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关键词： Immunotherapy   Magnesium sulfate   MIRN146a microRNA, Paclitaxel   Pain   Rat   Tumor necrosis factor-alph  

摘要： Neuropathic pain can arise from injury or illness affecting the somatosensory system. It can also be triggered by cancer or chemotherapy drugs like paclitaxel. Researchers have indicated that magnesium sulfate may help in preventing neuropathy. This study aimed to investigate the effect of magnesium sulfate on paclitaxel-induced neuropathic pain by inhibiting the Tumor Necrosis Factor (TNF) Alpha- receptor-associated factor 6- Nuclear factor kappa-light-chain-enhancer of activated B cells (TNF-alpha-TRAF6-NF-kappa B) axis. Twenty-four male rats were divided into four groups: experiment group (E)-1, E2, E3, and the control group (Co). The experimental groups and the control group received paclitaxel at a dosage of 8 mg/kg every other day, totaling four injections over seven days. In addition, magnesium sulfate was administered daily in three doses of 300, 150, and 75 mg/kg, amounting to seven injections over the course of seven days. On the seventh day, peripheral blood samples were collected from the rats, and sera were used for the analysis of TNF-alpha serum levels and MicroRNA-146a-5p expression using ELISA and qRT-PCR methods, respectively. The serum levels of TNF-alpha increased in the E1, E2, and E3 groups compared to the control group. However, there was a gradual decrease in the E1, E2 and E3 groups. The miR-146a-5p expression declined in the E1 group and increased in the E2 and E3 groups compared to the control group. This study demonstrated that administering 300 and 150 mg of magnesium sulfate decreased TNF-alpha synthesis and reduced the function of the TNF-alpha-TRAF6-NF-kappa B axis during the initiation step.

关键词： NGS   novel HLA allele   patient  

摘要： The novel HLA-B*40:01:92 allele differs from B*40:01:01:01 by a change of C -> A in exon 5.

关键词： Anakinra   IL-1 beta   inflammation   noise-induced hearing loss   treatment  

摘要： ObjectiveThis study aimed to attenuate cochlear inflammation following noise-induced hearing loss by targeting IL-1. We evaluated the effectiveness of IL-1 inhibition through auditory and histological assessments in an animal model. Study designExperimental animal study. SettingGazi University Faculty of Medicine, Ankara, Turkey. MethodsTwenty-four rats were randomly assigned into 3 groups: Anakinra, dexamethasone, and control groups. All animals were exposed to broadband noise (110 dB SPL, 8 hours), auditory brainstem response (ABR) tests were conducted before noise exposure, immediately after, and on Day 14. Anakinra, dexamethasone, and saline were administered intraperitoneally, cochlear tissues were harvested for histological and immunohistochemical evaluation. ResultsOn Day 14, ABR thresholds in Anakinra group were better than the control group across all frequencies, with a significant difference observed at 8 kHz (P = .036). The mean number of OHC was significantly higher in Anakinra group compared to the control group (P < .05). The mean number of IHC in the Anakinra group was greater than in the dexamethasone group. IL-1 beta immunopositivity in the stria vascularis and spiral ganglia was significantly higher in Anakinra group compared to dexamethasone group (P = .022 and P = .013, respectively). TNF-alpha immunopositivity in the stria vascularis and spiral ganglia was significantly greater in control group than in Anakinra group (P = .037 and P = .01, respectively). ConclusionThe comparable efficacy of Anakinra and dexamethasone in both histological and auditory assessments suggests that Anakinra may serve as a promising therapeutic option for noise-induced hearing loss.

关键词： Myricetin   Di(2-ethylhexyl) phthalate   RAW 264.7 murine macrophage cells   IL-1 beta   Nuclear factor-kappa B   NLRP3 inflammasome  

