Transesterification of RNA model induced by novel dinuclear copper (II) complexes with bis-tridentate imidazole derivatives.

Two novel bis-tridentate imidazole derivatives were conveniently synthesized using a 'one-pot' method. Their dinuclear (Cu2L1Cl4, Cu2L2Cl4) and mononuclear (CuL1Cl2, CuL2Cl2∙H2O) copper (II) complexes were synthesized to comparably evaluate their reactivities in the hydrolytic cleavage of 2-hydroxypropyl p-nitrophenyl phosphate (HPNP) as a classic RNA model. Single crystals of Cu2L1Cl4 and Cu2L2Cl4 indicate that both of them are centrosymmetric, and each central copper ion is penta-coordinated. Regarding the transesterification of HPNP, both of dinuclear ones exhibited excess one order of magnitude rate enhancement in contrast with auto-hydrolysis reaction. Under comparable conditions, dinuclear complexes displayed no more than twofold increase in activity over their mononuclear analogues, which verifies the lack of binuclear cooperation effect due to long Cu-to-Cu space.

Artificial phosphatase upon premicellar nanoarchitectonics of lanthanum complexes with long-chained imidazole derivatives.

Four novel long chain-containing tridentate imidazole derivatives (Ln, n = 1, 2, 3, 4) were synthesized for in situ formation of mononuclear lanthanum(III) complexes as artificial phosphodiesterases. These in-situ formed La(III) complexes (named LaLn) were used to catalyze the transesterification of 2-hydroxypropyl p-nitrophenyl phosphate (HPNP), a classic RNA model. Critical aggregation concentrations (CAC) were determined for the as-prepared tridentate imidazole derivatives as ligands and corresponding mixtures of equivalent ligand and La3+ ion with a mole rate of 1:1. It denotes that the introduction of La3+ ion increases the CAC values of imidazole derivatives by about 2 to 3 folds. Foaming test shows that the foam height is positively correlated with the length of hydrophobic chain. Transesterification of HPNP mediated by LaLn nanoarchitectonics indicates that the introducing of hydrophobic chain benefits rate enhancement, showing excess three orders of magnitude acceleration under physiological conditions (pH 7.0, 25 °C). Moreover, catalytic reactivities of these La(III) complexes increased along with the increase in chain length: LaL1 < LaL2 < LaL3 < LaL4, suggesting a positive correlation to hydrophobic chain length.

Discovery of natural alkaloids as potent and selective inhibitors against human carboxylesterase 2.

Human Carboxylesterase 2A (hCES2A), one of the most important serine hydrolases, plays crucial roles in the hydrolysis and the metabolic activation of a wide range of esters and amides. Increasing evidence has indicated that potent inhibition on intestinal hCES2A may reduce the excessive accumulation of SN-38 (the hydrolytic metabolite of irinotecan with potent cytotoxicity) in the intestinal tract and thereby alleviate the intestinal toxicity triggered by irinotecan. In this study, more than sixty natural alkaloids have been collected and their inhibitory effects against hCES2A are assayed using a fluorescence-based biochemical assay. Following preliminary screening, seventeen alkaloids are found with strong to moderate hCES2A inhibition activity. Primary structure-activity relationships (SAR) analysis of natural isoquinoline alkaloids reveal that the benzo-1,3-dioxole group and the aromatic pyridine structure are beneficial for hCES2A inhibition. Further investigations demonstrate that a steroidal alkaloid reserpine exhibits strong hCES2A inhibition activity (IC50 = 0.94 µM) and high selectivity over other human serine hydrolases including hCES1A, dipeptidyl peptidase IV (DPP-IV), butyrylcholinesterase (BChE) and thrombin. Inhibition kinetic analyses demonstrated that reserpine acts as a non-competitive inhibitor against hCES2A-mediated FD hydrolysis. Molecular docking simulations demonstrated that the potent inhibition of hCES2A by reserpine could partially be attributed to its strong σ-π and S-π interactions between reserpine and hCES2A. Collectively, our findings suggest that reserpine is a potent and highly selective inhibitor of hCES2A, which can be served as a promising lead compound for the development of more efficacious and selective alkaloids-type hCES2A inhibitors for biomedical applications.

Chromosome 1q21 translocation and spermatogenesis failure: Two case reports and review of the literature.

