The study of genomic divergence between humans and primates may provide insight into the origins of human beings and the genetic basis of unique human traits and diseases. Chromosome 21 is the smallest chromosome in the human genome, and some of its regions have been implicated in mental retardation and other diseases. In this study, we sequenced the coding and regulatory regions of 127 known genes on human chromosome 21 in DNA samples from human and chimpanzees and a part of the corresponding genes from orangutan, gorilla, and macaque. Overall, 3,003 nucleotide differences between human and chimpanzee were identified over Ϸ400 kb. The differences in coding, promoter, and exon-intron junction regions were 0.51 ؎ 0.02%, 0.88 ؎ 0.03%, and 0.85 ؎ 0.02%, respectively, much lower than the previously reported 1.23% in genomic regions, which suggests the presence of purifying selection. Significant variation in substitution rate among genes was observed by comparing the divergence between human and chimpanzee. Furthermore, by implementing a bioinformatics-based approach, we showed that the identification of genetic variants specific to the human lineage might lead to an understanding of the mechanisms that are attributable to the phenotypes that unique to humans, by changing the structure and͞or dosage of the proteins expressed. A phylogenetic analysis unambiguously confirms the conclusion that chimpanzees were our closest relatives to the exclusion of other primates and the relative divergence of the Homo-Pan and that of (Homo-Pan)-Gorilla are 4.93 million years and 7.26 million years, respectively.
Persistently increasing incident of cancer in human beings has served to emphasize the importance of studies on mechanism of antitumor substances. Chlorogenic acid (CA), extracted from folium cortex eucommiae, has been confirmed to have lots of biological activities encompassing inhibition of tumor. However, the anticancer mechanism of CA remains unclear. Here, we have utilized a whole mouse genome oligo microarray (4∗44K) to analyze gene expression level of female BALB/c mice (implanted with EMT-6 sarcoma cells) after treatment with low, medium, and high-dose CA (5 mg/kg, 10 mg/kg, and 20 mg/kg), docetaxel, interferon, and normal saline separately at 6 time points (3rd, 6th, 9th, 12th, 15th, and 18th days after administration). Differentially expressed genes screened out by time-series analysis, GO analysis, and pathway analysis, and four immune-related genes were selected for further confirmation using RT-qPCR. The results demonstrated that CA is able to change gene expression and that the responsive genes (CaN, NFATC2, NFATC2ip, and NFATC3) involved in immune pathways had been significantly upregulated by CA. Expression of immune factors such as IL-2R and IFN-γ can be improved by CA to promote activation and proliferation of T cells, macrophages, and NK cells, thus enhancing their surveillance and killing abilities, further suppressing the growth rate of tumor cells.
Head and neck cancers (HNC) are one of the ten leading cancers worldwide, including a range of malignant tumors arising from the upper neck. Due to the complex mechanisms of HNC and lack of effective biomarkers, the 5-year survival rate of HNC has been low and the mortality rate has been high in recent decades. Long noncoding RNAs (lncRNAs), noncoding RNAs longer than 200 bps, are a focus of current cancer research, closely related to tumor biology. LncRNAs have been revealed to be aberrantly expressed in various types of HNC, and the dysregulated lncRNAs participate in HNC progression and induce malignant behavior by modulating gene expression at diverse levels. This review will focus on the functions and molecular mechanisms of dysregulated lncRNAs in HNC tumorigenesis and progression, as well as their diagnostic, therapeutic or prognostic implications in HNC.
Object: The aims of the study were to explore the protective effects of S-propargyl-cysteine (SPRC) on periodontitis and to determine the underlying mechanisms.Methods: A rat periodontitis model was constructed by injecting LPS and SPRC (0, 25, and 50 mg/kg/d) was administered intraperitoneally. H2S and CSE level were detected. The alveolar bone level was evaluated by micro-CT, HE staining and methylene blue staining analysis. Inflammation-related factors, Treg and Th17 cells were detected by immunohistochemistry, RT-PCR, immunofluorescence, Western blot and flow cytometry. Phosphorylation levels of ERK1/2 and CREB were analysed.Results: The administration of SPRC significantly increased the expression of CSE in the gingival tissue and the concentration of endogenous H2S in the peripheral blood. Simultaneously, SPRC significantly inhibited the resorption of alveolar bone based on the H&E staining, micro-CT and methylene blue staining analysis. Compared with the periodontitis group, the levels of IL-17A, IL-10 were downregulated and IL-6,TGF-β1 were upregulated in the SPRC groups. In the SPRC group, the percentage of TH17 cells and the expression of ROR-γt were downregulated, while the percentage of Tregs and the expression of Foxp3 were upregulated accompanied with inhibition of phosphorylation ERK1/2 and CREB.Conclusion: SPRC can prevent the progression of periodontitis by regulating the Th17/Treg balance by inhibition of the ERK/CREB signalling pathway.
