Baroreflex Sensitivity as a Surrogate Biomarker for Concurrently Assessing the Severity of Arterial Stiffness and Cardiovascular Autonomic Neuropathy in Individuals with Type 2 Diabetes.

This study aimed to investigate whether baroreflex sensitivity (BRS) could serve as a reliable metric for assessing cardiovascular autonomic neuropathy (CAN) and concurrently act as a surrogate biomarker for evaluating the severity of arterial stiffness and CAN in individuals diagnosed with type 2 diabetes mellitus (T2DM). Participants underwent brachial-ankle pulse wave velocity (baPWV) as well as autonomic function evaluations encompassing the Sudoscan-based modified composite autonomic scoring scale (CASS), baroreflex sensitivity, and heart rate variability in time domains and frequency domains. Linear regression analysis was performed to evaluate the influence of independent variables on baPWV and modified CASS. Participants with higher baPWV values were older, with longer diabetes duration, lower body weight, body mass index, waist circumference, elevated systolic and diastolic blood pressure, and mean arterial blood pressure. They also exhibited a higher prevalence of retinopathy as the underlying disease and reduced estimated glomerular filtration rate. Multiple linear regression analysis revealed that age and BRS were significantly associated with baPWV while diabetes duration, UACR, and BRS were significantly associated with modified CASS. Our study confirms the significant association of BRS with baPWV and modified CASS in T2DM, highlighting its pivotal role in linking microvascular and macrovascular complications. This supports BRS as a surrogate marker for assessing both the severity of arterial stiffness and cardiovascular autonomic neuropathy in T2DM, enabling the early identification of complications.

Prescription characteristics of Xue-Fu-Zhu-Yu-Tang in pain management: a population-based study using the National Health Insurance Research Database in Taiwan.

Objective: To explore the prevalence and distinctive features of Xue-Fu-Zhu-Yu-Tang (XFZYT) prescriptions by analyzing the National Health Insurance Research Database (NHIRD) to identify the specific medical problems for which XFZYT is prescribed. Methods: This nationwide, population-based, cross-sectional study included 109,073 XFZYT users and 532,848 XFZYT non-users among Chinese herbal product (CHP) users in NHIRD. Chi-squared tests were used to analyze disparities between the XFZYT user and XFZYT non-user cohorts, and the mean age was evaluated using the Wilcoxon rank-sum test. Logistic regression was used to compute the odds ratios (ORs) and 95% confidence intervals (95% CIs). Results: XFZYT was frequently used to treat pain. The top five conditions for which the Taiwanese traditional Chinese medicine (TCM) practitioners would prescribe XFZYT were chest pain; headache; myalgia and myositis; lumbago; and neuralgia, neuritis, and radiculitis. Conclusion: This study represents an inaugural comprehensive survey conducted on the utilization of XFZYT prescriptions among patients with diverse diseases. XFZYT is mostly used to treat pain conditions in Taiwan. Combined with the combination use of other CHPs, XFZYT is used to treat symptoms of the chest and respiratory system, soft tissue conditions, menstruation disorders, and joint and back discomfort. These results suggest that further clinical trials are warranted to verify the effects of XFZYT in pain management.

Effect of light needle in the treatment of opioid use disorder: A protocol for a randomized controlled trial.

BACKGROUND: Opioid use disorder occurs worldwide and creates an increasing economic burden and public health crisis. Some problems are associated with using opioid agonists; therefore, there is a need to develop non-opioid treatments to improve acute and long-term opioid withdrawal syndromes. METHODS: We will enroll 100 participants with opioid use disorders receiving methadone maintenance treatment at an addiction treatment center and randomly allocate them to an experimental or control group. The experimental group will receive 12 sessions of light needle therapy within 4 weeks, while the control group will receive sham light needle treatment without any laser output. Urinary morphine levels were assessed before and after treatment. Participants will be asked to self-report their number of episodes or days of heroin use and heroin craving/refusal to use heroin in the previous week before and after treatment on a visual analogue scale score of 0 to 10. Quality of life will be reported using the Short Form-12v2 before and after 4 weeks of treatment. Pulse diagnosis and heart rate variability will be evaluated before and after treatment. Baseline patient characteristics will be compared between the groups using the independent t test and the χ2 test. Data between the 2 groups will be compared using generalized estimation equations, and paired t tests. OBJECTIVE: This study aims to investigate the effect of adjuvant light needle therapy in patients with opioid use disorder on methadone maintenance treatment.

