Gingivitis crónica y otros campos de interferencia en pacientes con artritis del hombro

Introducción: La odontología holística es parte de la medicina biológica o neurofocal, dirigida a la prevención, el diagnóstico y el tratamiento relacionados con las enfermedades del sistema estomatognático en correlación con otras estructuras anatómicas, a fin de tratar al paciente de manera integral, en cuerpo, mente y alma. Objetivo: Identificar la presencia de gingivitis crónica y de otros campos de interferencia en pacientes con artritis del hombro. Métodos: Se realizó un estudio observacional, descriptivo y transversal de 24 pacientes con artritis del hombro, pertenecientes al área de salud del Policlínico Docente Carlos Juan Finlay en Santiago de Cuba, quienes fueron atendidos en la Clínica Estomatológica Provincial Docente Mártires del Moncada, desde noviembre del 2021 hasta mayo del 2022. Resultados: En la serie predominaron el sexo femenino (62,5 %) y el grupo etario de 35-59 años (75,0 %). De igual modo, la mayoría de los pacientes padecía gingivitis crónica (87,5 %), en tanto, los otros campos de interferencia mayormente hallados fueron la placa dentobacteriana (100 %) y la caries dental (58,3 %), que figuraron en todos los molares según el holograma del microsistema de dientes alemán. Conclusiones: Los campos de interferencia identificados con más frecuencia en la casuística fueron la gingivitis crónica grave, la placa dentobacteriana y la caries dental, los cuales estuvieron asociados a la artritis del hombro que aquejaba a los pacientes.

Introduction: Holistic dentistry is part of the biological or neurofocal medicine, directed to the prevention, diagnosis and treatment related to the diseases of the stomatognatic system in correlation with other anatomical structures, in order to treat the patient in an integral way, in body, mind and soul. Objective: To identify the presence of chronic gingivitis and other interference fields in patients with shoulder arthritis. Methods: An observational, descriptive and cross-sectional study of 24 patients with shoulder arthritis was carried out, who belonged to the health area of Carlos Juan Finlay Teaching Polyclinic in Santiago de Cuba. They were assisted in Mártires del Moncada Teaching Provincial Stomatological Clinic, from November, 2021 to May, 2022. Results: In the series there was a prevalence of the female sex (62.5%) and the 35-59 age group (75.0%). In a same way, most of the patients suffered from chronic gingivitis (87.5%), as long as the other mostly found interference fields were the dentobacterial plaque (100%) and dental cavity (58.3%) that were in all the molars according to the hologram of the German teeth microsystem. Conclusions: Severe chronic gingivitis, dentobacterial plaque and dental cavity were the most frequently identified interference fields in the case material, which were associated to the shoulder arthritis in patients.

Interferencia positiva de las paraproteínas en la determinación de bilirrubina total y su rol en el diagnóstico de gammapatías monoclonales / Positive interference of paraproteins in the determination of total bilirubin and its role in the diagnosis of monoclonal gammopathies / Interferência positiva de paraproteínas na determinação da bilirrubina total e seu papel no diagnóstico de gamopatias monoclonais

Resumen La interferencia por paraproteínas en los análisis clínicos ha sido extensamente informada a nivel mundial. Si bien se han propuesto estrategias metodológicas para evitar el informe de datos erróneos asociados a interferencias (p. ej. confirmación manual, sistema de alerta), en pocos casos se ha propuesto su detección como herramienta diagnóstica de patologías no sospechadas desde la clínica. A partir del trabajo conjunto de dos hospitales de la provincia de Buenos Aires se describió: i) la presencia de interferencia positiva de paraproteínas en la determinación de bilirrubina total con reactivos y autoanalizadores Wiener, y ii) su contribución, en un período inferior a los seis meses, a la detección de cuatro gammapatías no sospechadas (tres monoclonales). Se recomienda dar difusión de esta inferencia a nivel nacional y se propone un esquema de trabajo en laboratorio para identificar la interferencia así como un perfil mínimo de determinaciones para evaluar la existencia de gammapatías desconocidas.

