Subcutaneous Infliximab (CT-P13) as Maintenance Therapy for Inflammatory Bowel Disease: 2 Randomized Phase 3 Trials.

BACKGROUND & AIMS: CT-P13 subcutaneous (SC), an SC formulation of the intravenous (IV) infliximab biosimilar CT-P13 IV, creates a unique exposure profile. We aimed to demonstrate superiority of CT-P13 SC vs placebo as maintenance therapy in patients with Crohn's disease (CD) and ulcerative colitis (UC). METHODS: Two randomized, placebo-controlled, double-blind studies were conducted in patients with moderately to severely active CD or UC and inadequate response or intolerance to corticosteroids and immunomodulators. All patients received open-label CT-P13 IV 5 mg/kg at weeks 0, 2, and 6. At week 10, clinical responders were randomized (2:1) to CT-P13 SC 120 mg or placebo every 2 weeks until week 54 (maintenance phase) using prefilled syringes. Co-primary end points were clinical remission and endoscopic response (CD) and clinical remission (UC) at week 54 (all-randomized population). RESULTS: Overall, 396 patients with CD and 548 patients with UC received induction treatment. At week 54 in the CD study, statistically significant higher proportions of CT-P13 SC-treated patients vs placebo-treated patients achieved clinical remission (62.3% vs 32.1%; P < .0001) and endoscopic response (51.1% vs 17.9%; P < .0001). In the UC study, clinical remission rates at week 54 were statistically significantly higher with CT-P13 SC vs placebo (43.2% vs 20.8%; P < .0001). Achievement of key secondary end points was significantly higher with CT-P13 SC vs placebo across both studies. CT-P13 SC was well tolerated, with no new safety signals identified. CONCLUSIONS: CT-P13 SC was more effective than placebo as maintenance therapy and was well tolerated in patients with moderately to severely active CD or UC who responded to CT-P13 IV induction. CLINICALTRIALS: gov, Numbers: NCT03945019 (CD) and NCT04205643 (UC).

Resistance band training with functional electrical stimulation improves force control capabilities in older adults: a preliminary study.

Resistance band training (RBT) with functional electrical stimulation (FES) may be an effective exercise regimen for improving age-related motor impairments. This preliminary study investigated the potential effects of bimanual RBT with FES on upper limb motor functions in older adults. This study randomly assigned 22 elderly people to the bimanual RBT with FES (Bi-RBT+FES) group and the RBT without FES (Bi-RBT) group. All participants performed isometric hand-grip force control tasks in unimanual (dominant and non-dominant) and bimanual conditions before and after four weeks of exercise for each group. We quantified the mean force, force accuracy, force variability, and force regularity at two targeted force levels (i.e., 10 % and 40 % of maximum voluntary contraction; MVC) to estimate changes in force control capabilities. The results revealed that the Bi-RBT+FES group demonstrated a greater force accuracy in the dominant hand at 10 % of MVC after training. Non-dominant hands in the Bi-RBT+FES group increased force accuracy at 40 % of MVC and reduced force variability collapsed across two targeted force levels. Both groups showed a decrease in force regularity after training. These preliminary results indicate that Bi-RBT+FES may be a viable option to facilitate functional recovery of the upper limbs in older adults.

Effects of physical exercise interventions on cognitive function in Parkinson's disease: An updated systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: To determine whether physical exercise interventions can improve cognitive function, including overall performance and specific domains, in patients with Parkinson's disease (PD) and to provide potential evidence on how cognitive benefits can be optimized by exercise prescriptions. METHODS: Using PubMed, Web of Science, and Cochrane Library (from inception to August 2022), four independent reviewers screened the search results and extracted data from randomized controlled trials of physical exercise interventions in patients with PD with an outcome measure of cognitive function. Random-effects meta-analysis models were used to report standardized mean differences (SMDs) with 95 % confidence intervals (CIs). RESULTS: Twenty-one randomized controlled trials including 761 patients with PD were eligible for inclusion. Physical exercise interventions led to significant improvements in global cognitive function (SMD = 0.69; 95 % CI = 0.31 to 1.06; P < 0.001). With respect to cognitive domains, the significant effect of exercise was found on executive function (SMD = 0.94; 95 % CI = 0.05 to 1.83; P = 0.039), but not on attention/working memory, language, memory, and visuospatial function. In moderator variable analyses, the effect on global cognition was observed in combined exercise programs (SMD = 0.79; 95 % CI = 0.46 to 1.12; P < 0.001), whereas there were no significant positive effects in aerobic exercise programs, strength exercise programs, and flexibility exercise programs. In addition, exercise interventions of light-to-moderate intensity with at least 60 min in duration, and of any frequency or period, were beneficial to the global cognitive function. CONCLUSION: This updated systematic review and meta-analysis suggests that physical exercise interventions are effective in improving global cognitive function and, to a lesser extent, executive function in patients with PD. At least 60 min a day of combined exercise programs on as many days of the week as feasible may be recommended as the non-pharmacological therapeutic option to improve cognitive function.