Laser meridian massage decreased craving in men with opioid use disorder on methadone maintenance treatment.

BACKGROUND: The incidence of opioid use disorder (OUD) is increasing worldwide, and the opioid-related overdose crisis is currently a major global challenge. This study investigated the effects of adjuvant laser meridian massage (LMM) in men with OUD undergoing methadone maintenance treatment (MMT). METHODS: A case-controlled study was conducted from February 2019 to April 2020. Fourteen men with OUD on MMT were enrolled from an addiction treatment center as an experimental group. An age-matched control group comprising 13 men was also enrolled. The experimental group received LMM on the back, including over the Bladder meridian and Governor Vessel, three times weekly for 4 weeks. The control group received only MMT. Urinary morphine levels, patients' self-reports of the number of episodes or days of heroin use, and visual analog scale scores for heroin craving/refusal to use heroin during the previous week were evaluated. Quality of life was reported using the Short Form (SF)-12v2. RESULTS: The experimental group showed a significant decrease in heroin use (p < 0.05), whereas the control group showed a significant increase in heroin craving (p < 0.05). The SF-12v2 Health Survey revealed a significant improvement in physical health in the experimental group (P < 0.05). CONCLUSION: The results of this study suggest that laser meridian massage can be considered a safe, well-tolerated, and potentially useful adjuvant intervention for opioid use disorder.

The Utilization of Chinese Herbal Products for Hyperthyroidism in National Health Insurance System (NHIRD) of Taiwan: A Population-Based Study.

Background: Traditional Chinese Medicine (TCM) relieves associated symptoms of hyperthyroidism such as heat intolerance, palpitations, tremor, anxiety, weight loss, increased frequency of bowel movements, and shortness of breath. However, there are no studies regarding the core prescription patterns of herbal formula and single herbs for hyperthyroidism in Taiwan. Materials and Methods: This is a retrospective, observational study using the National Health Insurance Research Database (NHIRD) in Taiwan to analyze the prescription patterns of TCM. Demographic factors, such as sex, age, occupational status, and residential area, and the risk factors for hyperthyroidism were also studied. Results: The outpatient or/and inpatient services for hyperthyroidism receive 17,707 cases in a year. Overall, there were 13,394 newly diagnosed patients. TCM was used in 73% of the patients, and 77.3% of the patients were females. The acceptability of TCM was higher among female patients. Most patients were diagnosed with hyperthyroidism between the ages of 30 and 49 years. The most common comorbidity identified was diabetes mellitus. The most commonly prescribed Chinese herbal product (CHP) formula was Jia-Wei-Xia-Yao-San, while Xia-Ku-Cao was the most commonly prescribed single CHP. There was a high coprescription rate for Xuan-Shen, Bei-Mu, and Mu-Li. Conclusion: This study describes the core prescription pattern of TCM used in the treatment of patients with hyperthyroidism in Taiwan. The most frequently used CHPs could be potential candidates for future pharmacologic studies or clinical trials.

Acute Effects of Tissue Flossing Coupled with Functional Movements on Knee Range of Motion, Static Balance, in Single-Leg Hop Distance, and Landing Stabilization Performance in Female College Students.

