Effect of electrochemically dealloying Ti6Al4V abutments on human gingival fibroblasts / 口腔疾病防治

Objective@#To investigate the effects of electrochemically dealloying of Ti6Al4V abutments on human gingival fibroblasts (HGFs) and to provide experimental evidence for surface modification of implant abutments.@*Methods@#The samples were divided into an NC group (negative control, no other treatment on a smooth surface), an NM-1 group (nanomesh-1, electrochemical dealloying treatment in 1 mol/L NaOH 1 h on 2 V voltage), and an NM-2 group (nanomesh-2, electrochemical dealloying treatment in 5 mol/L NaOH 1 h on 2 V voltage). The surface morphologies of the samples and the adhesion of HGFs on the sample surfaces were observed with scanning electron microscopy (SEM). The surface hydrophilicities of the samples were measured with a contact angle measuring instrument. The proliferation of HGFs on the different samples were evaluated with CCK-8, and the expression of adhesion-related genes, including collagen Ⅰ (COL1A1), collagen Ⅲ (COL3A1), fibronectin 1 (FN1), focal adhesion kinase (FAK), vinculin (VCL), integrin α2 (ITGA2), and integrin β1 (ITGB1), on the different samples was measured with qRT-PCR. The expression of vinculin on the surfaces of HGFs was observed via confocal laser scanning microscopy (CLSM) after immunofluorescent staining. Collagen fiber secretion and syntheses of HGFs from different samples were evaluated via Sirius red staining.@*Results@#SEM revealed the formation of ordered and uniform three-dimensional mesh structures on the surfaces of the NM-1 and NM-2 groups, with grid diameters of approximately 30 nm for the NM-1 group and approximately 150 nm for the NM-2 group. Compared with that of the NC group, the water contact angles of the NM-1 group and NM-2 groups were significantly lower (P<0.000 1). Cell proliferation in the NM-1 group was significantly greater than that in the NC group (P<0.01). Moreover, there was no significant difference in the water contact angles or cell proliferation between the NM-1 group and the NM-2 group. SEM revealed that HGFs were adhered well to the surfaces of all samples, while the HGFs in the NM-1 and NM-2 groups showed more extended areas, longer morphologies, and more developed pseudopodia than did those in the NC group after 24 h. qRT-PCR revealed that the expression levels of the adhesion-related genes COL1A1, COL3A1, FN1, FAK and VCL in the NM-1 group were significantly greater than those in the NC and NM-2 groups (P<0.01). The expression of vinculin protein in the NM-1 group was the highest, and the number of focal adhesions was greatest in the NM-1 group (P<0.01). The results of Sirius red staining showed that the NM-1 group had the highest secretion and syntheses of collagen fibers (P<0.000 1).@*Conclusion@#The three-dimensional nanomechanical structure of Ti6Al4V modified by electrochemical dealloying promoted the adhesion, proliferation, collagen fiber secretion and syntheses of HGFs, and electrochemical dealloying of Ti6Al4V with a grid diameter of approximately 30 nm obviously promoted HGF formation.

Synthesis and antibacterial activity evaluation of octapeptin derivatives / 药学学报

Octapeptin has strong antibacterial activity against Gram-negative bacteria such as Escherichia coli, Klebsiella pneumoniae and Acinetobacter baumannii, while it also has activity against some Gram-positive bacteria. This study used natural octapeptin A3 and B3 as lead compounds for structural modification. Twenty-one peptide derivatives (including A3 and B3) containing eight amino acid residues were prepared by solid-phase synthesis, and evaluated for antibacterial activity and renal cytotoxicity. Among them, three compounds 6, 7 and 17 exhibited broad-spectrum antibacterial activity and significantly enhanced the activity for Gram-positive bacteria while maintaining the activity of Gram-negative bacteria. Several compounds improved the activity for Pseudomonas aeruginosa. Compound 7 was active against all test strains and had relatively low renal cytotoxicity. The results provide a basis for the further development of novel polypeptide antibiotics.

