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This study aimed to explore the mechanism of Cistanches Herba in the treatment of cancer-induced fatigue(CRF) by network pharmacology combined with in vivo and in vitro experiments to provide a theoretical basis for the clinical medication. The chemical constituents and targets of Cistanches Herba were searched from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). The targets of CRF were screened out by GeneCards and NCBI. The common targets of traditional Chinese medicine and disease were selected to construct a protein-protein interaction(PPI) network, followed by Gene Ontology(GO) functional and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses. A visual signal pathway rela-ted to Chinese medicine and disease targets was constructed. The CRF model was induced by paclitaxel(PTX) in mice. Mice were divided into a control group, a PTX model group, and low-and high-dose Cistanches Herba extract groups(250 and 500 mg·kg~(-1)). The anti-CRF effect in mice was evaluated by open field test, tail suspension test, and exhaustive swimming time, and the pathological morphology of skeletal muscle was evaluated by hematoxylin-eosin(HE) staining. The cancer cachexia model in C2C12 muscle cells was induced by C26 co-culture, and the cells were divided into a control group, a conditioned medium model group, and low-, medium-, and high-dose Cistanches Herba extract groups(62.5, 125, and 250 µg·mL~(-1)). The reactive oxygen species(ROS) content in each group was detected by flow cytometry, and the intracellular mitochondrial status was evaluated by transmission electron microscopy. The protein expression levels of hypoxia-inducible factor-1α(HIF-1α), BNIP3L, and Beclin-1 were detected by Western blot. Six effective constituents were screened out from Cistanches Herba. The core genes of Cistanches Herba in treating CRF were AKT1, IL-6, VEGFA, CASP3, JUN, EGFR, MYC, EGF, MAPK1, PTGS2, MMP9, IL-1B, FOS, and IL10, and the pathways related to CRF were AGE-RAGE and HIF-1α. Through GO enrichment analysis, it was found that the main biological functions involved were lipid peroxidation, nutrient deficiency, chemical stress, oxidative stress, oxygen content, and other biological processes. The results of the in vivo experiment showed that Cistanches Herba extract could significantly improve skeletal muscle atrophy in mice to relieve CRF. The in vitro experiment showed that Cistanches Herba extract could significantly reduce the content of intracellular ROS, the percentage of mitochondrial fragmentation, and the protein expression of Beclin-1 and increase the number of autophagosomes and the protein expression of HIF-1α and BNIP3L. Cistanches Herba showed a good anti-CRF effect, and its mechanism may be related to the key target proteins in the HIF-1α signaling pathway.
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Cistanche , Medicamentos de Ervas Chinesas , Neoplasias , Animais , Camundongos , Farmacologia em Rede , Proteína Beclina-1 , Espécies Reativas de Oxigênio , Extratos Vegetais , Medicamentos de Ervas Chinesas/farmacologia , Simulação de Acoplamento Molecular , Medicina Tradicional Chinesa , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Neoplasias/genéticaRESUMO
Cistanche tubulosa is a traditional Chinese herbal medicine that is widely used to regulate immunity, and phenylethanol glycosides (CPhGs) are among the primary components responsible for this activity. However, the application of CPhGs is negatively affected by their poor absorption and low oral utilization. Targeted drug delivery is an important development direction for pharmaceutics. Previous studies have indicated that CPhGs could block the conduction of the signaling pathways in TGF-ß1/smad and inhibit the activation of hepatic stellate cells (HSCs). The aim of this study was to evaluate