RATIONALE: For the carriers of chromosome reciprocal translocation, the reason why some are fertile and others are infertile remains unclear. Here, we describe 2 patients who are carriers of chromosome 1q21 translocation with azoospermia. PATIENT CONCERNS: A 29-year-old male and a 33-year-old male presented at the clinic with a diagnosis of infertility. DIAGNOSIS: Both patients with azoospermia were diagnosed with Routine semen analysis, cytogenetic diagnosis and detection of serum reproductive hormones. The karyotype results of 2 patients were 46,XY,t(1;17)(q21;q23) and 46,XY,t(1;10)(q21;p12), respectively. INTERVENTIONS: After genetic counseling and informed consent, 1 patient (Case 2) chose microsopic testicular sperm extraction (micro-TESE). OUTCOMES: After micro-TESE, no sperm was found for the patient. Finally, both patients chose clinical treatment through artificial insemination with donor sperm. LESSONS: These outcomes suggest that breakpoint at 1q21 should be paid attention by physician in genetic counseling, may harbor some genes associated with spermatogenesis, and deserves further be studied on the function of related genes.

Catalyst-free visible-light-induced condensation to synthesize bis(indolyl)methanes and biological activity evaluation of them as potent human carboxylesterase 2 inhibitors.

A mild strategy for visible-light-induced synthesis of bis(indolyl)methanes was developed using aromatic aldehydes and indole as substrates. This reaction could be performed at room temperature under catalyst- and additive-free conditions to synthesize a series of bis(indolyl)methanes in good to excellent yields. In addition, all synthesized bis(indolyl)methanes together with ß-substituted indole derivatives synthesized according to our previous work, were evaluated for their inhibitory effect against human carboxylesterase (CES1 and CES2). Primary structure-activity relationship analysis of all tested compounds showed that the modifications of ß-substituted indole at the ß-site with another indolyl group led to a significant enhancement of the inhibitory effect on CES2, and the bisindolyl structure is essential for CES2 inhibition. These results demonstrated that these bis(indolyl)methanes are potent and selective CES2 inhibitors, which might be helpful for medicinal chemists to design and develop more potent and selective CES2 inhibitors for biomedical applications.

Effects of protease-treated royal jelly on muscle strength in elderly nursing home residents: A randomized, double-blind, placebo-controlled, dose-response study.

Although we have found that protease-treated royal jelly (pRJ) benefit for the skeletal muscle mass and strength in the aged animals, the potential beneficial effects have not been evaluated in humans. The aim of this study was to determine whether pRJ intake had beneficial effects on muscle strength in elderly nursing home residents. One hundred and ninety-four subjects enrolled into this multicenter, randomized, double-blind, placebo-controlled study. Subjects received either placebo(Group 1), pRJ 1.2 g/d(Group 2), or 4.8 g/d(Group 3). Data through 1 year are reported for 163 subjects. The primary outcome measure is handgrip strength. Secondary outcomes include several physical performance tests (six-minute walk test, timed up and go test, and standing on one leg with eyes closed). The dropout rate was 16.0%. The means (95% confidence interval) of change in handgrip strength for placebo, low-dose, and high-dose groups are -0.98(-2.04,0.08), 0.50(-0.65,1.65) and 1.03(-0.37,2.44) kg (P = 0.06, P for trend = 0.02), respectively. No significant effects of the interventions were observed for physical performances. These findings suggest that pRJ treatment might not improve, but rather attenuate the progression of decrease in muscle strength in elderly people. In addition, we have not found that pRJ intervention can achieve improvement or attenuating the decrease in physical performance.

Elevated serum complement C3 levels are associated with prehypertension in an adult population.

Prehypertension is a public health epidemic associated with various adverse outcomes, but can be reversed by timely intervention. However, little attention has been paid to prehypertension. Complement C3 is a central hub of complement-related immune system. We examined the association between C3 and prehypertension in an adult population for the first time, aiming to investigate whether pro-inflammatory immune response is involved in the prehypertensive state. About 7820 Tianjin residents without hypertension were categorized into sex-specific quintiles based on their serum concentration of complement C3. Adjusted logistic regression models were used separately by gender to assess the association between C3 quintiles and the prevalence of prehypertension. After multiple adjustment, the odds ratios (95% confidence interval) for prehypertension across increasing quintiles of C3 were 1.00 (reference), 1.02 (0.84, 1.25), 1.15 (0.94, 1.42), 1.25 (1.01, 1.54), and 1.71 (1.35, 2.17) (p for trend < 0.0001) among men and were 1.00 (reference), 1.17 (0.92, 1.49), 1.13 (0.88, 1.44), 1.15 (0.89, 1.48), and 1.40 (1.07, 1.84) (p for trend = 0.03) among women. The findings suggested that elevated serum C3 levels are associated with prehypertension. Reducing inflammation may be a potential therapeutic strategy for prehypertension and hypertension that is worthy of further studies and discussion.

Both muscle mass and muscle strength are inversely associated with depressive symptoms in an elderly Chinese population.

