Acupuncture Decreases Risk of Hypertension in Patients with Chronic Spontaneous Urticaria in Taiwan: A Nationwide Study.

Patients with chronic spontaneous urticaria (CSU) have a higher risk of developing hypertension. This study aimed to determine whether acupuncture could decrease the risk of hypertension in patients with CSU. We enrolled patients newly diagnosed with CSU between 1 January 2008, and 31 December 2018, from the Taiwanese National Health Insurance Research Database. The claims data were assessed from the index date to 31 December 2019. A Cox regression model was used to compare the hazard ratios (HRs) of the two cohorts. The cumulative incidence of hypertension was estimated using the Kaplan-Meier method. After propensity score matching with a 1:1 ratio, 43,547 patients with CSU who received acupuncture were matched with 43,547 patients with CSU who did not receive acupuncture in this study. After considering potential confounding factors, patients who received acupuncture had a significantly lower risk of hypertension than those in the control group (adjusted hazard ratio = 0.56, 95% confidence interval = 0.54-0.58). Patients who received medications combined with acupuncture tended to have the lowest risk of hypertension. This study revealed that acupuncture decreases the risk of hypertension in patients with CSU in Taiwan. The detailed mechanisms can be further clarified through prospective studies.

The mechanism of anticancer activity of the new synthesized compound - 6,7-Methylenedioxy-4-(2,4-dimethoxyphenyl)quinolin -2(1H)-one(12e) in human ovarian cancer cell lines.

OBJECTIVE: Ovarian cancer is the most lethal of the gynecologic malignancies. Most women have advanced disease at diagnosis and require extensive debulking surgery and aggressive chemotherapy. Induction of apoptosis in cancer cells has been used as an important approach for cancer therapy. We examined the anticancer effect of 6,7-methylenedioxy-4-(2,4-dimethoxyphenyl)quinolin-2(1H)-one (12e) in human ovarian cancer cell line. MATERIALS AND METHODS: The 6,7-methylenedioxy-4- (2,4-dimethoxyphenyl) quinolin-2 (1H) -one (12e) was synthesized and provided by Dr. Li-Jiau Huang of China Medical University. Cell viability analysis showed that 12e inhibited cell growth and induced cell death in time- and dose-dependent manners. In order to study the underlying cell death mechanism, 2774 and SKOV3 cells treated with 12e were studied by morphology, DAPI/TUNEL double staining, DNA gel electrophoresis. To search the mechanisms of anti-proliferative effect of 12e, cell cycle analysis was performed. Changes in proteins related to cell death were analyzed by Western blot. RESULTS: 12e significantly induced apoptosis evidenced by morphological changes, TUNEL-DAPI double-staining and DNA fragmentation. Western blot analysis demonstrated that the protein level of Bcl-2 was decreased after treatment with 12e, while the level of p53 and Bax was increased. 12e treatment resulted in G2/M arrest through down modulation of cyclin B1 and cdk1. CONCLUSION: These results suggested that 12e -induced growth inhibition was associated with cell cycle arrest and apoptosis.

Correlations between severity of anterior vaginal wall prolapse and parameters of urethral pressure profile.

OBJECTIVE: Previous studies have shown that anterior vaginal wall prolapse (AVWP) results in reduction of pressure in the proximal urethra. However, the effect of severity of AVWP on urethral pressure is controversial. This study aimed to evaluate parameters of the urethral pressure profile in different stages of AVWP. MATERIALS AND METHODS: From 2016 to 2017, 286 consecutive patients with urogynecologic complaints who were referred to our urodynamic unit were enrolled in this study to analyze their urethral pressure profiles. Stages of AVWP were regrouped into three groups ranging from mild to severe stages (groups 1-3). Maximal urethral pressure, urethral closure pressure, functional urethral length, length of continence zone, as well as area of continence zone were compared among these three groups. RESULTS: Distribution of age, parity, and menopausal women were significantly different among these three groups. Maximal urethral pressure (pressures for groups 1, 2, and 3 were 74.6∼75.9cmH2O, 69.7∼73.4cmH2O, and 58.3∼60.5cmH2O, respectively; all P<.05) and stress urethral closure pressure (pressures for groups 1, 2, and 3 were 69.3cmH2O, 62.3cmH2O, and 52.2cmH2O, respectively; all P<.05) gradually and significantly decreased, consistent with the severity of AVWP. However, the attenuated maximal urethral pressure and stress urethral closure pressure in accordance with severity did not show any significant difference after controlling for age, body mass index, parity, menopause, and stress urinary incontinence symptoms. CONCLUSION: Our results showed that AVWP significantly attenuated urethral pressure. However, patient age, menopausal status, and number of parities seem to be more influential in compromising urethral function than just AVWP alone.