the anti-hepatic fibrosis effect of CPhG liposomes by inhibiting HSC activation, promoting apoptosis, blocking the cell cycle, suppressing the conduction of signaling pathways in focal adhesion kinase(FAK)/phosphatidylinositol-3-kinase(PI3K)/protein kinase B(Akt), and determining their in vitro hepatoprotective activity. In vitro release studies demonstrated that CPhG liposomes have a sustained release effect compared to drug CPhGs. HSC proliferation was inhibited after treatment with the CPhG liposomes (29.45, 14.72, 7.36 µg/mL), with IC50 values of 42.54 µg/mL in the MTT assay. Different concentrations of the CPhG liposomes could inhibit HSC proliferation, promote apoptosis, and block the cell cycle. The MTT method showed an obvious inhibition of HSC proliferation after CPhG liposome and Recombinant Rat Platelet-derived growth factor-BB(rrPDGF-BB) treatment. The levels of collagen-1, metallopeptidase inhibitor 1 (TIMP-1), α smooth muscle actin (α-SMA), and phosphorylated PI3K/Akt were downregulated, and matrix metalloproteinase-1 (MMP-1) was upregulated, by pretreatment with different concentrations of CPhG liposomes. Moreover, 29.45 µg/mL of CPhG liposomes could decrease the expression of the FAK protein and the phosphorylated PI3K and Akt protein downstream of FAK by overexpression of the FAK gene. This experiment suggests that CPhG liposomes may inhibit the activation of HSCs by inhibiting FAK and then reducing the expression of phosphorylated Akt/PI3K, thereby providing new insights into the application of CPhGs for liver fibrosis.
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Cistanche/química , Sistemas de Liberação de Medicamentos , Glicosídeos/farmacologia , Álcool Feniletílico/farmacologia , Animais , Apoptose/efeitos dos fármacos , Becaplermina/química , Becaplermina/genética , Becaplermina/farmacologia , Proliferação de Células/efeitos dos fármacos , Quinase 1 de Adesão Focal/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Glicosídeos/química , Células Estreladas do Fígado/efeitos dos fármacos , Humanos , Imunidade/efeitos dos fármacos , Lipossomos/química , Lipossomos/farmacologia , Medicina Tradicional Chinesa , Álcool Feniletílico/química , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-akt/genética , RatosRESUMO
Cistanche tubulosa is a traditional Chinese herbal medicine widely used for regulating immunity and phenylethanol glycosides (CPhGs) are among the primary components responsible for this activity. Previous studies have indicated the preventive and therapeutic effects of CPhGs on bovine serum albumin (BSA)-induced hepatic fibrosis in rats. The aim of the study was to evaluate the anti-hepatic fibrosis effect of CPhGs and the monomers echinacoside and acteoside by inhibiting hepatic stellate cell (HSC) activation, blocking the conduction of signaling pathways in transforming growth factor-ß1 (TGF-ß1)/smad, and determine their in vitro hepatoprotective activity. HSC proliferation was obviously inhibited after treatment with CPhGs (100, 50 µg/mL)/echinacoside (500, 250, 125 µg/mL)/acteoside (6, 3 µg/mL), with IC50 values of 119.125, 520.345 and 6.999 µg/mL, respectively, in the MTT assay. Different concentrations of CPhGs/echinacoside/acteoside did not affect the cellular toxicity on HSC according to lactate dehydrogenase (LDH) measurements. Different concentrations of CPhGs/echinacoside/acteoside increased the mRNA level and protein expression of smad7, and decreased the mRNA levels of smad2, smad3 and the protein expression of smad2, phospho-smad2 (p-smad2), smad3, phospho-smad3 (p-smad3) in HSC. In summary, these results demonstrate that CPhGs/echinacoside/acteoside can block the conduction of the signaling pathways in TGF-ß1/smad, and inhibit the activation of HSC, suggesting that C. tubulosa may thus be a potential herbal medicine for the treatment of liver fibrosis.
