Visual and photoelectrochemical analysis of antibiotic resistance genes enabled by surface-engineered ZIF-8@Au cascade nanozymes.

The aggravation of antibiotic resistance genes (ARGs) in the environment has posed a significant global health crisis. Accurate evaluation of ARGs levels in a facile manner is a pressing issue for environmental surveillance. Here, we demonstrate a unique dumbbell-shaped cascade nanozyme for visual/photoelectrochemical (PEC) dual-mode detection of ARGs. Gold nanoparticles (AuNPs) with tunable exposed facets are controllably anchored onto ZIF-8 dodecahedrons, exhibiting glucose oxidase (GOx)-like (ZIF-8@Au/G) and peroxidase (POD)-like (ZIF-8@Au/P) activities. Upon the occurrence of ARGs, an asymmetric cascade-amplified "dumbbell" configuration is spontaneously generated via target-induced DNA hybridization, comprising GOx-like ZIF-8@Au/G with capture DNA on one side and POD-like ZIF-8@Au/P with signal DNA on the opposite side. Such a cascade nano-system can efficiently oxidize colorless 2, 2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) into its green oxidation state and synergistically decompose H2O2, realizing colorimetric/PEC dual-mode ARGs detection with a detection limit of 0.112 nM. The applicability of the present bioassay is validated through measuring ARGs in real sludge samples. This work suggests the possibility to rationally design task-specific nanozymes and develop target-responsive nano-cascade assays for environmental monitoring.

Diphthamide deficiency promotes association of eEF2 with p53 to induce p21 expression and neural crest defects.

Diphthamide is a modified histidine residue unique for eukaryotic translation elongation factor 2 (eEF2), a key ribosomal protein. Loss of this evolutionarily conserved modification causes developmental defects through unknown mechanisms. In a patient with compound heterozygous mutations in Diphthamide Biosynthesis 1 (DPH1) and impaired eEF2 diphthamide modification, we observe multiple defects in neural crest (NC)-derived tissues. Knockin mice harboring the patient's mutations and Xenopus embryos with Dph1 depleted also display NC defects, which can be attributed to reduced proliferation in the neuroepithelium. DPH1 depletion facilitates dissociation of eEF2 from ribosomes and association with p53 to promote transcription of the cell cycle inhibitor p21, resulting in inhibited proliferation. Knockout of one p21 allele rescues the NC phenotypes in the knockin mice carrying the patient's mutations. These findings uncover an unexpected role for eEF2 as a transcriptional coactivator for p53 to induce p21 expression and NC defects, which is regulated by diphthamide modification.

Association between sarcopenia grade and fall history among older adults in West China: A retrospective study.

OBJECTIVES: The association between sarcopenia severity and fall history remains under-researched at present. Accordingly, this study was developed to evaluate the relationship between sarcopenic status and prior fall events in a multiethnic group of older community-dwelling adults in Western China. DESIGN: A retrospective survey study, the data comes from the West China Health and Aging Trend study. SETTING: The study was based in Western China. PARTICIPANTS: In total, this retrospective analysis incorporated data from 2719 older adults (59.2% women). PRIMARY AND SECONDARY OUTCOME MEASURES: Grip strength, gait speed and skeletal muscle mass index values were analysed for all participants, and the Asian Working Group for Sarcopenia (AWGS) 2014 and 2019 consensus criteria were leveraged to assess sarcopenia status in these individuals. Prior fall history was defined by any incidents in which an individual unintentionally came to rest on the floor within the past year. The association between sarcopenia status and fall history was examined through a binary logistic regression approach, with p<0.05 as the threshold for significance. RESULTS: Using the AWGS2014 and AWGS2019 diagnostic criteria, of the individuals included in this study cohort 1851 (68.1%) were free of sarcopenia, 160 (5.9%) and 56 (2.1%) showed only muscle-mass loss, 322 (11.8%) and 267 (9.8%) exhibited non-severe sarcopenia and the remaining 386 (14.2%) and 545 (20.0%) exhibited severe sarcopenia, respectively. Previous fall events were reported for 14.8% of study cohort members. After full adjustment for potential confounders, a significant link between severe sarcopenia diagnosed by the AWGS2014 diagnostic criteria and fall history was observed (OR 1.397, 95% CI 1.029 to 1.896, p=0.032), while the AWGS2019 diagnostic criteria did not (OR 1.29, 95% CI 0.982 to 1.694, p=0.068). CONCLUSIONS: Severe sarcopenia, as defined per the AWGS2014 criteria, was associated with a significantly higher risk of falls in this multiethnic cohort of older adults from Western China, while the AWGS2019 diagnostic criteria did not. However, this relationship was not observed for individuals who experienced muscle mass loss or had non-severe sarcopenia, according to both the AWGS2014 and AWGS2019 diagnostic criteria.

