Can methylated purine bases act as photoionization hotspots?

The direct photoionization of DNA canonical bases under ultraviolet radiation is difficult due to the high ionization potentials. According to previous quantum chemical calculations, methylation can have great influence on the ionization potential. Are methylated nucleobases prone to photoionization and cause DNA damage? As an important epigenetic modification in transcription, expression, and regulation of genes, it is of great biological significance to explore the effect of methylation on base photoionization from the experimental perspective. Herein, we study the photoionization behavior of methylated purines 6 mA and 6mG at 266 nm using a nanosecond transient UV-Vis spectroscopy. The hydrated electron and methylated base radicals are observed, indicating the occurrence of photoionization for both 6mG and 6 mA. We measured one-photon ionization yields to be (5.0 ± 0.2) × 10-3 and (1.4 ± 0.2) × 10-3 for 6mG and 6 mA, respectively. These are higher than those of (dA)20 and (dA20 )·(dT20 ) previously reported, indicating that methylation significantly promotes base photoionization with a stronger effect than base stacking, consistent with calculations in literature. Given that the hydrated electrons and methylated base radicals from photoionization can trigger a cascade of deleterious reactions, the methylated purine bases may act as hotspots of DNA photoionization damage of living organisms.

A comparative study of bibliometric analysis on old adults' cognitive impairment based on Web of Science and CNKI via CiteSpace.

INTRODUCTION: The purpose of this study was to analyze the current status, the research hot spots and frontiers of cognitive impairment (CI) on old adults from 2012 to 2022 based on Web of Science (WoS) and China National Knowledge Infrastructure (CNKI) via CiteSpace, and provide new in-sights for researchers. METHODS: The articles regarding the old adults' CI in the WoS and CNKI were retrieved from 2012 to 2022. CiteSpaceV.6.1.R4 was used to generate network maps. RESULTS: Four thousand seven hundred thirteen publications and 304 publications from CNKI were retrieved. Overall, from 2012 to 2022, the trend of articles published in WoS and CNKI were increasing. Data from WoS showed that USA, University of California, Petersen RC were the most influential country, institution and author respectively; Folstein MF, Neurology and a diagnosis guideline of mild CI were the most cited author, journal and reference separately; while the keywords of CI could be summarized in 3 aspects: related disease and symptom, risk factors, manifestations. Data from CNKI illustrated that Peking Union Medical College, Dan Liu were the most influential institution and scholar respectively, while the keywords of CI could be summarized in 3 aspects: related disease and symptoms, risk factors, intervention. CONCLUSION: Articles published on old adults' CI were drawing an increasing amount of attention from 2012 to 2022 both in WoS and CNKI. Keywords of CI in WoS and CNKI both focused on risk factors, related disease and symptom, yet WoS contributed more to the mechanism and CNKI contributed more to the intervention.

Highly expressed long non-coding RNA SNHG14 activated MSU-induced inflammatory response in acute gout arthritis through targeting miR-223-3p.

AIM: According to reports, long non-coding RNAs (lncRNAs) are involved in the regulation of many inflammatory diseases. Here, our main purpose was to ascertain the expression data of lncRNA SNHG14 in acute gouty arthritis (AGA) and to explore its possible mechanism in the regulation of AGA. METHOD: Reverse transcription quantitative polymerase chain reaction technology was supplied to detect the lncRNA SNHG14 expression. A receiver operating characteristics curve was drawn to estimate the accuracy of lncRNA SNHG14 in AGA diagnosis. An in vitro AGA cell model was constructed by inducing THP-1 cells with monosodium urate (MSU). The concentrations of inflammatory factors such as interleukin-1ß, interleukin-6, and tumor necrosis factor-α were measured by enzyme-linked immunosorbent assay. The luciferase reporter gene was used to verify the relationship between lncRNA SNHG14 and miR-223-3p. RESULTS: In clinical analysis, the levels of serum lncRNA SNHG14 in AGA patients were significantly higher than those in the control group. Abnormally elevated lncRNA SNHG14 has high sensitivity and specificity for AGA diagnosis. In in vitro cell experiments, silencing lncRNA SNHG14 inhibited the inflammatory response of THP-1 cells stimulated by MSU, and the luciferase reporter gene proved that lncRNA SNHG14 could bind to miR-223-3p. In addition, the level of miR-223-3p declined in AGA patients and the AGA cell model. Overexpression of miR-223-3p is helpful to alleviate an MSU-induced inflammatory response. CONCLUSION: In the AGA cell model, lncRNA SNHG14, as an miR-223-3p sponge, induces a cellular inflammatory response by controlling the level of miR-223-3p, so aggravating the disease progress of AGA.

