Search

Both overproduced reactive oxygen species/reactive nitrogen species and hyperglycemic conditions accompany a significant increase in protein glycation and nitration that contribute to the initiation and progression of diabetic complications and neuronal disorders. In this study, 19 compounds, including steroidal saponins, alkaloids, cerebroside, phenolic compounds, sterols, and nucleosides, were isolated from cherry tomato (Solanum lycopersicum var. cerasiforme) juice, of which flazin showed good inhibition on monosaccharide-induced non-enzymatic bovine pancreas insulin and bovine serum albumin (BSA) glycation. Molecular dynamics simulations revealed that flazin continuously interacts with Phe1, Val2, Tyr26, and Lys29 insulin residues, which play a key role in insulin glycation/dimerization. In addition, depending upon the flazin dose, this blocked the tyrosine nitration of BSA via scavenging peroxynitrite anions. Taken together, our novel findings suggest that flazin could be a lead compound for the treatment of diabetes and neuronal disorders via the inhibition of non-enzymatic protein glycation and the elimination of peroxynitrite.

Peptidic and non-peptidic αvβ6 integrin-binding molecules have been used in the clinic for detection and treatment of tumors expressing αvβ6 integrin, because this protein is expressed in malignant epithelial cells of the oral cavity, pancreas, breast, ovary, colon and stomach carcinomas but it is not expressed in healthy adult tissue except during wound healing and inflammation. This review focuses on the landscape of αvβ6 integrinbinding molecules and their use in cancer treatment and detection, and discusses recent designs for tumor detection, treatment, and immunotherapy. In the last ten years, several reviews abamp;#945;vβ6 integrin-binding molecules and their role in cancer detection and treatment. Firstly, this review describes the role of the αvβ6 integrin in normal tissues, how the expression of this protein is correlated with cancer severity and its role in cancer development. Taking into account the potential of αvβ6 integrin-binding molecules in detection and treatment of specific tumors, special attention is given to several high-affinity αvβ6 integrin-binding peptides used for tumor imaging; particularly, the αvβ6-binding peptide NAVPNLRGDLQVLAQKVART [A20FMDV2], derived from the foot and mouth disease virus. This peptide labeled with either 18F, 111In or with 68Ga has been used for PET imaging of αvβ6 integrin-positive tumors. Moreover, αvβ6 integrin-binding peptides have been used for photoacoustic and fluorescence imaging and could potentially be used in clinical application in cancer diagnosis and intraoperative imaging of αvβ6-integrin positive tumors. Additionally, non-peptidic αvβ6-binding molecules have been designed and used in the clinic for the detection and treatment of αvβ6-expressing tumors. Anti-αvβ6 integrin antibodies are another useful tool for selective identification and treatment of αvβ6 (+) tumors. The utility of these αvβ6 integrin-binding molecules as a tool for tumor detection and treatment is discussed, considering specificity, sensitivity and serum stability. Another use of the αvβ6 integrin-binding peptides is to modify the Ad5 cell tropism for inducing oncolytic activity of αvβ6-integrin positive tumor cells by expressing A20FMDV2 peptide within the fiber knob protein (Ad5NULL-A20). The newly designed oncolytic Ad5NULL-A20 virotherapy is promising for local and systemic targeting of αvβ6-overexpressing cancers. Finally, new evidence has emerged, indicating that chimeric antigen receptor (CAR) containing the αvβ6 integrin- binding peptide on top of CD28+CD3 endodomain displays a potent therapeutic activity in a diverse repertoire of solid tumor models.

Objective To investigate the clinical effect of electroacupuncture combined with biofeedback on functional anorectal pain. Methods Sixty patients diagnosed functional anorectal pain were divided into three groups by random number table, namely electroacupuncture group, biofeedback group, and combination group, with 20 patients in each. In the electroacupuncture group, the electroacupuncture at Dong's points Sānqi (三其穴), including Qimen (其门), Qijiǎo (其角), and Qizheng (其正), and Linggǔ (灵骨), Dabai (大白), Changmen (肠门) of both sides was given; in the Biofeedback group, the biofeedback therapy was adopted; in the combination group, the electroacupuncture and biofeedback therapy were used. All patients were treated once a day, 30 min each time, 10 consecutive treatments as one treatment course, and the therapeutic effect was evaluated after 3 treatment courses. The observation indexes after the intervention: Visual analogue Scale (VAS) score, SF-36 Quality of Life Scale score, Self-rating Anxiety Scale (SAS) score, Self-rating Depression Scale (SDS) score, Anorectal manometry, Clinical efficacy, and patients’ adverse reactions. Results After treatment, the pain of patients in the three groups was alleviated than that before treatment, VAS score, SAS score, SDS score, and anorectal pressure were decreased (P Conclusion Electroacupuncture at Dong's points combined with biofeedback therapy has a significant effect on functional anorectal pain. The combined application of electroacupuncture and biofeedback therapy has a synergic action, and the analgesic effect is better than that of only using electroacupuncture or biofeedback therapy.

