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Previous genotyping-based assays have identified non-coding variants of several interleukins (ILs) being associated with genetic susceptibility to leprosy. However, understanding of the involvement of coding variants within all IL family genes in leprosy was still limited. To obtain the full mutation spectrum of all ILs in leprosy, we performed a targeted deep sequencing of coding regions of 58 ILs genes in 798 leprosy patients (age 56.2 ± 14.4; female 31.5%) and 990 healthy controls (age 38.1 ± 14.0; female 44.3%) from Yunnan, Southwest China. mRNA expression alterations of ILs in leprosy skin lesions or in response to M. leprae treatment were estimated by using publicly available expression datasets. Two coding variants in IL27 (rs17855750, p.S59A, p = 4.02 × 10-8 , odds ratio [OR] = 1.748) and IL1RN (rs45507693, p.A106T, p = 1.45 × 10-5 , OR = 3.629) were significantly associated with leprosy risk. mRNA levels of IL27 and IL1RN were upregulated in whole blood cells after M. leprae stimulation. These data showed that IL27 and IL1RN are leprosy risk genes. Further functional study is required for characterizing the exact role of ILs in leprosy.
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Predisposición Genética a la Enfermedad/genética , Interleucinas/genética , Lepra/genética , Polimorfismo de Nucleótido Simple/genética , Pueblo Asiatico/genética , Estudios de Casos y Controles , China , Femenino , Humanos , Masculino , Persona de Mediana Edad , ARN Mensajero/genéticaRESUMEN
Adult Eisenia fetida earthworms were exposed to sub-lethal concentrations of 1,2,4-trichlorobenzene to assess the toxicity of contaminated soils. The LC50 of 1,2,4-TCB at 7 and 14 d were 945±175 and 890±169 mg kg⻹. A lower dose of 1,2,4-TCB (25 mg g⻹) had stimulatory effects on SOD and AChE activities, but AChE activities were significantly inhibited at higher treatment levels (100 and 400 mg g⻹). SOD activities increased after 2, 7, and 14 d of exposure, but AChE activities were significantly inhibited at 400 mg/kg 1,2,4-TCB after 2, 7, and 14 d of exposure, and the inhibition rates were 25.41%, 28.65%, and 25.05%. Ultrastructural observation of the intestinal epithelium at three concentrations (control, 50, and 400 mg g⻹) revealed that the epicuticle, cuticle layer, and microvilli were damaged with increasing 1,2,4-TCB concentration. At 400 mg kg⻹, mitochondria were seriously injured and the smooth endoplasmic reticulum was seriously dilated.
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Clorobencenos/toxicidad , Oligoquetos/efectos de los fármacos , Contaminantes del Suelo/toxicidad , Acetilcolinesterasa/metabolismo , Animales , Relación Dosis-Respuesta a Droga , Dosificación Letal Mediana , Oligoquetos/enzimología , Oligoquetos/ultraestructura , Superóxido Dismutasa/metabolismoRESUMEN
The title compound, {(C(13)H(22)N(4))[Ag(2)I(4)]}(n), was prepared by reaction of 1,3-bis-(N-ethyl-imidazolium-1-yl)propane iodide with silver (I) oxide. In the 3,3'-diethyl-1,1'-(propane-1,3-di-yl)di(1H-imidazol-3-ium) cation, the dihedral angle between the imidazole rings is 49.3â (1)°. In the [Ag(2)I(4)](2-) anion, each Ag(I) atom is bonded to three iodide anions, the two Ag(I) atoms and two of the iodides forming Ag(2)I(2) square-planar (r.m.s. deviation = 0.01â Å) units·The remaining two iodides, which are placed on opposite sides of the square, together with their centrosymmetric counterparts, link the square-planar Ag(2)I(2) units into {[Ag(2)I(4)](2-)}(n) polymeric chains via Ag-I bonds.
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Shenqi Fuzheng Injection (SFI) is a traditional Chinese medicine injection with anticancer properties and is mainly composed of ginseng and astragalus. Its efficacy has been confirmed in clinical trials, but the mechanism remains unclear. We investigated the effect of SFI on vascular endothelial growth factor (VEGF) gene expression in hepatocellular carcinoma (HCC) cells and identified its possible mechanism of synergistic effects when combined with the chemotherapeutic drug interferon (IFN-) α. An MTT assay was used to measure the inhibition effects of low-dose IFN-α (6000 IU) with or without SFI (0.5 g/L) on the HCC cell line MHCC97. VEGF-silenced MHCC97L-mir200 cell lines were prepared using lentiviral vectors and evaluated by real-time PCR to determine the inhibition effect. We examined MHCC97L-mir200 and MHCC97L cells by MTT assay, using IFN-α alone or in combination with SFI. The inhibition ratio of IFN-α (6000 IU) was -29.5%, while that for IFN-α (6000 IU) + SFI (0.5 g/L) was 17.0%, which was significantly higher than that for the IFN-α group (P < 0.01). The VEGF gene was silenced successfully in MHCC97-L cells. After interference of VEGF, the inhibition by SFI and IFN-α in MHCC97L-mir200 did not differ from that in MHCC97-L cells (P > 0.05). SFI can reduce the expression of VEGF in HCC, which can increase the efficacy of IFN-α, providing a theoretical basis for clinical application.
