Effects of concomitant use of hydrogen water and photobiomodulation on Parkinson disease: A pilot study.

BACKGROUND: Parkinson disease (PD), the second most common neurodegenerative disease, has no cure or applicable disease-modifying approach, only symptomatic therapy. Oxidative stress and mitochondrial dysfunction play key roles in PD pathophysiology. Animal studies have demonstrated that photobiomodulation (PBM) may enhance mitochondrial function and boost adenosine triphosphate production, thus alleviating PD symptoms; however, this process can cause increased reactive oxygen species (ROS) production. Molecular hydrogen (H2) is a potent and possibly therapeutic antioxidant that can mitigate the effect of ROS. PBM targeting the brainstem may facilitate neuronal activity, and the concomitant H2 may clear additional ROS produced by PBM. Therefore, this study aimed to determine the safety and effectiveness of PBM + H2 in patients with PD. METHODS: We included 18 patients with PD (age 30-80 years) who were at Hoehn and Yahr stages II-III. All the participants received daily PBM + H2 therapy for 2 weeks. The adverse event and the Unified Parkinson Disease Rating Scale (UPDRS) scores were recorded. RESULTS: We noted that the UPDRS scores began significantly decreasing from the first week, and this improvement persisted until the end of therapy. Moreover, no adverse event was recorded. After 1 week of therapy cessation, UPDRS scores slightly increased but the improvement remained significant compared with the baseline. CONCLUSION: This novel, proof-of-concept study demonstrated that PBM+H2 therapy is safe and reduces disease severity. A larger-scaled clinical trial is warranted to completely investigate the effects of PBM + H2 therapy on PD.

Effects of Acupuncture on Delayed-Onset Muscle Soreness: A Systematic Review and Meta-Analysis.

OBJECTIVES: Evidence for the effects of acupuncture on delayed-onset muscle soreness (DOMS) is inconsistent. The aim of this study was to explore the effects of acupuncture on DOMS. METHODS: Studies investigating the effect of acupuncture on DOMS in humans that were published before March 2020 were obtained from eight electronic databases. The affected muscles, groups, acupuncture points, treatment sessions, assessments, assessment times, and outcomes of the included articles were reviewed. The data were extracted and analyzed via a meta-analysis. RESULTS: A total of 15 articles were included, and relief of DOMS-related pain was the primary outcome. The statistical meta-analysis showed that there were no significant differences between acupuncture and sham/control groups, except for acupuncture for DOMS on day 1 (total SMD = -0.62; 95% CI = -1.12∼0.11, P < 0.05) by comparing with control groups. CONCLUSION: Acupuncture for DOMS exhibited very-small-to-small and small-to-moderate effects on pain relief for the sham and no acupuncture conditions, respectively. Evidence indicating the effects of acupuncture on DOMS was little because the outcome data during the follow-up were insufficient to perform an effective meta-analysis.

Sorafenib with concurrent multiple-line therapies improves overall survival in advanced stage hepatocellular carcinoma.

The efficacy of sorafenib in combination with transarterial chemoembolization (TACE) or multiple-line therapies in patients with advanced hepatocellular carcinoma (HCC) remains unclear. This study aimed to investigate the overall survival (OS) of patients with advanced HCC in response to different combination therapies.We analyzed the treatment and OS of 401 patients with Barcelona clinic liver cancer stage C HCC between 2012 and 2017. Mortality was analyzed using multivariate Cox regression, and OS was analyzed by the Kaplan-Meier method.The mean age was 59 years and males were predominant. During a median follow-up time of 8.6 months (range, 1-80 months), 346 (86.2%) patients died. In the multivariate Cox regression analysis, primary tumor size ≥5 cm, serum alpha-fetoprotein ≥200, and serum albumin ≥3.5 were significantly associated with mortality. In addition, compared with sorafenib alone, multiple-line treatments with sorafenib and multiple-line treatments without sorafenib yielded significantly decreased mortality. In the Kaplan-Meier analysis, sorafenib with TACE, multiple-line treatments with sorafenib, third-line treatments with sorafenib, and multiple-line treatments without sorafenib yielded a significantly better median OS than sorafenib alone.Sorafenib with concurrent multiple-line therapies significantly improved OS. These combination therapies will provide important information for immunotherapy combination with locoregional therapies in advanced HCC.

Mitochondrial Transfer of Wharton's Jelly Mesenchymal Stem Cells Eliminates Mutation Burden and Rescues Mitochondrial Bioenergetics in Rotenone-Stressed MELAS Fibroblasts.