Flexibility, specifically that in the amplitude of sagittal-plane range of motion (ROM), can improve jump landing patterns and reduce the potential for sports injury. The use of floss bands (FLOSS) reportedly increases joint range of motion (ROM) in the shoulder, ankle, and elbow joints. However, little research on the effectiveness of FLOSS on the knee joint has been conducted. This study investigated the effects of FLOSS on knee ROM, static balance, single-leg-hop distance, and landing stabilization performance in women. This study had a crossover design. Twenty active female college students without musculoskeletal disorders were randomly assigned to receive a FLOSS intervention or elastic bandage (ELA) control on their dominant knees. The participants underwent FLOSS and ELA activities on two occasions with 48 h of rest between both sets of activities. The outcomes were flexibility of the quadriceps and hamstrings, how long one could maintain a single-leg stance (with and without eyes closed), distance on a single-leg triple hop, and score on the Landing Error Scoring System (LESS); these outcomes were evaluated at preintervention and postintervention (immediately following band removal and 20 min later). After the FLOSS intervention, the participants' hamstring flexibility improved significantly (immediately after: p = 0.001; 20 min later: p = 0.002), but their quadricep flexibility did not. In addition, FLOSS use did not result in worse single-leg stance timing, single-leg triple-hop distance, or landing stabilization performance relative to ELA use. Compared with the ELA control, the FLOSS intervention yielded significantly better LESS at 20 min postintervention (p = 0.032), suggesting that tissue flossing can improve landing stability. In conclusion, the application of FLOSS to the knee improves hamstring flexibility without impeding static balance, and improves single-leg hop distance and landing stabilization performance in women for up to 20 min. Our findings elucidate the effects of tissue flossing on the knee joint and may serve as a reference for physiotherapists or athletic professionals in athletic practice settings.

Autologous Adipose-Derived Mesenchymal Stem Cells Combined with Shockwave Therapy Synergistically Ameliorates the Osteoarthritic Pathological Factors in Knee Joint.

Adipose-derived mesenchymal stem cells (ADSCs) and shockwave (SW) therapy have been shown to exert a chondroprotective effect for osteoarthritis (OA). The results of this study demonstrated that autologous ADSCs had dose-dependent and synergistic effects with SW therapy (0.25 mJ/mm2 with 800 impulses) in OA rat knee joint. Autologous, high-dose 2 × 106 ADSCs (ADSC2 group) combined with SW therapy significantly increased the bone volume, trabecular thickness, and trabecular number among in the treatment groups. ADSC2 combined with SW therapy significantly reduced the synovitis score and OARSI score in comparison with other treatments. In the analysis of inflammation-induced extracellular matrix factors of the articular cartilage in OA, the results displayed that ADSC2 combined with SW therapy had a greater than other treatments in terms of reducing tumor necrosis factor-inducible gene (TSG)-6 and proteoglycan (PRG)-4, in addition to increasing tissue inhibitor matrix metalloproteinase (TIMP)-1 and type II collagen. Furthermore, ADSC2 combined with SW therapy significantly reduced the expression of inflammation-induced bone morphogenetic protein (BMP)-2 and BMP-6. Therefore, the results demonstrated that ADSC2 combined with SW therapy had a synergistic effect to ameliorate osteoarthritic pathological factors in OA joints.

Immediate effect of non-invasive auricular acupoint stimulation on the performance and meridian activities of archery athletes: A protocol for randomized controlled trial.

BACKGROUND: Archery has existed in human history for millenniums. Being a unique exercise and precision sport, the keys to performance are emotional control, attention, and concentration rather than explosive force, muscle power, and endurance. During the execution of archery, attention is the key to performance in elite players, especially in the initial period while drawing the bow. Auricular acupoint stimulation is one of the therapeutic methods of traditional Chinese medicine and has been reported for its use in amplifying the anesthesia effect, weight reduction, cessation of substance abuse, and autonomic nervous modulation. METHODS: The study will recruit archery players in school teams among junior and senior high schools and colleges. The subjects will be randomly assigned to the ear and sham acupressure groups. This is a randomized controlled trial with crossover design. The outcome measures will be obtained, including the meridian activities and balance index with Ryodoraku device, the movement stability with WIMU tracking system, the continuous heart rate record, and the scores of the 2 sections as the performance. The subjects will rate their attention and fatigue levels through self-reported questionnaires. OBJECTIVES: This study aims to investigate the immediate effect of non-invasive auricular acupoint stimulation on the performance and meridian activities of archery athletes. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04637607.

