PARP1 inhibition enhances reactive oxygen species on gut microbiota.

Poly(ADP-ribose) polymerase 1 (PARP1) plays a key role in genome stability by modulating DNA-damage responses. Activated by DNA interruptions through ultraviolet (UV) exposure, PARylation is synthesized by PARP1 and serves as a survival mechanism for cancer and metabolic diseases. Several strategies including ROS and antimicrobial peptides (AMPs) function in host defenses, while the targeted tissue and mechanism under DNA damage are unknown. Here, we show that DNA damage induces responses specifically in the gut tissue. The knockdown of PARP1 reduces the activation of PARylation. Parp1 knockdown under DNA damage results in over-accumulated ROS and secretion of AMPs through the regulation of Relish, a subunit of nuclear factor-κB (NF-κB). Double-knockdown of Parp1 and Relish specifically in the gut inhibits AMP secretion. In conclusion, the host defense is achieved through ROS accumulation rather than the AMPs under DNA damage. In contrast, the knockdown of PARP1 exacerbates ROS accumulation to a harmful level. Under this circumstance, NF-κb targeted AMP secretion is provoked for host defense. Microbiome and functional analysis provide evidence for the hazard of DNA damage and show variations in the metabolic pathways following Parp1 inhibition. Our findings suggest the notion that PARP1 inhibition contributes to ROS accumulation under DNA damage and its role in NF-κb activation for host defense.

Proteomics and Organoid Culture Reveal the Underlying Pathogenesis of Hashimoto's Thyroiditis.

Hashimoto's thyroiditis (HT) is an autoimmune disease, and its incidence continues to rise. Although scientists have studied this disease for many years and discovered the potential effects of various proteins in it, the specific pathogenesis is still not fully comprehended. To understand HT and translate this knowledge to clinical applications, we took the mass spectrometric analysis on thyroid tissue fine-needle puncture from HT patients and healthy people in an attempt to make a further understanding of the pathogenesis of HT. A total of 44 proteins with differential expression were identified in HT patients, and these proteins play vital roles in cell adhesion, cell metabolism, and thyroxine synthesis. Combining patient clinical trial sample information, we further compared the transient changes of gene expression regulation in HT and papillary thyroid carcinoma (PTC) samples. More importantly, we developed patient-derived HT and PTC organoids as a promising new preclinical model to verify these potential markers. Our data revealed a marked characteristic of HT organoid in upregulating chemokines that include C-C motif chemokine ligand (CCL) 2 and CCL3, which play a key role in the pathogenesis of HT. Overall, our research has enriched everyone's understanding of the pathogenesis of HT and provides a certain reference for the treatment of the disease.

The Efficacy of Tai Chi and Stretching Exercises Based on a Smartphone Application for Patients With Parkinson's Disease: A Protocol for a Randomized Controlled Trial.

Introduction: Parkinson's disease (PD) is a common neurodegenerative disease that seriously impairs patients' quality of life, and increases the burden of patients and caregivers. Both drugs and exercise can alleviate its motor and non-motor symptoms, improving the quality of life for PD patients. Telehealth, an increasingly popular tool, makes rehabilitation accessible at home, overcoming the inconvenience of traffic and scheduling. Care-PD is a phone application designed for rehabilitation training, which provides Tai Chi and stretching exercises through tutorial videos as well as an online evaluation system. In this protocol, we will explore the efficacy of Tai Chi and stretching exercises as a PD rehabilitation therapy based on the smartphone application Care-PD. Methods and Analysis: A double-blind, parallel randomized controlled trial will be conducted in this study. The recruitment, intervention, and evaluation processes will be implemented through the Care-PD application. Persons with PD will fill out questionnaires on Activities of Daily Living (ADL), upload the latest case report, and sign the informed consent form in the application. Afterward, doctors and researchers will screen and enroll 180 participants who will be randomly (1:1:1) assigned to Tai Chi group, stretching exercises group, or control group. The subjects will participate in a 1-h exercise session three times per week for 12 weeks, ending with another 4 weeks of follow-up study. Each exercise session includes 10 min of warm-up, 45 min of exercise, and 5 min of cool-down. The primary outcomes are Motor Aspects of Experiences of Daily Living and the 39-item Parkinson's disease Questionnaire. The secondary outcomes include the 9-item Wearing-Off Questionnaire, the Freezing of Gait Questionnaire, the Caregiver Strain Index, Non-motor Experiences of Daily Living, ADL, and Morse Fall Scale. All assessments will be performed at baseline, week 12 and 16. Discussion: Care-PD integrates subject recruitment, intervention, and evaluation, providing a new perspective on clinical rehabilitation for persons with PD. This study will evaluate the efficacy of Tai Chi and stretching exercises on patients' quality of life and disease progression based on a smartphone application. We aim to provide a new rehabilitation training platform for persons with PD. Ethics and Dissemination: This study was approved by the Scientific Research Ethics Committee (102772020RT132) of Shanghai University of Sport. Data collection begins after the approval of the ethics committee. The participants must sign an informed consent form before enrollment. The results will be published in relevant journals, seminars, and be disseminated among rehabilitation practitioners and patients with PD. Clinical Trial Registration: Chinese Clinical Trial Registry, identifier [ChiCTR2100042096]. Registered on January 13, 2021.