Effects of concurrent aerobic and resistance exercise in frail and pre-frail older adults: A randomized trial of supervised versus home-based programs.

BACKGROUND: This study aimed to investigate the effects of supervised and home-based exercise programs on older people with frailty or pre-frailty. METHODS: A total of 146 community-dwelling participants aged 65 and older who were prefrail or frail were randomly allocated into supervised exercise (N = 74) and home exercise (N = 72) groups. The 3-month supervised exercise training consisted of 3 exercise sessions per week, was performed at a hospital and supervised by a physical therapist. Home exercise participants took instructions on exercise and illustrated exercise handouts. The baseline and 3-month follow-up measurements included body composition, strength of selected upper and lower limb muscle groups, grip and leg press strengths, and five physical performance tests. Mixed-model repeated-measures analysis was applied to determine whether two groups differ in terms of changes before and after the intervention and to compare within-group improvements. RESULTS: After 3 months of supervised or home-based exercise, the average number of frailty criteria met and fat percentage decreased significantly. Strength of knee extensors, knee flexors and leg press improved significantly in supervised exercise group. In home-based exercise group, the strength of all muscle groups tested improved significantly, except for leg press strength. Walking speed improved in both groups, and timed-up-and-go and timed chair rise tests improved significantly only in supervised exercise group. CONCLUSIONS: Three-month supervised or home-based exercise improved walking speed and strength of the limb muscles. Supervised group showed more improvements in the physical performance tests compared with home-based exercise group.

Blue Mussel (Mytilus edulis) Water Extract Ameliorates Inflammatory Responses and Oxidative Stress on Osteoarthritis in Obese Rats.

PURPOSE: To investigate the effects of Mytilus edulis water extract (MWE) on an anterior cruciate ligament transection and a partial medial meniscectomy surgery to induced osteoarthritis (OA) with the high-fat diet (HFD)-induced obese rats. METHODS: The male Sprague-Dawley rats were fed with HFD for 4 weeks before surgery. The OA rats were orally administered with MWE (108.5, 217.0, and 542.5 mg/kg) for 6 weeks. RESULTS: The administration of MWE affected weight loss, triglycerides content, and total cholesterol level. MWE also enhanced the activity of superoxide dismutase and decreased lipid peroxidation degree. Moreover, MWE reduced proinflammatory cytokines level, alleviated inflammation and swelling of the osteoarthritic knee, and reduced loss of proteoglycan in articular cartilage tissue. CONCLUSION: MWE suppressed proinflammatory mediators and attenuated the cartilage degradation and pain in osteoarthritis rats under obesity condition. Therefore, MWE has the potential to act as an alternative for osteoarthritis treatment.

Structure-Activity Relationship of RGD-Containing Cyclic Octapeptide and αvß3 Integrin Allows for Rapid Identification of a New Peptide Antagonist.

The αvß3 integrin, a receptor for many extracellular matrix proteins with RGD-sequence motif, is involved in multiple physiological processes and highly expressed in tumor cells, therefore making it a target for cancer therapy and tumor imaging. Several RGD-containing cyclic octapeptide (named LXW analogs) were screened as αvß3 antagonists with dramatically different binding affinity, and their structure-activity relationship (SAR) remains elusive. We performed systematic SAR studies and optimized LXW analogs to improve antagonistic potency. The NMR structure of LXW64 was determined and docked to the integrin. Structural comparison and docking studies suggested that the hydrophobicity and aromaticity of the X7 amino acid are highly important for LXW analogs binding to the integrin, a potential hydrophobic pocket on the integrin surface was proposed to play a role in stabilizing the peptide binding. To develop a cost-efficient and fast screening method, computational docking was performed on LXW analogs and compared with in vitro screening. A consistency within the results of both methods was found, leading to the continuous optimization and testing of LXW mutants via in silico screening. Several new LXW analogs were predicted as the integrin antagonists, one of which-LXZ2-was validated by in vitro examination. Our study provides new insight into the RGD recognition specificity and valuable clues for rational design of novel αvß3 antagonists.

