Evaluation of risk profiles by subcutaneous adipose tissue topography in obese juveniles

Objective: To compare subcutaneous adipose tissue topography (SAT‐top) in obese juveniles with age‐matched normal‐weight controls. Research Methods and Procedures: The optical device LIPOMETER (European Patent EP 0516251) enables the non‐invasive, rapid, safe, and precise measurement of the thickness of subcutaneous adipose tissue. Fifteen defined body sites (1 = neck to 15 = calf) characterize the individual SAT‐top like an individual fingerprint. SAT‐top of 1351 juveniles (obese: 42 boys, 59 girls, normal weight: 680 boys, 570 girls) from 7 to 19 years of age were measured. For visual comparison, the 15‐dimensional SAT‐top information was condensed by factor analysis into a two‐dimensional factor plot. Results: Both female and male obese juveniles had markedly increased adipose tissue layers at 7 = upper abdomen, 8 = lower abdomen, 5 = front chest, and 6 = lateral chest. The pubertal changes of body shape and fat distribution of the normal‐weight boys and girls (boys show thinner adipose tissue layers on their legs, whereas girls had thicker adipose tissue layers at the extremities) were not seen in the obese group. Independently of age and sex, all of the obese juveniles showed a similar, more android body fat distribution with increased trunk fat. Discussion: SAT‐top of the obese juveniles is similar to that of patients with type 2 diabetes, polycystic ovary syndrome, and coronary heart disease. Patients with these metabolic disorders and obese juveniles are located in the factor plot in the same area. This body shape may indicate a risk profile for developing polycystic ovary syndrome (women), type 2 diabetes, and early atherosclerosis (both sexes).     

Impact of Land-use Change on Dengue and Malaria in Northern Thailand

Land-use change, a major constituent of global environmental change, potentially has significant consequences for human health in relation to mosquito-borne diseases. Land-use change can influence mosquito habitat, and therefore the distribution and abundance of vectors, and land use mediates human–mosquito interactions, including biting rate. Based on a conceptual model linking the landscape, people, and mosquitoes, this interdisciplinary study focused on the impacts of changes in land use on dengue and malaria vectors and dengue transmission in northern Thailand. Extensive data on mosquito presence and abundance, land-use change, and infection risk determinants were collected over 3 years. The results of the different components of the study were then integrated through a set of equations linking land use to disease via mosquito abundance. The impacts of a number of plausible scenarios for future land-use changes in the region, and of concomitant behavioral change were assessed. Results indicated that land-use changes have a detectable impact on mosquito populations and on infection. This impact varies according to the local environment but can be counteracted by adoption of preventive measures.     

长期住院老年精神疾病患者营养状况与认知功能的相关性研究

目的:了解长期住院老年精神疾病患者营养状况及与认知功能的相关性,为临床提供指导。方法:对住院3个月及以上的123例老年精神疾病患者采用简易精神状态检查量表(MMSE)评估认知功能,采用简易微型营养评定精简版(MNA-SF)评估营养状况,并采集一般资料、相关营养生化指标,应用Pearson相关分析MNA-SF评分与MMSE评分的相关性。结果:123例患者中,营养不良风险者67例(54.47%),营养不良者37例(30.08%),营养正常者19例(15.44%)。有认知障碍患者的营养不良发生率显著高于无认知障碍患者营养不良发生率(P<0.05),重度认知障碍者营养不良发生率显著高于轻、中度认知障碍者(P<0.05)。与无认知障碍者比较,中度、重度认知障碍者MNA-SF评分显著降低(P<0.05);与轻度、中度认知障碍者比较,重度认知障碍者MNA-SF评分显著降低(P<0.05)。营养不良者MMSE 6个认知领域评分和认知总评分均显著低于营养不良风险/正常者(P<0.05),Pearson相关分析显示:长期住院老年精神疾病患者MNA-SF评分与MMSE评分呈正相关(r=0.486, P=0.023<0.05)。结论:长期住院老年精神疾病患者营养不良发生率高,且与认知功能密切相关。临床部门需加强老年精神疾病患者,特别是有认知损害老人的营养关切。     