Transporter-mediated Nano-delivery System in Promoting Oral Absorption of Drugs：A Review / 中国实验方剂学杂志

Oral administration is the most convenient way of drug delivery， but due to the existence of intestinal barrier， the oral bioavailability of drugs is generally low， especially for drugs with low water solubility， poor permeability and macromolecules. For decades， researchers have demonstrated that nano-delivery system is one of the most effective strategies to solve this problem， but nano-delivery systems have shown limited improvement in the oral bioavailability of drugs. Therefore， researchers have proposed to use transporter-mediated nano-delivery systems to promote the oral absorption of drugs. The intestinal tract were highly expressed as a transporter for ingesting various nutrients（such as glucose， oligopeptides and bile acids）， which was an excellent target of oral drug delivery system. Its substrate were modified on the nano-delivery system， and the loaded drugs could cross the intestinal barrier and enter the systemic circulation more efficiently through the targeting effect of transporters. At present， more and more evidences supported the potential of transporters in the field of oral drug delivery system. Therefore， this paper reviewed the research on intestinal transporters-mediated nano-delivery system to promote oral absorption of drugs， including the distribution of intestinal transporters， three strategies of transporter substrate modification， the transport properties of different types of transporters and their effects of mediating the nano-delivery system for promoting the oral absorption of drugs or treating diseases， with the aim of providing an important theoretical reference for the development of intestinal targeted nano-delivery systems.

Tratamiento endovascular de aneurismas con anatomía aórtica compleja / Endovascular treatment of aneurysms with complex aortic anatomy

RESUMEN Introducción: la anatomía arterial es la principal limitante para el abordaje aórtico endovascular estándar. Presentamos nuestra experiencia para la reparación endovascular de aneurismas aórticos complejos. Material y métodos: estudio observacional retrospectivo en pacientes con aneurismas complejos (yuxta/pararrenales y toracoabdominales) tratados en forma consecutiva mediante: endoprótesis fenestradas (FEVAR), ramificadas (BEVAR), con EndoAnchors (ESAR), o en chimenea (ChEVAR). La decisión de la técnica fue determinada con base en la anatomía arterial. Resultados: se evaluaron los últimos 50 procedimientos (6 mujeres; edad promedio 71,3 años; diámetro 69,6mm; 3 pacientes con aneurismas complicados), de los cuales 22 recibieron FEVAR (2,8 fenestraciones / paciente), 11 BEVAR, 11 ESAR y 6 ChEVAR (1,8 chimeneas /paciente). La tasa de éxito técnico fue del 100% (ausencia de endoleak I o III con permeabilidad adecuada de los vasos viscerales). A 30 días 3 pacientes fallecieron (6%). Durante el seguimiento, 5 pacientes presentaron oclusión de la arteria renal, repermeabilizada en 4. Cuatro pacientes desarrollaron un endoleak tipo IA (3 ESAR secundarios y un ChEVAR), un paciente un endoleak IC y un cuarto uno IIIB (22%, 3 de los 11 ESAR, ninguno de los FEVAR industriales). En el análisis de supervivencia, la supervivencia global fue del 88,6% al año, y libre de reoperación del 86,5%. Conclusiones: se trata de la primera publicación en nuestro medio que muestra un enfoque global del paciente con un aneurisma de aorta complejo, de acuerdo con sus características anatómicas. Estas tecnologías ya desempeñan un papel primario en el tratamiento de estos pacientes.

ABSTRACT Background: Arterial anatomy is the main limiting factor for standard endovascular aortic (EVAR) approach. We present our experience for endovascular repair of complex aortic aneurysms. Material and Methods: This is a retrospective observational study in patients with complex aneurysms (juxta/pararenal and thoracoabdominal) treated consecutively with: fenestrated (FEVAR), branched (BEVAR), EndoAnchors (ESAR), or chimney (ChEVAR) stents. The decision of the technique was determined based on the arterial anatomy. Results: The last 50 procedures were evaluated (6 women; mean age 71.3 years; diameter 69.6 mm; and 3 patients with complicated aneurysms), among whom 22 received FEVAR (2.8 fenestrated stents/patient), 11 BEVAR, 11 ESAR and 6 ChEVAR (1.8 chimney stents/patient). Technical success rate was 100% (absence of type I or III endoleak with adequate patency of the visceral vessels). Three patients died within the first 30 days (6%). During follow-up, 5 patients presented with renal artery occlusion, treated successfully in 4 cases. Four patients developed type IA endoleak (3 secondary ESAR and one ChEVAR), one patient IC endoleak and almost a quarter of cases type IIIB endoleak (22%, 3 out of 11 patients receiving ESAR, none of the industrial FEVAR group). In survival analysis, overall survival analysis was 88.6% at one year, and 86.5% of cases were free from reoperation. Conclusions: This is the first publication in our setting that shows a global approach to the patient with complex aortic aneurysm, according to the anatomical characteristics. These technologies already play a primary role in the treatment of these patients.