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Cistanche/química , Glucosídeos/farmacologia , Glicosídeos/farmacologia , Células Estreladas do Fígado/efeitos dos fármacos , Fenóis/farmacologia , Substâncias Protetoras/farmacologia , Proteínas Smad/genética , Fator de Crescimento Transformador beta1/antagonistas & inibidores , Animais , Linhagem Celular , Regulação da Expressão Gênica , Glucosídeos/isolamento & purificação , Glicosídeos/isolamento & purificação , Células Estreladas do Fígado/citologia , Células Estreladas do Fígado/metabolismo , L-Lactato Desidrogenase/genética , L-Lactato Desidrogenase/metabolismo , Fenóis/isolamento & purificação , Extratos Vegetais/química , Substâncias Protetoras/isolamento & purificação , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Transdução de Sinais/efeitos dos fármacos , Proteínas Smad/metabolismo , Fator de Crescimento Transformador beta1/farmacologiaRESUMO
A type of novel rhodanine-based 4-anilinoquinazoline, which designed the combination between quinazoline as the backbone and various substituted biological rhodanine groups as the side chain, have been synthesized, and their antiproliferative activities were also evaluated firstly. These compounds displayed good antiproliferative activity and EGFR-TK inhibitory activity. Among them, compound 8d showed good inhibitory activity (IC50=2.7µM for Hep G2, IC50=3.1µM for A549) and molecular docking of 8d into EGFR TK active site was also performed, this inhibitor well fitting the active site might well explain its excellent inhibitory activity.
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Compostos de Anilina/síntese química , Antineoplásicos/síntese química , Receptores ErbB/antagonistas & inibidores , Inibidores de Proteínas Quinases/síntese química , Quinazolinas/síntese química , Rodanina/química , Compostos de Anilina/farmacologia , Antineoplásicos/farmacologia , Domínio Catalítico , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Receptores ErbB/química , Receptores ErbB/metabolismo , Humanos , Simulação de Acoplamento Molecular , Ligação Proteica , Inibidores de Proteínas Quinases/farmacologia , Quinazolinas/farmacologia , Relação Estrutura-AtividadeRESUMO
BACKGROUND: Patients rarely develop complicated infections in thyroid cysts. Here, we describe a patient with chronic infected unilateral giant thyroid cyst related to diabetes mellitus (DM). CASE SUMMARY: A 66-year-old male was admitted due to an evident neck lump for 5 d after approximately 40 years of gradually progressive neck mass and 7 years of DM. Doppler ultrasound and computed tomography scan showed a giant lump in the left thyroid gland lobe. He was diagnosed with a large thyroid nodule complicated by tracheal dislocation and had surgical indications. Surgical exploration revealed evident inflammatory edema and exudation between the left anterior neck muscles, the nodule and glandular tissue. Fortunately, inflammatory lesions did not affect major neck vessels. Finally, a left partial thyroidectomy was performed. Macroscopic observation showed that the cystic thyroid mass consisted of extensive cystic wall calcification and was rich in massive rough sand-like calculi content and purulent matter. Postoperative pathology confirmed benign thyroid cyst with chronic infection. CONCLUSION: The progression of this chronic infectious unilateral giant thyroid cyst may have been related to DM, and identifying blood vessels involvement can prevent serious complications during operation.
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Mornaphthoate E (MPE) is a prenylated naphthoic acid methyl ester isolated from the roots of a famous Chinese medicinal plant Morinda officinalis and shows remarkable cytotoxicity against several human tumor cell lines. In the current project, the first total synthesis of (±)-MPE was achieved in seven steps and 5.6% overall yield. Then the in vitro anti-tumor activity of MPE was first assessed for both enantiomers in two breast cancer cells, with the levoisomer exerting slightly better potency. The in vivo anti-tumor effect was further verified by applying the racemate in an orthotopic autograft mouse model. Notably, MPE exerted promising anti-metastasis activity both in vitro and in vivo and showed no obvious toxicity on mice at the therapeutic dosage. Mechanistic investigations demonstrated that MPE acted as a tubulin polymerization stabilizer and disturbed the dynamic equilibrium of microtubules via regulating PI3K/Akt signaling. In conclusion, our work has provided a new chemical template for the future design and development of next-generation tubulin-targeting chemotherapies.