Vitellaria paradoxa Nut Triterpene-Rich Extract Ameliorates Symptoms of Inflammation on Post-Traumatic Osteoarthritis in Obese Rats.

PURPOSE: To investigate the ameliorative effects of Vitellaria paradoxa (VP) nut extract for an anterior cruciate ligament transection with medial meniscectomy (ACLT+MMx)-induced osteoarthritis (OA) in high-fat diet (HFD)-induced obese rats. METHODS: The rats were fed by HFD for 5 weeks before surgery-induced OA. Rats were treated orally with three different doses of VP nut extract (111.6, 223.2, and 446.4 mg/kg) for 8 weeks. RESULTS: The VP nut triterpene-rich extract decreased the level of triglycerides and increased high-density lipoprotein-cholesterol. The level of nitric oxide, interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α decreased after treatment with VP nut triterpene-rich extract, especially in high-doses. The VP nut triterpene-rich extracts also alleviated swelling in the knee OA, weight-bearing difference, and suppressed cartilage degradation. CONCLUSION: The Vitellaria paradoxa nut triterpene-rich extract suppressed proinflammatory mediators and attenuated the cartilage degradation and pain in osteoarthritis with an obesity rat model. As such, Vitellaria paradoxa nut triterpene-rich extract can be used as an alternative for osteoarthritis treatment.

A dietary polysaccharide from Eucheuma cottonii downregulates proinflammatory cytokines and ameliorates osteoarthritis-associated cartilage degradation in obese rats.

Osteoarthritis (OA) is a common form of arthritis, which is characterized by the degeneration of articular cartilage, leading to joint dysfunction. Oral drug therapy seems to ameliorate some signs and symptoms of OA, but may be accompanied by side effects and does not appear to be effective long-term. Seaweed has received much attention for pharmacological application due to its various biomedical properties, including the anti-inflammation, antitumor, and antioxidant effects. This study investigated the ameliorative effects of a dietary polysaccharide from Eucheuma cottonii extract (ECE) on an anterior cruciate ligament transection with partial medial meniscectomy surgery (ACLT+MMx) to induce OA in high-fat diet (HFD)-induced obese rats. Male Sprague-Dawley rats were fed an HFD for 12 weeks before ACLT+MMx surgery, after which they were administered a daily oral gavage of saline (Sham, OB Sham, and OBOA) and either low-dose ECE (100 mg per kg body weight), high-dose ECE (400 mg per kg body weight), or glucosamine sulfate as a positive control (OBOAGS; 200 mg per kg body weight) for 5 weeks. Treatment with ECE decreased the body weight, triglyceride and total cholesterol (TC) levels, and the TC/high-density lipoprotein (HDL)-C ratio in the obese rats. Additionally, ECE downregulated the expression of proinflammatory cytokines, including tumor necrosis factor-α, interleukin-1ß, and leptin, and suppressed nuclear factor-kappa B and extracellular-signal-regulated kinase-1/2 expression, resulting in a decrease in the levels of matrix metalloproteinase (MMP)-1 and MMP-13 and prostaglandin-E2 and attenuated cartilage degradation. These results demonstrate that the dietary polysaccharide from ECE can suppress OA development in obese rats, suggesting its potential efficacy as a promising candidate for OA treatment.

Wernicke encephalopathy concurrent with polyradiculoneuropathy in a young man after bariatric surgery: A case report.