Impact of Training Programs on Awareness and Practice of Lifestyle Modifications among Hypertensive Patients Attending Outpatient Clinic of the University College Hospital, Ibadan, Nigeria

Aim: This study sought to investigate the impact of training programs on hypertensive patients' awareness and practice of lifestyle modifications in out-patient clinics of the University College Hospital (UCH) Ibadan, Nigeria. Methodology: The study design was a cross-sectional survey conducted at the out-patient clinics of the University College Hospital (UCH), Ibadan, Nigeria. This setting was chosen due to the accessibility of hypertensive patients receiving regular care and follow-up. The sample size comprised 274 hypertensive patients attending the out-patient clinics for regular hypertension management. A simple random sampling method was employed to select study participants, ensuring a fair representation of the target population. A structured questionnaire was used to collect data from the participants and results were analysed using SPSS. Results: Findings indicate that the training programs greatly increased awareness of hypertension and lifestyle factors affecting hypertension for most participants (74.42%), with all participants recommending the programs. A significant majority of participants (95.74%) reported being on hypertension medication, while nearly all (99.22%) had received some form of training or counselling on lifestyle modification for hypertension management. Notably, all participants reported having made lifestyle changes following the training programs, with the majority rating the effectiveness of the programs as highly effective (57.36%). Further analysis indicated a statistically significant relationship between the effectiveness of the training programs and the participants' age, sex, educational level, and occupation. The most frequent lifestyle modification post-training was dietary changes, with 54.65% of participants reporting that they always engage in a healthy diet for hypertension management. However, the frequency of engagement in other lifestyle modifications, such as regular physical activity and weight management, was not as high. The majority of participants reported significant improvements in hypertension symptoms following the lifestyle modifications. Conclusion: These findings demonstrate that targeted training programs can significantly enhance hypertensive patients' awareness and practice of beneficial lifestyle modifications, thus improving health outcomes. Further, the study underscores the need for such training programs to be tailored according to the age, sex, educational level, and occupation of the patients to maximize their impact.

Prevalence of normal weight obesity in young adults of Western Uttar Pradesh – A community-based study

Background: Obesity is described as a build-up of abnormal or excessive fat that risks life. A body mass index (BMI) is a screening tool for overweight and obesity. For a long time, BMI has been used as a marker to measure obesity. However, a significant limitation of using BMI is its failure to differentiate between a high body fat content and preserved or increased lean mass, especially in patients or subjects with a BMI <30 kg/m2. Normal weight obese (NWO) is such individuals who have high fat content but a normal BMI. To identify such individuals and to save them from morbidity associated with obesity, this study was carried out. Aims and Objectives: The objective of the study was to estimate the prevalence of NWO in healthy young adults (aged between 18 and 30 years) and to suggest the methods of primary prevention for obesity. Materials and Methods: In this observational cross-sectional study, the 324 subjects were selected randomly from the residents, students, and employees of Swami Vivekananda Subharti University. Subjects were chosen according to the study’s inclusion and exclusion criteria and also, based on the self-structure questionnaire. A general and systemic examination was carried out. The body composition of these subjects was done by bioelectric impedance analyzer BODY STAT QUAD SCAN 4000. Data were analysis using R-software (1.25 version), and unpaired t-test was applied. P < 0.05 was taken as significant in this study. Results: The prevalence of NWO in males was found to be 24.6% and females to be 13.4%. The body composition parameters of NWO and NWNO differed significantly. Conclusion: The increase rate of NWO is reason for concern and routine screening of body composition parameters should be done at health setups to identify that these NWO individuals and timely interventions can be made.