The Clinical Implication of Conversion Surgery in Patients with Stage IV Gastric Cancer Who Received Systemic Chemotherapy.

With the advances in chemotherapy and immunotherapy, a small subset of patients may be eligible for conversion surgery after achieving tumor regression with chemotherapy. This is a retrospective cohort study of 118 patients with stage IV gastric cancer who received palliative chemotherapy and conversion surgery with a negative resection margin at Samsung Medical Center. Baseline features included comorbidities, body mass index (BMI), carcinoembryonic antigen (CEA) level, primary tumor size, biopsy histology, distant metastatic sites, and molecular markers-HER2, MSI/MMR, PD-L1, and EBV. Post-chemotherapy features included BMI, CEA level, chemotherapy regimen, objective response to chemotherapy, and number of preoperative chemotherapy cycles. Post-operational features included tumor size, histologic differentiation and Lauren's classification, pathologic tumor and nodal stages, invasion of lymphatics/vessels/nerves, peritoneal cytology, and the receipt of postoperative chemotherapy. Of 118 patients, 60 patients received total gastrectomy and 58 patients received subtotal gastrectomy. In all, 21 patients achieved a pathologic complete response, and 97 patients achieved downstaging to yp stage I, II, or III. Before conversion surgery, patients received first-line capecitabine/oxaliplatin (62%), HER2 inhibitors combined with chemotherapy (18%), immune checkpoint inhibitors (15%), and inhibitors of MET or VEGFR2 (5%). In the multivariable analysis, BMI at the time of diagnosis, either HER2 positive, high MSI, or deficient MMR, and the use of targeted agents were significant prognostic factors. Conversion surgery could be considered in patients with stage IV gastric cancer regardless of the initial disease burden. BMI and molecular markers are important prognostic factors that can be used to select candidates.

Reconstruction of Hand Dorsum Defect Using Double Perforators-Based Anterior Interosseous Artery Island Flap: A Case Report and Description of a New Anterior Interosseous Artery Perforator.

The anterior interosseous artery (AIA) perforator flap is not commonly used in hand dorsum reconstruction compared with alternatives. However, it is a versatile flap with several advantages. Literature on the AIA perforator flap is based on the dorsal septocutaneous branch (DSB), which branches from the AIA and passes through fascia between the extensor pollicis longus (EPL) and extensor pollicis brevis muscles. In the described case, the authors reconstructed a hand dorsum defect in a 78-year-old man using an AIA perforator flap with double perforators supplied by the DSB and a new perforator branching from the distal than DSB. No complication was encountered, and the flap survived completely. A retrospective computed tomography review revealed the presence of the new perforator in 14 of 21 patients. Two types of new perforator were observed. One passed through the ulnar side of the extensor indicis proprius (EIP) muscle and penetrated fascia between the extensor digitorum minimi and extensor digitorum communis tendons, whereas the other passed between the EPL and EIP muscles. This report describes the anatomical location and clinical application of the new AIA perforators. The double perforators-based AIA flap provides a straightforward, reliable means of reconstructing hand dorsum defects.

Dual-hemisphere anodal transcranial direct current stimulation improves bilateral motor synergies.