RATIONALE: Bariatric surgery is the recommended treatment for morbid obesity because of its rapid and sustained body weight loss effect. Nutrient deficiency-related neurological complications after bariatric surgery are often disabling. Thus, early recognition of these complications is important. Neurological complications involving the central and peripheral nerve system after bariatric surgery were reported. However, the report on the clinical course of the concurrent involvement of central and peripheral nervous system is limited. We present a rare case of a patient who developed Wernicke encephalopathy concurrent with polyradiculoneuropathy after receiving bariatric surgery. PATIENT CONCERNS: A 22-year-old man with a history of morbid obesity presented progressive bilateral lower limbs weakness, blurred vision, and gait disturbance 2 months after receiving laparoscopic sleeve gastrectomy. Bilateral lower limb numbness and cognition impairment were also noted. DIAGNOSIS: Brain magnetic resonance imaging and electrophysiologic studies confirmed the diagnosis of Wernicke encephalopathy concurrent with acute polyradiculoneuropathy. INTERVENTIONS: Vitamin B and folic acid were given since admission. He also received regular intensive rehabilitation program. OUTCOMES: The subject's cognitive impairment and diplopia improved 1 week after admission under medical treatments, yet lower limb weakness and gait disturbance were still noted. After a month of intensive inpatient rehabilitation, he was able to ambulate with a walker for 30 munder supervision. LESSONS: Nutrient deficiency-related neurological complications after bariatric surgery are often disabling and even fatal. Prevention of neurological complications can be improved through close postsurgical follow-up of the nutritional status. Recognizing the signs and symptoms and evaluating the medical history are critical to the early diagnosis and treatment of this potentially serious yet treatable condition.

Effect of Fucoidan on Anterior Cruciate Ligament Transection and Medial Meniscectomy Induced Osteoarthritis in High-Fat Diet-Induced Obese Rats.

Osteoarthritis (OA) has become one of the most common disabilities among elders, especially in females. Obesity and mechanical injuries caused by OA are attributed to joint loading, cartilage disintegration, and bone loss, as well as inflammation. Pharmacological and non-pharmacological treatments can be used for OA. Fucoidan possesses several bioactivities such as antitumor, antiviral, anticoagulation, anti-obesity, and immunomodulation. This study aims to investigate the effect of fucoidan in surgery-induced OA on rats with diet-induced obesity. OA was induced by an anterior cruciate ligament transection and a partial medial meniscectomy (ACLT + MMx). The male SD rats were fed with a high-fat diet (HFD) for 4 weeks to induce obesity before causing ACLT + MMx to induce OA. The OA rats were administered with intragastric water or fucoidan in three different concentrations (32 mg/kg, 64 mg/kg, and 320 mg/kg) after the surgeries for 40 days with an HFD. We observed that the swelling in the knee joint was alleviated and the hind paw weight distribution was rectified after feeding them with fucoidan and that there was no significant effect on the weight gain and feed intake. Fucoidan administration indicated no significant variation on the high-density lipoprotein (HDL)-Cholesterol level, but it did indicate reduced plasma triglycerides and low-density lipoprotein (LDL)-Cholesterol levels. In addition, the weight-bearing tests showed an improvement in the fucoidan-treated group. Our results suggested that fucoidan may improve meniscal/ligamentous injury and obesity-induced OA.

Association between chronic idiopathic urticaria and hypertension: A population-based retrospective cohort study.

BACKGROUND: Chronic idiopathic urticaria (CIU) is defined as urticaria that is not caused by external triggers. The pathogenesis of CIU remains unknown. A previous study investigated whether hypertension is associated with extended duration of CIU. OBJECTIVE: To investigate the possible association between CIU and hypertension. METHODS: We performed a population-based retrospective cohort study of 2,460 patients with CIU and 9,840 age-, sex-, and index year-matched comparison patients, using the National Health Insurance of Taiwan database. The median follow-up periods were 7.13 years for the CIU cohort and 7.20 years for the non-CIU cohort. The distributions by sex and age were similar for both cohorts. RESULTS: The CIU cohort had a 1.37-fold (95% CI, 1.22-1.53) greater risk of developing subsequent hypertension than the non-CIU cohort after adjusting for sex, age, comorbidities, and nonsedating antihistamine use. CONCLUSION: This nationwide retrospective cohort study found that CIU is associated with a higher future risk of hypertension after adjusting for sex, age, comorbidities, and nonsedating antihistamine use. The detailed pathophysiologic mechanisms require further clarification in prospective studies.

Clinical effectiveness of acupuncture for carpal tunnel syndrome.

