Bridging the gap: Integrating exercise mimicry into chronic disease management through suppressing chronic inflammation.

BACKGROUND: Chronic inflammation is a common hallmark of many chronic diseases. Although exercise holds paramount importance in preventing and managing chronic diseases, adherence to exercise programs can be challenging for some patients. Consequently, there is a pressing need to explore alternative strategies to emulate the anti-inflammatory effects of exercise for chronic diseases. AIM OF REVIEW: This review explores the emerging role of green tea bioactive components as potential mitigators of chronic inflammation, offering insights into their capacity to mimic the beneficial effects of exercise. We propose that bioactive components in green tea are promising agents for suppressing chronic inflammation, suggesting their unique capability to replicate the health benefits of exercise. KEY SCIENTIFIC CONCEPTS OF REVIEW: This review focuses on several key concepts, including chronic inflammation and its role in chronic diseases, the anti-inflammatory effects of regular exercise, and bioactive components in green tea responsible for its health benefits. It elaborates on scientific evidence supporting the anti-inflammatory properties of green tea bioactive components, such as epigallocatechin gallate (EGCG), and theorizes how these bioactive components might replicate the effects of exercise at a molecular level. Through a comprehensive analysis of current research, this review proposes a novel perspective on the application of green tea as a potential intervention strategy to suppress chronic inflammation, thereby extending the benefits akin to those achieved through exercise.

Alzheimer's Disease Puzzle: Delving into Pathogenesis Hypotheses.

Alzheimer's disease (AD) is a prevalent neurodegenerative disease characterized by both amnestic and non-amnestic clinical manifestations. It accounts for approximately 60-70% of all dementia cases worldwide. With the increasing number of AD patients, elucidating underlying mechanisms and developing corresponding interventional strategies are necessary. Hypotheses about AD such as amyloid cascade, Tau hyper-phosphorylation, neuroinflammation, oxidative stress, mitochondrial dysfunction, cholinergic, and vascular hypotheses are not mutually exclusive, and all of them play a certain role in the development of AD. The amyloid cascade hypothesis is currently the most widely studied; however, other hypotheses are also gaining support. This article summarizes the recent evidence regarding major pathological hypotheses of AD and their potential interplay, as well as the strengths and weaknesses of each hypothesis and their implications for the development of effective treatments. This could stimulate further studies and promote the development of more effective therapeutic strategies for AD.

Efficacy and safety of ultra-short wave diathermy on COVID-19 pneumonia: a pioneering study.

Background: The ultra-short wave diathermy (USWD) is widely used to ameliorate inflammation of bacterial pneumonia, however, for COVID-19 pneumonia, USWD still needs to be verified. This study aimed to investigate the efficacy and safety of USWD in COVID-19 pneumonia patients. Methods: This was a single-center, evaluator-blinded, randomized controlled trial. Moderate and severe COVID-19 patients were recruited between 18 February and 20 April 2020. Participants were randomly allocated to receive USWD + standard medical treatment (USWD group) or standard medical treatment alone (control group). The negative conversion rate of SARS-CoV-2 and Systemic Inflammatory Response Scale (SIRS) on days 7, 14, 21, and 28 were assessed as primary outcomes. Secondary outcomes included time to clinical recovery, the 7-point ordinal scale, and adverse events. Results: Fifty patients were randomized (USWD, 25; control, 25), which included 22 males (44.0%) and 28 females (56.0%) with a mean (SD) age of 53 ± 10.69. The rates of SARS-CoV-2 negative conversion on day 7 (p = 0.066), day 14 (p = 0.239), day 21 (p = 0.269), and day 28 (p = 0.490) were insignificant. However, systemic inflammation by SIRS was ameliorated with significance on day 7 (p = 0.030), day 14 (p = 0.002), day 21 (p = 0.003), and day 28 (p = 0.011). Time to clinical recovery (USWD 36.84 ± 9.93 vs. control 43.56 ± 12.15, p = 0.037) was significantly shortened with a between-group difference of 6.72 ± 3.14 days. 7-point ordinal scale on days 21 and 28 showed significance (p = 0.002, 0.003), whereas the difference on days 7 and 14 was insignificant (p = 0.524, 0.108). In addition, artificial intelligence-assisted CT analysis showed a greater decrease in the infection volume in the USWD group, without significant between-group differences. No treatment-associated adverse events or worsening of pulmonary fibrosis were observed in either group. Conclusion: Among patients with moderate and severe COVID-19 pneumonia, USWD added to standard medical treatment could ameliorate systemic inflammation and shorten the duration of hospitalization without causing any adverse effects.Clinical Trial Registration: chictr.org.cn, identifier ChiCTR2000029972.

Mechanobiology-based physical therapy and rehabilitation after orthobiologic interventions: a narrative review.