Aceptación y compromiso versus coaching conductual en un programa nutricional y de actividad física contra el sobrepeso / Acceptance and Commitment Versus Behavioral Coaching in a Nutritional and Physical Activity Program Against to Overweight

Resumen En los últimos años, Colombia registra un aumento tanto de sobrepeso como de obesidad, aspecto que produce el establecimiento de modelos complejos de intervención que generen cambios de actitud, compromiso en las personas y el mejoramiento de hábitos alimenticios y de actividad física. Este estudio pretendió comparar la efectividad entre dos componentes psicológicos (estrategias conductuales tradicionales y un entrenamiento en aceptación y compromiso), sumados al entrenamiento físico concurrente y la educación nutricional (junto con una dieta hipocalórica), sobre variables antropométricas, la aptitud física, los aspectos de la conducta alimentaria y la sintomatología de salud mental. El diseño de investigación fue de caso único ABA (línea base-intervención-línea base) para cada condición de tratamiento. La muestra estuvo conformada por cinco mujeres y un hombre, entre los 33 y 49 años de edad, con preobesidad y obesidad tipo I, asignados entre los grupos de coaching conductual y entrenamiento en aceptación y compromiso. Los hallazgos muestran un mejoramiento en: composición corporal, resistencia aeróbica, fuerza prensil, compromiso y fusión cognitiva frente a situación de alimentación y actividad física en dos participantes de la estrategia de aceptación y compromiso, mientras que hubo mayor variación en los resultados de los participantes de coaching conductual. Este es un pilotaje de un estudio con mayor capacidad de inferencia.

Abstract There is an increase in both overweight and obesity in the world, aspect that tends for the approach of integral models of intervention, that generate changes in attitude, and commitment in people towards their eating habits and physical activity, that counteract a sedentary lifestyle and the influence of counterproductive processed foods for energy balance. This study aimed to compare the effectiveness between two psychological components (traditional behavioral strategies and a 6-session acceptance and commitment training), added together, each one: a) concurrent physical training (strength/endurance) with bioadaptation process, b) hypocaloric diet and c) Nutritional education. Measurements of anthropometric variables were obtained, physical fitness and mental health symptoms, while the average of steps was measured during the whole process, constituting this part in a single ABA case design for each treatment condition. The sample consisted of five women and one man, between 33 and 49 years of age, with pre-obesity and type I obesity, assigned in a non-random way between the behavioral coaching and acceptance and commitment training groups. In physical training, priority was initially given to the conditional capacity of strength, being an incident in the mobilization of large muscle groups (multi-joint) in order to generate a greater caloric expenditure, directly influencing exercises that optimize postural hygiene by working in the core zone and complementing training with synergistic or accompanying biarticular exercises in the movement of daily physical activities, subsequently the execution of aerobic resistance in search of the increase in the maximum oxygen consumption capacity ( max), ending with the implementation of vital flexibility exercises for physical exercise releasing muscle tension, favoring conditional physical ability. Regarding the intervention of the nutritional component, the most important input to begin to identify eating habits and subsequently modify them was the 24-hour reminder, applying in the first week of the baseline and the reversal phase. The nutritional intervention consisted of: (a) education so that participants understood and generated greater adherence to the nutritional proposal and (b) hypocaloric diet, reducing daily intake between 500 and 600 kilocalories per day. A follow-up anthropometric assessment was also carried out towards the third week of the intervention phase to obtain feedback on the incidence of their behavior on the anthropometric variables. Regarding the record of the number of steps, both in the baseline and reversion phases the monitor screens were covered, contrary to the intervention phase, since its observation allows self-monitoring towards the weekly personal goal of steps that was established and accompanied by a professional, who in turn generated a graph with the results of the week and gave feedback to each participant. The findings show an improvement in: body composition, aerobic endurance (VO2 max) and grip strength, being the main factor of result in the realization of the physical exercise. Likewise, an increase in the number of steps from the baseline is identified in both groups (X = 9 228.07; S = 1 985.89) to the intervention phase (X = 9 734.22; S = 1 660.86) and a decrease in reversion (X = 9 099.88; S = 2 328.69). In the acceptance and commitment group, no increase in mental health symptoms was identified, increased or sustained cognitive restriction and decreased scores for uncontrolled eating and emotional eating, while there was greater variation in the results of the behavioral coaching participants. This is a pilot of a study with greater capacity for inference.

Motivational Techniques and Hacks for Treating Childhood Obesity

Treating obesity in children and adolescents is not a cakewalk. Asking them directly to get up and run, or just serving them a four-quadrant plate won’t serve the purpose at all. An obese child is already under the repercussions of oppressive remarks by the society. If at home as well, their mental milieu is not taken care of, there are chances of them being trapped in the shackles of depression. To avoid such drastic consequences, one must be prudent enough, while conversing with their children/patients regarding their weight. Motivation enhancement is very crucial in childhood obesity management, as the required changes in diet, behavior and physical activity are difficult to carry out with an insufficient level of motivation.1 The motivational hacks presented here might be helpful for parents and health care professionals in convincing their children/patients to stride through the road to health.