To investigate the effect of Kangquan Recipe (康泉方, KQR) on bone morphogenetic protein and activin membrane-bound inhibitor (BAMBI) expression and its mechanism in rats with benign prostatic hyperplasia (BPH). Forty-eight male Sprague-Dawley rats were divided into 6 groups using a random number table, with 8 in each group: the normal group (normal saline 10 mL/kg), the model group (normal saline 10 mL/kg), the finasteride group (0.5 mg/kg), the low-dose KQR group (3.5 g/kg), the middle-dose KQR group (7 g/kg), and the high-dose KQR group (14 g/kg). The 40 rats were subcutaneously injected with testosterone propionate after castration for 30 days to establish the BPH rat model except for those in the normal group. At the same time, the corresponding drugs were administered by gavage for 30 consecutive days. The effects of different doses of KQR on the protate wet weight, prostate volume and prostate index (PI) were observed. The changes in histopathology were monitored with hematoxylin-eosin staining. BAMBI protein and mRNA expression contents were determined by Western blot and quantitative real-time polymerase chain reaction, respectively. All doses of KQR could decrease prostatic epithelial tissue proliferation. Compared to the model group, the high and middle-dose KQR significantly reduced prostate wet weight, prostate volume and PI; increased BAMBI protein expression in the hypothalamus, pituitary and prostate tissue; all doses of KQR up-regulated BAMBI mRNA expression in serum, prostatic fluid and prostate tissue (P

Luteolin, a flavonoid widely distributed in the plant kingdom, contains two benzene rings and hydroxyl groups, and this structural specificity contributes to its diverse biological activities. However, no previous studies have simultaneously investigated the therapeutic potency of luteolin isolated from a plant as an antipsychotic and antidepressant. Here, luteolin exhibited selective inhibition of hMAO-A (IC50 = 8.57 ± 0.47 μM) over hMAO-B (IC50 > 100 μM). In silico proteochemometric modeling predicted promising targets of luteolin, and verification via cell-based G protein-coupled receptor functional assays showed that luteolin is a selective antagonist of the vasopressin receptor V1AR (IC50 = 19.49 ± 6.32 μM) and the dopamine D4 receptor (IC50 = 39.59 ± 1.46 μM). Molecular docking showed the tight binding of luteolin with a low binding score and the high stability of the luteolin-receptor complex, corroborating its functional effect. Thus, hMAO-A, hD4R, and hV1AR are prime targets of luteolin and potential alternatives for the management of neurodegenerative diseases.

Background Joint activity and protection are key components in the management of rheumatoid arthritis (RA). Despite a shift from care in health settings to empowering patients to play an active role in the day-to-day management of their own chronic conditions, there is little evidence on RA self-management, especially for Chinese patients. Purpose This pilot study sought to determine the feasibility and acceptability of a self-management program for patients with RA in Taiwan. Methods Participants were recruited at a medical center in northern Taiwan. The intervention group participated in a 6-week self-management program; the control group received standard rheumatology care. Both groups underwent baseline assessments before the intervention and at 12 weeks. Results A total of 32 participants were recruited: 15 in the intervention group and 17 in the control group. Patients in the intervention group found the self-management protocol beneficial to their joint protection and activity behaviors and reported higher motivation to perform RA self-management. The posttest score for joint protection and activity self-management behavior were significantly greater for the intervention group than for the control group (p = .02). Conclusions Participants in the intervention group were highly satisfied with home visits (which included peer story-telling and goal setting) and telephone calls to support their daily home-based joint protection and self-management activities (which included self-monitoring and self-evaluation). To mitigate the fear of scammers, researchers should begin by building a trust relationship with participants.

A 90% ethanol extract of Corni fructus was fractioned and the active components (i.e., morroniside, loganin) were isolated for functional food materialization. More specifically, the ethanol extract was fractioned according to the solvent polarity (i.e., n-hexane, ethyl acetate, and n-butanol), and the ethyl acetate fraction was found to exhibiti the highest antioxidant capacities (i.e., total phenolic content = 145.84 GAE mg/100 mL, DPPH radical scavenging activity = 7.91 mM GAE, FRAP activity = 18.86 mM TE, ABTS radical scavenging activity = 13.36 mM TE). Diaion HP 20 gel was used for separation of the ethyl acetate fraction, and 20%, 40%, 60%, and 80% ethanol fractions were also examined. The 40% ethanol fraction was found to exhibit the highest DPPH radical scavenging activity (10.22 mM GAE), ABTS radical scavenging activity (37.29 mM TE), and FRAP activity (27.32 mM TE) (p

Progressive degeneration of dopaminergic neurons in the substantia nigra is the characteristic feature of Parkinson's disease (PD) and the severity accelerates with aging. Therefore, improving dopamine level or dopamine receptor signaling is a standard approach for PD treatment. Herein, our results demonstrate that bromophenols 2,3,6-tribromo-4,5-dihydroxybenzyl alcohol (1), 2,3,6-tribromo-4,5-dihydroxybenzyl methyl ether (2), and bis-(2,3,6-tribromo-4,5-dihydroxybenzyl) ether (3) from red alga Symphyocladia latiuscula are moderate-selective human monoamine oxidase-A inhibitors and good dopamine D3/D4 receptor agonists. Bromophenol 3 showed a promising D4R agonist effect with a low micromole 50% effective concentration (EC50) value. All of the test ligands were docked against a three-dimensional (3D) model of hD3R and hD4R, and the result demonstrated strong binding through interaction with prime interacting residues-Asp110, Cys114, and His349 on hD3R and Asp115 and Cys119 on hD4R. Overall, the results demonstrated natural bromophenols, especially 1 and 3, from Symphyocladia latiuscula as multitarget ligands for neuroprotection, especially in PD and schizophrenia.