Abies spectabilis-Mediated Silver Nanoparticles Inhibits Cell Growth and Promotes Apoptosis in Breast Cancer MCF-7 Cells.

Breast cancer is the second most cause of mortality among women worldwide due to the uncontrolled proliferation of tumor cells in the mammary epithelial tissues. The silver nanoparticles were formulated from the Abies spectabilis leaf (AS-AgNPs) and characterized by various practices like UV-vis spectroscopy, FTIR, SEM, and XRD. The in vitro anticancer potential of fabricated AS-AgNPs against the MCF-7 cells were analyzed. The MTT test was executed to investigate the cytotoxic nature of fabricated AS-AgNPs against MCF-7 cells. The magnitudes of ROS accumulation and MMP level in the AS-AgNPs supplemented MCF-7 cells were studied using fluorescent staining techniques. Caspase activities were studied using assay kits. The contents of oxidative stress and antioxidant biomarker (TBARS, SOD, CAT, and GSH) levels were scrutinized by standard methods. The expressions of apoptotic markers like Bax and Bcl-2 in the AS-AgNPs administered MCF-7 cells were detected by RT-PCR assay. The MTT findings showed that both extract and fabricated AS-AgNPs remarkably decreased the MCF-7 cells. Nonetheless, both plant extract and AS-AgNPs did not affect the cell viability of MCF-10A cells. Furthermore, the fabricated AS-AgNPs improved the ROS accumulation, and depleted the MMP status in the MCF-7 cells. AS-AgNPs administered MCF-7 cells demonstrated the improved TBARS content and depleted antioxidants. The treatment with AS-AgNPs considerably elevated the caspase-9 and -3 activities and Bax expression, while decreasing the Bcl-2 expression in MCF-7 cells. Hence the current investigation reports that the formulated AS-AgNPs exhibited remarkable in vitro anticancer action against MCF-7 cells through increased ROS, oxidative stress, and apoptotic protein expression. The fabricated AS-AgNPs could be a possible anticancer remedy in the future.

Effects of microRNA-146a on the proliferation and apoptosis of human osteoarthritis chondrocytes by targeting TRAF6 through the NF-κB signalling pathway.

The present study aims to investigate the effects of miR-146a on the proliferation and apoptosis of human osteoarthritis (OA) chondrocytes by targeting tumour necrosis factor receptor-associated factor 6 (TRAF6) through nuclear factor-κB (NF-κB) signalling pathway. Human normal and OA chondrocytes were selected and divided into the normal group, blank group, negative control (NC) group, miR-146a mimics group, miR-146a inhibitors, miR-146a inhibitor + si-TRAF6 group and si-TRAF6 group. Quantitative real-time PCR (qRT-PCR) was applied to detect the expressions of miR-146a, TRAF6 mRNA and NF-κB mRNA. Western blotting was used to detect the protein expressions of TRAF6 and NF-κB. CCK-8 assay and flow cytometry were used to detect cell proliferation and apoptosis. Compared with normal chondrocytes, the expression of miR-146a decreased, while the mRNA and protein expressions of TRAF6 and NF-κB increased in OA chondrocytes. OA chondrocytes had a lower proliferation rate and a higher apoptosis rate than the normal chondrocytes. Compared with the blank, NC and si-TRAF6 groups, the expression of miR-146a increased in the miR-146a mimics group, but decreased in the miR-146a inhibitors and miR-146a inhibitor + si-TRAF6 groups. Compared with the blank, NC and miR-146a inhibitor + si-TRAF6 groups, the mRNA and protein expressions of TRAF6 and NF-κB decreased, cell proliferation rate increased and cell apoptosis rate decreased in the miR-146a mimics and si-TRAF6 groups, while opposite trends were observed in the miR-146a inhibitors group. Our study suggests that miR-146a could promote proliferation and inhibit apoptosis of OA chondrocytes by inhibiting TRAF6 expression and suppressing the activation of NF-κB signalling pathway.