Validated Tools for Screening Sarcopenia: A Scoping Review.

OBJECTIVE: Choosing the optimal sarcopenia screening tool for a specific clinical scenario is challenging. We aimed to summarize all validated sarcopenia screening tools with diagnostic accuracy tested in one or more study populations. DESIGN: Scoping review. SETTING AND PARTICIPANTS: Hospitals, nursing homes, communities, or health checkups. METHODS: We systematically searched 3 databases in April 2022: MEDLINE, EMBASE, and CENTRAL. Two review authors independently performed the study selection and data extraction. The included tools' contents, characteristics, and number of citations were summarized and visualized. RESULTS: We summarized 102 diagnostic accuracy studies involving 53 screening tools, classified into 7 groups: questionnaires (n = 13); serum biomarkers (n = 10); formulas, algorithms, and models (n = 9); physical ability tests (n = 9); integration tools (n = 7); anthropometric indices (n = 3); and ultrasound or bioimpedance analysis (n = 2). The most commonly used questionnaire was SARC-F (770 citations), followed by SARC-CalF (254 citations) and MSRA-7 (61 citations). Handgrip strength and Ishii score were the most widely used physical performance tests (331 citations) and formulas (294 citations), respectively. Sarcopenia index (based on serum cystatin C and creatinine) and calf circumference were the most commonly used serum biomarkers (123 citations) and anthropometric indexes (127 citations), respectively. Ultrasound was the most commonly used imaging tool for screening sarcopenia (57 citations). The included tools varied significantly in content. Various tools assessed some or all components of sarcopenia with different methods, and others assessed different domains, such as age, body mass index, falls, diet, and even mental health. We also summarized the screening tools that were validated in different clinical settings (hospitals, communities, nursing homes, and health checkups). CONCLUSIONS AND IMPLICATIONS: More than 50 validated tools are currently available for screening sarcopenia in different clinical settings. The results of this review may help clinicians and researchers in selecting optimal tools for sarcopenia in different clinical scenarios and in developing future tools.

DNA damage-mediated cellular senescence promotes hand-foot syndrome that can be relieved by thymidine prodrug.

Hand-foot syndrome (HFS) is a widely recognized dose-limiting cutaneous toxicity effect of fluoropyrimidine chemotherapy agents that impairs clinical benefits and treatment outcomes. Even though the cause and pathophysiology of HFS are relatively widely reported, how the toxicity of fluoropyrimidine translates into persistent inflammation has not been studied. Additionally, prevention and treatment strategies for HFS based on its mechanistic occurrence and development are scarce. In our study, we demonstrated that cGAS-STING signaling pathway-mediated cellular senescence played a critical role in the inflammatory reaction and provided a therapeutic solution for HFS. Mechanistically, DNA damage, as the primary cytotoxic cause, in keratinocytes induces cell cycle arrest, activates the cGAS-STING signaling pathway, and subsequently mediates cellular senescence, ultimately fueling a robust secondary inflammatory response that results in HFS. More importantly, the thymidine prodrug thymidine diacetate was proven to be effective in preventing HFS by compensating for thymidylate deficiency to facilitate the replication and repair of DNA and thus causing the escape from cellular senescence. These data highlight the importance of DNA damage-mediated cellular senescence in the etiology of HFS and provide a potential therapeutic anchor point for fluoropyrimidine-induced HFS.