The highly pathogenic avian influenza A (H5N6) virus has caused sporadic human infections with a high case fatality rate. Due to the continuous evolution of this virus subtype and its ability to transmit to humans, there is an urgent need to develop effective antiviral therapeutics. In this study, a murine monoclonal antibody 9F4 was shown to display broad binding affinity against H5Nx viruses. Furthermore, 9F4 can neutralize H5N6 pseudotyped particles and prevent entry into host cells. Additionally, ADCC/ADCP deficient L234A, L235A (LALA) and CDC deficient K322A mutants were generated and displayed comparable binding affinity and neutralizing activity as wild type 9F4 (9F4-WT). Notably, 9F4-WT, 9F4-LALA and 9F4-K322A exhibit in vivo protective efficacies against H5N6 infections in that they were able to reduce viral loads in mice. However, only 9F4-WT and 9F4-K322A but not 9F4-LALA were able to reduce viral pathogenesis in H5N6 challenged mice. Furthermore, depletion of phagocytic cells in mice lungs nullifies 9F4-WT's protection against H5N6 infections, suggesting a crucial role of the host's immune cells in 9F4 antiviral activity. Collectively, these findings reveal the importance of ADCC/ADCP function for 9F4-WT protection against HPAIV H5N6 and demonstrate the potential of 9F4 to confer protection against the reassortant H5-subtype HPAIVs.

This study aimed to determine whether there were gender differences in the effectiveness of a 12-week dietary self-management program for older community-dwelling adults in northeast Taiwan. This was a secondary analysis of a previous study; participants (N = 58) were purposively sampled from two public health centers. Non-parametric models examined differences in outcome measures because of the small sample size; 20 males and 38 females completed the study. The results showed males scored significantly better than females for nutritional status, internal health locus of control, and responsibility for food preparation, which may have implications for older female adults' nutritional health.

This qualitative descriptive study aimed to explore expectations of patients and healthcare experts for an online self-management program for rheumatoid arthritis. Participants were recruited from rheumatology clinics, medical centers, and universities in Taiwan. Individual face-to-face, semi-structured interviews were conducted with patients ( n = 16) and healthcare experts ( n = 7). Content analysis of the interview data resulted in five subthemes for expectations of an online self-management program: information about how the disease trajectory would impact future health status, availability of opportunities for self-monitoring, opportunities to interact with fellow patients and healthcare providers, simplicity and ease-of-use of the program, and methods to facilitate patient-motivation. These subthemes formulated two overarching themes: content and format. An online self-management program for patients with rheumatoid arthritis should provide evidence-based information about disease variables and behaviors aligned with the specific needs of the individual and adopt strategies that encourage and increase motivation and confidence.

Rheumatoid arthritis results in progressive destruction of the joints. However, descriptions of patient’s experiences with the disease are limited. This qualitative study aimed to explore patients’ personal experiences with rheumatoid arthritis in Taiwan. Face-to-face interviews were conducted with 30 patients from January to May 2019; interview data were analyzed with content analysis. Most participants were female (90%); their mean age was 57 years. Three main categories emerged from analysis of the data: “physical suffering,” “limitations of abilities,” and “coexisting with the disease.” Physical suffering was due to personal lifelong hardships from chronic pain and stiffness. Limitations of abilities occurred from loss of physical function and limited social life, due to participants discomfort with joint deformities and their appearance to others. Participants coexisted with the disease by making changes in their outlook and comparing their lives with others in order to gain a positive perspective.

In recent years, Cassia seed extract has been reported as a neuroprotective agent in various models of neurodegeneration, mainly via an antioxidant mechanism. However, no one has previously reported the effects of Cassia seed extract and its phytochemicals on human monoamine oxidase (hMAO) enzyme activity. The seed methanol extract, the solvent-soluble fractions, and almost all isolated compounds displayed selective inhibition of hMAO-A isozyme activity. Interestingly, compounds obtusin (3), alaternin (8), aloe-emodin (9), questin (12), rubrofusarin (13), cassiaside (15), toralactone 9-O-β-gentiobioside (26), and (3S)-9,10-dihydroxy-7-methoxy-3-methyl-1-oxo-3,4-dihydro-1H-benzo[g]isochromene-3-carboxylic acid 9-O-β-d-glucopyranoside (38) showed the most promising inhibition of the hMAO-A isozyme with IC50 values of 0.17-11 μM. The kinetic study characterized their mode of inhibition and molecular docking simulation predicted interactions with Ile-335 and Tyr-326 in support of the substrate/inhibitor selectivity in respective isozymes. These results demonstrate that Cassia seed extract and its constituents inhibit hMAO-A enzyme activity with high selectivity and suggest that they could play a preventive role in neurodegenerative diseases, especially anxiety and depression.

Background and objectives: Lipoteichoic acid (LTA) is a structural component of Staphylococcus aureus (S. aureus) that induces severe infection disease and skin inflammation such as atopic dermatitis (AD), the biological function of LTA is still unclear. Dendritic cells (DC) are important regulators in the immune system, and the cells ectopically recognize agents that have an influence on the host immune response. We aimed to reveal the DC-based immune response against LTA to understand the novel mechanism in S. aureus related acute skin inflammation. Materials and Methods: Different doses of LTA were applied on the epidermal barrier dysfunction mice in order to evaluate the epidermal thickness, DC activation, and subsequent immunological response such as effector T-cell (Teff) activation. In addition, bone marrow-derived dendritic cells (BMDCs) were also treated with LTA, and the immunoregulatory mechanism was investigated. Results: A low dose of LTA did not induce skin inflammation at all, however, a high dose of LTA induced severe skin inflammation on epidermalba rrier dysfunction mice. Those symptoms were correlated with the DC and Teff activation status. The low-dose treatment of LTA showed a suppressive effect in pro-inflammatory cytokine production via a Toll-like receptor 2 (TLR2)-dominant manner, and the effect was significant regarding the co-treatment with another stimulatory signal such as TLR4 by lipopolysaccharide (LPS). Meanwhile, a high-dose treatment of LTA completely abolished the suppressive effect of a low-dose treatment. This phenomenon was based on C-type lectin receptors (CLRs), because the high dose of LTA greatly enhanced the expression of CLRs in the activated DCs. Conclusions: DCs sensed the dose difference of LTA, and the mechanism contributed to regulating immune responses such as effector T-cell activation, which was directly correlated with inflammatory response. This finding might provide an understanding for the novel immunological effect of LTA and S. aureus pathogenesis under inflammation, as well as the mechanism of symbiosis.