摘要： Myricetin, a flavonoid present in numerous fruits, vegetables, and medicinal plants, is recognized for its potent antioxidant, anti-inflammatory, and anti-cancer activities. Nevertheless, its involvement in mitigating inflammation caused by the endocrine-disrupting chemical Di(2-ethylhexyl) phthalate (DEHP), commonly used in polyvinyl chloride (PVC) manufacturing to improve flexibility, has not been investigated. Here, we found that DEHP markedly increased IL-1 beta production through inflammatory pathways in RAW 264.7 murine macrophages. Treatment with myricetin at a concentration of 10 mu M significantly reduced the elevated IL-1 beta levels. Myricetin achieves this by inhibiting the activation of protein kinase C (PKC) and extracellular signal-regulated kinase (ERK), which are driven by reactive oxygen species (ROS), thereby suppressing IL-1 beta transcription via nuclear factor-kappa B (NF-kappa B). Additionally, myricetin prevents ROS-induced activation of the NLRP3 inflammasome and subsequent caspase-1 activation, further decreasing IL-1 beta production. These dual actions highlight myricetin's therapeutic potential in countering the oxidative stress-mediated inflammatory pathways triggered by environmental toxins like DEHP.

关键词： Viral gene expression   Ubiquitination   Transfection   Viral transmission and infection   Genetic interference   Macrophages   Interferons   Vesicular stomatitis virus  

摘要： E3 ubiquitin ligases are key molecules in regulating the innate immune responses against virus. They catalyze the activation or degradation of various signaling proteins involved in the innate immune responses. Herein, we found the regulatory role of RNF149 in the host's innate immune responses against viral infection. Virus infection induced the expression of RNF149. Overexpression of RNF149 was associated with reduced production of IFN-beta and enhanced viral replication. Mechanically, RNF149 interacted with IRF3 and downregulated its protein level. As an E3 ubiquitin ligase, RNF149 promoted the K27-linked ubiquitination of IRF3 at K409 and K33-linked ubiquitination at K366 and K409, which promoted IRF3 degradation through the proteasome pathway. Our results revealed the regulatory mechanism of RNF149 during viral infection and provided new insights into host cells responding to viral infection. Downregulating the expression of RNF149 may help enhance the antiviral ability of host cells and inhibit viral replication, thus providing a new strategy for the treatment of viral infection.

关键词： Systemic lupus erythematosus   Lupus nephritis   Neuropsychiatric systemic lupus erythematosus   Gene polymorphism  

摘要： Objective To comprehensively investigate the impact of candidate loci on the susceptibility to neuropsychiatric systemic lupus erythematosus (NPSLE) in a cohort of Chinese children with lupus nephritis (LN). Methods This case-control study included sixty-two patients. And the case group consisted of 12 LN patients appearing NPSLE, while the control group consisted of 50 LN patients. A total of fifty-four single nucleotide polymorphisms (SNPs) across twenty genes were genotyped using the Agena Bioscience MassArray iPLEX platform. The associations between susceptibility to NPSLE and candidate SNPs were assessed using SNPStats online software. We evaluated the influence of candidate SNPs on the risk of NPSLE through odds ratios (OR) and 95 % confidence intervals (CI). Additionally, linkage disequilibrium (LD) and coefficient (D ' and r(2)) for haplotypes and their frequencies were performed using the genetic statistical online software SHEsis. Results Three significant SNPs were identified: IL17RA rs2895332, IL23R rs10889677, and FCGR3A rs396991. AA genotype of FCGR3A rs396991, GG genotype of IL17RA rs2895332 and AA genotype of IL23R rs10889677 exhibited a decreased risk of NPSLE compared to CA and CC genotypes, GA and AA genotypes, and CA and CC genotypes (rs396991 AA vs. CA-CC, OR 5.00, 95 %CI 0.99-25.17, P = 0.029;rs2895332 GG vs. GA-AA, OR 7.83, 95 %CI 1.47-41.79, P = 0.017;rs10889677 AA vs. CA-CC, OR 4.50, 95 %CI 1.08-18.69, P = 0.027). Furthermore, the haplotype A-T-G (STAT4 rs13426947, rs1551443 and rs3024866) appeared to confer protection against the development of NPSLE. The multivariate logistic regression analysis indicated that two specific SNPs were significantly associated with an increased risk of NPSLE: [FCGR3A rs396991 (OR = 6.444, 95 %CI = 1.1-37.736, P = 0.039), IL17RA rs2895332 (OR = 0.128, 95 %CI = 0.017-0.963, P = 0.046)]. Notably, the RegulomeDB score of them reached 1 f. Using HaploReg, these loci were in strong LD (r(2)>0.8) with several SNPs.