Association between Poststroke Depression and Psychological Crisis: A Retrospective Cross-Sectional Study.

OBJECTIVE: To investigate the association between poststroke depression (PSD) and psychological crisis in patients who have experienced a stroke within 6 months. METHODS: This was a retrospective cross-sectional study that enrolled patients within 6 months after stroke onset. The investigators reviewed medical charts to obtain patients' baseline characteristics, and a psychologist evaluated each patient for depression using the Taiwanese Depression Questionnaire (TDQ) and for psychological crisis using the Triage Assessment System (TAS). A generalized linear model (GLM) was used to analyze the association between the results of the TDQ and TAS. RESULTS: Ninety-seven patients with stroke were included. Age (p = 0.003), time since onset of stroke (p = 0.041), diabetes mellitus (p = 0.004), hypertension (p = 0.016), heart disease (p = 0.005), and TDQ score were significantly different between the hemorrhagic stroke group and the ischemic stroke group. The TDQ score was significantly lower in the hemorrhagic stroke group (p = 0.012). The TDQ score was associated with the TAS total score and each domain score, and the presence of heart disease was associated with poorer TAS score in the behavioral domain (p = 0.016). CONCLUSION: PSD is likely an important component of psychological crisis in stroke patients. For clinicians, a comprehensive psychologic evaluation is necessary to optimize treatment.

Toona sinensis modulates autophagy and cytokines in lipopolysaccharide-induced RAW 264.7 macrophages.

Toona sinensis (TS) is a medicinal herb possessing anti-apoptotic, anti-oxidant, and anti-inflammatory properties and is used to treat diabetes, cancer, and inflammatory diseases. In traditional Chinese medicine theory, TS clears dampness and heat, strengthens the stomach function, and regulates vital energy flow. TS is also used as an astringent and a pesticide. In this study, we aimed to evaluate how TS influences autophagy and cytokines during the inflammatory process in RAW 264.7 macrophages. The treatment groups were pre-supplemented with TS leaf extract; rapamycin was used to enhance autophagy and lipopolysaccharide (LPS) was used to induce inflammation. The expression of autophagy-related proteins was analyzed by western blotting. The survival rate of, and chemokine expression and oxidative stress in the cells were also assessed. TS leaf extract inhibited mammalian target of rapamycin (mTOR) phosphorylation at site S2448 in the macrophages. At relatively higher concentrations (50 and 75 µg/mL), TS elevated the expression of light chain 3 II (LC3-II), which further modulated autophagy. Pre-supplementation with TS leaf extract elevated the total glutathione (GSH) level and GSH/oxidized GSH (GSSG) ratio, but it decreased the GSSG, total nitric oxide, nitrate, nitrite, malondialdehyde, and superoxide anion levels. TS reversed the effects of LPS-induced cytokines, including interleukin (IL)-6 and IL-10. TS did not induce significant toxicity at the studied concentrations. In conclusion, TS leaf extract may modulate autophagy during inflammation. Furthermore, it may prevent cell damage via anti-inflammation and anti-oxidation. Thus, this study supports the ethnomedical use of TS in the prevention of inflammation-related diseases.

Combined effect of laser acupuncture and electroacupuncture in knee osteoarthritis patients: A protocol for a randomized controlled trial.