Background Most qualitative studies on caregivers of cancer patients have explored the experiences of family members and friends in Western or European countries. Little is known about the experience of spousal caregivers of patients recently diagnosed with cancer in a Chinese population. Aim The aim of this study was to explore the lived experience of spouses of patients recently diagnosed with cancer in Taiwan. Methods This qualitative study analysed focus groups interview data using thematic analysis. Participants were purposively sampled from a medical hospital in central Taiwan. Four focus group interviews were conducted; 15 spousal caregivers participated. Findings Research findings from the spouses, seven husbands and eight wives, included four main themes: handling emotions to make decisions quickly, experiencing meaningful support from a right and good physician, struggling with changes in daily life, and placing a peaceful mindset at the centre of life. Discussion Chinese collectivistic culture expects family members to make medical decisions and filter information a patient receives. Spousal caregivers informed patients about their cancer in order to avoid or reduce the amount of psychological harm. Spouses' strong commitments to caregiving provided them with power and motivation to continue caregiving. A peaceful mindset, influenced by the traditional Chinese philosophy of Buddhism, was considered critical for prolonging the patient's life and maintaining the caregiver's emotional health. Conclusions It is important for healthcare professionals to understand Chinese cultural influences and concerns of spousal caregivers when caring for Chinese patients to manage patients and caregivers effectively.

Aims The present study aims to investigate the utilization pattern of prenatal care and correlates for women with opioid use disorders (OUD) in Taiwan. Method Using the data linkage between the Methadone Maintenance Treatment (MMT) register with national health insurance, national birth notification system, and birth registration system, we identified 1712 pregnancies with 20 or more gestational weeks from women enrolled in the MMT (heroin-exposed: receiving no methadone treatment during pregnancy, n = 1053 by 882 women; methadone-treated: receiving methadone for at least one day during pregnancy, n = 659 by 574 women) and their 1:10 matched pregnancies from 17,060 women without substance use disorder in the period of 2004-2013. The generalized linear mixed models with negative binomial and logit distributions were performed to evaluate the relationship between individual sociodemographic, health, and addiction treatment characteristics with the number of prenatal visits and receiving prenatal care in the first trimester (i.e., early entry). Findings Eighteen percent of pregnancies by women with OUD received no prenatal services and 21% had started prenatal care in the first trimester as compared with 1% and 46% in pregnancies by women without substance use disorders. For pregnancies by women with OUD, methadone treatment was not linked associated with prenatal care visits (adjusted relative risk [aRR] = 1.02; 95% = 0.92, 1.12). For methadone-treated pregnancies, treatment enrollment before pregnancy and spousal methadone treatment elevated prenatal visits by 8% and 18% (0.48 and 1.08 visits, respectively). Additionally, HIV infection (adjusted odds ratio [aOR] = 0.30, 95% CI = 0.10, 0.83) and prior delivery (aOR = 0.05, 95% CI = 0.01, 0.19) significantly reduced the odds of early entry into prenatal care. Conclusion Integrating addiction treatment programs with prenatal care is urgently needed to increase adequate prenatal care for pregnant women with OUD, especially the multiparous ones.

Objective To assess the public health risk to Singapore posed by the emergence of artemisinin-resistant (ART-R) malaria in the Greater Mekong Subregion (GMS). Methods We assessed the likelihood of importation of drug-resistant malaria into Singapore and the impact on public health of its subsequent secondary spread in Singapore. Literature on the epidemiology and contextual factors associated with ART-R malaria was reviewed. The epidemiology of malaria cases in Singapore was analysed. The vulnerability and receptivity of Singapore were examined, including the connectivity with countries reporting ART-R malaria, as well as the preparedness of Singaporean health authorities. Sources of information include international journals, World Health Organization guidelines, data from the Singapore Ministry of Health and National Public Health Laboratory of the National Centre for Infectious Diseases, and the International Air Transport Association. Results The importation of ART-R malaria into Singapore is possible given the close proximity and significant travel volume between Singapore and the GMS countries reporting artemisinin resistance. Singapore's vulnerability is further enhanced by the presence of foreign workers from neighbouring endemic countries. Nonetheless, the overall likelihood of such an event is low based on the rarity and decreasing trend of imported malaria incidence.​: With the presence of Anopheles vectors in Singapore, imported cases of drug-resistant malaria could cause secondary transmission. Nevertheless, the risk of sustained spread is likely to be mitigated by the comprehensive surveillance and control system in place for both infected vectors and human cases. Discussion This risk assessment highlights the need for a continued high degree of vigilance of ART-R malaria locally and globally to minimize the risk and public health impact of drug-resistant malaria in Singapore.

BACKGROUND "Normalization" refers to the process whereby a household with a chronically ill member returns to a normal life to reduce its distress. There has been no valid and reliable instrument to investigate such normalization in Taiwan. OBJECTIVE The aims of this study were to develop and validate a Chinese version of the Normalization Assessment Measure for Caregivers of Children With Cancer (NAM-CCC). METHODS Translation and revision of the Normalization Assessment Measure into Chinese. Psychometric testing was conducted on 241 caregivers of children with cancer who were treated at a medical center in northern Taiwan. RESULTS The Cronbach's α of the NAM-CCC (Chinese version) was .93. The construct validity was analyzed by exploratory factor analysis, and 1 factor was extracted. The known group validity indicated that the rate of normalization is higher in the follow-up stage than in the treatment stage (P < .00). The criterion-related validity of the Taiwan version of the World Health Organization Quality of Life assessment is 0.475 (P < .01). The content validity is 0.88 to 0.99. CONCLUSION The results indicate that the NAM-CCC possesses good reliability and validity when administered to caregivers of children with cancer in Taiwan. IMPLICATIONS FOR PRACTICE The instrument can be used to measure normalization in the caregivers of children with cancer. In addition, it will help us understand what support these individuals require to construct normal lives.