Transcranial direct current stimulation (tDCS) is one of the non-invasive brain stimulation techniques that can improve motor functions. As bimanual motor actions require high motor cortical activations between hemispheres, applying bilateral anodal stimulation on left and right sides of primary motor cortex (M1) can improve for improvements in bimanual motor tasks. This study investigated which bilateral tDCS protocol effectively improves bimanual hand-grip force control capabilities in healthy young adults. We used three different bilateral tDCS protocols: (a) dual-anodal stimulation on the M1 of bilateral hemispheres (Bi-AA), (b) anodal-cathodal stimulation on the M1 of dominant and nondominant hemispheres (Bi-AC), and (c) sham stimulation (Sham). The results indicated that applying the Bi-AA significantly improved bilateral motor synergies estimated by uncontrolled manifold analysis relative to Sham. However, these differences were not observed in the comparison between Bi-AA and Bi-AC as well as between Bi-AC and Sham. These findings suggest that facilitating motor cortical activations between both hemispheres may be an additional option for advancing interlimb motor coordination patterns.

Repetitive transcranial magnetic stimulation improves cardiovascular autonomic nervous system control: A meta-analysis.

BACKGROUND: Cardiovascular autonomic system (ANS) may be affected by altered neural activations in the brain. This systematic review and meta-analysis investigated potential effects of repetitive transcranial magnetic stimulation (rTMS) protocols on cardiovascular ANS control. METHODS: Through 19 qualified studies, we acquired 70 comparisons for data synthesis. Individual effect sizes were estimated by comparing changes in following cardiovascular ANS control variables between active and sham stimulation conditions: (a) blood pressure (BP), (b) heart rate (HR), and (c) heart rate variability (HRV). Moreover, two moderator variable analyses determined whether changes in cardiovascular ANS control were different based on (a) rTMS protocols (excitatory rTMS versus inhibitory rTMS) and (b) specific targeted cortical regions, respectively. RESULTS: The random-effects model meta-analysis revealed significant improvements in cardiovascular ANS control after the rTMS protocols. Specifically, applying excitatory and inhibitory rTMS protocols significantly decreased values of BP and HR variables. For HRV variables, excitatory rTMS protocols showed significant positive effects. These improvements in cardiovascular ANS control were observed while applying either excitatory rTMS protocols to the left dorsolateral prefrontal cortex or inhibitory rTMS protocols to the right dorsolateral prefrontal cortex. LIMITATIONS: Relatively small number of studies for inhibitory rTMS on the right dorsolateral prefrontal cortex were included in this meta-analysis. CONCLUSION: These findings suggest that applying excitatory and inhibitory rTMS protocols on prefrontal cortical regions may be effective to improve cardiovascular ANS control.

Surgical treatment of postauricular hidradenitis suppurativa with delayed diagnosis: a case report and literature review.

Hidradenitis suppurativa (HS) is a chronic inflammatory condition that is difficult to diagnose, with a period of 10.0± 9.6 years from symptom onset to diagnosis. A 32-year-old Asian man presented with bilateral postauricular abscesses that first appeared 5 years previously. Despite several incisions and drainage, the symptoms only temporarily improved and continued to recur. On physical examination, chronic scars and sinus tracts were observed around the lesion. Postauricular HS was diagnosed, and surgical treatment was performed. We performed a wide excision and reconstructed the defect using a posterior auricular artery perforator-based keystone flap. Histological examination confirmed the diagnosis of HS. The reconstruction was successful, and there was no recurrence for 2 years after surgery. HS is difficult to diagnose without specific attention. Although the postauricular region is not a typical site of HS, it can occur in this area. Therefore, if a patient presents with recurrent abscesses in the postauricular region, HS should be considered. Additionally, if HS is diagnosed in the postauricular region, wide excision with reconstruction using a posterior auricular artery perforator-based keystone flap can lead to a favorable outcome.

Altered Bimanual Kinetic and Kinematic Motor Control Capabilities in Older Women.