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Carcinoma Hepatocelular/metabolismo , Medicamentos Herbarios Chinos/farmacología , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Silenciador del Gen , Interferón-alfa/biosíntesis , Neoplasias Hepáticas/metabolismo , Proteínas de Neoplasias/biosíntesis , Factor A de Crecimiento Endotelial Vascular/biosíntesis , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Humanos , Interferón-alfa/genética , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Proteínas de Neoplasias/genéticaRESUMEN
Four bis-benzimidazolium salts, 1,4-bis[1'-(N-R-benzimidazoliumyl)methyl]-2,3,5,6-tetramethylbenzene 2X- (L 1 H 2 ·(PF 6 ) 2 : R = ethyl, X = PF6; L 2 H 2 ·Br 2 : R = picolyl, X = Br; L 3 H 2 ·Br 2 : R = benzyl, X = Br; and L 4 H 2 ·Br 2 : R = allyl, X = Br), and their three N-heterocyclic carbene (NHC) Pd(II) and Ag(I) complexes, L 1 Pd 2 Cl 4 (1), L 2 Ag 2 Br 2 (2), and L 4 (AgBr) 2 (3), as well as one anionic complex L 3 H 2 ·(Ag 4 Br 8 ) 0.5 (4), have been synthesized and characterized. Complex 1 adopts a funnel-like type of structure, complex 2 adopts a cyclic structure, and complex 3 is an open structure. In the crystal packing of 1-4, one-dimensional polymeric chains and two-dimensional supramolecular layers are formed via intermolecular weak interactions, including hydrogen bonds, π-π interactions, and C-H···π contacts. The catalytic activities of NHC Pd(II) complex 1 in three types of C-C coupling reactions (Suzuki-Miyaura, Heck-Mizoroki, and Sonogashira reactions) were studied. The results show that this catalytic system is efficient for these C-C coupling reactions.
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Objective To systematically review the efficacy and safety of bevacizumab biosimilars versus original drugs in treatment of metastatic colorectal cancer.Methods PubMed,Embase,Cochrane Library,CNKI,WanFang Data,VIP and SinoMed databases were electronically searched to collect the randomized controlled trials(RCTs)of bevacizumab biosimilar in patients with metastatic colorectal cancer from inception to June 18,2023.Two reviewers independently screened the literature,extracted data,and assessed the risk of bias of the included studies,and a meta-analysis was conducted using Stata 17.0 software.Results A total of 4 RCTs involving 1 052 patients were included.The results of meta-analysis showed that no significant difference was found in overall response rate(RD=﹣0.01,95%CI ﹣0.06 to 0.05,P=0.86),progression free survival(HR=1.00,95%CI 0.91 to 1.09,P=0.94),the total incidence of adverse drug reactions(RR=1.05,95%CI 0.85 to 1.31,P=0.91)and the incidence of severe adverse events(RR=0.886,95%CI 0.377 to 2.081,P=0.60)between bevacizumab biosimilars group and original drugs group.Conclusion The current evidence shows that bevacizumab biosimilar is equivalent to original drugs in treatment of metastatic colorectal cancer.Due to limited quality and quantity of the included studies,more high quality studies are required to verify the above conclusions.
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Objective The pathogenesis of orla ulcer has not been fully and thoroughly studied. This study aimed to investi-gate the effect and mechanism of Rosmarinic acid (RA)on oral ulcer. Methods 60 SD rats were randomly divided into control group,model group,RA groups(20,40,80 mg/kg) and Watermelon Frost group. The control group rats were fed normally and with-out any treatment. The oral ulcer model was established in the other three groups. The oral ulcer model of rat was established by injec-tion of 40% glacial acetic acid on the oral mucosa of cheek in rat. One day after the formation of ulcers,RA(20,40,80 mg/kg) and watermelon frost (200 mg/kg) was administrated. The ulcer area was measured 3,5,7 days after establishing the model. The concen-tration of IL-18 and IL-1β in ulcer tissue was measured by ELISA method and the expression of NLRP3 mRNA was measured by qRT-PCR. Results Compared with the model group, the ulcer area in the RA group and Watermelon Frost group was significantly de-ceased(P<0.05). Compared with the control group,NLRP3,IL-18 and IL-1β in the ulcer tissue was significantly elevated in model group,RA groups (20,40,80 mg/kg) and Watermelon Frost group (P<0.01). NLRP3 expressed lower in RA (40,80 mg/kg) and wa-termelon frost (200 mg/kg) group(5.27 ± 0.53, 3.25 ± 0.46, 4.75 ± 0.51) than in model group(8.71±0.35)( P<0.05). IL-18 expressed lower in RA (40, 80 mg/kg) and watermelon frost (200 mg/kg) group [(174.21±18.21), (110.12±14.23), (142.25±12.61) pg/mL] than in model group [(246.21±26.21) pg/mL](P<0.05). IL-1β expressed lower in RA (40, 80 mg/kg) and watermelon frost(200 mg/kg) group [(94.76±7.26),(81.77±7.80),(90.21±8.71) pg/mL] than in model group [(133.01±11.69) pg/mL](P<0.05). Conclusion RA has some therapeutic effect on oral ulcers,the mechanism may be related to NLRP3.