Abstract Paraprotein interference in clinical biochemistry has been widely reported around the world. Methodological strategies have been proposed to avoid reporting erroneous data due to interferences (i.e. manual check, alert system); however, few cases have suggested its use as a diagnostic tool for unsuspected pathologies. Based on the joint work of two hospitals from Buenos Aires Province, the following has been described: i) the presence of positive interference of paraproteins in the assessment of total bilirubin with Wiener chemistry and autoanalizers, and ii) its contribution, in less than six months, to the diagnosis of four gammophaties previously unsuspected (three monoclonal ones). Sharing the occurrence of this interference in our country is recommended. An interference identification workflow is also propose, as well as a set of biochemical assays to evaluate the occurrence of unsuspected gammophaties.

Resumo A interferência da paraproteína na bioquímica clínica tem sido amplamente relatada em todo o mundo. Embora estratégias metodológicas para evitar a comunicação de dados errôneos associados a interferências tenham sido propostas (p. ex., verificação manual, sistema de alerta), em poucos casos sugerem seu uso como ferramenta diagnóstica para patologias não suspeitas a partir da clínica. Com base no trabalho conjunto de dois hospitais da Província de Buenos Aires, foi descrita: i) a presença de interferência positiva de paraproteínas na determinação da bilirrubina total com reagentes e autoanalisadores Wiener e ii) sua contribuição, em um período inferior aos seis meses, para o diagnóstico de quatro gamopatias não suspeitas (três monoclonais). Recomenda-se difundir essa interferência em nível nacional e se propõe um esquema de trabalho em laboratório para identificar a interferência bem como um perfil mínimo de determinações para avaliar a ocorrência de gamopatias desconhecidas.

Development of Vital Signal Monitoring System Based on Accelerometer / 中国医疗器械杂志

OBJECTIVE@#Reduce the number of false alarms and measurement time caused by movement interference by the sync waveform of the movement.@*METHODS@#Vital signal monitoring system based on motion sensor was developed, which collected and processed the vital signals continuously, optimized the features and results of vital signals and transmitted the vital signal results and alarms to the interface.@*RESULTS@#The system was tested in many departments, such as digestive department, cardiology department, internal medicine department, hepatobiliary surgery department and emergency department, and the total collection time was 1 940 h. The number of false electrocardiograph (ECG) alarms decreased by 82.8%, and the proportion of correct alarms increased by 28%. The average measurement time of non-invasive blood pressure (NIBP) decreased by 16.1 s. The total number of false respiratory rate measurement decreased by 71.9%.@*CONCLUSIONS@#False alarms and measurement failures can be avoided by the vital signal monitoring system based on accelerometer to reduce the alarm fatigue in clinic.

Prokaryotic expression, polyclonal antibody preparation, spatio-temporal expression profile and functional analysis of c-Myc of Helicoverpa armigera (Lepidoptera: Noctuidae) / 生物工程学报

c-Myc protein encoded by c-Myc (cellular-myelocytomatosis viral oncogene) gene regulates the related gene expression through the Wnt/β-catenin signaling pathway, and has received extensive attention in recent years. The purpose of this study was to express Helicoverpa armigera c-Myc gene (Ha-c-Myc) by using prokaryotic expression system, prepare the polyclonal antibody, examine the spatio-temporal expression profile of Ha-c-Myc, and investigate the possible function of Ha-c-Myc in regulating H. armigera sterol carrier protein-2 (SCP-2) gene expression. The Ha-c-Myc gene was amplified by PCR and cloned into a prokaryotic expression plasmid pET-32a(+). The recombinant plasmid pET-32a-Ha-c-Myc was transformed into Escherichia coli BL21. IPTG was used to induce the expression of the recombinant protein. Protein was purified by Ni2+-NTA column and used to immunize New Zealand rabbits for preparing the polyclonal antibody. The Ha-c-Myc expression levels in different developmental stages (egg, larva, prepupa, pupa, and adult) of H. armigera and different tissues (midgut, fat body, head, and epidermis) of the prepupa were determined by real-time quantitative reverse transcription PCR (qRT-PCR). Ha-c-Myc siRNA was synthesized and transfected into H. armigera Ha cells. The relative mRNA levels of Ha-c-Myc and HaSCP-2 in Ha cells were detected by qRT-PCR. Results showed that the pET-32a-Ha-c-Myc recombinant plasmid was constructed. The soluble Ha-c-Myc protein of about 65 kDa was expressed in E. coli. The polyclonal antibody was prepared. Western blotting analysis suggested that the antibody had high specificity. Enzyme linked immunosorbent assay (ELISA) showed that the titer of the antibody was high. Ha-c-Myc gene expressed at all developmental stages, with high levels in the early and late instars of larva, and the prepupal stage. Tissue expression profiles revealed that Ha-c-Myc expressed in various tissues of prepupa, with high expression level in the midgut, but low levels in the epidermis and fat body. RNAi results showed that the knockdown of Ha-c-Myc expression significantly affected transcription of HaSCP-2, leading to a 50% reduction in HaSCP-2 mRNA expression level. In conclusion, the Ha-c-Myc was expressed through a prokaryotic expression system, and the polyclonal anti-Ha-c-Myc antibody was obtained. Ha-c-Myc may promote the expression of HaSCP-2 and play an important role in the lipid metabolism of H. armigera. These results may facilitate further study on the potential role and function mechanism of Ha-c-Myc in H. armigera and provide experimental data for exploring new targets of green pesticides.