OBJECTIVE: Few population studies have examined the association between skeletal muscle and depressive symptoms. The aim of this study was to examine whether low muscle mass and muscle strength were associated with the depressive symptoms in elderly Chinese. METHODS: A cross-sectional study was conducted with 1046 elderly in Tianjin, China. Depressive symptoms were examined using the 30-item Geriatric Depression Scale. A Geriatric Depression Scale score of ≥11 was used to indicate depressive symptoms. Skeletal muscle mass was indicated using a skeletal muscle mass index (SMI) that was measured by bioimpedance analysis and muscle strength was measured by dynamometer. RESULTS: In a multiple logistic regression analysis, subjects in the lowest quartile of SMI or muscle strength had a significantly higher risk for depressive symptoms compared with those in the fourth quartile. The odds ratios and 95% confidence interval for depressive symptoms risk in the lowest quartile of SMI compared with the highest after adjusting for potential confounding factors were 10.1 (2.25, 58.3) in men and 3.17 (1.07, 9.95) in women. The odds ratios (95% confidence interval) for depressive symptoms risk in the lowest quartile of muscle strength compared with the highest after adjusting for potential confounding factors were 2.55 (1.02, 6.67) in men and 4.18 (1.83, 10.2) in women. CONCLUSIONS: Both muscle mass and muscle strength are inversely associated with depressive symptoms in elderly Chinese. These findings may provide novel insights linking skeletal muscle and depressive symptoms. Copyright © 2016 John Wiley & Sons, Ltd.

Dietary patterns are associated with depressive symptoms among Chinese adults: a case-control study with propensity score matching.

PURPOSE: Previous studies have indicated that consumption of particular foods or nutrients is associated with depressive symptoms, but little is known about the role of overall dietary patterns in depressive symptoms. We design this case-control study to evaluate the associations between dietary patterns and high depression symptoms in Chinese adults. METHODS: A total of 1351 participants with high depressive symptoms were matched with 1351 controls using the 1:1 ratio propensity score matching method. Dietary intake was assessed using a valid self-administered food frequency questionnaire, and high depressive symptoms were assessed with the Zung Self-Rating Depression Scale, wherein cutoff point of 45 was used as a definition of high depressive symptoms. RESULTS: Exploratory factor analysis revealed three dietary patterns (vegetables and fruits pattern; sweets pattern; and animal foods pattern) explaining 25.1 % of the total variance. Compared with the participants in the lowest quartile, the participants in the highest quartile of vegetables and fruits pattern, which was defined as a healthy pattern, were associated with reduced odds of high depressive symptoms (OR 0.65, 95 % CI 0.52-0.83, P for trend <0.001) while the sweets pattern (OR 1.33, 95 % CI 1.06-1.66) and the animal foods pattern (OR 1.79, 95 % CI 1.43-2.24, P for trend <0.0001) were associated with increased prevalence of high depressive symptoms, respectively. CONCLUSION: The present study adds to the evidence that the sweets pattern and animal foods pattern are positively associated with the prevalence of high depressive symptoms. In contrast, the dietary pattern rich in vegetables, fruits, and soya bean products, but low in animal foods, candied fruits, cakes, ice cream, sugared beverages, and alcoholic drinks is negatively associated with the prevalence of high depressive symptoms.

Association between dietary patterns and metabolic syndrome in Chinese adults: a propensity score-matched case-control study.

Previous studies indicated that dietary patterns were associated with metabolic syndrome (MS), but little is known in Chinese. We design this case-control study to evaluate the associations between dietary patterns and MS in Chinese adults. In this study, 1492 participants with MS were matched with 1492 controls using the 1:1 ratio propensity score matching methods. Dietary intake was assessed using a valid self-administered food frequency questionnaire, and MS was defined in accordance with the criteria of the American Heart Association scientific statement of 2009. Higher scores for the high-protein/cholesterol pattern were associated with higher prevalence of MS. Compared with the participants in the lowest quartile, the odds ratio (OR) for the extreme quartile was 1.36 (95% confidence interval (CI), 1.10-1.68) and the P for trend <0.01 after adjusted for the other two dietary pattern scores. We also found a moderate consumption of the balanced pattern was associated with the lowest prevalence of MS. The ORs across quartiles of the balanced pattern were 1 (reference), 0.83 (95% CI, 0.68-1.02), 0.69 (95% CI, 0.56-0.85), and 0.84 (95% CI, 0.68-1.04) after adjustment. Our study demonstrates that there is a strong association between a diet rich in animal offal, animal blood, meat, and sausage and a higher prevalence of MS.

Mobility and Muscle Strength Together are More Strongly Correlated with Falls in Suburb-Dwelling Older Chinese.