Background. Heart failure patients often experience a high-level symptom burden, and the symptoms are greatly influenced by sodium and water intake. Moreover, Chinese older adults have specific dietary customs and rely on their families for food preparation. Aims. To determine the effectiveness of a self-management program for older adults with heart failure using randomized controlled trial Methods. Data were collected from August 2012 to July 2015, and 175 participants were randomly assigned to three groups, including patients alone and with caregiver-involved intervention (n = 60 and 55, respectively) who received an 8-week self-management program, and a control group (n = 60) receiving standard cardiology care only. Heart failure symptoms and self-efficacy for salt and fluid control were measured at baseline, 3rd, 6th, and 12th months. The generalised estimating equation was used to analyse the data. Findings. Results showed that the heart failure self-management program improved patients' symptoms significantly, but no differences were observed in self-efficacy for salt and fluid control. No significant differences were observed in intervention effects in patients with and without caregiver involvement. Discussion. Having a caregiver involvement or not made no difference in effects of the program. The Chinese culture provides an explanation because older adults tend to live with their family, even if the caregiver did not enroll in the program, patients still received help from their family. Conclusion. For older adult patients, home-based program allows nurses to evaluate and intervene on an individual basis, and providing booster sessions or individual follow-up are suggested to help patients adhere to long-term behaviour change.

This study examined whether serotonin and two of its derivatives, [Formula: see text]-feruloylserotonin and [Formula: see text]-([Formula: see text]-coumaroyl) serotonin, have a renoprotective effect in a mouse model of cisplatin-induced acute renal failure. Cisplatin (20[Formula: see text]mg/kg body weight) was administered by intraperitoneal injection to male BALB/c mice that had received oral serotonin, [Formula: see text]-feruloylserotonin or [Formula: see text]-([Formula: see text]-coumaroyl) serotonin (7.5[Formula: see text]mg/kg body weight per day) during the preceding 2 days. At 3 days after the cisplatin injection, serum and renal biochemical factors, oxidative stress, inflammation and apoptosis-related protein expression were evaluated, and histological examinations were performed. Cisplatin caused reduction in body weight and an increase in kidney weight; however, [Formula: see text]-([Formula: see text]-coumaroyl) serotonin and [Formula: see text]-feruloylserotonin attenuated these effects. Moreover, the serotonin derivatives significantly decreased serum urea nitrogen and creatinine levels. They also significantly reduced the level of reactive oxygen species and upregulated the expression of glutathione peroxidase in the kidney. Furthermore, the serotonin derivatives improved the abnormal expression of mitogen-activated protein kinases activation-dependent inflammation- and apoptosis-related protein and caused less renal damage. These results provide important evidence that [Formula: see text]-([Formula: see text]-coumaroyl) serotonin and [Formula: see text]-feruloylserotonin exert a pleiotropic effect on several parameters related to oxidative stress, inflammation and apoptosis. The derivatives also have a renoprotective effect in cisplatin-treated mice; however, this effect is higher with [Formula: see text]-([Formula: see text]-coumaroyl) serotonin.

The aim of the present study was a comparative investigation of water and 70% ethanol extracts derived from yellow and red onion (Allium cepa L.) peels against diabetes and diabetic complications. The total phenolic contents (TPCs) and total flavonoid contents (TFCs) of each cultivar, measured to assess phytochemical characteristics, showed a direct correlation with the in vitro antioxidant effects. Among the two captives, the yellow onion peel extract showed higher antioxidant activity than red one. However, all extracts exhibited significant protein tyrosine phosphatase 1B (PTP1B) inhibitory activity (IC50; 0.30–0.86 μg/ml), showing water extracts more potent (IC50; approximately 0.3 μg/mL), than the 70% ethanol extracts (IC50; approximately 0.8 μg/ml). Similarly, in insulin‐resistant HepG2 cells, all extracts enhanced the glucose uptake and reduced the expression of PTP1B in a concentration‐dependent manner, water extract displaying better activity. Our results overall suggest that in vitro antioxidant and antidiabetic potentials vary among red and yellow cultivars and extracting solvents, which could therefore be a promising strategy to prevent diabetes and associated complications.

Phlorotannins are polyphenolic compounds in marine alga, especially the brown algae. Among numerous phlorotannins, dieckol and phlorofucofuroeckol-A (PFF-A) are the major ones and despite a wider biological activity profile, knowledge of the G protein-coupled receptor (GPCR) targets of these phlorotannins is lacking. This study explores prime GPCR targets of the two phlorotannins. In silico proteocheminformatics modeling predicted twenty major protein targets and in vitro functional assays showed a good agonist effect at the α2C adrenergic receptor (α2CAR) and an antagonist effect at the adenosine 2A receptor (A2AR), δ-opioid receptor (δ-OPR), glucagon-like peptide-1 receptor (GLP-1R), and 5-hydroxytryptamine 1A receptor (5-TH1AR) of both phlorotannins. Besides, dieckol showed an antagonist effect at the vasopressin 1A receptor (V1AR) and PFF-A showed a promising agonist effect at the cannabinoid 1 receptor and an antagonist effect at V1AR. In silico molecular docking simulation enabled us to investigate and identify distinct binding features of these phlorotannins to the target proteins. The docking results suggested that dieckol and PFF-A bind to the crystal structures of the proteins with good affinity involving key interacting amino acid residues comparable to reference ligands. Overall, the present study suggests α2CAR, A2AR, δ-OPR, GLP-1R, 5-TH1AR, CB1R, and V1AR as prime receptor targets of dieckol and PFF-A.