BACKGROUND: Knee osteoarthritis (KOA) is a common degenerative joint disorder that affects 250 million people globally. KOA can lead to disability and is often associated with cardiovascular disease, poor quality of life, and mortality. The most common treatment for KOA is non-steroidal anti-inflammatory drug administration. However, the analgesic effect is limited and often accompanied by multiple side effects. Hence, many KOA patients opt for complementary and alternative medicine. Acupuncture is one of the most popular complementary treatments with great analgesic effect and minimal side effect. Electroacupuncture (EA) and laser acupuncture (LA) have been known to reduce pain in KOA patients. However, to date, no study has assessed the benefits of combining these two therapies. METHODS: Fifty participants diagnosed with KOA, aged 50 years or older, and with consistent knee pain for more than 3 months were recruited and randomly assigned to the treatment group (EA plus LA) or control group (EA plus sham LA without laser output). All subjects in the treatment group will undergo a combined EA and LA treatment thrice a week for 4 weeks. The acupuncture will be performed on GB33, GB34, SP9, SP10, and ST36 sites. The treatment group will receive acupuncture with a transcutaneous electrical nerve stimulator at GB33, GB34, SP9, and SP10 sites and with LA at EX-LE5, ST35, and BL40 sites. The subjects in the control group will undergo the same treatment modality as the treatment group, except these subjects will not be exposed to laser output. Outcome measurements will include visual analog scale, Western Ontario McMaster Universities Osteoarthritis Index, Knee injury and osteoarthritis outcome, body composition analysis, knee range of motion, quadriceps muscle stiffness, one-leg standing with eyes open test, and the 30-s chair stand test before and after 4 weeks of intervention. OBJECTIVES: This protocol aims to investigate the combined effect of EA and LA in KOA patients.

Laser acupuncture for refractory coccydynia after traumatic coccyx fracture: A case report.

RATIONALE: Coccyx fracture is an injury usually caused by trauma. In most cases, the fractures recover after conservative therapy. For refractory cases that exhibit coccydynia after more than 2 months of conservative treatment, coccygectomy is indicated. However, limited information about the efficacy of this procedure is available, and it is known to have a high complication rate. As such, other therapeutic approaches are needed. Here, we report our experience using another conservative treatment option, low-level laser therapy, to successfully reduce refractory coccydynia in a patient with coccyx fracture. PATIENT CONCERNS: A 23-year-old woman had refractory coccydynia and increased pain after a traffic accident-induced coccyx fracture. DIAGNOSES: Initially, the patient reported transient improvement after conservative treatment with non-steroidal anti-inflammatory drugs. However, the pain increased in severity (numerical rating scale score of 8) soon after she resumed work in her office, and progressed in the following 2 months. Surgical intervention was suggested owing to the prolonged coccydynia following the failure of conservative treatment and difficulties in performing daily life activities. However, she sought other conservative therapy options, because she was concerned about the risks associated with the coccygectomy surgery. INTERVENTIONS: The patient received low-level laser therapy once a week, for 24 weeks. OUTCOMES: After 11 weeks of treatment, the patient reported significant improvements in her symptoms; her pain was reduced to a numerical rating scale score of 2 and bone healing was noted on radiographs. The patient could eventually perform her daily activities satisfactorily, without coccydynia, after 24 weeks of treatment. LESSONS: Laser acupuncture produced analgesic effects in this patient with refractory coccydynia after traumatic coccyx fracture. This is the first case report to apply laser acupuncture for refractory coccydynia after traumatic coccyx fracture. Our findings imply that laser acupuncture may be a good conservative therapy option for coccyx fracture.

Chinese Herbal Products for Non-Motor Symptoms of Parkinson's Disease in Taiwan: A Population-Based Study.