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BACKGROUND: The association between tumor-infiltrating lymphocyte (TIL) levels and the response to neoadjuvant therapy (NAT) in patients with triple-negative breast cancer (TNBC) remains unclear. AIM: To investigate the predictive potential of TIL levels for the response to NAT in TNBC patients. METHODS: A systematic search of the National Center for Biotechnology Information PubMed database was performed to collect relevant published literature prior to August 31, 2023. The correlation between TIL levels and the NAT pathologic complete response (pCR) in TNBC patients was assessed using a systematic review and meta-analysis. Subgroup analysis, sensitivity analysis, and publication bias analysis were also conducted. RESULTS: A total of 32 studies were included in this meta-analysis. The overall meta-analysis results indicated that the pCR rate after NAT treatment in TNBC patients in the high TIL subgroup was significantly greater than that in patients in the low TIL subgroup (48.0% vs 27.7%) (risk ratio 2.01; 95% confidence interval 1.77-2.29; P < 0.001, I 2 = 56%). Subgroup analysis revealed that the between-study heterogeneity originated from differences in study design, TIL level cutoffs, and study populations. Publication bias could have existed in the included studies. The meta-analysis based on different NAT protocols revealed that all TNBC patients with high levels of TILs had a greater rate of pCR after NAT treatment in all protocols (all P ≤ 0.01), and there was no significant between-protocol difference in the statistics among the different NAT protocols (P = 0.29). Additionally, sensitivity analysis demonstrated that the overall results of the meta-analysis remained consistent when the included studies were individually excluded. CONCLUSION: TILs can serve as a predictor of the response to NAT treatment in TNBC patients. TNBC patients with high levels of TILs exhibit a greater NAT pCR rate than those with low levels of TILs, and this predictive capability is consistent across different NAT regimens.
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I2-promoted domino reactions of isatins or 3-hydroxyindolin-2-one derivatives with enaminones under O2 conditions have been established. The reactions of isatins with enaminones afforded functionalized tetracyclic pyrrolo[2,3,4-kl]acridine derivatives in moderate to good yields through domino cyclization and C-H oxidation. The reactions of 3-hydroxyindolin-2-one derivatives with enaminones proceeded well to give functionalized pyrrolo[2,3,4-kl]acridine derivatives via tandem ring-opening/recyclization/methyl migration sequences with two C-C bonds cleaved.
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Acridinas/síntese química , Aminas/química , Indóis/química , Iodo/química , Isatina/química , Oxigênio/química , Pirróis/síntese química , Acridinas/química , Ciclização , Estrutura Molecular , Pirróis/químicaRESUMO
BACKGROUND: Over the past several decades the prevalence of adolescent non-suicidal self-injury (NSSI) has been rising steadily. Understanding the factors associated with NSSI is a critical public health concern. The current study aims to explore the critical factors related to NSSI among Chinese adolescents. METHODS: A systematic literature search was conducted to identify the studies meeting our eligibility criteria (published until June 2022) in PubMed, Web of Science, Science Direct, Springer Link, CNKI, VIP, and Wanfang data. The meta-package of R language was used to perform a meta-analysis to compute the pooled effect (r). RESULTS: A total of 59 studies were included in this analysis, with a sample size of 192,546. Twenty-four democratic, personal, and social factors were examined in current study. The pooled effect value (r) has revealed that 23 factors are associated with NSSI behaviors among Chinese adolescents. The factor, Internet addiction, has demonstrated the greatest association with NSSI compared to other factors. CONCLUSION: Consistent with previous studies on adolescent NSSI, findings have demonstrated that a number of demographic, personal, and social factors significantly contribute to NSSI behaviors among Chinese adolescents. Future research on prevention and intervention for adolescent NSSI may benefit from targeting these factors.