PURPOSE: This review aims to summarize the evidence for the role of mechanotherapies and rehabilitation in supporting the synergy between regeneration and repair after an orthobiologic intervention. METHODS: A selective literature search was performed using Web of Science, OVID, and PubMed to review research articles that discuss the effects of combining mechanotherapy with various forms of regenerative medicine. RESULTS: Various mechanotherapies can encourage the healing process for patients at different stages. Taping, bracing, cold water immersion, and extracorporeal shockwave therapy can be used throughout the duration of acute inflammatory response. The regulation of angiogenesis can be sustained with blood flow restriction and resistance training, whereas heat therapy and tissue loading during exercise are recommended in the remodeling phase. CONCLUSION: Combining mechanotherapy with various forms of regenerative medicine has shown promise for improving treatment outcomes. However, further studies that reveal a greater volume of evidence are needed to support clinical decisions.

Constraint-Induced Movement Therapy Combined With Botulinum Toxin for Post-stroke Spasticity: A Systematic Review and Meta-Analysis.

Stroke is considered one of the main causes of adult disability and the second most serious cause of death worldwide. The combination of botulinum toxin type A (BTX) with rehabilitation techniques such as modified constraint-induced movement therapy (mCIMT) has emerged as a highly efficient intervention for stroke patients to start synchronized motor function along with spasticity reduction. The current systematic review and meta-analysis were conducted in order to evaluate the available literature about the safety and efficacy of constraint-induced movement therapy (CIMT) combined with BTX in stroke patients with upper limb spasticity. Searches were conducted on WoS (Web of Science), Ovid, EBSCO-ASC&BSC, and PubMed for identifying relevant literature published from 2000-2020. Randomized Controlled Trials (RCTs) and Quasi-experimental studies were considered for inclusion. Rayyan (systematic review tool) QCRI (Qatar Computing Research Institute) was used for independent screening of the studies by two reviewers. For risk of bias and study quality assessment, Cochrane risk of bias tool (RoB 2) and Physiotherapy Evidence Database (PEDro) scales were used. Cochrane review manager was used to carry out the meta-analyses of the included studies. The search resulted in a total of 13065 references, of which 4967 were duplicates. After the title, abstract and full-text screening, two RCTs were deemed eligible for inclusion. Both the RCTs scored 8 on PEDro and were level evidence. The studies were heterogeneous. The findings of this meta-analysis in all the three joints post-stroke spasticity assessed on modified Ashworth scale (MAS) at four weeks post-injection aren't statistically significant (elbow P-value 0.74, wrist P-value 0.57, fingers P-value 0.42), however, according to one of the included studies the therapeutic efficacy of the combination of BTX-mCIMT injection assessed at four weeks post-injection in wrist and finger flexors was promising.  The effectiveness of BTX-CIMT combination over conventional therapy (CT) for improving post-stroke spasticity still needs to be explored with long-term, multicenter rigorously designed RCTs having a good sample size. However, the BTX-CIMT combination is promising for enhancing motor function recovery and improving activities of daily living (ADLs).

Temporal expression profiles of lncRNA and mRNA in human embryonic stem cell-derived motor neurons during differentiation.

BACKGROUND: Human embryonic stem cells (hESC) have been an invaluable research tool to study motor neuron development and disorders. However, transcriptional regulation of multiple temporal stages from ESCs to spinal motor neurons (MNs) has not yet been fully elucidated. Thus, the goals of this study were to profile the time-course expression patterns of lncRNAs during MN differentiation of ESCs and to clarify the potential mechanisms of the lncRNAs that are related to MN differentiation. METHODS: We utilized our previous protocol which can harvest motor neuron in more than 90% purity from hESCs. Then, differentially expressed lncRNAs (DElncRNAs) and mRNAs (DEmRNAs) during MN differentiation were identified through RNA sequencing. Bioinformatic analyses were performed to assess potential biological functions of genes. We also performed qRT-PCR to validate the DElncRNAs and DEmRNAs. RESULTS: A total of 441 lncRNAs and 1,068 mRNAs at day 6, 443 and 1,175 at day 12, and 338 lncRNAs and 68 mRNAs at day 18 were differentially expressed compared with day 0. Bioinformatic analyses identified that several key regulatory genes including POU5F1, TDGF1, SOX17, LEFTY2 and ZSCAN10, which involved in the regulation of embryonic development. We also predicted 283 target genes of DElncRNAs, in which 6 mRNAs were differentially expressed. Significant fold changes in lncRNAs (NCAM1-AS) and mRNAs (HOXA3) were confirmed by qRT-PCR. Then, through predicted overlapped miRNA verification, we constructed a lncRNA NCAM1-AS-miRNA-HOXA3 network.