Older women may experience critical neuromuscular impairments interfering with controlling successful bimanual motor actions. Our study aimed to investigate altered bimanual motor performances in older women compared with younger women by focusing on kinetic and kinematic motor properties. Twenty-two older women and 22 younger women performed bimanual kinetic and kinematic motor tasks. To estimate bimanual kinetic functions, we calculated bimanual maximal voluntary contractions (i.e., MVC) and force control capabilities (i.e., mean force, accuracy, variability, and regularity of the total force produced by two hands) during bimanual hand-grip submaximal force control tasks. For bimanual kinematic performances, we assessed the scores of the Purdue Pegboard Test (i.e., PPT) in both hands and assembly tasks, respectively. For the bimanual MVC and PPT, we conducted an independent t-test between two groups. The bimanual force control capabilities were analyzed using two-way mixed ANOVAs (Group × Force Level; 2 × 2). Our findings revealed that the older women showed less bimanual MVC (p = 0.046) and submaximal force outputs (p = 0.036) and greater changes in bimanual force control capabilities as indicated by a greater force variability (p = 0.017) and regularity (p = 0.014). Further, the older women revealed lower scores of PPT in both the hands condition (p < 0.001) and assembly task condition (p < 0.001). The additional correlation analyses for the older women showed that lower levels of skeletal muscle mass were related to less bimanual MVC (r = 0.591; p = 0.004). Furthermore, a higher age was related to lower scores in the bimanual PPT assembly task (r = -0.427; p = 0.048). These findings suggested that older women experience greater changes in bimanual motor functions compared with younger women.

Transcranial direct current stimulation influences repetitive bimanual force control and interlimb force coordination.

This study aimed to investigate the potential effect of bilateral transcranial direct current stimulation (tDCS) on repetitive bimanual force control and force coordination in healthy young adults. In this sham-controlled crossover study, 18 right-handed young adults were enrolled. Repetitive bimanual handgrip force control trials were performed by the participants at 40% of maximum voluntary contraction until task failure. We randomly provided bilateral active and sham tDCS to the primary motor cortex (M1) of each participant before conducting the repetitive bimanual force control task. We quantified the number of successful trials to assess the ability to maintain bimanual force control across multiple trials. Moreover, we estimated bimanual force control and force coordination by quantifying force accuracy, variability, regularity, and correlation coefficient in maximal and adjusted successful trials. Force asymmetry was calculated to examine potential changes in motor dependency on each hand during the task. Bilateral tDCS significantly increased the number of successful trials compared with sham tDCS. The adjusted successful trial revealed that participants who received bilateral tDCS maintained better bimanual force control and coordination, as indicated by decreased force variability and regularity as well as more negative correlation coefficient values in comparison with sham condition. Moreover, participants who received bilateral tDCS produced more force from the dominant hand than from the nondominant hand in both maximal and adjusted successful trials. These findings suggest that bilateral tDCS on M1 successfully maintains bimanual force control with better force coordination by modulating motor dependency.

Chromosomal Abnormality, fetal/neonatal Death and Socioeconomic Status: A Prospective Cohort Study.

OBJECTIVES: To assess the risk gradient of chromosomal abnormalities and fetal or neonatal death across a socioeconomic spectrum of pregnant women. METHODS: We used the data from the Korean Prenatal Diagnosis Study (KPDS), which included singleton pregnancies who were candidates for fetal aneuploidy screening enrolled from the Seoul Capital Area from December 2016 to April 2018. We analyzed chromosomal abnormalities which were diagnosed pre- or postnatally, and fetal or neonatal death. The highest level of education among the women and the average monthly household income were used as proxies for socioeconomic status. RESULTS: Among the 6,715 women, the majority of were 30-39 years old and university graduates, with a reported household income higher than the national median. Chromosomal abnormalities occurred in 45 women (6.7 per 1,000). Fetal or neonatal death occurred in 70 (11.3 per 1,000), excluding pregnancies affected by chromosomal abnormality diagnosis. The adjusted odds ratio for chromosomal abnormalities was higher when household income was < 4,484 USD per month. For fetal or neonatal death, the risk estimates for lower education and lower household income were generally positive but remained imprecise. CONCLUSION: We observed some evidence of an inverse association between the risk of fetal chromosomal abnormality and level of household income in a prospective cohort of pregnant women. Interventions to reduce socioeconomic disparities in perinatal health should focus on those with a low household income.

Early Infliximab Trough Levels Predict the Long-term Efficacy of Infliximab in a Randomized Controlled Trial in Patients with Active Crohn's Disease Comparing, between CT-P13 and Originator Infliximab.