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OBJECTIVES: Primary gallbladder neuroendocrine carcinomas (GB-NEC) are malignant neoplasms that remained to be studied. In this study we aimed to summarize their clinicopathological characteristics, effective treatment and prognostic factors for patients with GB-NEC. METHODS: Patients with GB-NEC admitted to Shanghai Jiao Tong University Affiliated Sixth People's Hospital and Renji Hospital, School of Medicine, Shanghai Jiao Tong University from October 2012 to August 2020 were enrolled. Clinicopathological characteristics of our patients and those reported in previous studies were recorded. The Kaplan-Meier method and univariate and multivariate Cox regression analyses were used for survival analysis. RESULTS: Altogether 15 patients from our hospitals and 47 patients from previous studies were included. A total of 55 patients who underwent surgical resection, including R0 and non-R0 resection, had significantly longer overall survival compared with the other seven patients. A univariate analysis indicated that patients aged 60 years or older, with jaundice, carcinoid syndrome, non-R0 resection, and advanced stage were associated with worse survival. A multivariate analysis showed that patients aged 60 years or older, carcinoid syndrome and non-R0 resection, but not lymphadenectomy and adjuvant chemotherapy, were independently related to reduced survival. CONCLUSIONS: R0 resection should be the first-line treatment for GB-NEC. Older age, carcinoid syndrome and non-R0 resection are independently associated with reduced survival after surgical resection.
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Carcinoma Neuroendócrino , Neoplasias da Vesícula Biliar , Carcinoma Neuroendócrino/patologia , Carcinoma Neuroendócrino/cirurgia , China/epidemiologia , Vesícula Biliar/patologia , Neoplasias da Vesícula Biliar/cirurgia , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos RetrospectivosRESUMO
A simple and efficient protocol was developed for the preparation of challenging α-aryl primary amides. This metal-free coupling process was triggered by TfOH-promoted electrophilic activation of α-silyl nitrile to generate keteniminium ion species, followed by reaction with aryl sulfoxide through [3,3]-sigmatrophic rearrangement to provide the target product. To the best of our knowledge, α-silyl nitrile has been rarely used as a pro-electrophilic reagent. Computational investigations confirmed the transient existence of a highly electrophilic keteniminium intermediate.
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Phenylethanol glycosides (CPhGs) are the core material basis of pharmacological activity in Cistanche tubulosa and have a variety of pharmacological effects. However, it is unclear whether CPhGs have an ameliorative effect on pressure overload-induced myocardial hypertrophy. In this study, male SD rats weighing (200 ± 20) g were established cardiac hypertrophy models by abdominal aortic coarctation (AAC). After operation, the rats were gavaged with corresponding medicine for 6 weeks (CPhGs 125, 250, and 500 mg/kg/d and valsartan 8.3 mg/kg/d). Echocardiography, heart weight index (HWI), cross-sectional area of cardiomyocytes (CSCA), fibrosis area, plasma endothelin 1(ET-1), and proinflammatory factors levels were detected. Our results showed that different CPhGs dosage decreased left ventricular posterior wall thickness (LVPWT), left ventricular end-diastolic diameter (LVED), HWI, CSCA, fibrosis area, ET-1, proinflammatory factors, arterial natriuretic peptide (ANP), brain natriuretic peptide (BNP), endothelin converting enzyme 1(ECE-1) mRNA levels, cyclooxygenase 2 (COX-2), high mobility group box 1 (HMGB-1) protein levels, and ECE-1 demethylation level while increasing left ventricular ejection fractions (LVEF), left ventricular fractional shortening (LVFS), phosphorylated phosphatidylinositol 3-kinase (p-PI3K), phosphorylated protein kinase B (p-PKB), and phosphorylated endothelial nitric oxide synthetase (p-eNOS). The indexes of CPhGs 250 and 500 mg/kg group were significantly different from AAC group; compared with valsartan group (AV), the indexes of CPhGs 500 mg/kg group were not significantly different. In conclusion, CPhGs ameliorated myocardial hypertrophy rats by AAC, which may be related to ECE-1 demethylation inhibition and PI3K/PKB/eNOS enhancement.