Wharton's jelly mesenchymal stem cells (WJMSCs) transfer healthy mitochondria to cells harboring a mitochondrial DNA (mtDNA) defect. Mitochondrial myopathy, encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) is one of the major subgroups of mitochondrial diseases, caused by the mt.3243A>G point mutation in the mitochondrial tRNALeu(UUR) gene. The specific aim of the study is to investigate whether WJMSCs exert therapeutic effect for mitochondrial dysfunction in cells of MELAS patient through donating healthy mitochondria. We herein demonstrate that WJMSCs transfer healthy mitochondria into rotenone-stressed fibroblasts of a MELAS patient, thereby eliminating mutation burden and rescuing mitochondrial functions. In the coculture system in vitro study, WJMSCs transferred healthy mitochondria to rotenone-stressed MELAS fibroblasts. By inhibiting actin polymerization to block tunneling nanotubes (TNTs), the WJMSC-conducted mitochondrial transfer was abrogated. After mitochondrial transfer, the mt.3243A>G mutation burden of MELAS fibroblasts was reduced to an undetectable level, with long-term retention. Sequencing results confirmed that the transferred mitochondria were donated from WJMSCs. Furthermore, mitochondrial transfer of WJMSCs to MELAS fibroblasts improves mitochondrial functions and cellular performance, including protein translation of respiratory complexes, ROS overexpression, mitochondrial membrane potential, mitochondrial morphology and bioenergetics, cell proliferation, mitochondrion-dependent viability, and apoptotic resistance. This study demonstrates that WJMSCs exert bioenergetic therapeutic effects through mitochondrial transfer. This finding paves the way for the development of innovative treatments for MELAS and other mitochondrial diseases.

The Antioxidant from Ethanolic Extract of Rosa cymosa Fruits Activates Phosphatase and Tensin Homolog In Vitro and In Vivo: A New Insight on Its Antileukemic Effect.

Rosa cymosa Tratt is a Chinese herbal remedy that is used in the treatment of diarrhea, burns, rheumatoid arthritis, and hemorrhage. Despite its use in Asian folk medicine, there are limited reports on the biological activity of R. cymosa fruits. This study focused on the investigation of the antitumor effect of the antioxidative ethanolic extract of R. cymosa fruits (RCE) along with its underlying mechanism of action. RCE showed a potent cytotoxic effect against Sup-T1 and Molt-4 lymphoblastic leukemia cells. In the xenograft animal model, the tumor size was significantly reduced to about 59.42% in the RCE-treated group in comparison with the control group. The use of RCE (37.5, 75, or 150 µg/mL) triggered apoptosis by 26.52-83.49%, disrupted mitochondrial membrane potential (MMP) by 10.44-58.60%, and promoted calcium release by 1.29-, 1.44-, and 1.71-fold compared with the control group. The extract induced redox oxygen species (ROS) generation through the elimination of Nrf2/Keap1/P62-mediated oxidative stress response. The loss of phosphatase and tensin homolog (PTEN) activation by RCE impaired PI3K/Akt/Foxo and Jak/Stat activation pathways, which contributed to tumorigenesis. These multiple targets of R. cymosa against hematologic cancer cells suggested its potential application as an antileukemic dietary supplement.

Rapid determination of bioactive compounds in the different organs of Salvia Miltiorrhiza by UPLC-MS/MS.

Salvia miltiorrhiza has been widely used in Asia for medicinal purposes for >1000 years due to the high levels of bioactive constituents it contains. In this study, a simple and rapid ultrasound-assisted liquid extraction (5 min) was applied for the extraction of these bioactive constituents. The extracts were analyzed by using rapid ultrahigh performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) with simultaneous positive and negative electrospray ionization in a single analytical run. Eight analytes were separated within 2.2 min during 6 min of run time with UHPLC-MS/MS operated in multiple reaction monitoring (MRM) mode. The concentration of salvianolic acids and tanshinones in the different organs of different varieties of Salvia miltiorrhiza ranged from 6.4 to 382.1 mg/g and 0.03 to 31.7 mg/g, respectively. To the best of our knowledge, this is the first report to characterize the tanshinone compounds found in the flower and stem/leaf of Salvia miltiorrhiza by UHPLC-MS/MS.

Effect of Uveitis on the Development of Keratopathy: A Population-Based Cohort Study.