Advances in surface treatment of dental implants: a literature review

Amplamente utilizados para substituir dentes perdidos, os implantes dentários nos últimos anos vêm apresentando tecnologias como superfícies com micro e nanotopografia e ajustes nas composições químicas, dentre outros, para melhorar a osseointegração e reduzir o prazo de tratamento, permitindo, assim, carga funcional imediata ou precoce em pacientes com densidade óssea reduzida. Vários métodos são aplicados com intuito de modificar a superfície do implante, como jateamento com areia, corrosão ácida, oxidação anódica, tratamento com flúor, usinagem, pulverização de plasma de titânio e revestimento de fosfato de cálcio; esses métodos podem aumentar notavelmente a área de superfície quando operada a técnica adequadada de modificação, quer por procedimento de adição ou subtração. Tais modificações promovem superfícies rugosas, as quais aumentam a porcentagem de contato osso-implante (BIC) durante o processo de cicatrização óssea inicial. Os principais benefícios da modificação da superfície são melhorar a molhabilidade (hidrofilicidade), adesão e fixação de células a implantes e proliferação celular. Dentre os tratamentos de superfície de implantes dentários destaca-se o jateamento de areia com granulação grossa e ataque-ácido com HCL/H2SO4 (SLA) em altas temperaturas, o revestimento de superfície do implante com hidroxiapatita, oxidação anódica e o duplo ataque ácido. O objetivo deste trabalho é realizar uma revisão de literatura discutindo a importância e eficácia desses métodos para a osseointegração e, por conseguinte, para a redução do período de tratamento.

Widely used to replace lost teeth, dental implants have been presenting technologies such as surfaces with micro and nano topography and adjustments in chemical compositions, among others, to improve osseointegration and reduce treatment time, thus allowing immediate or early functional load in patients with reduced bone density. Several methods are applied to modify the implant surface, such as sandblasting, acid corrosion, anodic oxidation, fluoride treatment, machining, titanium plasma spraying, and calcium phosphate coating; these methods can notably increase the surface area when the appropriate modification technique is operated, either by the addition or subtraction procedure. Such modifications promote rough surfaces, which increase the percentage of bone-implant contact (BIC) during the initial bone healing process. The main benefits of surface modification are to improve wettability (hydrophilicity), adhesion and attachment of cells to implants, and cell proliferation. Among the surface treatments for dental implants, sandblasting with large grit and acid-etching with HCL/H2SO4 (SLA) stands out at high temperatures. The surface coating of the implant with hydroxyapatite, anodic oxidation, and double acid-etching. This work aims to conduct a literature review discussing the importance and effectiveness of these methods for osseointegration and, therefore, for reducing the treatment period.

Baru nuts reduce abdominal adiposity in type 2 diabetic adults: a randomized, placebo-controlled, crossover trial / Amêndoa de baru reduz a adiposidade abdominal de adultos com diabetes Mellitus tipo 2: um estudo randomizado, placebo-controlado, crossover

ABSTRACT Objective: This study aimed to evaluate the effect of baru nuts supplementation on body composition and metabolic profile in adults with type 2 diabetes. Methods: This is a randomized, placebo-controlled, crossover trial with 30 adults with type 2 diabetes. The assay had two periods of 12 weeks each, with a washout period of 12 weeks between treatments. The subjects were randomized and received the two treatments in alternate periods: supplementation of 30g baru nuts or placebo. Anthropometry, body composition, blood pressure, blood sampling, food intake, and physical activity data were analyzed. Results: Baru nut intake reduced waist circumference (p=0.032), compared to placebo group. In the intra-group analysis, baru nut intake reduced total cholesterol (p=0.012) and LDL-c (p=0.017). Conclusion: The daily intake of baru nuts improved abdominal adiposity. Therefore, these nuts should be included in the diet to improve the health status of adults with type 2 diabetes.