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Deformities of the maxillofacial region following trauma and ablative surgery are devastating and not uncommon. Reconstruction of such defects is a surgically challenging procedure. Conventionally, reconstruction of dental arch defects lacks preoperative customised planning and relies heavily on the surgeon experience to ensure optimum surgical outcomes. The restoration of the dental arch shape and function has taken precedence after an extensive tumour resection surgery, especially in the current age of technological advancement. Thus, personalised and accurate reconstruction of dental arch defects has become a new goal. Computer-assisted surgery, especially navigation-assisted surgery, has gained popularity of late, in reconstructing deformities and restoring facial symmetry, appearance and function in the maxillofacial region. This technology provides a clearer three-dimensional visualisation of the area of interest and its relationship with the adjacent vital structures. Together with preoperative virtual surgical planning, it allows more specific and accurate osteotomies, thus reducing the ischemia and total operating times substantially. The risk of complications is also minimised whilst improving the final surgical outcomes. The use of the intraoperative navigation system and other computer-assisted surgical techniques during surgery can significantly improve the precision of the reconstruction of dental arch deformities, and achieve personalised and functional reconstructive goals while enhancing the quality of life of patients postoperatively. The Society of Oral and Maxillofacial Surgery, Chinese Stomatological Association provides the present professional perspective and treatment protocol for navigation-guided reconstruction of dental arch defects, to allow standardisation of the technique while promoting its application among oral and maxillofacial surgeons.
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Procedimentos de Cirurgia Plástica , Cirurgia Assistida por Computador , Algoritmos , Consenso , Humanos , Imageamento Tridimensional , Qualidade de VidaRESUMO
The zygoma is located in the medial and lateral parts of the face, supporting the midfacial contour. The forward projection of the zygoma and the zygomatic arch often expose them to injury. Fractures of the zygoma can lead to the displacement of the zygoma and the zygomatic arch, causing facial collapse deformity. For delayed zygomatic fractures, the loss of normal anatomical landmarks caused by the malunion of the fracture lines and remodelling of the bony contour makes it difficult to determine the correct positions of the zygomatic bones. In such cases, ideal and steady outcomes with satisfactory midface symmetry have been difficult to obtain using traditional surgical methods. Nowadays, the application of digital surgical software and surgical navigation helps surgeons to perform accurate preoperative simulations to obtain ideal three-dimensional virtual surgical plans and achieve accurate reduction by intraoperative navigation systems, which increase the accuracy and predictability of fracture reduction outcomes. Experts from the Society of Oral and Maxillofacial Surgery, Chinese Stomatological Association have fully discussed and formulated an expert consensus on navigation-guided unilateral delayed zygomatic fracture reconstruction techniques to standardise the clinical operation procedures and promote the application.
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Procedimentos de Cirurgia Plástica , Fraturas Zigomáticas , Consenso , Ossos Faciais , Humanos , ZigomaRESUMO
Orbital fracture and orbital floor reconstruction surgery is characterised by limited surgical exposure and high risks. Before the advent of digital technology, the design and implementation of the surgical scheme for orbital floor reconstruction surgery mainly depended on the intuitive understanding of imaging and the clinical experience of surgeons, with strong unpredictability and experience dependence. Surgical navigation systems with real-time positioning and imaging functions, when used in orbital reconstruction surgery, can detect the real-time intraoperative position, avoid risks, and assist in locating the reconstruction position to ensure the accuracy of orbital reconstruction, with the help of a preoperative surgical plan. Many studies have confirmed its effect. Unilateral orbital fracture and orbital floor reconstruction surgery is one of the earliest and most widely used surgical techniques in maxillofacial surgery. Experts from the Society of Oral and Maxillofacial Surgery, Chinese Stomatological Association have fully discussed and formulated this expert consensus on navigation-guided unilateral orbital fracture and orbital floor reconstruction techniques to standardise the clinical surgical procedures and promote its application.