The Effect of Low and Moderate Exercise on Hyperuricemia: Protocol for a Randomized Controlled Study.

Background: Hyperuricemia (HUA) is a metabolic disease by purine metabolism disorders. It is a risk factor for many chronic diseases, including diabetes, hypertension, and heart disease. Studies have shown that exercise can effectively reduce serum uric acid (SUA), but the optimal exercise dose, intensity, and mode of exercise for improving HUA have not been verified in clinical studies. Therefore, this study aims to explore the effect of different exercise intensities in improving SUA of patients with HUA. Methods and Analysis: A randomized, single-blind, parallel controlled trial will be conducted in this study. 186 HUA patients who meet the inclusion criteria will be randomly divided into a 1:1:1 ratio (1): control group (2), low-intensity exercise group (brisk walking, 57-63% maximum heart rate, 150 min/week, 12 months), and (3) moderate-intensity exercise group (jogging, 64-76% maximum heart rate, 150 min/week, 12 months). The three groups of subjects will receive the same health education and prohibition of high-purine diet during the intervention period. The primary outcomes will be SUA concentration, SUA concentration change (mg/dL), SUA change rate (%), and the proportion of HUA patients. Secondary outcomes will include anthropometric parameters (body weight, waist circumference, hip circumference, BMI); physiological indicators (blood pressure, grip, vital capacity, maximum oxygen); biochemical indicators (blood lipid, blood sugar, liver enzyme, creatinine, and blood urea nitrogen). Each group of patients will go through an assessment at baseline, 3rd, 6th, and 12th months. Discussion: This study will evaluate the effect of 12-month low-intensity exercise and moderate-intensity exercise on HUA patients. We hypothesize that both low-intensity and moderate-intensity exercise would improve HUA as compared with no-exercise control, and that moderate-intensity exercise would be more effective than low-intensity exercise in improving HUA. These results can provide a basis for the current physical activity guidelines for HUA's healthy lifestyle management. Ethics and Dissemination: This study has been approved by the Ethical Review Committee of the Shanghai University of Sport (approval number: 102772020RT005). Informed consent will be obtained from all participants or their guardians. The authors intend to submit the study findings to peer-reviewed journals or academic conferences to be published. Clinical Trial Registration: Chinese Clinical Trial Registry, identifier ChiCTR2100042643.

A Novel Management Platform Based on Personalized Home Care Pathways for Medicine Management and Rehabilitation of Persons With Parkinson's Disease-Requirements and Implementation Plan of the Care-PD Program.

As the percentage of the aging population increases, the incidence of Parkinson's disease (PD) in China is increasing year by year. PD is both a public health and social problem facing the government and society as a whole. Persons with PD need reasonable medication management and rehabilitation strategies after a clear diagnosis. A proper home care plan can effectively slow the progression of PD. However, people with PD lack an effective way to manage their illnesses and cannot achieve the recommended clinical path in a family environment. Medication management, condition monitoring, and rehabilitation training are important components of the home care plan for PD. Persons with PD require strategies that delay the development of the disease and to adhere to treatment, which would contribute to improving their quality of life. Thus, we developed a small program called Care-PD to build a medicine management and service platform for PD. The development of Care-PD is a multi-dimensional model designed for PD, which is funded by the National Key R&D Program of China (No. 2018YFC1314700), and includes services such as medication management, symptom monitoring, professional counseling, home life, and community communication. Care-PD can become a key technology that increases the compliance of persons with PD with home care plans and improve measures to control the disease. In this article, we describe the medication management and services for PD based on the Care-PD program and its structure. The small program will improve the adverse conditions faced by persons with PD by combining the latest technology and clinical approaches. Meanwhile, we describe a verification strategy to evaluate the effectiveness of the Care-PD program as a comprehensive management strategy for PD.

Characteristics of Physical Fitness and Cardiometabolic Risk in Chinese University Students with Normal-Weight Obesity: A Cross-Sectional Study.