Cut-off points of the Ishii test to diagnosing severe sarcopenia among multi-ethnic middle-aged to older adults: results from the West China Health and Aging Trend study.

Objective: This study was designed to establish the cut-off value and diagnostic utility of the Ishii test, which gauges the odds of severe sarcopenia based on the results of an equation based upon age, grip strength, and calf circumference among middle-aged and older adults in Western China. Methods: This study incorporated adults ≥ 50 years of age from the West China Health and Aging Trend (WCHAT) study. Severe sarcopenia was defined as per the Asian Working Group for Sarcopenia: 2019 Consensus (AWGS2019) recommendations, with the odds of severe sarcopenia being estimated with the Ishii test score chart. The diagnostic utility of the Ishii test in this patient cohort was assessed by analyzing its sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and the area under the ROC curve (AUC). Results: In total, 4,177 individuals ≥ 50 years of age were included in this study including 2668 females (63.9%) and 1,509 males (36.1%). These included 568 (13.6%) participants affected by severe sarcopenia, of whom 237 were male (15.7%) and 331 were female (12.4%). Optimal Ishii test cut-off values established based on Youden's index were ≥ 114 for males and ≥ 120 for females when using the AWGS2019 reference standard. The sensitivity/specificity/PPV/NPV of the Ishii test when screening for severe sarcopenia were 89.45%/77.15%/0.42/0.98 in males and 90.03%/77.05%/0.36/0.98 in females. The AUC values for the Ishii test in males and females were 0.899 (95% CI, 0.883-0.916) and 0.905 (95% CI, 0.892-0.917), respectively. Conclusion: These data indicate that the Ishii test offers value as a candidate diagnostic test that can be used to screen for severe sarcopenia, with recommended diagnostic cut-off values of ≥ 114 for males and ≥ 120 for females.

PCP4 Promotes Alzheimer's Disease Pathogenesis by Affecting Amyloid-ß Protein Precursor Processing.

BACKGROUND: Down syndrome (DS) is caused by an extra copy of all or part of chromosome 21. The patients with DS develop typical Alzheimer's disease (AD) neuropathology, indicating the role of genes on human chromosome 21 (HSA21) in the pathogenesis of AD. Purkinje cell protein 4 (PCP4), also known as brain-specific protein 19, is a critical gene located on HSA21. However, the role of PCP4 in DS and AD pathogenesis is not clear. OBJECTIVE: To explore the role of PCP4 in amyloid-ß protein precursor (AßPP) processing in AD. METHODS: In this study, we investigated the role of PCP4 in AD progression in vitro and in vivo. In vitro experiments, we overexpressed PCP4 in human Swedish mutant AßPP stable expression or neural cell lines. In vitro experiments, APP23/PS45 double transgenic mice were selected and treated with AAV-PCP4. Multiple topics were detected by western blot, RT-PCR, immunohistochemical and behavioral test. RESULTS: We found that PCP4 expression was altered in AD. PCP4 was overexpressed in APP23/PS45 transgenic mice and PCP4 affected the processing of AßPP. The production of amyloid-ß protein (Aß) was also promoted by PCP4. The upregulation of endogenous AßPP expression and the downregulation of ADAM10 were due to the transcriptional regulation of PCP4. In addition, PCP4 increased Aß deposition and neural plaque formation in the brain, and exuberated learning and memory impairment in transgenic AD model mice. CONCLUSION: Our finding reveals that PCP4 contributes to the pathogenesis of AD by affecting AßPP processing and suggests PCP4 as a novel therapeutic target for AD by targeting Aß pathology.

The accuracy of body mass index and calf circumference values when assessing sarcopenia in a multi-ethnic cohort of middle-aged and older adults: West China health and aging trend study results.