Acupuncture and electroacupuncture treatments of symptomatic carpal tunnel syndrome (CTS) may improve symptoms and aid nerve repair as well as improve sensory and motor functions. However, limited evidence is available regarding the effects of these treatments based on comprehensive evaluation methods. This research completed the treatment and evaluation of 26 patients with confirmed CTS. Participants were divided into two treatment groups based on a modified neurophysiological grading scale. Of the total number of participants, 15 received acupuncture and 11 received electroacupuncture on both upper limbs. Acupoints were PC-7 (Daling) and PC-6 (Neiguan) along the pericardial meridian compatible with the median nerve tract. The treatment program consisted of 24 sessions of 15 min duration over 6 weeks. After electroacupuncture treatments, symptom severity was evaluated using the short clinical questionnaire by Lo and Chiang, which indicated improvements in the respective symptom severity score. After the acupuncture treatment, grip strength in the major symptomatic side in CTS patients could be significantly increased. Electrophysiology evaluation likewise indicated a significant increase in the distal median motor amplitude of the palm-wrist segment. In addition, Tinel's sign significantly decreased in the major symptomatic side. Our findings indicated that electroacupuncture could improve symptomatology, while acupuncture could exert positive therapeutic effects for CTS patients, as evidenced by improved symptomatology, grip strength, electrophysiological function, and physical provocation sign.

2,3-Diamino acid modifying 3S-tetrahydroisoquinoline-3-carboxylic acids: leading to a class of novel agents with highly unfolded conformation, selective in vitro anti-platelet aggregation and potent in vivo anti-thrombotic activity.

In the preparation of anti-thrombotic agents the 2- and 3-positions of 3S-tetra-hydroisoquinoline-3-carboxylic acid (THIQA) were simultaneously modified with amino acids to form 20 novel N-(3S-N-aminoacyl-1,2,3,4-tetrahydroisoquinoline-3-carbonyl)amino acids (8a-t). On an in vitro platelet aggregation model 8a-t selectively inhibit ADP-induced platelet aggregation and their IC(50) values are leas than 3.5 nM. On an extracorporeal circulation of arterioveinos cannula model of rats both orally and intraveously effective doses of 8a-t are less than 30 nmol/kg. Cerius(2) based stereoview of explores 8a-t having highly unfolded conformation. 3D QSAR analysis gives the importance of the unfolded conformation to high in vitro anti-platelet aggregation and in vivo anti-thrombotic potency rational understanding.

A class of novel N-(3S-1,2,3,4-tetrahydroisoquinoline-3-carbonyl)-L-amino acid derivatives: their synthesis, anti-thrombotic activity evaluation, and 3D QSAR analysis.

To find new anti-thrombotic agents, a natural amino acid was introduced into the 3-position of anti-platelet aggregation active 3S-tetrahydroisoquinoline-3-carboxylic acid (THIQA), and 20 novel dipeptide derivatives, 3S-tetrahydroisoquinoline-3-carboxyamino acids (6a-t), targeting the intestinal peptide transport system were provided. In vitro anti-platelet aggregation assay of 6a-t indicated that their potencies of inhibiting adenosine diphosphate (ADP), arachidonic acid (AA), platelet-activating factor (PAF), and thrombin (TH) induced platelet aggregations were higher than that of THIQA, and the in vivo anti-thrombotic assay of 6a-t indicated that their potencies of inhibiting thrombogenesis in rats were also higher than that of THIQA. According to MFA based Cerius2 QSAR module, using training/test set of 6a,b,d,g-p/6c,e,f,q and training/test set of 6a-p/6q-t, two equations (r, 0.984 and 0.996) correlating the structures with in vitro or in vivo activity of 6a-t were established.

N-[2-chloro-9H-purin-6-yl]-N-cyclopropylglycylamino acids and derivatives: synthesis, evaluation as a class of novel analgesics, and 3D QSAR analysis.

Via a five-step-reaction procedure for the preparation of 19 known N-[2-chloro-9-(tetrahydropyran-2-yl)-9H-purin-6-yl]-N-cyclopropylglycylamino acid benzylesters (6a-s) and successive removal of 9-(tetrahydropyran-2-yl) and benzylester groups 19 novel N-[2-chloro-9H-purin-6-yl]-N-cyclopropylglycylamino acid benzylesters (7a-s) and 19 novel N-[2-chloro-9H-purin-6-yl]-N-cyclopropylglycylamino acids (8a-s) were provided. On tail-flick mouse model the in vivo analgesic activities of these 38 novel compounds were measured and most of them were defined as good analgesics. Based on Molecular Field Analysis of the pain threshold variations of the mice receiving 48 compounds in terms of the descriptors proton and methyl an equation was established. The data points (n), correlation coefficient (r), and square correlation coefficient (r(2)) of this equation were 48, 0.923, and 0.852, respectively. Using this equation pain threshold variations of 9 compounds were predicted and the errors ranged from 1.71 to 8.92.