Falls are common in older adults and result in adverse outcomes. Impaired mobility and poor muscle strength have been consistently identified as the main contributors to falls. We choose three easy-to-perform tests (i.e. Timed Up and Go test (TUGT), walking speed (WS) and grip strength (GS)) in order to assess mobility and muscle strength to further define their relationship with falls. This study is cross-sectional, consisting of 1092 residents over 60-year-old; 589 were female. 204 (18.68%) participants reported falling at least once in the past year. It was found that, of the three tests evaluated independently, a TUGT < 9.1750 s had the strongest association with fewer falls. When evaluating these tests as pairs, the combination of a TUGT < 9.1750 s and a WS < 0.9963 m/s was the best protective indicator of falls after adjusting for age, sex and other variables. When evaluating all three tests in conjunction with each other, the combination of a TUGT < 9.1750 s, a WS < 0.9963 m/s, and a GS > 0.3816 was most correlated with less possibility of falls. The combination of a better TUGT performance, a stronger GS, and a slower WS is the most strongly correlated with less possibility of falls.

Prevalence and Factors Associated With Sarcopenia in Suburb-dwelling Older Chinese Using the Asian Working Group for Sarcopenia Definition.

BACKGROUND: Sarcopenia is a common condition in older people. The aim of the present study was to examine the prevalence and factors associated with sarcopenia in an elderly Chinese suburb-dwelling population. METHODS: This study was conducted on 1,069 Chinese suburb-dwelling participants aged ≥60 years to evaluate sarcopenia using the Asian Working Group for Sarcopenia criteria. Sociodemographic and behavioral characteristics, as well as medical conditions, were considered independent variables to determine factors associated with sarcopenia using a logistic regression model. RESULTS: The prevalence of sarcopenia was 6.4% in men and 11.5% in women. Age was a significant factor in both sexes. In addition, presence of sarcopenia was inversely associated with BMI for both sexes. The odds ration and 95% confidence interval for factors statistically significantly associated with sarcopenia were 5.04 (1.70-14.89) and 2.36 (1.06-5.25) for diabetes in males and females, respectively; 10.60 (1.75-64.24) for daily consumption of alcohol (daily drinkers), 5.58 (2.13-14.59) for peptic ulcer in female (not statistically significant in males). CONCLUSIONS: The Asian Working Group for Sarcopenia criterion is useful for defining sarcopenia, and our data suggest that the prevalence of sarcopenia in the general elderly suburb-dwelling Chinese population is high. Moreover, we find that high body mass index is inversely associated with the likelihood of being sarcopenic and that several others factors such as diabetes, peptic ulcer, and drinking habits increase the prevalence of sarcopenia.

Clinical Relevance of Different Handgrip Strength Indexes and Mobility Limitation in the Elderly Adults.

BACKGROUND: More efficient clinical indexes are needed to identify older people most likely to present mobility impairments. The aim of the present study was to determine which handgrip strength (HS) indexes are clinically relevant to detect risk of mobility limitation in the elderly adults. In addition, we attempted to determine an optimal cutoff point for the most relevant index. METHODS: Data are from 469 men and 609 women aged 60 years and older recruited in the Hangu area of Tianjin, China. Participants scoring in the top 20% on the Timed Up and Go Test or in the slowest 20% for the 4-m walk test were defined as having mobility limitation. RESULTS: The prevalence of mobility limitation was 27.6% in women and 24.5% in men. The area under the receiver-operating characteristic curve for HS/body fat mass was 0.723 (95% confidence interval [CI] = 0.658-0.788) in men and for HS/weight was 0.684 (95% CI = 0.628-0.739) in women. These values were indicated higher levels of mobility limitation compared with HS and other relative HS indexes. The cutoffs of the most relevant index in men and women that effectively identified individuals at risk of mobility limitation were 1.884 and 0.281, respectively. CONCLUSION: HS/body fat mass and HS/weight appear to be the indices best associated with mobility limitation for men and women, respectively. Optimal cutoffs for clinically relevant index have the potential to identify elderly adults at risk of mobility limitation.

Body mass index is associated with physical performance in suburb-dwelling older chinese: a cross-sectional study.

BACKGROUND: Physical performance is reported to have various beneficial effects on human health, especially in older individuals. Although such effects are associated with body mass index (BMI), the relationship between BMI and physical performance has not been clarified. DESIGN: We conducted a cross-sectional study of 966 suburb-dwelling Tianjin individuals aged ≥ 60 years (average age 67.5±6.02, men 435, women 531). Mobility, balance, and muscle strength were assessed by walking speed, timed up-and-go test (TUGT), and grip strength, respectively. The subjects were categorized into three groups based on BMI (kg/m2) as follows: normal weight, 18.5 ≤ BMI ≤ 23.9; overweight, 24.0 ≤ BMI ≤ 27.9; and obese, BMI ≥ 28.0. RESULT: After adjusting for all other variables, relative grip strength decreased when BMI increased in both men and women (P for trend <0.001 and <0.001, respectively). BMI may be negatively associated with TUGT performance in the women only. There was no apparent association between walking speed and BMI in either sex, but after adjusting for age, walking speed was faster when BMI increased in women (P for trend= 0.0162). CONCLUSION: This study suggests that in older individuals, higher BMI is associated with poor muscle strength in both sexes.