Objective: Combinations of Chinese herbal products (CHPs) are widely used for Parkinson's disease (PD) in Taiwan. Thereby, we investigated the use of CHPs in patients with PD. Methods: This study was a population-based cohort study that analyzed the data of patients with PD from the National Health Insurance Research Database. A total of 9,117 patients were selected from a random sample of one million individuals included in this database. We used multiple logistic regression models to estimate the adjusted odds ratios of the demographic factors and analyzed the formula and single CHPs commonly used for PD. Results: Traditional Chinese medicine users were more commonly female, younger, of white-collar status, and residents of Central Taiwan. Chaihu-Jia-Longgu-Muli-Tang was the most commonly used formula, followed by Ma-Zi-Ren-Wan and then Shao-Yao-Gan-Cao-Tang. The most commonly used single herb was Uncaria tomentosa (Willd. ex Schult.) DC., followed by Gastrodia elata Blume and then Radix et Rhizoma Rhei (Rheum palmatum L., Rheum tanguticum Maxim. ex Balf., and Rheum officinale Baill.). Chaihu-Jia-Longgu-Muli-Tang and U. tomentosa (Willd. ex Schult.) DC. have shown neuroprotective effects in previous studies, and they have been used for managing non-motor symptoms of PD. Conclusion: Chaihu-Jia-Longgu-Muli-Tang and U. tomentosa (Willd. ex Schult.) DC. are the most commonly used CHPs for PD in Taiwan. Our results revealed the preferences in medication prescriptions for PD. Further studies are warranted to determine the effectiveness of these CHPs for ameliorating the various symptoms of PD, their adverse effects, and the mechanisms underlying their associated neuroprotective effects.

Adjuvant laser meridian massage in men with opioid use disorder on methadone maintenance treatment: Protocol for a case-controlled study.

BACKGROUND: Heroin addiction remains a significant public health problem worldwide, and relapse to heroin use following cessation of agonist maintenance treatment is common. The problems associated with use of opioid agonists mean that non-opioid therapies need to be developed to ameliorate acute and protracted opioid withdrawal syndromes. METHODS: Fifteen men with opioid use disorder on methadone maintenance treatment have been enrolled from an addiction treatment center as an experimental group in this case-controlled study. This group is receiving laser meridian massage on the back, including the Bladder meridian and Governor Vessel, 3 times weekly for 4 weeks. An age-matched control group that does not receive laser meridian massage has also been enrolled. Urinary morphine levels are being checked before and after 2 and 4 weeks of treatment. Subjects are requested to self-report their number of episodes or days of heroin use and 0 to 10-point visual analogue scale scores for heroin craving/refusal to use heroin during the previous week before and after 2 and 4 weeks of treatment. Quality of life will be reported using the Short Form-12v2 before and after 4 weeks of treatment. Pulse diagnosis will be recorded and heart rate variability calculated after one single treatment session. The baseline patient characteristics will be compared between the experimental and control groups using the independent t test and Chi-square test. Data are compared between the 2 groups using repeated-measures analysis of variance, generalized estimating equations, and the paired t test. OBJECTIVE: To investigate the effect of adjuvant laser meridian massage in men with opioid use disorder on methadone maintenance treatment. TRIAL REGISTRATION: ClinicalTrials.gov NCT04003077.

Therapeutic effects of acupuncture plus fire needle versus acupuncture alone in lateral epicondylitis: A randomized case-control pilot study.

BACKGROUND: The aim of this study was to compare the short-term and intermediate-term efficacy of acupuncture plus fire needle therapy with that of acupuncture alone in the treatment of lateral epicondylitis (LE). METHODS: Thirty-eight patients with LE who had persisted for at least 2 months were enrolled in this prospective, assessor-blinded, randomized controlled pilot trial. Twenty-one patients were randomized to the acupuncture plus fire needle group and 17 to the acupuncture-only group. The primary outcome was the visual analog scale pain score for the previous 24 hours and the secondary outcomes were the maximum grip strength, Patient-rated Forearm Evaluation Questionnaire score, and Medical Outcomes Study 36-Item Short-form Health Survey score. The values at baseline (pretreatment), at the end of treatment, and at 3 months after treatment were used to assess the short-term and intermediate-term effects of treatment. The data were analyzed using the Chi-square test and t test. RESULTS: Within-group analyses showed better results for acupuncture plus fire needle therapy in the short term and intermediate term. Differences in the severity of pain and secondary outcomes were significant in the intermediate term in the acupuncture group. At the end of treatment, none of the differences in outcome scores were significant, except for maximum grip strength in the affected hand in the acupuncture group. No significant between-group differences in short-term or intermediate-term outcomes were observed. CONCLUSION: Acupuncture plus fire needle therapy was effective in the short term in patients seeking improvement of LE. Twelve treatments were effective for relieving pain and improving disability in the intermediate term in patients with chronic LE in both study groups. The findings of the pilot study confirm the feasibility of proceeding to a larger randomized controlled study of the longer-term effects of acupuncture plus fire needle therapy in patients with LE.

