism of Gandou Bushen Decoction(GDBSD)for improving reproductive disorders in male mouse models of Wilson disease(WD).Methods Sixty male homozygous TX mice were randomized equally into 4 groups and treated with daily gavage of saline(WD model group),penicillamine(0.09 g/kg),or GDBSD(0.2 mL/10 g),or with intraperitoneal injection of U0126(20 mg/kg)in addition to GDBSD gavage,with 15 male DL mice as control.After 4 weeks of treatment,copper content in testicular tissue of the mice was detected,and histopathology of the testes and epididymis was examined using HE staining and electron microscopy.TUNEL staining was used to identify apoptotic cells in the testes.The protein expressions of Bcl-2,Cytc,caspase-3,ERK,and p-ERK in the testicular tissue were evaluated with Western blotting,and BrdU-positive cells were detected with immunohistochemical labeling.Sperm density,viability,malformation rate and fertility levels of male mice were studied.Results Treatment with penicillamine and GDBSD obviously improved pathological changes of the testis,increased sperm density and motility,lowered sperm abnormality rate,fertility levels and increased testicular JOHNSEN score of TK mice,but the therapeutic effect of GDBSD was blocked by U0126.GDBSD treatment significantly lowered Cytc and caspase-3 expressions and increased Bcl-2 expression in the testicular tissue of TX mice(P<0.05),while U0126 treatment significantly lowered testicular Bcl-2 expression level.No significant differences were found in total protein expression levels of ERK1/2 among the 5 groups,but p-ERK protein expression was significantly reduced in WD and U0126 groups and increased in penicillamine and GDBSD groups.Conclusion GDBSD can improve spermatogenesis and enhance fertility of male TX mice with WD possibly by activating the ERK signaling pathway to enhance proliferation and reduce apoptosis of the spermatogenic cells.

Objective To investigate the therapeutic mechanism of Gandou Bushen Decoction(GDBSD)for improving reproductive disorders in male mouse models of Wilson disease(WD).Methods Sixty male homozygous TX mice were randomized equally into 4 groups and treated with daily gavage of saline(WD model group),penicillamine(0.09 g/kg),or GDBSD(0.2 mL/10 g),or with intraperitoneal injection of U0126(20 mg/kg)in addition to GDBSD gavage,with 15 male DL mice as control.After 4 weeks of treatment,copper content in testicular tissue of the mice was detected,and histopathology of the testes and epididymis was examined using HE staining and electron microscopy.TUNEL staining was used to identify apoptotic cells in the testes.The protein expressions of Bcl-2,Cytc,caspase-3,ERK,and p-ERK in the testicular tissue were evaluated with Western blotting,and BrdU-positive cells were detected with immunohistochemical labeling.Sperm density,viability,malformation rate and fertility levels of male mice were studied.Results Treatment with penicillamine and GDBSD obviously improved pathological changes of the testis,increased sperm density and motility,lowered sperm abnormality rate,fertility levels and increased testicular JOHNSEN score of TK mice,but the therapeutic effect of GDBSD was blocked by U0126.GDBSD treatment significantly lowered Cytc and caspase-3 expressions and increased Bcl-2 expression in the testicular tissue of TX mice(P<0.05),while U0126 treatment significantly lowered testicular Bcl-2 expression level.No significant differences were found in total protein expression levels of ERK1/2 among the 5 groups,but p-ERK protein expression was significantly reduced in WD and U0126 groups and increased in penicillamine and GDBSD groups.Conclusion GDBSD can improve spermatogenesis and enhance fertility of male TX mice with WD possibly by activating the ERK signaling pathway to enhance proliferation and reduce apoptosis of the spermatogenic cells.