Multiplex gene editing and regulation techniques based on CRISPR/Cas system / 生物工程学报

The CRISPR/Cas systems comprising the clustered regularly interspaced short palindromic repeats (CRISPR) and its associated Cas protein is an acquired immune system unique to archaea or bacteria. Since its development as a gene editing tool, it has rapidly become a popular research direction in the field of synthetic biology due to its advantages of high efficiency, precision, and versatility. This technique has since revolutionized the research of many fields including life sciences, bioengineering technology, food science, and crop breeding. Currently, the single gene editing and regulation techniques based on CRISPR/Cas systems have been increasingly improved, but challenges still exist in the multiplex gene editing and regulation. This review focuses on the development and application of multiplex gene editing and regulation techniques based on the CRISPR/Cas systems, and summarizes the techniques for multiplex gene editing or regulation within a single cell or within a cell population. This includes the multiplex gene editing techniques developed based on the CRISPR/Cas systems with double-strand breaks; or with single-strand breaks; or with multiple gene regulation techniques, etc. These works have enriched the tools for the multiplex gene editing and regulation and contributed to the application of CRISPR/Cas systems in the multiple fields.

Influence of different tasks on gait characteristics and task cost in early childhood / 中国康复理论与实践

ObjectiveTo investigate the influence of interference tasks and age on gait characteristics and task costs of children aged three to eight years. MethodsFrom April to August, 2021, 200 children from a kindergarten and primary school in Cangzhou, Hebei were enrolled to collect gait spatiotemporal parameters and kinematics data with infrared motion capture system; ground reaction force was collected with the Kistler force platform and simulated with Anybody 7.0, as walking naturally (standard gait), answering question (cognitive gait) and crossing obstacle (obstacle-crossing gait). ResultsA total of 182 children finished the test. The main effect of task was significant on spatiotemporal parameters (F > 5.167, P < 0.01), as well as age (F > 2.321, P < 0.05), except on stride width and speed; while the interaction effect of task and age was significant on double stance phase, single stance phase and step length (F > 3.040, P < 0.01). The main effect of task was significant on kinematics data (F > 83.019, P < 0.001), as well as age (F > 2.359, P < 0.05), except on range of motion of knee and maximum angular velocity of ankle; while the interaction effect of task and age was significant (F > 2.066, P < 0.05), except on range of motion of hip. The main effect of task and age was significant on kinetic parameters (F > 4.032, P < 0.05); while the interaction effect of task and age was significant (F > 2.189, P < 0.05), except on the strength of medial soleus, lateral gastrocnemius, medial gastrocnemius and tibialis anterior. The coefficient of variation was the most for cognitive gait, and then for the obstacle-crossing gait and standard gait. The main effect of task and age was significant on the cost of task for stride length and speed (F > 3.368, P < 0.01), while the interaction effect was not significant. ConclusionGait of early childhood is influenced by interference tasks and age. Under interference tasks, gait cycle increases, while single stance phase, stride length, frequency and speed decrease; and task costs increase, and overall gait stability decrease. Cognitive tasks impact on gait greater than obstacle crossing, which may be due to the higher costs of tasks. In terms of age, gait exhibits a non-linear age trend.