Heteronemin, a Spongean Sesterterpene, Induces Cell Apoptosis and Autophagy in Human Renal Carcinoma Cells.

Heteronemin is a bioactive marine sesterterpene isolated from the sponge Hyrtios sp. Previous reports have shown that heteronemin possesses anticancer activity. Here, heteronemin displayed cytotoxic effects against three human cancer cell lines (A549, ACHN, and A498) and exhibited potent activity in A498 human renal carcinoma cells, with an IC50 value of 1.57 µM by MTT assay and a GI50 value of 0.77 µM by SRB assay. Heteronemin initiates apoptotic cell death by downregulating Bcl-2 and Bcl-xL and upregulating Bax, leading to the disruption of the mitochondrial membrane potential and the release of cytochrome c from the mitochondria. These effects were associated with the activation of caspase-3/caspase-8/caspase-9, followed by PARP cleavage. Furthermore, heteronemin inhibited the phosphorylation of AKT signaling pathway and ERK and activated p38 and JNK. The specific inhibition of the p38 pathway by SB203580 or p38 siRNA treatment reversed the heteronemin-induced cytotoxicity and apoptotic signaling. Heteronemin also induced autophagy in A498 cells, and treatment with chloroquine (autophagy inhibitor) or SP600125 (JNK inhibitor) inhibited autophagy and increased heteronemin-induced cytotoxicity and apoptotic signaling. Taken together, this study proposes a novel treatment paradigm in which the combination of heteronemin and autophagy inhibitors leads to enhanced RCC cell apoptosis.

NPRL-Z-1, as a new topoisomerase II poison, induces cell apoptosis and ROS generation in human renal carcinoma cells.

NPRL-Z-1 is a 4ß-[(4"-benzamido)-amino]-4'-O-demethyl-epipodophyllotoxin derivative. Previous reports have shown that NPRL-Z-1 possesses anticancer activity. Here NPRL-Z-1 displayed cytotoxic effects against four human cancer cell lines (HCT 116, A549, ACHN, and A498) and exhibited potent activity in A498 human renal carcinoma cells, with an IC50 value of 2.38 µM via the MTT assay. We also found that NPRL-Z-1 induced cell cycle arrest in G1-phase and detected DNA double-strand breaks in A498 cells. NPRL-Z-1 induced ataxia telangiectasia-mutated (ATM) protein kinase phosphorylation at serine 1981, leading to the activation of DNA damage signaling pathways, including Chk2, histone H2AX, and p53/p21. By ICE assay, the data suggested that NPRL-Z-1 acted on and stabilized the topoisomerase II (TOP2)-DNA complex, leading to TOP2cc formation. NPRL-Z-1-induced DNA damage signaling and apoptotic death was also reversed by TOP2α or TOP2ß knockdown. In addition, NPRL-Z-1 inhibited the Akt signaling pathway and induced reactive oxygen species (ROS) generation. These results demonstrated that NPRL-Z-1 appeared to be a novel TOP2 poison and ROS generator. Thus, NPRL-Z-1 may present a significant potential anticancer candidate against renal carcinoma.