Objective: This analysis was designed to explore the utility of body mass index (BMI) and calf circumference (CC) values in the diagnosis of sarcopenia. Methods: A cross-sectional analysis of community-dwelling adults ≥50 years old was conducted. An InBody 770 bioimpedance analysis (BIA) device was used for measuring muscle mass, a grip-strength dynamometer was used to assess muscle strength, and a 4 m gait speed (GS) analysis was used to gauge physical function. The Asian Working Group for Sarcopenia (AWGS) 2019 criteria were used to define sarcopenia. The cut-off values for BMI and CC were based on the computed Younden's index values and AWGS 2019 criteria, respectively. The area under the ROC curves (AUC), specificity, sensitivity, and positive and negative predictive values (PPV and NPV) were calculated to establish the value of BMI and CC for the diagnosis of sarcopenia. Results: In total, the data of 4177 participants ≥50 years of age were analyzed. These included 2668 (63.9%) females and 1509 (36.1%) males. Of these participants, 946 (22.6%) met the criteria for sarcopenia, including 408 (27%) males and 538 (20.2%) females. The sensitivity, specificity, and NPVs obtained when using BMI and CC values to predict sarcopenia were as follows: 84.03%/65.51%/0.90 and 74.76%/83.51%/0.87, respectively, in males; 87.36%/64.12%/0.94 and 78.25%/82.09%/0.93, in females. The respective AUC values for BMI and CC in males were 0.83 (0.80-0.85) and 0.85 (0.83-0.88), while in females they were 0.85 (0.83-0.87) and 0.88 (0.87-0.90). Conclusions: These data suggest that BMI and CC can both serve as accurate predictors of sarcopenic incidence in a multi-ethnic population ≥50 years of age. The specificity values for BMI were relatively low in both males and females, however, underscoring the relative advantages of measuring CC when assessing individual sarcopenia risk.

Bisphenol F induced hyperglycemia via activation of oxidative stress-responsive miR-200 family in the pancreas.

Bisphenol F (BPF), BPS and BPAF are gaining popularity as main substitutes to BPA, but there is no clear evidence that these compounds disrupt glycemic homeostasis in the same way. In this study, four bisphenols were administered to C57BL/6 J mice, and showed that the serum insulin was elevated in the BPA and BPS exposed mice, whereas BPF exposed mice exhibited lower serum insulin and higher blood glucose. BPF decreased oxidized glutathione/reduced glutathione ratio (GSSG/GSH) and N6-methyladenosine (m6A) levels, which was responsible for pancreatic apoptosis in mice. Additionally, the downregulation of Nrf2 and the aberrant regulation of the p53-lncRNA H19 signaling pathway further increased miR-200 family in the BPF-exposed pancreas. The miR-200 family directly suppressed Mettl14 and Xiap by targeting their 3' UTR, leading to islet apoptosis. Antioxidant treatment not only elevated m6A levels and insulin contents but also suppressed the miR-200 family in the pancreas, ultimately improving BPF-induced hyperglycemia. Taken together, miR-200 family could serve as a potential oxidative stress-responsive regulator in the pancreas. And moreover, we demonstrated a novel toxicological mechanism in that BPF disrupted the Keap1-Nrf2 redox system to upregulate miR-141/200b/c which controlled pancreatic insulin production and apoptosis via Mettl14 and Xiap, respectively. As the major surrogates of BPA in various applications, BPF was also diabetogenic, which warrants attention in future research.

Transcriptional activation of CSTB gene expression by transcription factor Sp3.

CSTB has been reported to be associated with the pathogenesis of many malignant tumors, especially hepatocellular carcinoma (HCC). However, how the expression of this gene is regulated is largely unknown. We initially cloned and analyzed the promoter region of the CSTB gene by luciferase assay and the Sp3 binding site (CCCCGCCCCGCG) was found in it. The results of electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) experiments verified that the transcription factor, Sp3 could bind to the " CCCCGCCCCGCG ″ site of the CSTB gene promoter. We showed that the overexpression of Sp3 significantly increased the endogenous mRNA and protein expression levels of CSTB, whereas knockdown of Sp3 decreased the mRNA and protein expression levels according to quantitative real-time PCR (qRT‒PCR) and western blotting. In conclusion, CSTB gene expression is closely regulated by transcription factor Sp3, which may be a potential mechanism for the dysregulation of CSTB expression in HCC.

Capecitabine induces hand-foot syndrome through elevated thymidine phosphorylase-mediated locoregional toxicity and GSDME-driven pyroptosis that can be relieved by tipiracil.