PURPOSE: To (i) describe the characteristics of physical fitness and cardiometabolic risk in Chinese university students with normal-weight obesity (NWO); (ii) assess the association between NWO with physical fitness and cardiometabolic risk. METHODS: A total of 249 participants from the 2018 Shanghai University of Sport Alumni Health Cohort Study in China formed the study cohort. NWO was defined as normal body mass index (17.9-23.9 kg/m2 for males; 17.2-23.9 kg/m2 for females) but with excess body-fat percentage (≥20% for males; ≥30% for females). Body composition was assessed by dual-energy X-ray absorptiometry. Physical-fitness scores were calculated from a battery of sex-specific tests. Cardiometabolic risk was calculated using a continuous clustered risk (MetS) score. RESULTS: We found that 16.7% of male and 45.3% of female university students were classified as having NWO. Participants with NWO showed worse cardiorespiratory fitness than those with normal weight (NW) (male NWO (37±8) vs male NW (41±6) mL/kg/min, p<0.01; female NWO (31±4) vs female NW (33±6) mL/kg/min, p<0.01). NWO was associated negatively with the fitness score (OR = 0.853; 95% CI = 0.793-0.917) and was associated positively with the MetS score (1.280; 1.162-1.410). CONCLUSION: University students with NWO were characterized by higher cardiometabolic risk and lower levels of physical fitness. Our findings implied that university students with NWO should be mindful of the potential hidden health risks of excess body fat and participate in exercise to enhance physical fitness.

Transient Receptor Potential Ankyrin Type-1 Channels as a Potential Target for the Treatment of Cardiovascular Diseases.

Cardiovascular disease is one of the chronic conditions with the highest mortality rate in the world. Underlying conditions such as hypertension, metabolic disorders, and habits like smoking are contributors to the manifestation of cardiovascular diseases. The treatment of cardiovascular diseases is inseparable from the development of drugs. Consequently, this has led to many researchers to focus on the search for effective drug targets. The transient receptor potential channel Ankyrin 1 (TRPA1) subtype is a non-selective cation channel, which belongs to the transient receptor potential (TRP) ion channel. Previous studies have shown that members of the TRP family contribute significantly to cardiovascular disease. However, many researchers have not explored the role of TRPA1 as a potential target for the treatment of cardiovascular diseases. Furthermore, recent studies revealed that TRPA1 is commonly expressed in the vascular endothelium. The endothelium is linked to the causes of some cardiovascular diseases, such as atherosclerosis, myocardial fibrosis, heart failure, and arrhythmia. The activation of TRPA1 has a positive effect on atherosclerosis, but it has a negative effect on other cardiovascular diseases such as myocardial fibrosis and heart failure. This review introduces the structural and functional characteristics of TRPA1 and its importance on vascular physiology and common cardiovascular diseases. Moreover, this review summarizes some evidence that TRPA1 is correlated to cardiovascular disease risk factors.

A Mobile Phone App-Based Tai Chi Training in Parkinson's Disease: Protocol for a Randomized Controlled Study.

Introduction: With an increasing number of China's aging population, Parkinson's disease (PD) increases year by year. Persons with PD exhibit abnormal balance functions, leading to motor skills difficulties, such as unstable walking or even falling. Therefore, activities of daily living and quality of life are affected. This study aims to explore the effectiveness of Tai Chi training based on the mobile phone app in improving the balance ability of persons with PD. Methods and Analysis: A randomized, single-blind, parallel controlled trial will be conducted in this study. One hundred forty-four persons with PD who meet the inclusion criteria will be randomly divided into a 1:1:1 ratio: (1) control group, (2) basic experimental group (basic app with no Tai Chi training features), and (3) balanced-enhanced experimental group (basic app with Tai Chi training features). Individuals with PD will be evaluated on balance and motor function outcomes. The primary outcome measure is the limits of stability (including the maximum excursion and direction control); the secondary outcome measures include the Unified Parkinson's Disease Rating Scale III (UPDRS-III), Berg Balance Scale (BBS), Functional Reach Test (FRT), Timed Up & Go (TUG), 6-Minute Walk Test (6MWT), and 39-item Parkinson's Disease Questionnaire (PDQ-39). Each group of patients will go through an assessment at baseline, 17 and 33 weeks. Discussion: This study will evaluate the effectiveness of the mobile phone app Tai Chi training on the balance function of persons with PD. We assume that a challenging Tai Chi project based on a mobile phone app will improve balance in the short and long term. As walking stability progresses, it is expected that daily activities and quality of life improve. These findings will be used to improve the effectiveness of future home management measures for persons with PD. Ethics and Dissemination: This study has been approved by the ethical review committee of the Shanghai University of Sport (approval number: 102772019RT056). Informed consent will be obtained from all participants or their guardians. The authors intend to submit the study findings to peer-reviewed journals or academic conferences to be published. Clinical Trial Registration: Chinese Clinical Trial Registry (ChiCTR2000029135).