High-quality epitaxial layers are directly related to internal quantum efficiency. The methods used to design such epitaxial layers are reviewed in this article. The ultraviolet C (UVC) light-emitting diode (LED) epitaxial layer structure exhibits electron leakage; therefore, many research groups have proposed the design of blocking layers and carrier transportation to generate high electron–hole recombination rates. This also aids in increasing the internal quantum efficiency. The cap layer, p-GaN, exhibits high absorption in deep UV radiation; thus, a small thickness is usually chosen. Flip chip design is more popular for such devices in the UV band, and the main factors for consideration are light extraction and heat transportation. However, the choice of encapsulation materials is important, because unsuitable encapsulation materials will be degraded by ultraviolet light irradiation. A suitable package design can account for light extraction and heat transportation. Finally, an atomic layer deposition Al2O3 film has been proposed as a mesa passivation layer. It can provide a low reverse current leakage. Moreover, it can help increase the quantum efficiency, enhance the moisture resistance, and improve reliability. UVC LED applications can be used in sterilization, water purification, air purification, and medical and military fields.

BackgroundHemp seed, the dried fruit of Cannabis sativa L., has been well documented as a folk source of food due to its nutritional and functional value. The aim of this study was to evaluate the estrogen-like effect of hemp seed oil (HSO) and analyze its action on the development of ovary and uterus of mice, concentration of sex hormones, endometrial thickness, and ER𝛼 and ER𝛽 expression. MethodsIn the present work, virgin and ovariectomized kunming mice were subject to treat with HSO. Gonad morphous was detected by Hematoxylin-Eosin (HE) staining, serum levels of E2, FSH and LH was determined used ELISA to evaluate the function of hypothalamic-pituitary-ovarian axis, and ERα and ERβ immunohistochemistry were used to evaluate gonad function. ResultsThe results showed that HSO can promote the vaginal opening time of virgin mice. There was significant increase in the gonad coefficient. Moreover, the endometrial thickness, number of primary follicles, secondary follicles and mature follicles were significantly increased, the uterus and ovary were well developed, the ERα and ERβ positive cells and intensity were increased in the virgin mouse ovary. The level of serum E2 was significantly increased, and the levels of FSH and LH were decreased. HSO could obviously relieve the endocrine disorders, modulate organ atrophy, and restore ER𝛼 and ER𝛽 expression in the ovariectomized mice model. ConclusionsHemp seed oil can accelerate the virgin mice mature and balance sex hormones, modulates organ atrophy, and restores in ovariectomized mice through upregulates ER𝛼 and ER𝛽 expressions. This study demonstrated that HSO activity is mediated through estrogenic components, and provided evidence for HSO treatment for post-menopausal symptoms.

Objectives This review summarized the applicability of various decision-making tools for helping people with dementia or mild cognitive impairment (MCI) and their families make decisions. Design This study was a narrative literature review. The protocol of this review was registered in the International Prospective Register of Systematic Reviews (PROSPERO ID: CRD42020182259). Setting and Participants People with dementia or MCI and their families were included in this study. Methods This review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. We searched the Cochrane Library, PubMed, Embase, Cumulative Index to Nursing and Allied Health Literature, and Chinese Electronic Periodical Services databases from inception to May 2021. The Joanna Briggs Institute Critical Appraisal Checklists for a variety of study designs were used. Results Topics related to decision-making were categorized as everyday activity decisions or medical treatment decisions. Various types of decision-making tools were identified, and we observed that decision aids can be modified and used for both everyday activity decisions and medical treatment decisions. In addition to highlighting decision aids for specific decisional issues and topics, we also elucidated other validated tools that can be used to facilitate the decision-making process. Conclusions and Implications This study highlighted the topics involved in decision-making and using decision-making tools. The current review provides information that can help individuals and health care professionals choose optimal decision-making tools. On the basis of our findings, future studies can determine the most appropriate tools for intervention or outcome measures.

AimsThe global health system is facing a serious challenge after the recent outbreak of COVID-19 coronavirus infection which was first identified in Wuhan, China in November 2019 and declared as a pandemic in March 2020 by WHO. There is a wide consensus that this pandemic has negative psychosocial consequences as well as unforeseeable provision of mental health care services and just not on physical health alone. The aim of this research study is to determine the prevalence of psychological distress and to identify the sociodemographic variables with the main attributable factors associated with the psychological distress among healthcare workers and suggestions on how to reduce the impact on the mental health of healthcare workers during the COVID-19 pandemic in different regions of the world.MethodWe performed a cross-sectional study from September-November 2020. We used a self-administered survey tool which was distributed electronically to healthcare workers across the globe. The data were stored on an online database with password protected devices where survey responses were restricted to investigators exclusively.Data collected were: 1) Socio-demographic data (age, gender, marital status, ethnicity, religion, role in the healthcare, region of practice); 2) Psychological General Well-Being Index (PGWBI) questionnaire which contains 22 standardized items. This is a subjective assessment to score the degree of psychological well-being by focusing on 6 domains: depression; anxiety; positive-well-being; self-control; vitality and general health; 3) Subjective assessment from respondents of the main attributable factors causing psychological distress and suggested methods to help reduce the impact on mental health on health care workers.ResultMajority out of the 217 respondents were from a younger age group; females and married/domestic partnership, mainly from Western Pacific Region, South East Asian and the African Region. More than half the respondents were moderate-severely psychologically distressed and the three main attributable factors causing psychological distress were: fear of family/friends contracting COVID-19 followed by lack of PPE and discomfort caused by wearing PPE for long hours. Respondents suggested that the distress would be reduced if: more resources were provided in hospital; protocols and guidelines were implemented and counselling facilities with recreational activities were available to frontline workers.ConclusionThis study showed that the COVID-19 pandemic has affected the mental health of healthcare workers and more support or strategies need to come in place to protect frontline workers at the time of crises.