Scaling the Need, Benefits, and Risks Associated with COVID-19 Acute and Postacute Care Rehabilitation: A Review.

Coronavirus is an RNA virus, which attacks the respiratory system causing complications including severe respiratory distress and pneumonia and many other symptoms. Recently, a novel coronavirus (COVID-19) outbreak emerged in Wuhan, which caused a significant number of infections in China and resulted in a global pandemic. The main aim of this study is to review and summarize the evidence regarding the supportive role of physical rehabilitation techniques in managing COVID-19-associated pneumonia. In this review, we also emphasize the use of rehabilitation techniques in the management of pneumonia in COVID-19-infected patients. Based on the evidence presented, we conclude that certain physical rehabilitation techniques and modalities could be of great support in the management of COVID-19-associated pneumonia. The safety of staff and patients when applying rehabilitation intervention requires attention. The combination of physical rehabilitation and medical treatment would result in improved treatment outcomes, faster recovery, and shorter hospital stay. Many rehabilitation techniques are safe and feasible and can be easily incorporated into the management protocol of COVID-19 victims. Decisions of early rehabilitation induction should be based on the patient's medical condition and tolerability.

The curative effects of shortwave diathermy on treating Novel coronavirus (COVID-19) pneumonia: A structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: To evaluate the therapeutic effects of ultra-short-wave diathermy (SWD) on COVID-19 pneumonia. The hypothesis is that SWD may minimise pneumonic inflammation and shorten the duration of the time to positive-to-negative conversion of COVID-19 nucleic acid test. TRIAL DESIGN: This is a single centre, 2-arm (1:1 ratio), evaluator blinded, parallel group design superiority randomised, controlled clinical trial. PARTICIPANTS: The inclusion criteria were: (1) Age 18-65 years, (2) COVID-19 nucleic acid test is positive, (3) Lung CT showed multiple patchy ground glass shadows or other typical manifestations of both lungs. The exclusion criteria were: (1) Patients who need ICU management, (2) Positive tests for other pathogens such as Tuberculosis, Mycoplasma, (3) Patients with respiratory failure or requiring mechanical ventilation, (4) Patients with metal implants or pacemakers, (5) Those with shock (6) Those that have bleeding tendency or active bleeding in the lungs, (7) Patients with multiple organ failure who need ICU monitoring and treatment, (8) Cancer patients and those with severe underlying diseases, (9) Pregnant or lactating women, (10) Patients with severe cognitive impairment who cannot follow the instructions to complete the treatment, (11) Those without signed informed consent and (12) Those with other contraindications to short wave. This study will be conducted in Tongji Hospital, Caidian, Wuhan, People's Republic of China. INTERVENTION AND COMPARATOR: The experimental group will be given the nationally recommended standard medical treatment + ultra-short-wave diathermy treatment. Ultra-short-wave therapy treatment will be performed through application of ultra-short-wave therapy machine electrodes on the anterior and posterior parts of the trunk for 10 minutes, twice a day for 12 consecutive days. The comparator will be the control, not receiving ultra-short-wave therapy, and will be given only the nationally recommended standard medical treatment. MAIN OUTCOMES: The primary outcome measures will be time to positive-to-negative conversion of COVID-19 nucleic acid test by pharyngeal swab, in days assessed at 7th, 14th ,21st and 28th days. The secondary outcome measures include nucleic acid test rate and recovery from symptoms, Vital signs assessment, Computed Tomography, Complete blood count, serum analysis and SIRS scale scores. Blinded evaluation will be at baseline (the day of starting ultra-short-wave diathermy) and after 28 days following the interventions. RANDOMISATION: A Randomization plan will be generated online on www.randomization.com using permuted blocks method, by a statistician who will not be part of the study. Small blocks of various sizes will be used. Patients will be randomized (1:1) between the experimental and control groups BLINDING (MASKING): This will be an evaluator blinded study. Due to the nature of the intervention, blinding of patients and healthcare workers is not possible. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): A total of 410 patients will be randomised in 1:1 ratio to two groups: experimental group (n=205) and control group (n=205). TRIAL STATUS: Protocol version 1 was approved on 02/12/2020. Recruitment for this trial began on 02/18/2020 and will be ongoing till the required sample size is reached. The analysis deadline is August 2020. TRIAL REGISTRATION: This randomised controlled trial has been prospectively registered with the Chinese Clinical Trials ( ChiCTR2000029972 ) on 17 February 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol." The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).

Human adipose-derived Mesenchymal stem cells, low-intensity pulsed ultrasound, or their combination for the treatment of knee osteoarthritis: study protocol for a first-in-man randomized controlled trial.