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Fraturas Orbitárias , Procedimentos de Cirurgia Plástica , Cirurgia Assistida por Computador , Consenso , Humanos , ÓrbitaRESUMO
Skull base surgery is an interdisciplinary subject. The anatomical structures in the skull base related to oral and maxillofacial surgery include the parapharyngeal space, the pterygopalatine fossa and the infratemporal space. This operative area is one of the most challenging surgical areas in oral and maxillofacial surgery due to its deep site, complex anatomy and high risk. Obtaining pathological information of the tumour preoperatively may help surgeons optimise their treatment plan. Needle biopsy is one of the major minimally invasive techniques that allows preoperative pathological results to be obtained. The navigation technology, which is developing rapidly nowadays, provides a reliable assistance for deep tissue biopsy surgery. Experts from the Society of Oral and Maxillofacial Surgery, Chinese Stomatological Association formulated an expert consensus on the procedures and operations of navigation-guided needle biopsy techniques for skull base tumours, so as to standardise and promote the application and operation of navigation-guided needle biopsy for skull base tumours.
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Neoplasias da Base do Crânio , Biópsia por Agulha , Consenso , Endoscopia , Humanos , Base do CrânioRESUMO
In the title compound, C(16)H(13)N(3)S(2), the dihedral angle between the two benzothia-zole ring systems is 20.41â (2)°. In the crystal structure, inter-molecular N-Hâ¯N hydrogen bonds link mol-ecules into a chain along the b axis. The packing is further stabilized by C-Hâ¯π stacking inter-actions involving the two benzothia-zole ring systems.
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In the title compound, C(14)H(19)N(3)O(2)S, the N atom of the dimethyl-amino group and the S atom are displaced by 0.078â (2) and 0.084â (2)â Å, respectively, from the naphthalene ring plane. The 2-amino-ethyl group has a coiled conformation with an N-C-C-NH(2) torsion angle of 53.6â (4)°. In the crystal structure, inter-molecular N-Hâ¯N and weak C-Hâ¯O hydrogen bonds link mol-ecules into chains along [001].
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The rs2910164 single nucleotide polymorphism (SNP) in miR-146a has been implicated in the etiology of psoriasis in different relevant studies with contradictory conclusions and limited sample size. Therefore, the aim of this study was to undertake a systematic review and meta-analysis to estimate the association between rs2910164 SNP and psoriasis. We searched the databases of PubMed, EMBASE, Web of Science, WanFang, and Chinese National Knowledge Infrastructure (CNKI) to identify relevant literatures published before July 15, 2018. Four case-control studies including 2212 cases and 2274 healthy controls from 4 different countries met the predetermined criteria. The effect size was pooled by odds ratios (ORs) and 95% confidence intervals (95%CIs). Recessive model (CC vs CG+GG) was confirmed to be the optimal model. The results indicated that rs2910164 SNP was significantly associated with psoriasis (ORâ=â0.74, 95%CI 0.60-0.91, Pâ=â.004), and individuals with CC-genotype were predisposed to have decreased risk of psoriasis.
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Predisposição Genética para Doença/genética , MicroRNAs/genética , Polimorfismo de Nucleotídeo Único/genética , Psoríase/genética , Estudos de Casos e Controles , Estudos de Associação Genética , Genótipo , Humanos , Razão de ChancesRESUMO
In the title mol-ecule, C(15)H(15)N(3)O(2)S, the dihedral angle between the naphthalene ring system and the imidazole ring is 86.1â (2)°. In the crystal structure, weak inter-molecular C-Hâ¯O and C-Hâ¯N hydrogen bonds, as well as weak C-Hâ¯π inter-actions, connect mol-ecules, forming a two-dimensional network.