Aims Morus, a member of the family Moraceae and commonly known as the mulberry, comprises a pharmaceutically important plant group whose major constituents are the moracins. Moracin derivatives have received great attention because they exhibit a diverse range of biological functionalities. However, no studies have considered the anti-Alzheimer's disease (AD) and anti-glycation potential of moracin derivatives. Main methods We designed the current study to explore the anti-AD activity of moracin derivatives via in vitro inhibition of BACE1 and cholinesterase, their antioxidant activity via scavenging ONOO− and ABTS + radicals, and their anti-diabetic activity through inhibition of advanced glycation end-products (AGEs) formation. Moreover, to define the mechanism of action of moracin derivatives in depth, we performed in silico molecular modeling using a computer-assisted drug design and modeling program. Key findings Among the four Morus-derived moracins tested, moracin S, which has a prenyl moiety in the 2-aryl benzofuran scaffold, possessed the highest BACE1 inhibitory activity. It also, in a dose-dependent fashion, decreased ONOO−-mediated bovine serum albumin (BSA) nitration and formation of AGEs and amyloid cross-β structures in the glycated BSA system, and it showed notable radical scavenging activity. In addition, enzyme kinetic and molecular docking studies demonstrated that moracin S is a potent, competitive BACE1 inhibitor that could interact with key catalytic aspartyl residues. Significance The prenyl moiety in the 2-aryl benzofuran structure plays a crucial role in inhibition of BACE1. These in vitro and in silico results provide valuable information for the design of anti-AD drugs.

Young offspring of individuals with opioid use disorders have great exposure to a wide array of social disadvantages and stressors. This study aimed to investigate excess mortality before the age of six and predictors of premature death in children born to opioid-involved parents.A total of 3210 children born between 2004 and 2009 to parents with opioid use disorders (roughly a quarter of whom were born after parental methadone treatment enrollment) were identified in Taiwan. Information concerning sociodemographic characteristics, history of medical condition, and survival status was obtained through data linkage with the National Health Insurance Database and death registration. The age-, birth year-, and sex-adjusted standardized mortality ratios (SMRs) and survival analyses were used to assess risk estimates and evaluate predictors.The overall SMR for children with opioid-involved parents was 2.31 (95% confidence interval [CI] = 1.68-3.10), with the estimate reaching 4.23 (95% CI = 2.37-6.97) when the causes of death were unnatural (e.g., injury and accident). The most salient predictors of premature death were low birth weight and paternal opioid problem severity, which increased risk of premature death 2.5--5.2-fold (all P 0.05). Being born after parents enrolled in methadone treatment was slightly associated with a reduced risk of death in those mothered by opioid users (adjusted hazard ratio = 0.30).The elevated risk of premature death in the offspring of opioid-addicted parents suggests the need to prioritize resource allocation to safeguard this marginalized and vulnerable segment of the pediatric population.

Cisplatin, a platinum chelate with potent antitumor activity against cancers of the testis, ovary, urinary bladder, prostate, and head and neck, has adverse effects on the kidney, bone marrow, and digestive organs, and its use is particularly limited by nephropathy as a side effect. In the present study, safflower seed extract was administered to a mouse model of cisplatin-induced acute renal failure to investigate its activity. Cisplatin (20[Formula: see text]mg/kg body weight) was administered by intraperitoneal injection to mice that had received oral safflower seed extract (100 or 200[Formula: see text]mg/kg body weight per day) for the preceding 2 days. Three days after the cisplatin injection, serum and renal biochemical factors; oxidative stress, inflammation, and apoptosis-related protein expression; and histological findings were evaluated. Cisplatin-treated control mice showed body-weight, food intake and water intake loss, and increased kidney weight, whereas the administration of safflower seed extract attenuated these effects ([Formula: see text], [Formula: see text]). Moreover, safflower seed extract significantly decreased the renal functional parameters urea nitrogen and creatinine in the serum ([Formula: see text] and [Formula: see text], respectively). Safflower seed extract also significantly reduced the enhanced levels of reactive oxygen species in the kidney observed following cisplatin treatment, with significance. The expression of proteins related to the anti-oxidant defense system in the kidney was down-regulated following cisplatin treatment, but safflower seed extract significantly up-regulated the expression of the anti-oxidant enzyme catalase. Furthermore, safflower seed extract reduced the overexpression of phosphor (p)-p38, nuclear factor-kappa B p65, cyclooxygenase-2, inducible nitric oxide synthase, ATR, p-p53, Bax, and caspase 3 proteins, and mice treated with safflower seed extract exhibited less renal histological damage. These results provide important evidence that safflower seed extract exerts a pleiotropic effect on several oxidative stress- and apoptosis-related parameters and has a renoprotective effect in cisplatin-treated mice.