Knockdown of the aryl hydrocarbon receptor attenuates excitotoxicity and enhances NMDA-induced BDNF expression in cortical neurons.

NMDA receptors play dual and opposing roles in neuronal survival by mediating the activity-dependent neurotrophic signaling and excitotoxic cell death via synaptic and extrasynaptic receptors, respectively. In this study, we demonstrate that the aryl hydrocarbon receptor (AhR), also known as the dioxin receptor, is involved in the expression and the opposing activities of NMDA receptors. In primary cultured cortical neurons, we found that NMDA excitotoxicity is significantly enhanced by an AhR agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin, and AhR knockdown with small interfering RNA significantly reduces NMDA excitotoxicity. AhR knockdown also significantly reduces NMDA-increases intracellular calcium concentration, NMDA receptor expression and surface presentation, and moderately decreases the NMDA receptor-mediated spontaneous as well as miniature excitatory post-synaptic currents. However, AhR knockdown significantly enhances the bath NMDA application- but not synaptic NMDA receptor-induced brain-derived neurotrophic factor (BDNF) gene expression, and activating AhR reduces the bath NMDA-induced BDNF expression. Furthermore, AhR knockdown reveals the calcium dependency of NMDA-induced BDNF expression and the binding activity of cAMP-responsive element binding protein (CREB) and its calcium-dependent coactivator CREB binding protein (CBP) to the BDNF promoter upon NMDA treatment. Together, our results suggest that AhR opposingly regulates NMDA receptor-mediated excitotoxicity and neurotrophism possibly by differentially regulating the expression of synaptic and extrasynaptic NMDA receptors.

(3S)-N-(L-Aminoacyl)-1,2,3,4-tetrahydroisoquinolines, a class of novel antithrombotic agents: synthesis, bioassay, 3D QSAR, and ADME analysis.

To increase antithrombotic activity, 3S-tetrahydroisoquinoline-3-carboxylic acid (1) was modified with natural amino acids to form 19 novel dipeptide analogs, 3S-tetrahydroisoquinoline-3-carboxyamino acids (5a-s), targeting the intestinal peptide transport system. In vitro assay of 5a-s indicated that their potencies for inhibiting adenosine diphosphate (ADP), arachidonic acid (AA), platelet-activating factor (PAF), and thrombin (TH)-induced platelet aggregations were higher than that of 1. Additionally, in vivo assay of 5a-s indicated that their potencies for inhibiting thrombogenesis in rats were also higher than that of 1. Among the candidates, 5h with Ser attachment showed the most impressive features for further development. According to molecular field analysis based Cerius(2) QSAR module, two equations (r, 0.961 and 0.988) correlating the structures with both in vitro and in vivo activities of 5a-s were established. ADMET calculations predict higher intestinal absorption for compounds 5a-s. Further investigation with 5h as a lead compound is underway.

Improved anti-osteoporosis potency and reduced endometrial membrane hyperplasia during hormone replacement therapy with estrogen-RGD peptide conjugates.

To improve the specificity and potency of estrogen replacement therapy therapeutics while also minimizing the side effects such as bone resorption and thickening of the uterine wall, a series of novel estrogen-derived conjugates estradiol-3-RGD, estradiol-17-RGD, and estrone-3-RGD peptides have been prepared. In a mouse model, intraperitoneal (i.p.) administration of these estrogen-RGD peptide conjugates resulted in decreased serum concentrations of calcium and alkaline phosphatase, as well as increased levels of calcium, phosphorus, and minerals in the mouse femur. Furthermore, the anti-osteoporosis action of these conjugates followed a dose-dependent manner and was accompanied with no observable effects on endometrial cell hyperplasia. In addition to all of these compounds exhibiting biological activity when administered by the i.p. route, we were particularly pleased to note that the estradiol-3-RGD and estradiol-17-RGD conjugates were both orally active.