Background/Aims: The clinical efficacy and safety of CT-P13 are comparable to originator infliximab for Crohn's disease in CT-P13 3.4 study (NCT02096861). We performed a multivariate logistic analysis to demonstrate the association between early infliximab trough levels and treatment outcomes of CT-P13 and originator infliximab. Methods: Early serum infliximab trough levels and anti-drug antibody (ADA) levels were compared between CT-P13 (n=100) and originator infliximab (n=98) groups. Receiver operating characteristic (ROC) analysis and multivariate logistic analysis were conducted to identify optimal cutoffs of serum infliximab trough levels and predictive factors for clinical outcomes. Results: The median infliximab trough levels were not different between CT-P13 and originator infliximab groups at week 6, week 14, and in median ADA levels at week 14, respectively. ROC analysis found an infliximab concentration threshold of 4.5 µg/mL at week 6 and 4.0 µg/mL at week 14 as the cutoff value with the highest accuracy for the prediction of clinical outcomes. Serum infliximab trough levels at weeks 6 and 14 predicted clinical remission at weeks 30 and 54, and endoscopic remission at week 54. The combinations of clinical remission or C-reactive protein normalization with an early infliximab trough level improved the prediction of long-term clinical or endoscopic remission. Conclusions: A threshold in serum infliximab trough level at week 6 and week 14 was highly predictive for long-term clinical outcomes. There were no statistical differences in serum infliximab trough levels and ADA levels between CT-P13 and originator infliximab.

Coexistence of condyloma acuminatum and extramammary Paget's disease on penis and scrotum: A rare case report.

RATIONALE: Extramammary Paget's disease (EMPD) is a rare skin cancer that commonly occurs in sites rich in apocrine glands, such as perineum, vulva, axilla, scrotum, and penis. On the other hand, condyloma acuminatum (CA; also referred to as anogenital warts) is a common benign neoplasm caused by human papillomavirus. Few cases of coexistent EMPD and CA have been reported because of the rarity of the condition. PATIENT CONCERNS AND DIAGNOSIS: A 72-year-old man with a genital mass, which appeared to be composed of multiple papillomatous masses, was referred for surgical resection. The lesion was first noticed 6 months previously and grew rapidly. CO2 ablative laser therapy was performed twice at a primary clinic, but the mass recurred. INTERVENTION AND OUTCOMES: Excisional biopsy revealed the presence of coexistent EMPD and CA. Additional wide excision was performed, and postoperative biopsy confirmed no residual tumor. Two years after surgery, no recurrence had occurred. LESSONS: CA can co-occur with several types of skin malignancies, and a skin malignancy coexisting with CA is difficult to diagnose visually. Therefore, even if a skin lesion in the genital region is considered to be CA, we recommend punch biopsy before treatment because it can benefit prognosiss.

Sensitivity towards HDAC inhibition is associated with RTK/MAPK pathway activation in gastric cancer.

Gastric cancer ranks the fifth most common and third leading cause of cancer-related deaths worldwide. Alterations in the RTK/MAPK, WNT, cell adhesion, TP53, TGFß, NOTCH, and NFκB signaling pathways could be identified as main oncogenic drivers. A combination of altered pathways can be associated with molecular subtypes of gastric cancer. In order to generate model systems to study the impact of different pathway alterations in a defined genetic background, we generated three murine organoid models: a RAS-activated (KrasG12D , Tp53R172H ), a WNT-activated (Apcfl/fl , Tp53R172H ), and a diffuse (Cdh1fl/fl , Apcfl/fl ) model. These organoid models were morphologically and phenotypically diverse, differed in proteome expression signatures and possessed individual drug sensitivities. A differential vulnerability to RTK/MAPK pathway interference based on the different mitogenic drivers and according to the level of dependence on the pathway could be uncovered. Furthermore, an association between RTK/MAPK pathway activity and susceptibility to HDAC inhibition was observed. This finding was further validated in patient-derived organoids from gastric adenocarcinoma, thus identifying a novel treatment approach for RTK/MAPK pathway altered gastric cancer patients.

Prenatal Diagnosis of Congenital Heart Diseases and Associations with Serum Biomarkers of Aneuploidy: A Multicenter Prospective Cohort Study.