RESUMO: Objetivo: Avaliar o efeito da suplementação com amêndoa de baru sobre a composição corporal e perfil metabólico de adultos com diabetes Mellitus tipo 2. Métodos: Este é um estudo randomizado, placebo-controlado, crossover com 30 adultos com diabetes Mellitus tipo 2. O ensaio clínico foi dividido em dois períodos de 12 semanas cada, com um washout de 12 semanas entre os tratamentos. Os sujeitos foram randomizados e receberam dois tratamentos em períodos alternativos: suplementação com 30 g de amêndoa de baru ou placebo. Foram coletados dados referentes à antropometria, composição corporal, pressão arterial, amostras de sangue, ingestão de alimentos e práticas de atividade física. Resultados: A ingestão de amêndoa de baru reduziu a circunferência da cintura (p=0,032), em comparação com o grupo placebo. Na análise intragrupo, a ingestão de amêndoa de baru também reduziu o colesterol total (p=0,012) e LDL-c (p=0,017). Conclusão: A ingestão diária de amêndoa de baru melhorou a adiposidade abdominal, portanto, deve ser incluída na dieta para a melhora do estado de saúde de adultos com diabetes Mellitus tipo 2.

Dihydrotanshinone I preconditions myocardium against ischemic injury via PKM2 glutathionylation sensitive to ROS

Ischemic preconditioning (IPC) is a potential intervention known to protect the heart against ischemia/reperfusion injury, but its role in the no-reflow phenomenon that follows reperfusion is unclear. Dihydrotanshinone I (DT) is a natural compound and this study illustrates its role in cardiac ischemic injury from the aspect of IPC. Pretreatment with DT induced modest ROS production and protected cardiomyocytes against oxygen and glucose deprivation (OGD), but the protection was prevented by a ROS scavenger. In addition, DT administration protected the heart against isoprenaline challenge. Mechanistically, PKM2 reacted to transient ROS via oxidization at Cys423/Cys424, leading to glutathionylation and nuclear translocation in dimer form. In the nucleus, PKM2 served as a co-factor to promote HIF-1α-dependent gene induction, contributing to adaptive responses. In mice subjected to permanent coronary ligation, cardiac-specific knockdown of Pkm2 blocked DT-mediated preconditioning protection, which was rescued by overexpression of wild-type Pkm2, rather than Cys423/424-mutated Pkm2. In conclusion, PKM2 is sensitive to oxidation, and subsequent glutathionylation promotes its nuclear translocation. Although IPC has been viewed as a protective means against reperfusion injury, our study reveals its potential role in protection of the heart from no-reflow ischemia.

RNA Modification in Carcinogenesis and Development of Gastric Cancer / 肿瘤防治研究

The occurrence of gastric cancer is closely related to environmental, genetic, and epigenetic factors. Currently, RNA modification is a research frontier and hotspot in the field of epigenetics. With the advancements in analytical chemistry and high-throughput sequencing technologies, new technologies and methods of exploring RNA modification are constantly being presented. Numerous studies have confirmed the involvement of RNA modifications in the occurrence and development of various diseases. Recent studies have shown that RNA modifications such as m6A, m5C, and ac4C regulate the malignant progression of various tumors, including gastric cancer, liver cancer, colorectal cancer, and leukemia. This article systematically reviews the research status and mechanism of different RNA modifications in the occurrence and development of gastric cancer, as well as discusses its potential value in the diagnosis and treatment of gastric cancer.

The key role of RNA N 6-methyladenosine (m 6A) methylation in tumor radiotherapy and radiation damage repair / 中华放射医学与防护杂志

N 6-methyladenosine (m 6A) is the most abundant epigenetic modification in eukaryotic messenger RNA (mRNA), which could be catalyzed by m 6A methyltransferase (Writers), recognized by methylation recognition enzymes (Readers), and removed by demethylase (Erasers). RNA splicing, translation, and stability could be modulated by m 6A methylation modification. The m 6A methylation modification is involved in the biological regulation of a variety of important functional genes in cellular activities. Importantly, abnormal m 6A modification affects the occurrence, development, metastasis and recurrence of tumors. Ionizing radiation can affect the level of m 6A and m 6A methylation-related enzymes. Recently, m 6A methylation is reported to regulate the efficacy of tumor radiotherapy by affecting DNA damage and radiosensitivity of tumor cells. In addition, ionizing radiation can also affect the level of m 6A modification in normal cells to regulate the progress of radiation-induced injuries. This review summarizes the research progress on the roles of m 6A methylation in tumor radiosensitivity and radiation-induced injuries, with the aim of providing novel strategies for the development of clinical tumor radiosensitizers and radioprotective agents.