Objective: This study aimed (1) to study the effects of health education on preventive behaviors and cancer literacy among women with cervical intraepithelial neoplasia (CIN), (2) to compare the effects of mobile application program (App)-assisted health education with traditional book-form health education. Participants: A total of 132 women ages 20 to 69 years women. Methods: This prospective longitudinal study enrolled 132 CIN women who were evaluated three times. Propensity score matching was used by controlling subjects’ age strata, body mass index, education level, occupation, and type of surgery. Results: The influences of various educational tools were investigated. Four domains were assessed, including health behavior, attitude towards behavior change, self-efficacy of behavior, and cervical cancer (CCa) literacy. Significant improvements in behavior change and CCa literacy due to a health education program were observed (p ≤ 0.002). The App combined with a traditional booklet had the highest score for behavior change and was significantly greater than the booklet-only learning (p = 0.002). The App-assisted form, either App alone or combined with booklet, had a significantly better impact on health promotion when compared to the booklet alone (p = 0.045 and 0.005, respectively). App-only learning had the highest score of CCa literacy (p = 0.004). Conclusion: Health education interventions can have positive effects in terms of change of behavior and CCa literacy. App-assisted learning could be used as a supportive technology, and App learning alone or combined with a traditional booklet may be an innovative model of clinical health promotion for women with CIN.

In this study, deep ultraviolet light-emitting diodes (DUV-LEDs) with a reflective passivation layer (RPL) were investigated. The RPL consists of HfO2/SiO2 stacks as distributed Bragg reflectors, which are deposited on two DUV-LEDs with different p-GaN thicknesses. The RPL structure improved the external quantum efficiency droops of the DUV-LEDs with thick and thin p-GaN, thereby increasing their light output power by 18.4% and 39.4% under injection current of 500 mA and by 17.9% and 37.9% under injection current of 1000 mA, respectively. The efficiency droops of the DUV-LEDs with and without the RPL with thick p-GaN were 20.1% and 19.1% and with thin p-GaN were 18.0% and 15.6%, respectively. The DUV-LEDs with the RPL presented improved performance. The above results demonstrate the potential for development of the RPLs for DUV-LED applications.

Diabetes mellitus is one of the greatest global health issues and much research effort continues to be directed toward identifying novel therapeutic agents. Insulin resistance is a challenging integrally related topic and molecules capable of overcoming it are of considerable therapeutic interest in the context of type 2 diabetes mellitus (T2DM). Protein tyrosine phosphatase 1B (PTP1B) negatively regulates insulin signaling transduction and is regarded a novel therapeutic target in T2DM. Here, we investigated the inhibitory effect of α-methyl artoflavanocoumarin (MAFC), a natural flavanocoumarin isolated from Juniperus chinensis, on PTP1B in insulin-resistant HepG2 cells. MAFC was found to potently inhibit PTP1B with an IC50 of 25.27 ± 0.14 µM, and a kinetics study revealed MAFC is a mixed type PTP1B inhibitor with a K i value of 13.84 µM. Molecular docking simulations demonstrated MAFC can bind to catalytic and allosteric sites of PTP1B. Furthermore, MAFC significantly increased glucose uptake and decreased the expression of PTP1B in insulin-resistant HepG2 cells, down-regulated the phosphorylation of insulin receptor substrate (IRS)-1 (Ser307), and dose-dependently enhanced the protein levels of IRS-1, phosphorylated phosphoinositide 3-kinase (PI3K), Akt, and ERK1. These results suggest that MAFC from J. chinensis has therapeutic potential in T2DM by inhibiting PTP1B and activating insulin signaling pathways.

Cross-matching of records between Singapore's tuberculosis and HIV registries showed that 3.3% of individuals with tuberculosis (TB) were coinfected with HIV (2000-2014), the TB incidence among individuals with HIV infection was 1.65 per 100 person-years, and 53% of coinfections were diagnosed within 1 month of each other. The findings supported joint prevention programmes for early diagnosis and treatment.

Ferulic acid is a hydroxycinnamic acid that widely presents in plant cell wall components. It has been demonstrated that ferulic acid can reverse depressive-like behaviors in both forced swimming test and tail suspension test. However, it is unclear whether chronic ferulic acid treatment can ameliorate the depressive-like behaviors in chronic unpredictable mild stress (CUMS). Because of the putative relationship between neurotrophic system and antidepressant-like activity, we also investigated the effects of chronic ferulic acid on the brain-derived neurotrophic factor (BDNF), postsynaptic protein PSD95, presynaptic protein synapsin I in both prefrontal cortex and hippocampus. The results showed that ferulic acid significantly alleviated CUMS-induced depressive-like behaviors in sucrose preference test and forced swimming test. In addition, ferulic acid significantly up-regulated the levels of BDNF, PSD95 and synapsin I in the prefrontal cortex and hippocampus. The present data indicated that ferulic acid exerted the antidepressant-like effects on behaviors by increasing neurotrophin-related synaptic protein levels in CUMS mice.

RUNX1-ETO, the t(8;21)-derived fusion protein, is a recurrent somatic lesion detected in approximately 12% of de novo acute myeloid leukemia (AML) and up to 40% of M2 subtype AML at diagnosis. RUNX...

To determine the durability of concrete in the actual temperature and humidity of the tunnel environment, this study investigates the mechanical properties, permeability of chloride ion, relative dynamic elastic modulus, and mass loss ratio of concrete specimens cured in the temperature which varied from normal, 40, 60, 75, and 90°C, and the humidity was kept at 90% continuously. Experimental results reveal that the hot temperature curing environment may benefit early stage strength development but reduce the long-term strength. It is proved that 60°C is a critical point. At above 60°C, the strength of the concrete material and its resistance to chloride ion permeability showed a decreasing trend; however, in the appropriate temperature range, the frost resistance properties of the concrete are improved with increasing temperature.