Abstract. Laryngeal adenoid cystic carcinoma (ACC) is extremely rare, worldwide. From January 1994 to January 2014, all cases of laryngeal ACC that were diagnosed in the four largest hospitals in Hainan province, were reviewed. Only two such cases were identified. The first patient had a tumor in the subglottic region and the second patient, in the glottic region. The patient with subglottic ACC, who had experienced ongoing symptoms for 3 years, had previously been diagnosed with asthma, at a local hospital. Both presented at an advanced stage. The patient with subglottic disease received a total laryngectomy with a positive surgical margin, was treated with adjuvant radiotherapy, and later succumbed to a pleural effusion as a result of pulmonary metastases. The patient with glottic disease received a partial laryngectomy and declined adjuvant radiotherapy. Subsequently, she developed recurrent disease and passed away following an episode of asphyxia at 14 months post-surgery. Each of these cases had a poor prognosis at presentation. For patients with locoregionally advanced laryngeal ACC, more effective management strategies are required.
Porphyromonas gingivalis (P. gingivalis) is a Gram-negative anaerobic pathogen that is involved in the pathogenesis of periodontitis and systemic diseases. P. gingivalis has recently been detected in rheumatoid arthritis (RA), cardiovascular disease, and tumors, as well as Alzheimer’s disease (AD), and the presence of P. gingivalis in these diseases are correlated with poor prognosis. Macrophages are major innate immune cells which modulate immune responses against pathogens, however, multiple bacteria have evolved abilities to evade or even subvert the macrophages’ immune response, in which subsequently promote the diseases’ initiation and progression. P. gingivalis as a keystone pathogen of periodontitis has received increasing attention for the onset and development of systemic diseases. P. gingivalis induces macrophage polarization and inflammasome activation. It also causes immune response evasion which plays important roles in promoting inflammatory diseases, autoimmune diseases, and tumor development. In this review, we summarize recent discoveries on the interaction of P. gingivalis and macrophages in relevant disease development and progression, such as periodontitis, atherosclerosis, RA, AD, and cancers, aiming to provide an in-depth mechanistic understanding of this interaction and potential therapeutic strategies.
The early detection of surgical site infection (SSI) remains an unsolved problem. Inflammatory factors in fluids drained from surgical sites may be a promising tool for predicting SSI. Previous attempts to predict SSI via such factors have not taken baseline concentrations into account. However, this may have comprised predictive efficacy. In the current study, concentrations of C-reactive protein (CRP) and interleukin 6 (IL-6) in fluid samples drained from surgical sites in 20 patients with SSI and 60 matched controls were assessed, and concentrations from day 2 to day 4 were divided by the concentration at day 1 to achieve concentration standardization. There were no significant differences of CRP or IL-6 concentrations at day 1 or day 2 ( p > 0.05), but there were significant differences at day 3 and day 4 ( p < 0.05). The areas under the curve (AUCs) for SSI of standardized concentrations were higher than those of the corresponding absolute concentrations of CRP and IL-6 in fluid drained at days 3 and 4. Standardized concentrations of CRP at day 4 yielded the highest AUC (0.92; 95% confidence interval: 0.84–0.97), with a sensitivity of 90% and specificity of 80% at the best cutoff. Concentration standardization may improve the efficacy of predicting SSI via CRP and IL-6 in fluids drained from surgical sites. Although the sample size was small, the study demonstrated the feasibility of non-invasive, accurate, and early detection of postoperative SSI in a diverse real population. Further studies are needed to validate the results of the present study and investigate their broader applicability. Impact statement The ability to predict surgical site infections (SSIs) early would be advantageous. Previous studies have investigated the use of inflammatory factors in fluids drained from surgical sites to predict SSI, but the diagnostic efficacy of this method requires improvement. Baseline levels of inflammatory factors vary between individuals, but this variation tends to differ in patients with and without SSIs. Therefore, we standardized subsequently acquired concentrations of interleukin 6 and C-reactive protein in fluids drained from surgical sites by dividing them by the concentrations determined at day 1 to preclude the confounding effects of differences in baseline levels. The standardized concentrations had higher predictive efficacy than the absolute concentrations. Standardizing the data rendered SSI prediction more precise and practical in a diverse group of real patients. This translational study suggests that inflammatory factors in fluid drained from injury sites are promising tools for the prediction of SSI in the clinic.
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