Correlates for academic performance and school functioning among youths with and without persistent attention-deficit/hyperactivity disorder.

Childhood attention-deficit hyperactivity disorder (ADHD) is associated with academic underachievement and school dysfunction. Little is known whether such association varies with the persistence of ADHD symptoms. The authors investigated school functioning among youths with and without persistent ADHD and identified the clinical correlates for school functioning in a large sample of 333 youths with persistent ADHD, 166 with non-persistent ADHD, and 266 without ADHD. The participants and their mothers received structured interviews for diagnosis of ADHD and other psychiatric conditions according to the DSM-IV diagnostic criteria by using the Kiddie epidemiologic version of the Schedule for Affective Disorders and Schizophrenia, and for school functioning by using the Chinese Social Adjustment Inventory for Children and Adolescents. The results showed that both ADHD groups had more impairment in all domains of school functioning than youths without ADHD with a gradient relationship in the order of persistent ADHD, non-persistent ADHD, and non-ADHD. The most consistent correlates for all domains of impaired school functioning were youth- and mother-reported inattention symptoms and increased age. Childhood hyperactivity-impulsivity symptoms also predicted more severe problems in social interactions and school behaviors. Psychiatric comorbid conditions also predicted poorer attitudes toward school works and interactions at school. Our findings indicate that lifetime diagnosis of ADHD, regardless of persistence of ADHD, associate with the impairment of overall school functioning sustaining from childhood into adolescence, and imply that early intervention of childhood inattention may offset school dysfunction at late childhood and adolescence.

Physalin F induces cell apoptosis in human renal carcinoma cells by targeting NF-kappaB and generating reactive oxygen species.

BACKGROUND: The aim of this study was to determine the molecular mechanisms of physalin F, an effective purified extract of Physalis angulata L. (Solanacae), in renal carcinoma A498 cells. METHODOLOGY/PRINCIPAL FINDINGS: Physalin F was observed to significantly induce cytotoxicity of three human renal carcinoma A498, ACHN, and UO-31 cells in a concentration-dependent manner; this was especially potent in A498 cells. The physalin F-induced cell apoptosis of A498 cells was characterized by MTT assay, nuclear DNA fragmentation and chromatin condensation. Using flow cytometry analysis, physalin F induced A498 cell apoptosis as demonstrated by the accumulation of the sub-G1 phase in a concentration- and time-dependent manner. Moreover, physalin F-mediated accumulation of reactive oxygen species (ROS) caused Bcl-2 family proteins, Bcl-2, and Bcl-xL degradation, which led to disruption of mitochondrial membrane potential and release of cytochrome c from the mitochondria into the cytosol. These effects were associated with induction of caspase-3 and caspase-9 activity, which led to poly(ADP-ribose) polymerase cleavage. However, the antioxidant N-acetyl-(L)-cysteine (NAC) and glutathione (GSH) resulted in the inhibition of these events and reversed physalin F-induced cell apoptosis. In addition, physalin F suppressed NF-κB activity and nuclear translocation of p65 and p50, which was reversed by NAC and GSH. CONCLUSION: Physalin F induced cell apoptosis through the ROS-mediated mitochondrial pathway and suppressed NF-κB activation in human renal cancer A498 cells. Thus, physalin F appears to be a promising anti-cancer agent worthy of further clinical development.

Rapid response to antipsychotic treatment on psychotic prodrome: implications from a case series.

The feasible intervention strategy at the prodromal state of psychosis is under debate. We report nine subjects clinically in a putative prodromal state of psychosis who responded to low-dose aripiprazole within the first week of medication. We conjecture that the pathophysiological processes might be easier to modify by antipsychotics in the prodromal state and we believe a short-term low-dose trial of antipsychotic agents is a convenient option for subjects at ultra high risk of psychosis. We urge specific attention to monitor the dissolution of psychotic-like symptoms carefully in order to have a better understanding of the pathogenesis and pharmacotherapy in the inception of psychosis.