Purpose: The purpose of this study was to evaluate the effect of uveitis on the development of various keratopathies via the use of the National Health Insurance Research Database (NHIRD) in Taiwan. Methods: Approximately 1 million patients were randomly sampled from the registry of the NHIRD. Patients diagnosed with uveitis by ophthalmologists were enrolled in the study group after exclusion. Each individual in the study group was age and sex matched to four non-uveitis individuals who serve as the control group. In addition to keratopathy, other possible risk factors and medications were included in the multivariate model, and the effects of different subtypes of uveitis for developing keratopathies were also analyzed. Results: A total of 4773 uveitis patients (2662 male and 2111 female) and 19,092 non-uveitis patients (10,648 male and 8444 female) were enrolled. There were 406 events of keratopathy in the study group, and another 764 events occurred in the control group. A higher incidence rate was found in the study group after adjustment (adjusted hazard ratio [aHR]: 1.772), with a greater cumulative probability (P < 0.0001). For the subgroup analysis, anterior uveitis (aHR = 1.765) and panuveitis (aHR = 3.386) increased the risk of developing keratopathies. Moreover, male sex was associated with a higher aHR than female sex for developing keratopathies in the study group. Conclusions: The presence of uveitis significantly elevates the risk for developing keratopathy.

A rapid, simple, and high-throughput UPLC-MS/MS method for simultaneous determination of bioactive constituents in Salvia miltiorrhiza with positive/negative ionization switching.

The dried root of Danshen (Salvia miltiorrhiza) is a Chinese medicine that has been used in traditional treatments for more than 2000 years in Asia. It has also been used to treat cardiovascular diseases for decades. The goal of this study was to develop a new, fast, and simple ultrahigh-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) analytical method for the analysis of phenolic acids and tanshinones in Danshen. The samples were separated on a Kinetex F5 column (2.1 x 100 mm, 1.7 µm, pentafluorophenyl) using 78% acetonitrile with 0.1% formic acid as the mobile phase with isocratic elution while the flow rate was set at 0.45 mL/min. The analysis was performed in a Waters Xevo TQ mass spectrometer via multiple reaction monitoring (MRM) in polarity switching mode. The linearity values of the calibration curves of eight compounds were in the range from 3 to 3200 ng/mL (r2 > 0.99). Method validation was performed in terms of linearity, the relative standard deviations (RSDs) of the intra-day and inter-day, and it was found that precisions were within 15% and the accuracy ranged from 93% to 118%. The recovery was more than 87%. The limit of detection (LOD) and limit of quantification (LOQ) values of the eight analytes varied between 0.023 to 0.75 ng/mL and 0.375 to 1.5 ng/mL, respectively. This approach has the shortest analysis time for the separation of phenolic acids and tanshinones in Danshen using a UPLC core-shell column with F5 stationary phase. Meanwhile, this robust and high-throughput method not only has a short run time (2 min) but also reduce the consumption of organic solvents.

Mitochondrial Transfer from Wharton's Jelly Mesenchymal Stem Cell to MERRF Cybrid Reduces Oxidative Stress and Improves Mitochondrial Bioenergetics.

Myoclonus epilepsy associated with ragged-red fibers (MERRF) is a maternally inherited mitochondrial disease affecting neuromuscular functions. Mt.8344A>G mutation in mitochondrial DNA (mtDNA) is the most common cause of MERRF syndrome and has been linked to an increase in reactive oxygen species (ROS) level and oxidative stress, as well as impaired mitochondrial bioenergetics. Here, we tested whether WJMSC has therapeutic potential for the treatment of MERRF syndrome through the transfer of mitochondria. The MERRF cybrid cells exhibited a high mt.8344A>G mutation ratio, enhanced ROS level and oxidative damage, impaired mitochondrial bioenergetics, defected mitochondria-dependent viability, exhibited an imbalance of mitochondrial dynamics, and are susceptible to apoptotic stress. Coculture experiments revealed that mitochondria were intercellularly conducted from the WJMSC to the MERRF cybrid. Furthermore, WJMSC transferred mitochondria exclusively to cells with defective mitochondria but not to cells with normal mitochondria. MERRF cybrid following WJMSC coculture (MF+WJ) demonstrated improvement of mt.8344A>G mutation ratio, ROS level, oxidative damage, mitochondrial bioenergetics, mitochondria-dependent viability, balance of mitochondrial dynamics, and resistance against apoptotic stress. WJMSC-derived mitochondrial transfer and its therapeutic effect were noted to be blocked by F-actin depolymerizing agent cytochalasin B. Collectively, the WJMSC ability to rescue cells with defective mitochondrial function through donating healthy mitochondria may lead to new insights into the development of more efficient strategies to treat diseases related to mitochondrial dysfunction.

Auditory and Visual Attention Performance in Children With ADHD: The Attentional Deficiency of ADHD Is Modality Specific.