Reduced miR­26a and miR­26b expression contributes to the pathogenesis of osteoarthritis via the promotion of p65 translocation.

Osteoarthritis (OA) is a common chronic joint disease, the etiology of which is complex. Disturbance to proinflammatory and anti­inflammatory signaling pathways is a major cause of OA. MicroRNAs (miRNAs/miR) are a group of endogenous, short, non­coding RNAs, the expression profile of which is disturbed in the cartilage of patients with OA. To determine the function of miRNAs during the progression of OA, the present study detected the expression levels of nine candidate miRNAs in cartilage samples from 33 patients with OA. The results demonstrated that miR­26a, miR­26b, miR­138 and miR­140 were downregulated in patients with OA. As predicted by a bioinformatics analysis and confirmed by luciferase assay and western blotting, the present study revealed that miR­26a and miR­26b are able to suppress karyopherin subunit alpha 3 (KPNA3) expression by targeting its 3'­untranslated region. Since KPNA3 is an important mediator that modulates nuclear factor (NF)­κB p65 translocation, the present study examined the impact of miR­26a and miR­26b on NF­κB signaling. The results indicated that transfection of cells with a miR­26a or miR­26b inhibitor may promote NF­κB p65 translocation from the cytoplasm to the nucleus via the upregulation of KPNA3. Furthermore, the expression levels of matrix metalloproteinase­3, ­9, ­13 and cyclooxygenase­2 were upregulated following transfection with a miR­26a or miR­26b inhibitor. These results indicate that downregulation of miR­26a and miR­26b may contribute to the pathogenesis of OA via promotion of the NF­κB signaling pathway. The present study sheds light on the pathogenesis of OA and may provide a target for the development of therapeutic methods for the treatment of OA.

[Diagnosis and treatment under arthroscope in meniscus injury in middle and old aged people].

OBJECTIVE: To summarize the characteristic manifestations in the middle and old aged people with meniscus injury and the outcome of the treatment under the arthroscope. METHODS: Fifty-two patients, aged 52-58 years, with meniscus injury to a total of 57 knee joints, were diagnosed and treated under the arthroscope. The history of their knee diseases was 1-21 years. Horizontal tears occurred in 19 knee joints, degenerative tears in 13 knee joints, complex tears in 9 knee joints, longitudinal tears in 5 knee joints, oblique tears in 4 knee joints, radial tears in 4 knee joints, and flap tears in 3 knee joints. Three meniscus tears were sutured and 54 meniscus tears were cut fully or partly under the arthroscope. RESULTS: All the postoperative patients were followed up for 6-15 months, and the average follow-up period after operation was 9 months. According to the DONG Tianxiang's standards for the therapy under the arthroscope, the excellent result was achieved in 39 knee joints, good in 12 knee joints, and fair in 6 knee joints, with no failure. The excellent and good rate was 89.5%. CONCLUSION: The clinical manifestations of meniscus injury are not typical in the middle and old aged people. The therapeutic effect with the help of the arthroscope is satisfactory with an advantage of minimal traumatic invasiveness to the knee joint.