Antitumor synergism between PAK4 silencing and immunogenic phototherapy of engineered extracellular vesicles

Immunotherapy has revolutionized the landscape of cancer treatment. However, single immunotherapy only works well in a small subset of patients. Combined immunotherapy with antitumor synergism holds considerable potential to boost the therapeutic outcome. Nevertheless, the synergistic, additive or antagonistic antitumor effects of combined immunotherapies have been rarely explored. Herein, we established a novel combined cancer treatment modality by synergizing p21-activated kinase 4 (PAK4) silencing with immunogenic phototherapy in engineered extracellular vesicles (EVs) that were fabricated by coating M1 macrophage-derived EVs on the surface of the nano-complex cores assembled with siRNA against PAK4 and a photoactivatable polyethyleneimine. The engineered EVs induced potent PAK4 silencing and robust immunogenic phototherapy, thus contributing to effective antitumor effects in vitro and in vivo. Moreover, the antitumor synergism of the combined treatment was quantitatively determined by the CompuSyn method. The combination index (CI) and isobologram results confirmed that there was an antitumor synergism for the combined treatment. Furthermore, the dose reduction index (DRI) showed favorable dose reduction, revealing lower toxicity and higher biocompatibility of the engineered EVs. Collectively, the study presents a synergistically potentiated cancer treatment modality by combining PAK4 silencing with immunogenic phototherapy in engineered EVs, which is promising for boosting the therapeutic outcome of cancer immunotherapy.

Mitigating of the interference of anti-CD47 monoclonal antibody on transfusion compatibility detection / 中国输血杂志

【Objective】 To evaluate the interference of anti-CD47 monoclonal antibody on transfusion compatibility detection, in order to establish methods for removing interference and evaluate its efficacy. 【Methods】 Blood samples from 8 patients in our clinical trial who were treated with anti-CD47 monoclonal antibody from Tianjing and Xinda were collected. ABO and Rh blood group antigen identification, direct anti-human globulin test, unexpected antibody screening test and cross-matching test were performed by ZZAP, Gamma-clone(an anti-globulin reagent lacking IgG4) and Immucor Capture-R solid phase agglutination kit. 【Results】 ABO blood group identification of 5 subjects were interfered after treatment with anti-CD47 monoclonal antibody. All 8 subjects showed 2+ to 4+ agglutination intensity on direct anti-human globulin test and 3+ to 4+ on unexpected antibody screening. The results of unexpected antibody screening by Gamma-clone and Immucor Capture-R solid phase agglutination kit were all negative, while the cross-matching test were compatible. Patients with anemia caused by CD47 monoclonal antibody treatment were transfused with 2 U suspension red blood cells, and the evaluation showed that the transfusion was effective. 【Conclusion】 The CD47 monoclonal antibody can interfere with transfusion compatibility detection, and the use of antiglobulin reagents lacking IgG4 and Immucor Capture-R solid phase agglutination kit can remove the interference, with good transfusion efficacy in patients.

Research progress on transcranial electrical stimulation for deep brain stimulation / 生物医学工程学杂志

Transcranial electric stimulation (TES) is a non-invasive, economical, and well-tolerated neuromodulation technique. However, traditional TES is a whole-brain stimulation with a small current, which cannot satisfy the need for effectively focused stimulation of deep brain areas in clinical treatment. With the deepening of the clinical application of TES, researchers have constantly investigated new methods for deeper, more intense, and more focused stimulation, especially multi-electrode stimulation represented by high-precision TES and temporal interference stimulation. This paper reviews the stimulation optimization schemes of TES in recent years and further analyzes the characteristics and limitations of existing stimulation methods, aiming to provide a reference for related clinical applications and guide the following research on TES. In addition, this paper proposes the viewpoint of the development direction of TES, especially the direction of optimizing TES for deep brain stimulation, aiming to provide new ideas for subsequent research and application.

