Loss of Aβ-nerve endings associated with the Merkel cell-neurite complex in the lesional oral mucosa epithelium of lichen planus and hyperkeratosis

The Merkel cell-neurite complex initiates the perception of touch and mediates Ap slowly adapting type I responses. Lichen planus is a chronic inflammatory autoimmune disease with T-cell-mediated inflammation, whereas hyperkeratosis is characterized with or without epithelial dysplasia in the oral mucosa. To determine the effects of lichen planus and hyperkeratosis on the Merkel cell-neurite complex, healthy oral mucosal epithelium and lesional oral mucosal epithelium of lichen planus and hyperkeratosis patients were stained by immunohistochemistry （the avidin-biotin-peroxidase complex and double immunofluorescence methods）using pan cytokeratin, cytokeratin 20 （K20, a Merkel cell marker）, and neurofilament 200 （NF200, a myelinated Aβ- and Aδ-nerve fibre marker） antibodies. N F200-immunoreactive （ir） nerve fibres in healthy tissues and in the lesional oral mucosa epithelium of lichen planus and hyperkeratosis were counted and statistically analysed. In the healthy oral mucosa, K20-positive Merkel cells with and without close association to the intraepithelial NF200-ir nerve fibres were detected. In the lesional oral mucosa of lichen planus and hyperkeratosis patients, extremely rare NF200-ir nerve fibres were detected only in the lamina propria. Compared with healthy tissues, lichen planus and hyperkeratosis tissues had significantly decreased numbers of NF200-ir nerve fibres in the oral mucosal epithelium. Lichen planus and hyperkeratosis were associated with the absence of Aβ-nerve endings in the oral mucosal epithelium. Thus, we conclude that mechanosensation mediated by the Merkel cell-neurite complex in the oral mucosal epithelium is impaired in lichen planus and hvperkeratosis.

Does endurance training improve red blood cell aging and hemorheology in moderate-trained healthy individuals?

Objective:To examine the impact of a 6-week endurance training on red blood cell(RBC)aging and deformability of healthy participants to detect possible improved hemorheological and performance-related adaptations.Methods:A total of 31 participants(17 females and 14 males)performed a 6-week moderate training protocol(three 1-h running sessions per week at 70%of maximal heart rate).Blood was sampled before and after the training.RBCs from each participant were fractioned according to density and age into 4 RBC subfractions.Subfractions were examined for changes of RBC properties,including aging distribution,RBC deformability,RBC microparticles,and phosphatidylserine concentrations.RBC and plasma nitrite levels were measured as indicators of nitric oxide metabolism.Results:Aerobic performance,peak oxygen consumption,ventilatory thresholds,velocity at the aerobic-anaerobic threshold,and lactate at exhaustion improved after training.The relative amount of both young RBCs and old RBCs increased,and the amount of the main RBC fraction decreased.Phosphatidylserine externalization and RBC-derived microparticles decreased.Overall deformability expressed as shear stress required to achieve half-maximum deformation to theoretical maximal elongation index at infinite shear stress improved in unfractioned RBCs(p<0.001).Nitrite decreased in total(p=0.001),young(p<0.001),main(p<0.001),and old(p=0.020)aged RBCs and in plasma(p=0.002),but not in very old RBCs.Conclusion:These results indicate that non-endurance-trained healthy participants benefit from a regular moderate running training program because performance-related parameters improve and a younger RBC population with improved RBC properties is induced,which might support oxygen supply in the microcirculation.

评价四氢喋呤(BH_4)作为勃起功能障碍治疗药物的可能性(英文)

目的:一氧化氮(NO)介导的平滑肌舒张可诱导阴茎勃起。内皮性一氧化氮合酶(eNOS)的辅酶四氢喋呤(BH_4) 能够把 eNOS 介导的催化反应从氧自由基转换成 NO 产物,促进内皮细胞功能和血管平滑肌的舒张。方法:使用定量免疫组化法,比较17个有勃起能力和7个无勃起能力的男性阴茎海绵体组织中8-异前列素和硝化酪氮酸的浓度,并且观察口服单剂量 BH_4对阴茎坚硬和肿大的作用。对18位在接受视觉性刺激有勃起功能障碍(ED)的病人进行随机、对照、双盲交叉设计的实验,观察口服单剂量 BH4对阴茎坚硬和肿胀的药效学作用。结果:无勃起能力的病人内皮和平滑肌中8-异前列素显著偏高,而 ED 病人的硝化酪氨酸水平无改变。相对于安慰剂,单剂量200毫克 BH_4可使阴茎维持坚硬的平均时间增加>60%以上(最短36.1分钟[95%可信限(CI):16.3-51.8],最长33.7分钟[95%CI:8.9-42.2])。500毫克 BH_4可使阴茎维持坚硬的平均时间增加>60%以上(最短33.5分钟[95%CI:13.1-49.3],最长29.4分钟[95%CI:11.4-43.9]),且治疗能被良好耐受。结论:BH_4治疗被认为通过改变 eNOS 催化超级氧化物变成 NO 的活性作用,导致活性自由基产物8-异前列素形成减少,但不改变硝化酪氨酸。观察结果认为 BH_4能重组 eNOS 被改变的催化活性,可作为治疗ED 的一种候选药物。

Exercise precision medicine for type 2 diabetes:Targeted benefit or risk?

Concurrent exercise and metformin administration may reduce the acute and chronic effects of exercise on glucose metabolism in the patients with type 2 diabetes(T2D).However,several studies suggest that combing metformin and exercise treatment may have neither additive effect nor even cause adverse effects in T2D patients.This case report aimed to highlight the challenges associated with prescribing exercise to type 2 diabetes patients undergoing metformin treatment.A 67-years old woman was followed-up for five months,including assessment of the acute and chronic glucose and lactate metabolism induced by concomitant exercise and metformin.The findings were four-fold:1)During a high-intensity interval training bout,blood glucose systematically decreased,while blood lactate concentrations fluctuated randomly;2)Basal blood lactate levels were well above 2 mmol/L on days with medication only;3)Combined exercise and metformin administration induced additive effects on the normalization of glucose and 4)high levels of physical activity had a positive impact on the continuous glucose fluctuations,while decreased levels of physical activity induced a large fluctuation of glucose due to home confinement of an infectious disease caused by the SARS-CoV-2 virus.Our findings showed that when combined with exercise and metformin treatment for T2D patients,exercise may contribute to improving glycemic control while metformin may elevate lactate levels in the long term.The observed results underline the need to prescribe exercise and monitor lactate levels for reducing possible risks associated with metformin treatment and reinforce the importance of tailoring exercise therapy.

Advanced Exercise Prescription for Cancer Patients and its Application in Germany

The scientific interest of exercise medicine for the treatment of cancer is ever expanding.Recently published and updated guidelines for exercise training in cancer patients by the American College of Sports Medicine(ACSM),the Clinical Oncol-ogy Society of Australia(COSA)or the Exercise and Sports Science Australia(ESSA)are leading the way towards an indi-vidualized approach for exercise prescription.These guidelines provide physicians and therapists with a comprehensive and detailed overview about the beneficial effects of exercise training and,more so,summarize the evidence on potential dose-response mechanisms,including pathways of exercise-induced stimuli to counteract tumour microenvironmental pathologies.However,the most optimal types and doses of exercise training across the cancer disease and treatment continuum are yet to be determined.Therefore,the purpose of this narrative review was to illustrate the current implications but also limitations of exercise training during the different stages of cancer therapy,as well as to discuss necessary future directions.As a second purpose,special attention will be given to the current role of exercise in the treatment of cancer in Germany.