OBJECTIVE: This study explored auditory and visual attention in children with ADHD. METHOD: In a randomized, two-period crossover design, 50 children with ADHD and 50 age- and sex-matched typically developing peers were measured with the Test of Various Attention (TOVA). RESULTS: The deficiency of visual attention is more serious than that of auditory attention in children with ADHD. On the auditory modality, only the deficit of attentional inconsistency is sufficient to explain most cases of ADHD; however, most of the children with ADHD suffered from deficits of sustained attention, response inhibition, and attentional inconsistency on the visual modality. Our results also showed that the deficit of attentional inconsistency is the most important indicator in diagnosing and intervening in ADHD when both auditory and visual modalities are considered. CONCLUSION: The findings provide strong evidence that the deficits of auditory attention are different from those of visual attention in children with ADHD.

The Effects of Tai Chi Chuan on Improving Mind-Body Health for Knee Osteoarthritis Patients: A Systematic Review and Meta-Analysis.

Purpose. To conduct a meta-analysis and systematic review examining whether Tai Chi Chuan could have mental and physical benefits for patients with knee osteoarthritis. Methods. MEDLINE, PUBMED, EMBASE, and CINAHL databases were searched for relevant studies. Data of the studies were collected, and outcomes were classified using the International Classification of Functioning, Disability, and Health model. Effect sizes of the mental and physical components were determined, along with the recommendation grades of Philadelphia Panel Classification System for Tai Chi Chuan on knee osteoarthritis. Results. Eleven studies were selected and retrieved from the databases. The results of meta-analysis revealed that the effects of Tai Chi Chuan were observed for physical components in the body functions and structures domain. The effects favoring Tai Chi Chuan were observed in the physical component in the activities and participation domain. Insufficient data was included in the meta-analysis of the mental component. Conclusions. The review revealed that Tai Chi Chuan had beneficial outcomes for patients with knee osteoarthritis. The evidence-based results represented that it had small-to-moderate effects on body functions and structures, activities, and participation of physical component. However, there was insufficient evidence to support that Tai Chi Chuan had beneficial mental effect.

Effects of Kinesio Taping versus McConnell Taping for Patellofemoral Pain Syndrome: A Systematic Review and Meta-Analysis.

Objectives. To conduct a systematic review comparing the effects of Kinesio taping with McConnell taping as a method of conservative management of patients with patellofemoral pain syndrome (PFPS). Methods. MEDLINE, PUBMED, EMBASE, AMED, and the Cochrane Central Register of Control Trials electronic databases were searched through July 2014. Controlled studies evaluating the effects of Kinesio or McConnell taping in PFPS patients were retrieved. Results. Ninety-one articles were selected from the articles that were retrieved from the databases, and 11 articles were included in the analysis. The methods, evaluations, and results of the articles were collected, and the outcomes of patellar tapings were analyzed. Kinesio taping can reduce pain and increase the muscular flexibility of PFPS patients, and McConnell taping also had effect in pain relief and patellar alignment. Meta-analysis showed small effect in pain reduction and motor function improvement and moderate effect in muscle activity change among PFPS patients using Kinesio taping. Conclusions. Kinesio taping technique used for muscles can relieve pain but cannot change patellar alignment, unlike McConnell taping. Both patellar tapings are used differently for PFPS patients and substantially improve muscle activity, motor function, and quality of life.

Subtoxic Levels of Apigenin Inhibit Expression and Secretion of VEGF by Uveal Melanoma Cells via Suppression of ERK1/2 and PI3K/Akt Pathways.

The effects of apigenin on the expression of VEGF in uveal melanoma cells have not been reported. We studied this effect and relevant signaling pathways in two human uveal melanoma cell lines (SP6.5 and C918). ELISA assay revealed that the constitutive secretion of VEGF by uveal melanoma cells was 21-fold higher than that in normal uveal melanocytes. Apigenin at subtoxic levels (1-5 µ M) significantly suppressed the secretion of VEGF in a dose- and time-dependent manner in melanoma cells. VEGF levels in the conditioned culture media from SP6.5 and C918 cell lines treated with 5 µ M apigenin for 24 h reduced to 29% and 21% of those in cells not treated with apigenin, respectively. RT-PCR analysis found that apigenin also decreased the expression of VEGF mRNA in melanoma cells. ELISA study of various signal pathways showed that apigenin significantly decreased phosphorylated Akt and ERK1/2 but increased phosphorylated JNK1/2 and p38 MAPK levels in melanoma cells. PI3K/Akt or ERK1/2 inhibitors significantly decreased, but JNK1/2 and p38 MAPK inhibitors did not influence the secretion of VEGF by melanoma cells, suggesting that apigenin suppresses the secretion of VEGF mainly through the inhibition of PI3K/Akt and ERK1/2 pathways.