An overview of disease treatment strategies targeting the alternative splicing of pre-mRNA / 药学学报

Alternative splicing of pre-messenger RNA (pre-mRNA) is a crucial mechanism for the diversity of the human transcriptome and proteome. Alternative splicing is a complex gene regulation process. Whole-transcriptome analysis shows that 95% of human exonic genes are alternatively spliced, involving various cis-acting elements and trans-acting factors. Any changes in any component or step may cause erroneous splicing events and lead to the occurrence of various related diseases. In addition to gene replacement therapy that directly changes the splicing results, RNA splicing modification is expected to become a new therapeutic strategy to alleviate or treat diseases by targeting and correcting abnormal pre-mRNA splicing. Splicing modification tools currently developed including RNA trans-splicing, antisense oligonucleotides, small interfering RNA, and small molecule drugs can correct abnormal splicing through different ways. This article reviews the resent progress of epigenetic regulation of pre-mRNA alternative splicing in recent years, and discusses the occurrence and regulation of alternative splicing, the types of diseases caused by related splicing defects, and the current-used tools for targeting and altering splicing. The importance of splicing modification strategies in the future treatment of human diseases is envisioned.

Use of sail excision in Alar Morphology modification of asian noses

@#Globular hanging nasal alae, described as convex round shaped alar lobule which may be an aesthetic nuisance in the final result of rhinoplasty, are commonly seen among Southeast Asian noses. Such alar lobule morphology is an important part of nasal aesthetics and should not be disregarded. Surgical techniques used to address a hanging ala include direct external approaches. External rim excision was proposed to address hidden columella, sigmoid alae, small nostrils, dropped rim and foreshortened nose.1,2 Rim tissue was excised in full thickness fashion and sutured in one layer. Others proposed alar groove excision followed by alar repositioning and full-thickness skin grafting to reposition the alar base and correct hanging alae.3 Although these approaches have been proven to correct hanging alae, they leave a visible scar and/or permanent alar rim deformity if not done cautiously, especially on thick skinned patients.1-3 The alar rim may not be natural looking since it is lined by a scar, thus losing the lobular texture of the rim. A vestibular incision has been proposed to correct a hanging ala with unsightly scar.4 A maximum of 3mm elliptical vestibular skin was recommended to be removed to lift the alar rim with significant results. However, this recommendation was based on estimates and surgeon’s experience in western noses and may be insufficient for Asian noses. In addition, performing this technique without specific landmarks is difficult in achieving accurate results, especially when performed by a novice surgeon. Hence, further modification is important to address these concerns. Attempting to address the hanging alae in Asian noses, the senior author (ECY) modified the vestibular incision and came up with the sail excision technique based on the patient’s nasal anatomy.5 By presenting definite landmarks, the technique resulted in an alar lift procedure with reproducible outcomes. Furthermore, after performing sail excision in several patients, the authors noted the effect of this technique on alar morphology. This procedure is done by excising a precisely marked piece of inner nasal vestibular skin that is shaped like the sail of a boat to achieve a symmetrical and redictable result. This creates a lifting effect and improves the alar columellar disproportion specially when combined with septal advancement techniques.6,7 Furthermore, limiting the excision along the inner vestibular area and rolling the alar rim skin inwards results in correction of hanging ala (with a hidden scar) without an obvious, external scar. After performing the technique on several patients, we observed that in addition to its effect on lifting a hanging ala, the sail excision technique also changes the alar morphology from a globular-shaped lobule to a more aesthetically pleasing ridge-shaped lobule. To the best of our knowledge, such an effect of sail excision on alar morphology has not been described in the literature. This article aims to demonstrate the effect of the sail excision technique on alar rim morphology of Asian noses by describing the step-by-step procedure, surgical landmarks, and pearls in performing this technique.

Research advances on the role of epigenetic modifications in the long-term progression of alcoholic liver disease / 药学学报

There are more than 60 million alcoholic liver disease (ALD) patients in China, which has become a public health problem that cannot be ignored. Moreover, the social problem of "alcohol culture" is still hardly to solve, so that safe and effective prevention and treatment for ALD are in urgent need clinically. Previous studies on ALD have focused on the direct damaging effects of alcohol and its toxic metabolites, while recent studies have shown that the pathogenesis of ALD also include alcohol metabolic reprogramming and endogenous metabolites disorder. Although the endogenous metabolites have no direct toxicity, its long-term effect should not be ignored. These endogenous metabolites could change epigenetic modifications, cause widespread and persistent abnormal gene expression and signal pathway activation abnormally to promote metabolic reprogramming and stamp it as "metabolic memory", which manifest pathological changes and promote ALD, especially liver fibrosis/cirrhosis and liver cancer. Based on this, the article reviews the important epigenetic modifications caused by related metabolites in ALD and their associated effects. The role of traditional Chinese medicine (TCM) and its active ingredients in regulating epigenetics was also analyzed. The results suggest that regulation of epigenetics and alteration of "metabolic memory" may be a novel mechanism of TCM in the prevention and treatment of ALD.