BACKGROUND: Hand-foot syndrome (HFS) is a serious dose-limiting cutaneous toxicity of capecitabine-containing chemotherapy, leading to a deteriorated quality of life and negative impacts on chemotherapy treatment. The symptoms of HFS have been widely reported, but the precise molecular and cellular mechanisms remain unknown. The metabolic enzyme of capecitabine, thymidine phosphorylase (TP) may be related to HFS. Here, we investigated whether TP contributes to the HFS and the molecular basis of cellular toxicity of capecitabine. METHODS: TP-/- mice were generated to assess the relevance of TP and HFS. Cellular toxicity and signalling mechanisms were assessed by in vitro and in vivo experiments. RESULTS: TP-/- significantly reduced capecitabine-induced HFS, indicating that the activity of TP plays a critical role in the development of HFS. Further investigations into the cellular mechanisms revealed that the cytotoxicity of the active metabolite of capecitabine, 5-DFUR, was attributed to the cleavage of GSDME-mediated pyroptosis. Finally, we demonstrated that capecitabine-induced HFS could be reversed by local application of the TP inhibitor tipiracil. CONCLUSION: Our findings reveal that the presence of elevated TP expression in the palm and sole aggravates local cell cytotoxicity, further explaining the molecular basis underlying 5-DFUR-induced cellular toxicity and providing a promising approach to the therapeutic management of HFS.

Sp4 Regulates PTTG1IP Gene Transcription and Expression.

Pituitary tumor-transforming gene 1 protein (PTTG)-interacting protein, also known as PTTG-binding factor (PBF), is encoded by a proto-oncogene PTTG1IP. PBF has been identified through its interaction with PTTG. Similar to PTTG, PBF has been implicated in the etiology of several tumors, including pituitary, thyroid, and breast cancer. PBF can induce the translocation of PTTG into the nucleus, and then lead to tumorigenesis. Studies have shown that PBF plays a vital and complex role in increasing tumor development. However, the transcriptional regulation of PTTG1IP gene remains undefined. In this study, we have cloned a 467-bp fragment of the 5' flanking region of the human PTTG1IP gene and identified the region (-212 to +7 bp) necessary for PTTG1IP gene promoter activity by luciferase assay. Electrophoretic mobility shift assay revealed PTTG1IP gene promoter containing Sp4 response elements. Overexpression of Sp4 increased PTTG1IP gene transcription and expression in HeLa cells. Our study demonstrates that Sp4 regulates PTTG1IP gene transcription and expression.

Regulation of the Human IL-10RB Gene Expression by Sp8 and Sp9.

BACKGROUND: Interleukin-10 (IL-10) is a classic anti-inflammatory cytokine that exerts its effects via the receptor complexes IL-10RA and IL-10RB. Loss of IL-10RB results in many diseases. Moreover, IL-10RB is closely associated with neuronal survival and synaptic formation. However, the regulation of IL-10RB gene expression remains elusive. OBJECTIVE: To investigate whether the expression of IL-10RB gene is increased in brain of Alzheimer's disease (AD) and its transcriptional regulation. METHODS: We examined the gene expression of AD patient brain from public database and detected the protein expression of AD model mouse brain by western blot. We constructed a variety of reporter gene plasmids with different lengths or mutation sites, tested the promoter activity and defined the functional region of the promoter with the luciferase reporter assay. The protein-DNA binding between transcription factors and the promoter was analyzed using chromatin immunoprecipitation (ChIP) and electrophoretic mobility shift assay (EMSA). RESULTS: We found that the IL-10RB is elevated in the brain of AD patient and AD model mice. The minimal promoter of the IL-10RB gene is located in the -90 to +51 bp region (relative to the transcriptional start site) and is sufficient for high-level expression of the IL-10RB gene. Transcription factors Sp8 and Sp9 bind to the IL-10RB promoter in vitro. The overexpression or knockdown of Sp8 and Sp9 affected the IL-10RB promoter activity and its gene expression. CONCLUSION: Our study functionally characterized the promoter of the IL-10RB gene and demonstrated that Sp8 and Sp9 regulated its expression.