Effects of the expression of miR-375 on the proliferation and invasion of choroidal melanoma cells / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the effect of the expression of miR-375 on the proliferation and invasion of choroidal melanoma(CM)MUM-2B cells.METHODS: MUM-2B cells were cultured and were transfected with miR-375 mimic sequence(mimic group), miR-375 inhibitor sequence(inhibitor group), negative control group and no treatment(blank group). The qRT-PCR, CCK-8, apoptosis and Transwell experiments were used respectively to detect the expression of miR-375, cell proliferation activity, apoptosis, cell migration and invasion.RESULTS: Compared with the negative control group(1.01±0.10)and the blank group(1.03±0.07), the expression level of miR-375 in the cells of the mimic group(2.65±0.15)was increased, while the expression level of miR-375 in the cells of the inhibitor group(0.28±0.06)was decreased(P&#x003C;0.05). Compared with the blank group and negative control group, the OD values of the cells in the mimic group at 24, 48, 72, and 96h were decreased(P&#x003C;0.05), while the OD values of the cells in the inhibitor group at 24, 48, 72, and 96h were increased(P&#x003C;0.05). Compared with the apoptosis rates in the blank group and negative control group, which were(20.54±4.01)% and(22.80±4.28)%, the apoptosis rate in the mimic group(39.11±3.37)% was increased(P&#x003C;0.05), while it was decreased in the inhibitor group(10.13±2.17)%(P&#x003C;0.05). Compared with the blank group and negative control group, the number of migration cell and the number of invasion cell in the mimic group were decreased(P&#x003C;0.05), while the number of migration cell and the number of invasion cell in the inhibitor group were increased(P&#x003C;0.05). CONCLUSIONS: Up-regulating the expression of miR-375 in MUM-2B cells can reduce cell proliferation activity, accelerate cell apoptosis, and inhibit cell migration and invasion, while down-regulating the expression of miR-375 has the opposite effect. It indicates that miR-375 may play the function of tumor suppressor in the course of CM.

Effects of angiotensin-converting enzyme on reproduction of Culex pipiens pallens / 中国血吸虫病防治杂志

Objective To investigate the role of angiotensin-converting enzyme (ACE) in the reproduction of Culex pipiens pallens, so as to provide insights into selection of targets for controlling mosquito vector populations. Methods Cx. pipiens pallens was collected from Tangkou County, Shandong Province in 2009. Female and male mosquitoes were selected at 72 hours post-eclosion, and quantitative real-time reverse transcription PCR (qPCR) assay was used to detect the expression of ACE gene in the whole body and reproductive tissues of male mosquitoes and fertilized female mosquitoes before (0 h) and after blood meals (24, 48, 72 h), respectively. Then, 150 female and 150 male mosquitoes at 0 to 4 hours post-eclosion were selected and divided into the wild-type group (WT group), small interfering RNA-negative control group (siNC group) and small interfering RNA-ACE group (siACE group), of 50 mosquitoes in each group. Mosquitoes in the WT group were given no treatment, and mosquitoes in the siNC and siACE groups were given microinjection of siNC and siACE into the hemolymph at a dose of 0.3 μg per mosquito. The knockdown efficiency was checked using qPCR assay, and the reproductive phenotype of mosquitoes was observed. Results The relative ACE gene expression was higher in the whole body of male mosquitoes (5.467 ± 1.006) relative to females (1.199 ± 0.241) (t = 5.835, P = 0.004) at 72 h post-eclosion, and the highest ACE expression was seen in reproductive tissues of male mosquitoes (199.100 ± 24.429), which was 188.3 times higher than in remaining tissues (1.057 ± 0.340) (t = 6.602, P = 0.002). Blood meal induced high ACE expression in all body tissues of fertilized female mosquitoes, with peak expression at 24 h after blood meals (14.957 ± 2.815), which was 14.8 times higher than that before blood meals (1.009 ± 0.139) (P = 0.002). The transcriptional level of ACEs continued to increase in the ovaries of female mosquitoes after blood meals during the vitellogenesis phase, peaking at 48 h after blood meals (5.500 ± 0.734), which was 5.1 times higher than that before blood meals (1.072 ± 0.178) (P = 0.002). Small RNA interference targeting ACE resulted in a 57.2% reduction in ACE expression in female mosquitoes in the siACE group (0.430 ± 0.070) relative to the siNC group (1.002 ± 0.070) (P = 0.001), and a 41.1% reduction in male mosquitoes in the siACE group (0.588 ± 0.067) relative to the siNC group (1.008 ± 0.131) (P = 0.016). Knockdown of ACE expression resulted in a 48.0% decrease in the number of eggs laid by female mosquitoes in the siACE group [(94.000 ± 27.386) eggs] relative to the siNC group [(180.800 ± 27.386)] (P < 0.001), and a 45.0% decrease in the number of eggs laid by wild female mosquitoes mated with males in the siACE group [(104.500 ± 20.965) eggs] relative to the siNC group [(190.050 ± 10.698) eggs] (P < 0.001). Conclusions Reduced ACE expression may inhibit the fecundity of male and female mosquitoes, and ACE may be as a potential target for mosquito vector population suppression.