Design and synthesis of peptide-drug conjugates and fluorescent probe based on α-conotoxin ArIBV11L,V16D / 药学学报

italic>α-Conotoxin ArIB[V11L,V16D] is currently the most optimal selective inhibitor of α7 nicotinic acetylcholine receptor (nAChR) known. In order to explore chemical modification methods and enrich its application in targeting nAChR, this study utilized the linker to covalently connect camptothecin and 7-amino-4-methylcoumarin to the [2,4] disulfide bond of ArIB[V11L,V16D]. Therefore, two peptide-drug conjugates (PDCs), ArIB[V11L,V16D]-5 and ArIB[V11L,V16D]-6, and one fluorescent-labeled peptide, ArIB[V11L,V16D]-7 were constructed. Cytotoxicity evaluation showed that the IC50 values against non-small cell lung cancer cell line A549 of the two PDCs were respectively 1.3 and 4.1 times of camptothecin, indicating slight reduction in activity at the cellular level which was related to the linker structure. Fluorescence spectrum scanning revealed that the excitation and emission wavelength of the fluorescent-labeled peptide were 340 nm and 403 nm respectively, and the fluorescence features of 7-amino-4-methylcoumarin as a marker were retained without fluorescence quenching. This modification strategy laid a solid foundation for the further application of α-conotoxin ArIB[V11L,V16D] in PDCs and fluorescent probes.

Advances in histone epigenetic enzyme inhibitors based on proteomics / 药学学报

As an important component of nucleosomes on the chromatin of eukaryotic cells, histones play an important role in the development and progression of tumour diseases by regulating epigenetic post-translational modifications such as acetylation and methylation. In addition, development of inhibitors targeting methyltransferase and deacetylase provides novel therapeutic strategies for cancer treatment. Mass spectrometry-based proteomics can reveal the global changes of histone modifications under the action of drugs during disease progression, which in turn provides important support for revealing drug action mechanism, drug resistance mechanism, and investigating novel drug combination strategies. This article focuses on the progress and status of proteomic research on a variety of histone modifying enzyme inhibitors, including methyltransferase inhibitors and histone deacetylase inhibitors, which will help to understand the current and further utilization of proteomics in studying histone modifications.

Research progress on vesicle-associated membrane protein 8 / 中国生物制品学杂志

@#Membrane fusion is essential for all life activities of eukaryotes and the fusion process requires the interaction of different vesicular transporters,which are highly conserved in eukaryotes,to coordinate specifically and facilitate the fusion of different biofilms. Vesicle associated membrane protein 8(VAMP8)mainly locates in vesicular as well as lysosomal membranes,and plays a vital role in the fusion of many different biofilms. This paper focused on the molecular structure,transcriptional regulation,post-translational modification and biological function of VAMP8 as well as the research progress on its correlation with human diseases,so as to provide new ideas for the treatment of related diseases and the development of effective therapeutics targeting VAMP8.

Research progress on mechanism and protein modification of Beclin1 in autophagy / 中国生物制品学杂志

@#Autophagy is a process of self-phagocytosis of lysosomal degrading substances in cells. Under normal conditions,cells can use autophagy to remove their own garbage to provide energy,while in a state of stress,autophagy can also be activated,resulting in cell damage and death,which can seriously lead to cancer. B-cell lymphoma-2-interacting myosin-like coiled-coil protein(Beclin1) is a central node in the autophagy pathway and interacts with a variety of proteins to regulate the formation and maturation of autophagosomes. Kinase mediates the protein modification of Beclin1 during autophagy,which will affect its activity and interaction with other autophagy-related proteins. Beclin1 is closely related to the occurrence and development of tumors. Therefore,this paper focused on the research progress on the mechanism and protein modification of Beclin1 in autophagy,in view to providing a reference for the research of targeted drugs of tumor autophagy.