PURPOSE: We assessed prenatal detection rates of congenital heart disease (CHD) and associations between maternal serum biomarkers and non-chromosomal CHD in singleton pregnancies. MATERIALS AND METHODS: This study was conducted as a secondary analysis of data obtained during a multicenter prospective cohort study that investigated the cost-effectiveness of prenatal testing for fetal aneuploidy. We analyzed the prenatal detection rate and accuracy for CHD screening via ultrasound during the second trimester, as well as associations between serum biomarkers and CHDs, in singleton newborns without chromosomal abnormalities. RESULTS: Among 6715 women, 142 (2.1%) newborns were born with CHDs, of which 67 (1.0%) newborns had major CHDs. The prenatal detection rate for all CHDs and major CHDs were 34.5% and 58.2%, respectively. After excluding isolated ventricular septal defects, the detection rate for critical CHDs was 85.9%. Women with low pregnancy-associated plasma protein A (PAPP-A) (<0.4 multiples of the median, MOM) face increased risks of non-chromosomal CHDs [adjusted odds ratio (aOR) 2.76; 95% confidence interval (CI) 1.36-5.13] and major CHDs (aOR 7.30; 95% CI 3.18-15.59), compared to those without CHDs. A higher inhibin A level (≥2.5 MOM; aOR 4.84; 95% CI 1.42-12.46) was associated with non-chromosomal major CHDs. CONCLUSION: Ultrasonography performed during the second trimester by obstetricians detected over 85% of critical CHDs. Low maternal serum PAPP-A or high inhibin-A was associated with non-chromosomal CHDs. These results may contribute to an improvement in prenatal diagnosis of CHDs.

Insecticide resistance in pepper greenhouse populations of Aphis gossypii (Hemiptera: Aphididae) in Korea.

The cotton aphid or melon aphid, Aphis gossypii Glover (Hemiptera: Aphididae), is a polyphagous insect pest with a wide host range. Two distinct genetic clusters were found in A. gossypii populations in Korea. To determine whether the division of the genetic clusters was driven by insecticide selection pressure, the frequencies of insecticide resistance-associated mutations on three representative insecticide target genes [i.e., nicotinic acetylcholine receptor gene (nAChR), voltage-gated sodium channel gene (vgsc), and acetylcholinesterase 1 gene (ace-1)] were predicted in A. gossypii populations with known genetic structures. Most populations revealed heterozygosity-resistant alleles for the nAChR R81T and vgsc M918L mutations, but homozygous-resistant alleles for the ace-1 S431F mutation. However, assessment of the three mutation frequencies revealed no apparent correlation between the genetic structures and the resistance profiles. The regression analysis revealed no correlation between the genetic cluster ratios and resistance allele frequencies (R81T, S431F, and M918L). We used three insecticides that are commonly used in greenhouses: imidacloprid (neonicotinoid), acephate (organophosphate), and esfenvalerate (pyrethroid), to test resistance and susceptibility in A. gossypii populations. The bioassay results revealed that the BS_19 (Busan) and JE_19 (Jeongeup) populations were resistant to imidacloprid and acephate, the HS_19 (Honseong) population was resistant to acephate and esfenvalerate, and susceptible lab strains only exhibited resistance to acephate. The bioassay results were correlated with mutation frequency, but no correlation was detected among genetic clusters. These results suggest that the distinct genetic structure observed in the Korean populations of A. gossypii is not likely influenced by insecticide resistance traits, but rather by other factors.

Development of in vitro three-dimensional drug screening system for obesity-related metabolic syndrome.

Metabolic syndrome is increasingly common, and closely related with overweight or obesity. In the obese state, macrophages infiltrate to the adipose tissue (AT), resulting in chronic inflammation and insulin resistance in the AT cells. Recently, attention has been paid to the role of AT macrophages in metabolic disorders should be applied to the initial drug screening step, but it was difficult to mimic the inflammatory adipocytes using the traditional 2-dimensional (2D) culture. In this study, we developed the 3-dimensional (3D) culture system to overcome this limitation. After adipogenic differentiation, lipid droplets were highly accumulated in cells, and differentiation of preadipocytes was not declined by macrophage co-culture. However, only co-cultured cells expressed the insulin resistance features. Compare to mono-cultured adipocytes, co-cultured adipocytes showed reduced glucose uptake and GLUT4 did not translocated to cell membrane even though treatment of high concentration of insulin. Using 3D co-culture model, we develop a microwell-scale drug screening protocol to test anti-obesity effect. 3D cultured cells reacted more sensitive to drugs, and PPARγ antagonist GW9662 (10, 20 µM) repressed adipogenic differentiation in a concentration-dependent manner in 3D co-cultured cells.