综述与专论：免疫吸附治疗自身免疫疾病的研究进展

自身免疫疾病治疗的常规方法 (如免疫抑制剂和血浆置换等)缺乏足够的安全性和有效性,因此,寻找新的治疗方法十分必要。免疫吸附(immunoadsorption,IA)是一种通过选择性或非选择性去除自身致病抗体,从而实现对自身免疫疾病治疗的方法。本文介绍了免疫吸附在扩张型心肌病、特发性膜性肾病、系统性红斑狼疮、重症肌无力4种自身免疫疾病中的研究和临床应用,讨论了该治疗方法的有效性和安全性;同时指出,免疫吸附要在更多的疾病中实现临床应用,还需要在可信度、地域性、样本量等方面做更加深入的临床前试验。     

有氧运动对非酒精性脂肪肝小鼠肝脏CNPY2-PERK通路的影响*

目的: 探讨有氧运动对高脂诱导小鼠非酒精性脂肪肝(NAFLD)的影响及其肝脏冠层成纤维细胞生长因子信号调节器 2 (CNPY2) - PKR样内质网激酶(PERK)机制。方法: 8周龄雄性C57BL/6J小鼠随机分为对照组(C)、对照+运动组(CE),NAFLD模型组(M)和NAFLD模型+运动组(ME),每组10只。C组和CE组小鼠给予普通饲料,M组和ME组小鼠给予高脂饲料(脂肪供能占比为60 %),连续喂养18周至实验结束,取小鼠血清和肝脏。CE组和ME组从第10周起进行有氧跑台训练(12 m/min,每次60 min,每周5 d)。检测小鼠血清总胆固醇(TC)、总甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-c)、低密度脂蛋白胆固醇(LDL-c)、丙氨酸氨基转移酶(ALT)和天冬氨酸转氨酶(AST)水平;观察小鼠肝组织病理学形态;检测肝组织CNPY2、PERK、p-eIF2a、CHOP、CNPY2 mRNA、PERK mRNA表达和CNPY2、PERK的阳性表达。结果: 与C组比较,M 组小鼠的血清LDL-c、TC、TG、ALT和AST水平显著升高(P＜0.05),HDL-c水平显著降低(P＜0.05);小鼠肝组织可见明显的肝脂肪性变,肝细胞脂滴数量增加,肝组织的CNPY2、CNPY2 mRNA、PERK、PERK mRNA、p-eIF2a、CHOP表达、CNPY2和PERK阳性表达均显著升高(P＜0.05);而CE组的上述指标均没有显著性差异(P＞0.05 )。与M 组比较,ME组小鼠的血清LDL-c、TC、TG、ALT和AST水平显著降低(P＜0.05),小鼠肝组织脂肪性变明显减轻,肝细胞脂滴数量显著减少,肝组织的CNPY2、CNPY2 mRNA、PERK、PERK mRNA、p-eIF2a、CHOP表达、CNPY2和PERK阳性表达均显著降低(P＜ 0.05)。结论: CNPY2-PERK通路参与NAFLD的形成。有氧运动可有效改善NAFLD,其机制可能与有氧运动降低CNPY2-PERK通路相关分子表达有关。     

干扰素通路调控与自身免疫疾病

干扰素信号通路是细胞抵抗病原微生物侵染的重要防线。通过识别病源相关模式分子、激活下游通路,干扰素的表达被显著上调并分泌于细胞外,作用于自身和周围细胞,引发众多下游基因的转录激活。这些基因产物直接参与抗侵染过程或调控机体免疫反应。干扰素信号通路需要被正确调控,其异常激活会导致炎症和自身免疫疾病的发生。正确地识别“自己”和“非己”分子是首要的一步。鉴于干扰素通路所抵抗的微生物侵染中,核酸分子是重要的免疫原性分子,内源性核酸分子的代谢调控显得尤为重要。细胞编码一系列参与核酸代谢的酶,这些蛋白质功能的发挥对保持细胞核酸稳态至关重要。以单基因突变引发的自身免疫疾病Aicardi-Goutières综合征为例,目前发现9种基因可突变致病,均来自DNA代谢相关的和RNA代谢相关的基因。尽管这9种基因突变都导致干扰素通路的异常激活,但中间所依赖的参与蛋白并不相同。可见,同样症状的疾病,其致病机理也可能不同,这也将影响有效治疗方案的确定,凸显基因检测在诊治自身免疫疾病中的必要性。本综述通过阐述细胞内环境稳态对干扰素通路正确识别“自己”和“非己”的重要作用,帮助理解自身免疫疾病的发病机理。     