Targeted delivery of RNAi to cancer cells using RNA-ligand displaying exosome

Exosome is an excellent vesicle for in vivo delivery of therapeutics, including RNAi and chemical drugs. The extremely high efficiency in cancer regression can partly be attributed to its fusion mechanism in delivering therapeutics to cytosol without endosome trapping. However, being composed of a lipid-bilayer membrane without specific recognition capacity for aimed-cells, the entry into nonspecific cells can lead to potential side-effects and toxicity. Applying engineering approaches for targeting-capacity to deliver therapeutics to specific cells is desirable. Techniques with chemical modification in vitro and genetic engineering in cells have been reported to decorate exosomes with targeting ligands. RNA nanoparticles have been used to harbor tumor-specific ligands displayed on exosome surface. The negative charge reduces nonspecific binding to vital cells with negatively charged lipid-membrane due to the electrostatic repulsion, thus lowering the side-effect and toxicity. In this review, we focus on the uniqueness of RNA nanoparticles for exosome surface display of chemical ligands, small peptides or RNA aptamers, for specific cancer targeting to deliver anticancer therapeutics, highlighting recent advances in targeted delivery of siRNA and miRNA that overcomes the previous RNAi delivery roadblocks. Proper understanding of exosome engineering with RNA nanotechnology promises efficient therapies for a wide range of cancer subtypes.

Anti-oxidative Stress Effect and Mechanism of Huangqintang on Caco-2 Cells Through Nrf2 Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo verify the anti-oxidative stress effect of Huangqintang based on the nuclear factor E2-related factor 2 （Nrf2） signaling pathway by using Caco-2 cells as a carrier and RNA interference （RNAi） technology with in vitro experiments. MethodThe Caco-2 cells in the logarithmic growth phase were transfected with siRNA to construct siRNA Caco-2 cells. After normal Caco-2 cells and siRNA Caco-2 cells were incubated with Huangqintang of different doses， RNA and protein were extracted. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot were used to detect the mRNA and protein expression of heme oxygenase-1 （HO-1）， NAD（P）H quinone oxidoreductase 1 （NQO1）， glutathione S-transferase （GST）， Kelch-like ECH-associated protein 1 （Keap1）， and Nrf2. Meanwhile， the activities of superoxide dismutase （SOD） and GSH-Px， as well as the expression levels of malondialdehyde （MDA） and reactive oxygen species （ROS）， were detected by the colorimetric method and the probe method. ResultCompared with the results in the normal group， only the 400 mg·L-1 Huangqintang group and the sulforaphane （SFN） group could reduce the content of ROS and MDA in Caco-2 cells （P<0.01）， while the activities of SOD and GSH-Px in the cells of the Huangqintang groups and the SFN group showed an upward trend. Furthermore， there were significant differences in the 400 mg·L-1 Huangqintang group/the SFN group and the normal group （P<0.01）. Meanwhile， the protein and mRNA expression levels of HO-1， GST， Keap1， NQO1， and Nrf2 showed an upward trend in all groups （P<0.05， P<0.01）. After transfection， compared with the normal group， the model group showed increased content of MDA and ROS， blunted activities of GSH-Px and SOD， and reduced protein and mRNA expression of HO-1， GST， Keap1， and NQO1 （P<0.05， P<0.01）. After drug incubation， compared with the model group， the SFN group showed potentiated SOD activity， and the SFN group and the Huangqintang groups showed enhanced GSH-Px activity （P<0.01）. Moreover， the activities of SOD and GSH-Px in the 400 and 200 mg·L-1 Huangqintang groups and the SFN group showed an upward trend （P<0.01）， and the content of MDA in the 400 mg·L-1 Huangqintang group and the SFN group showed a downward trend. ROS decreased in all groups with drug intervention （P<0.01）， and the protein and mRNA expression of HO-1， GST， Keap1， NQO1， and Nrf2 increased to varying degrees （P<0.05， P<0.01）. ConclusionHuangqintang can play an anti-oxidative stress role by regulating the Nrf2 pathway.