Higher uric acid serum levels are associated with sarcopenia in west China: a cross-sectional study.

BACKGROUND: Sarcopenia is the decline in muscle strength and mass attributed to aging. The pathogenesis of sarcopenia may be triggered by oxidative stress and uric acid (UA) has strong antioxidant properties. The aim of this study was to investigate the relationship between UA and sarcopenia in community-dwelling adults of West China using the baseline data of West China Health and Aging Trend (WCHAT) study. DESIGN: A cross-sectional study. METHODS: 4236 adults aged 50 years or older in communities of west China were enrolled in this study. We applied Asian Working Group for Sarcopenia (AWGS) 2019 criteria to define sarcopenia. Muscle mass was measured using skeletal muscle index (SMI) based on bioimpedance analysis (BIA). Handgrip strength (HGS) and gait speed (GS) were recorded, respectively. Different variables like anthropometry measures, life styles, chronic disease and blood test were collected. General linear model was done to investigate the relationship between UA and HGS/GS/SMI, adjusting age, ethnic groups, sleeping quality, education level, cognitive function, smoking history, drinking history, ADL score, and chronic disease. RESULTS: Participants were grouped according to UA quartiles by gender. After adjusting for potential confounders, a negative association between serum UA levels and sarcopenia was shown both in men and women. And a significant association between serum UA levels and HGS in women was shown as an inverted J shape. Besides, a positive association between the UA quartiles and SMI was observed, irrespective of gender. CONCLUSIONS: Our results showed that higher uric acid levels were significantly correlated with higher muscle mass and grip strength among Chinese adults aged over 50. Higher UA serum levels might slow down the progression of sarcopenia.

Gallic acid inhibits neuroinflammation and reduces neonatal hypoxic-ischemic brain damages.

Neuroinflammation is a leading cause of secondary neuronal injury in neonatal hypoxic-ischemic encephalopathy (HIE). Regulation of neuroinflammation may be beneficial for treatment of HIE and its secondary complications. Gallic acid (GA) has been shown to have anti-inflammatory and antioxidant effects. In this report we found that oxygen-glucose deprivation and/reoxygenation (OGD/R)-induced cell death, and the generation of excessive reactive oxygen species (ROS) and inflammatory cytokines by microglia were inhibited by GA treatment. Furthermore, GA treatment reduced neuroinflammation and neuronal loss, and alleviated motor and cognitive impairments in rats with hypoxic-ischemic brain damage (HIBD). Together, our results reveal that GA is an effective regulator of neuroinflammation and has potential as a pharmaceutical intervention for HIE therapy.

The accuracy of the Ishii score chart in predicting sarcopenia in the elderly community in Chengdu.

BACKGROUND: Sarcopenia is a disorder associated with age that reduces the mass of skeletal muscles, the strength of muscles, and/or physical activity. It increases the risk of fall incidence which can result in fractures, hospitalizations, limited movement, and considerably decreased quality of life. Hence, it is needed to explore candidate screening tools to evaluate sarcopenia in the initial phases. The reported studies have been revealed that the sensitivity and specificity of the Ishii score chart are higher. However, the Ishii score chart is principally based on the European Working Group on Sarcopenia in Older People (EWGSOP) consensus. Recently, the Asian Working Group for Sarcopenia (AWGS) 2019 consensus has updated its diagnostic criteria for sarcopenia,which was previously similar to the EWGSOP. Hence, it is necessary to determine whether the Ishii score chart is appropriate for use among the elderly population in China. The current study aimed to validate the precision of the Ishii score chart, within the Chinese old aged community to establish an effective model for the evaluation of sarcopenia. METHODS: The AWGS2019 sarcopenia diagnostic criteria were used as a standard, and among the elderly community, the accuracy of the Ishii score chart was determined by using indicators, including specificity, sensitivity, negative and positive predictive values, negative and positive likelihood ratios, Youden index, and receiver operating characteristic (ROC) curve. RESULTS: In the elderly Chengdu community, the prevalence rate of sarcopenia was 18.38 %, 19.91 % for males and 16.91 % for females. The Ishii score chart predicts sarcopenia at an AUC value of 0.84 with 95 % confidence interval (CI), ranging between 0.80 and 0.89 for females, and at an AUC value of 0.81 with 95 % CI, ranging between 0.75 and 0.86 for males.According to the original cut-off, which was set at 120 points for females, the corresponding sensitivity was 46.91 % and the specificity was 93.22 %. The 105 cut-off points (original) set for males revealed a corresponding sensitivity of 64.94 % and the specificity of 85.46 %. However, the original cut-off value exhibited low sensitivity, hence, we selected a new cut-off value. With the new cut-off value, the sensitivity, specificity, positive and negative predictive values for sarcopenia were 75.31 %, 79.9 %, 43 %, and 94 % for females, and 70.65 %, 81.35 %, 49 %, and 92 % for males, respectively. CONCLUSIONS: The Ishii score chart was used for the prediction of sarcopenia in the old-age people of the Chengdu community and the obtained results showed a high value of predictability. Hence, more than 95 and 102 points were suggested for males and females, accordingly which can set to be the diagnostic cut-off values for the prediction of sarcopenia.