The role of autophagy in maintaining intestinal mucosal barrier

The intestinal mucosal barrier is the first line to defense against luminal content penetration and performs numerous biological functions. The intestinal epithelium contains a huge surface that is lined by a monolayer of intestinal epithelial cells (IECs). IECs are dominant mediators in maintaining intestinal homeostasis that drive diverse functions including nutrient absorption, physical segregation, secretion of antibacterial peptides, and modulation of immune responses. Autophagy is a cellular self-protection mechanism in response to various stresses, and accumulating studies have revealed its importance in participating physiological processes of IECs. The regulatory effects of autophagy depend on the specific IEC types. This review aims to elucidate the myriad roles of autophagy in regulating the functions of different IECs (stem cells, enterocytes, goblet cells, and Paneth cells), and present the progress of autophagy-targeting therapy in intestinal diseases. Understanding the involved mechanisms can provide new preventive and therapeutic strategies for gastrointestinal dysfunction and diseases.     

Autophagy and senescence: A new insight in selected human diseases

Senescence and autophagy play important roles in homeostasis. Cellular senescence and autophagy commonly cause several degenerative processes, including oxidative stress, DNA damage, telomere shortening, and oncogenic stress; hence, both events are known to be interrelated. Autophagy is well known for its disruptive effect on human diseases, and it is currently proposed to have a direct effect on triggering senescence and quiescence. However, it is yet to be proven whether autophagy has a positive or negative impact on senescence. It is known that elevated levels of autophagy induce cell death, whereas inadequate autophagy can trigger cellular senescence. Both have important roles in human diseases such as aging, renal degeneration, neurodegenerative disorders, and cancer. Therefore, this review aims to highlight the relevance of senescence and autophagy in selected human ailments through a summary of recent findings on the connection and effects of autophagy and senescence in these diseases.     

What role does pyroptosis play in microbial infection?

Pyroptosis, a type of programmed cell death mediated by gasdermin, is characterized by the swelling and rupture of cells, release of cellular contents and a strong inflammatory response, which is critical for controlling microbial infection. Pattern recognition receptors recognize the intracellular and extracellular pathogenic microbial components and stimulate the organism's inflammatory response by activating the pyroptosis signaling pathway and releasing interleukin-1β (IL-1β), IL-18, and other inflammatory factors to promote pathogen clearance and prevent infection. In the process of continuous evolution, pathogens have developed multiple strategies to modulate the occurrence of pyroptosis and thus enhance their ability to induce disease; that is, the competition between host cells and pathogens controls the occurrence of pyroptosis. Competition can directly affect tissue inflammation outbreaks and even alter cell survival. Studies have shown that various bacterial infections, including Shigella flexneri, Salmonella, Listeria monocytogenes, and Legionella pneumophila, can lead to pyroptosis. Pyroptosis is associated with the occurrence and development of various diseases caused by microbial infection, and the identification of molecules related to the pyroptosis signaling pathway may provide new drug targets for the treatment of related diseases. This study reviews the molecular mechanisms of pyroptosis and the role of pyroptosis in microbial infection-related diseases.     

Exosomes as a novel cell-free therapeutic approach in gastrointestinal diseases

Cell communication through extracellular vesicles (EVs) has been defined for many years and it is not limited only to neighboring cells, but also distant ones in organisms receive these signals. These vesicles are secreted from the variety of cells and are composed of a distinctive component such as proteins, lipids, and nucleic acids. EVs have different classified subgroups regarding their cell origin, in this context, exosomes are the most appealing particles in cell biology, especially clinical in recent years and are represented as novel therapeutic agents with numerous advantages alongside and/or over cell therapy. However, cell therapy had a hopeful outcome in gastrointestinal diseases which have minimal alternatives in their treatments. Inflammatory bowel disease (IBD), liver fibrosis, gastrointestinal cancers are the examples that cell therapy and immunotherapy were applied in their treatment, therefore, the cell products like exosomes are the beneficial option in their treatment even cancers with promising results in animal models. In this review, we consider the main defined biogenesis, function, and component of secreted exosomes in different cells with a specific focus on the potential application of these exosomes as a cell-free therapeutic approach in gastrointestinal diseases like IBD, gastric cancer, and colon cancer. Additionally, exosomes role as therapeutic reagents mainly mesenchymal stem cells and dendritic cell-derived exosomes in different studies have been under intense investigation and even they are being studied in different clinical trials. Therefore, all these striking functions described for secretome implies the importance of these biocarriers.