BACKGROUND: Human adipose-derived Mesenchymal stem cells (HADMSCs) have proven their efficacy in treating osteoarthritis (OA), in earlier preclinical and clinical studies. As the tissue repairers are under the control of mechanical and biochemical signals, improving regeneration outcomes using such signals has of late been the focus of attention. Among mechanical stimuli, low-intensity pulsed ultrasound (LIPUS) has recently shown promise both in vitro and in vivo. This study will investigate the potential of LIPUS in enhancing the regeneration process of an osteoarthritic knee joint. METHODS: This study involves a prospective, randomized, placebo-controlled, and single-blind trial based on the SPIRIT guidelines, and aims to recruit 96 patients initially diagnosed with knee osteoarthritis, following American College of Rheumatology criteria. Patients will be randomized in a 1:1:1 ratio to receive Intraarticular HADMSCs injection with LIPUS, Intraarticular HADMSCs injection with shame LIPUS, or Normal saline with LIPUS. The primary outcome is Western Ontario and McMaster Universities Index of OA (WOMAC) score, while the secondary outcomes will be other knee structural changes, and lower limb muscle strength such as the knee cartilage thickness measured by MRI. Blinded assessments will be performed at baseline (1 month prior to treatment), 1 month, 3 months, and 6 months following the interventions. DISCUSSION: This trial will be the first clinical study to comprehensively investigate the safety and efficacy of LIPUS on stem cell therapy in OA patients. The results may provide evidence of the effectiveness of LIPUS in improving stem cell therapy and deliver valuable information for the design of subsequent trials. TRIAL REGISTRATION: This study had been prospectively registered with the Chinese Clinical Trials Registry. registration number: ChiCTR1900025907 at September 14, 2019.

Dry Cupping, Ischemic Compression, or Their Combination for the Treatment of Trigger Points: A Pilot Randomized Trial.

Background: Chronic neck pain (NP) attributed to myofascial pain syndrome is one of the particularly common skeletal muscle disorder associated with the hyperirritable zone in the taut band of muscle. Trigger points (TPs) are the physical interpretation of the myofascial pain syndrome. In the United States, 30%-85% of pain patients have been affected by myofascial TPs. Objectives: To reveal preliminary evidence on the clinical efficacy of ischemic compression therapy, dry cupping, and their combination on improving the TPs' pressure pain threshold (PPT), neck range of motion (NROM), and neck disability index (NDI) in patients with TPs and nonspecific NP. Besides, assess the feasibility of conducting a randomized clinical trial (RCT). Design: A randomized pilot study was conducted on 24 patients with TPs and nonspecific NP. Patients were randomly assigned to three groups: the cupping group, the ischemic compression group, and the combination therapy group. PPT, NROM, and NDI were assessed before and after 4 weeks of treatment. Results: The results showed a statistically significant improvement in NDI, PPT, and NROM compared with values before the treatment (p < 0.05) in all groups. Although no significant difference was detected between ischemic compression (IC) and dry cupping, the combination approach showed significantly higher and faster improvement (p < 0.05). Conclusions: It is feasible to conduct a main RCT. Both IC and dry cupping may hold promise in treating TPs; a combination of the two therapies may provide superior improving rate.

Comparison of the effects of modified constraint-induced movement therapy and intensive conventional therapy with a botulinum-a toxin injection on upper limb motor function recovery in patients with stroke.

Stroke is the second leading cause of mortality worldwide and one of the main causes of adult disability. Many studies have suggested that combination therapies provide better outcomes in patients with stroke than monotherapies. The combination of botulinum-A toxin (BTX) injection with rehabilitation methods, such as modified constraint-induced movement therapy (BTX-mCIMT), has emerged as a highly promising intervention for promoting motor recovery after stroke. Thus, the present study compared the effectiveness of the combination of BTX with high-dose conventional therapy (BTX-ICT) and BTX-mCIMT for improving motor recovery and reducing spasticity of the upper limb in patients with stroke. This study recruited 64 patients with stroke. The patients were randomly allocated to two groups, namely, BTX-ICT and BTX-mCIMT. Modified Ashworth scale (MAS), Fugl-Meyer assessment (FMA), and Barthel index (BI) assessment scores were determined for the patients in both the groups before and at 4 weeks after the BTX injection. After four weeks of treatment, the MAS, FMA, and BI assessment scores of the patients in both groups were significantly higher than the scores before the treatments (P < 0.05). At the end of 4 weeks, the patients in the BTX-mCIMT group showed significantly higher mean FMA and BI assessment scores than the patients in the BTX-ICT group (P < 0.05). However, no significant statistical difference was observed in the MAS score of the patients in the two groups (P > 0.05). Our results indicated that while both BTX-mCIMT and BTX-ICT promoted motor function recovery in patients with stroke, BTX-mCIMT exerted higher therapeutic effects than BTX-ICT on motor function recovery and in the activities of daily living of patients with stroke.