Strategies for exogenous RNA delivery in RNAi-mediated pest management / 生物工程学报

Plant diseases and insect pests threaten the safety of crop production greatly. Traditional methods for pest management are challenged by the problems such as environmental pollution, off-target effects, and resistance of pathogens and insects. New biotechnology-based strategies for pest control are expected to be developed. RNA interference (RNAi) is an endogenous process of gene regulation, which has been widely used to study the gene functions in various organisms. In recent years, RNAi-based pest management has received increasing attention. The effective delivery of the exogenous interference RNA into the targets is a key step in RNAi-mediated plant diseases and pest control. Considerable advances were made on the mechanism of RNAi, and various RNA delivery systems were developed for efficient pest control. Here we review the latest advances on mechanisms and influencing factors of RNA delivery, summarize the strategies of exogenous RNA delivery in RNAi-mediated pest control, and highlight the advantages of nanoparticle complexes in dsRNA delivery.

Nucleic acid nanoassembly-enhanced RNA therapeutics and diagnosis

RNAs are involved in the crucial processes of disease progression and have emerged as powerful therapeutic targets and diagnostic biomarkers. However, efficient delivery of therapeutic RNA to the targeted location and precise detection of RNA markers remains challenging. Recently, more and more attention has been paid to applying nucleic acid nanoassemblies in diagnosing and treating. Due to the flexibility and deformability of nucleic acids, the nanoassemblies could be fabricated with different shapes and structures. With hybridization, nucleic acid nanoassemblies, including DNA and RNA nanostructures, can be applied to enhance RNA therapeutics and diagnosis. This review briefly introduces the construction and properties of different nucleic acid nanoassemblies and their applications for RNA therapy and diagnosis and makes further prospects for their development.

Concurrent silencing of TBCE and drug delivery to overcome platinum-based resistance in liver cancer

Platinum-based chemotherapy resistance is a key factor of poor prognosis and recurrence in hepatocellular carcinoma (HCC). Herein, RNAseq analysis revealed that elevated tubulin folding cofactor E (TBCE) expression is associated with platinum-based chemotherapy resistance. High expression of TBCE contributes to worse prognoses and earlier recurrence among liver cancer patients. Mechanistically, TBCE silencing significantly affects cytoskeleton rearrangement, which in turn increases cisplatin-induced cycle arrest and apoptosis. To develop these findings into potential therapeutic drugs, endosomal pH-responsive nanoparticles (NPs) were developed to simultaneously encapsulate TBCE siRNA and cisplatin (DDP) to reverse this phenomena. NPs (siTBCE + DDP) concurrently silenced TBCE expression, increased cell sensitivity to platinum treatment, and subsequently resulted in superior anti-tumor effects both in vitro and in vivo in orthotopic and patient-derived xenograft (PDX) models. Taken together, NP-mediated delivery and the co-treatment of siTBCE + DDP proved to be effective in reversing chemotherapy resistance of DDP in multiple tumor models.

Comparison of efficacy of Gabapentin versus Pregabalin in patients of painful diabetic peripheral neuropathy – A randomized, open label, and parallel group study

Background: Diabetes is a form of chronic illness requiring a collective treatment approach such as glycemic monitoring, self-management, education, and adequate support to prevent the occurrence of acute complications. One of the most frequently occurring complication in Type 2 diabetes has been diabetic peripheral neuropathy (DPN) or distal symmetrical polyneuropathy. Newer anticonvulsants such as Gabapentin and Pregabalin have been proven beneficial in patients with peripheral neuropathic pain. Aims and Objectives: The aim of the study was to compare the efficacy of Gabapentin and Pregabalin in relieving the pain in patients of DPN. Materials and Methods: This is an open label, randomized, multi-dose, two treatment, single-period, single-center, parallel study comparing Gabapentin and Pregabalin for efficacy in patients suffering with DPN using visual analog scale, daily sleep interference score, patient’s global impression of change, and clinician’s global impression of change. Results: One hundred patients were randomized into two groups and the treatment started as and when they reported to the hospital. Statistical analysis was done in SPSS version 23 and intent to treat principle is employed for analysis. Results were distributed in demographics and treatment comparison. Decreased sleep interference and global impression of change reported during first visit, in which participants under Pregabalin group had better improvement score comparing Gabapentin group alone was found statistically significant (P < 0.05). Conclusion: Our study revealed that Pregabalin is found to be more efficacious when compared to Gabapentin among Type 2 diabetes mellitus patients with painful peripheral neuropathy. Hence, we conclude that Pregabalin provided significant improvement in pain relief and other perspectives.