Synthesis and assessment of the antioxidant and antitumor properties of asymmetric curcumin analogues.

In this study, 12 asymmetric curcumin (CUR) analogues and 5 symmetric curcumin derivatives were synthesized, the antioxidant activity of these derivatives were evaluated by radicals 1,1-diphenyl-2-picryl-hydrazyl (DPPH) assay, 2,2-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) assay, ROO (TRAP) assay and O(2-) (NET) assay and anti-proliferative activities of these analogues were assessed against the human hepatoma cell line (SMMC-7721), the human breast cancer cell line (MCF-7) and the human prostate cancer cell lines (PC-3). Most of the asymmetric compounds showed stronger antioxidant activities than Vitamin C (Vc). Curcumin analogues reducing free radicals contain two reaction mechanisms: H-atom and electron transfer mechanisms. Compound 14 showed the most significant antioxidant activity compared with curcumin and other derivatives. Shorted the carbon chain of 14 can reduce the O-H bond dissociation enthalpy (BED) to improve the antioxidant activity. The antioxidant activity of 25 was similar to curcumin. All of the compounds performed better in an anti-proliferate assay than curcumin, especially compound 25, which exhibited the preferential cytotoxic activity against MCF-7 cells(25, IC50 = 9.11 µM, curcumin, IC50 = 70.2 µM). Considering these data, future studies should be performed to assess the therapeutic values of these asymmetric curcumin analogues.

Transport and killing mechanism of a novel camptothecin-deoxycholic acid derivate on hepatocellular carcinoma cells.

Abstract Camptothecin-20(s)-O-glycine ester-[N-(3'α, 12'α-dihydroxy-24'-carbonyl-5'ß-cholan)] (A2), 10-(3'α,12'α-dihydroxy-5'ß-cholan-24'-carboxyl)-(20 s)-camptothecin (C2), and 10-O-(3-O-(3'α, 12'α-dihydroxy-24'-carbonyl-5'ß-cholan)-propyl)-(20S)-camptothecin (D2) are novel camptothecin-deoxycholic acid analogues. MTT assays were performed to assess the anticancer activity of these compounds against hepatocellular carcinoma SMMC-7721, breast carcinoma MCF-7, and colorectal carcinoma HCT-116 cells. A2 had a high killing ability on SMMC-7721 cells selectively, but C2 and D2 did not exhibit selectivity with regard to SMMC-7721 killing. Uptake assays were performed in an effort to elucidate the transport mechanisms of A2 into SMMC-7721 cells. A2 increased the mRNA expression of OATP1B3 (an organic anion-transporting polypeptide) and uptake of A2 was inhibited by rifampin (inhibitor of OATP1B3), which indicated that the transporter-mediated transport of A2 was mediated by OATP1B3. In addition, according to the western blot and apoptosis assays, we found that A2 killed SMMC-7721 cells by inducing cell apoptosis mainly via an AIF (apoptosis-inducing factor) pathway and a caspase-dependent mitochondria apoptosis pathway.