Efficacy of the herbal pair, Radix Achyranthis Bidentatae and Eucommiae Cortex, in preventing glucocorticoid-induced osteoporosis in the zebrafish model.

OBJECTIVE: In traditional Chinese medicine, the herbal pair, Radix Achyranthis Bidentatae (RAB) and Eucommiae Cortex (EC), is widely used to treat osteoporosis. Herein, we determined whether this herbal pair can be used to ameliorate glucocorticoid (GC)-induced osteoporosis (GIOP) and find its optimal dosage in zebrafish. METHODS: The characteristics of the aqueous extract of RAB and EC were separately characterized using high-performance liquid chromatography. Osteoporosis was induced in 5-day post-fertilization zebrafish larvae by exposing them to 10 µmol/L dexamethasone (Dex) for 96 h. Seven combinations of different ratios of RAB and EC were co-administered. Treatment efficacy was determined by calculating zebrafish vertebral area and sum brightness, via alizarin red staining, and by detecting alkaline phosphatase (ALP) activity. Multiple regression analysis was conducted to test the optimal dosage ratio. RESULTS: According to the Chinese Pharmacopoeia (2015), ß-ecdysone (ß-Ecd) is a major bioactive marker in RAB extract, while pinoresinol diglucoside (PDG) is the major marker in EC extract. Both of ß-Ecd and PDG content values aligned with the Chinese Pharmacopoeia standards. Treatment with 10 µmol/L Dex reduced zebrafish vertebral area, sum brightness, and ALP activity, but RAB and EC attenuated these effects. Combining 50 µg/mL RAB and 50 µg/mL EC was optimal for preventing GIOP in zebrafish. Reverse transcription-quantitative polymerase chain reaction was used to evaluate the mRNA expression of osteogenesis-related genes. A treatment of 10 µmol/L Dex decreased runt-related transcription factor 2 (Runx2), osteogenic protein-1 (OP-1), bone γ-carboxyglutamic acid-containing protein (BGLAP), and ß-catenin levels. This effect was counteracted by RAB and EC co-treatment (P < 0.05). Additionally, the effect of using the two herbal extracts together was better than single-herb treatments separately. These results demonstrated that RAB and EC preserve osteoblast function in the presence of GC. The best mass ratio was 1:1. CONCLUSION: RAB and EC herbal pair could ameliorate GC-induced effects in zebrafish, with 1:1 as the optimal dosage ratio.

Functional response of Amblyseius eharai (Acari: Phytoseiidae) on Tetranychus urticae (Acari: Tetranychidae).

Amblyseius eharai is a generalist predatory mite that consumes spider mites, rust mites, thrips, and pollen, with a high adaptability to various plants. To better understand ecological and behavioral aspects of this species, we investigated its functional response to different stages of two-spotted spider mite, Tetranychus urticae. Furthermore, we compared its environmental adaptability with that of other referenced phytoseiids using a temperature-dependent model of the intrinsic rate of increase. We were able to calculate the functional response parameters of both sexes of A. eharai when preying on eggs or larvae of T. urticae and, for females only, when preying on the deutonymph of T. urticae. Among the various combinations tested herein, A. eharai females preying on T. urticae larvae had the highest attack rate and shortest handling time. For eggs of T. urticae, A. eharai showed a lower attack rate; however, its handling time for eggs was significantly shorter compared to other phytoseiids. Using T. urticae larva as a prey, the attack rate of female A. eharai was higher and the handling time of both sexes of this species was shorter than those of other phytoseiid mites. Amblyseius eharai populations can show maximum performance quickly due to this species' lower optimal temperature for population growth (28.1°C) compared to other phytoseiid mites. Thus, we provided evidence that this predatory mite has the potential to be a new, effective biological control agent of greenhouse pests such as T. urticae due to its high predation capacity and low optimal temperature.