Gene Silencing Therapeutics in Cardiology: A Review Article

Abstract Therapeutics that inhibit enzymes, receptors, ion channels, and cotransporters have long been the mainstay of cardiovascular medicine. Now, oligonucleotide therapeutics offer a modern variation on this paradigm of protein inhibition. Rather than target a protein, however, small interfering ribonucleic acids and antisense oligonucleotides target the messenger RNA (mRNA) from which a protein is translated. Endogenous, cellular mechanisms enable the oligonucleotides to bind a selected sequence on a target mRNA, leading to its degradation. The catalytic nature of the process confers an advantage over the stoichiometric binding of traditional small molecule therapeutics to their respective protein targets. Advances in nucleic acid chemistry and delivery have enabled development of oligonucleotide therapeutics against a wide range of diseases, including hyperlipidemias and hereditary transthyretin-mediated amyloidosis with polyneuropathy. While most of these therapeutics were initially designed for rare diseases, recent clinical trials highlight the potential impact of oligonucleotides on more common forms of cardiovascular disease.

Os LncRNAs Estão Envolvidos no Processo de Aterosclerose em Diversos Níveis / LncRNAs are Involved in the Process of Atherosclerosis at Diverse Levels

Resumo A aterosclerose é a causa mais comum de doença cardiovascular em todo o mundo, ela está associada a uma alta incidência de eventos clínicos. O acúmulo de evidências elucidou que os RNAs longos não codificantes (LncRNAs) são uma nova classe de transcritos com papéis críticos nos processos fisiopatológicos da aterosclerose. Nesta revisão, resumimos o progresso recente dos LncRNAs no desenvolvimento da aterosclerose. Descrevemos principalmente os diversos mecanismos regulatórios dos LncRNAs nos níveis transcricionais e pós-transcricionais. Este estudo pode fornecer informações úteis sobre os LncRNAs como alvos terapêuticos ou biomarcadores para o tratamento da aterosclerose.

Abstract Atherosclerosis is the most common cause of cardiovascular disease globally, associated with a high incidence of clinical events. Accumulating evidence has elucidated that long non-coding RNAs (lncRNAs) as a novel class of transcripts with critical roles in the pathophysiological processes of atherosclerosis. In this review, we summarize the recent progress of lncRNAs in the development of atherosclerosis. We mainly describe the diverse regulatory mechanisms of lncRNAs at the transcriptional and post-transcriptional levels. This study may provide helpful insights about lncRNAs as therapeutic targets or biomarkers for atherosclerosis treatment.

Effect of polycystin2 on differentiation and maturation of osteoblasts promoted by low-frequency pulsed electromagnetic fields / 生物工程学报

It is known that low-frequency pulsed electromagnetic fields (PEMFs) can promote the differentiation and maturation of rat calvarial osteoblasts (ROBs) cultured in vitro. However, the mechanism that how ROBs perceive the physical signals of PEMFs and initiate osteogenic differentiation remains unknown. In this study, we investigated the relationship between the promotion of osteogenic differentiation of ROBs by 0.6 mT 50 Hz PEMFs and the presence of polycystin2 (PC2) located on the primary cilia on the surface of ROBs. First, immunofluorescence staining was used to study whether PC2 is located in the primary cilia of ROBs, and then the changes of PC2 protein expression in ROBs upon treatment with PEMFs for different time were detected by Western blotting. Subsequently, we detected the expression of PC2 protein by Western blotting and the effect of PEMFs on the activity of alkaline phosphatase (ALP), as well as the expression of Runx-2, Bmp-2, Col-1 and Osx proteins and genes related to bone formation after pretreating ROBs with amiloride HCl (AMI), a PC2 blocker. Moreover, we detected the expression of genes related to bone formation after inhibiting the expression of PC2 in ROBs using RNA interference. The results showed that PC2 was localized on the primary cilia of ROBs, and PEMFs treatment increased the expression of PC2 protein. When PC2 was blocked by AMI, PEMFs could no longer increase PC2 protein expression and ALP activity, and the promotion effect of PEMFs on osteogenic related protein and gene expression was also offset. After inhibiting the expression of PC2 using RNA interference, PEMFs can no longer increase the expression of genes related to bone formation. The results showed that PC2, located on the surface of primary cilia of osteoblasts, plays an indispensable role in perceiving and transmitting the physical signals from PEMFs, and the promotion of osteogenic differentiation of ROBs by PEMFs depends on the existence of PC2. This study may help to elucidate the mechanism underlying the promotion of bone formation and osteoporosis treatment in low-frequency PEMFs.