The efficacy and safety of venetoclax combined with demethylating agents in elderly patients with acute myeloid leukemia: a systematic review and meta-analysis.

OBJECTIVE: The aim of this study was to evaluate the efficacy and adverse effects of venetoclax in combination with hypomethylating agents in elderly with acute myeloid leukemia. MATERIALS AND METHODS: A comprehensive literature search identified related studies from PubMed, Medline, Embase, Scopus, and Cochrane Library. Overall complete remission (CR) and overall response rate (ORR) were applied to evaluate the efficacy of venetoclax in combination with hypomethylating agents in elderly with acute myeloid leukemia, and incidence of grade 3-4 adverse events were used to evaluate the safety. RESULTS: 10 studies, including a total of 930 patients, were identified in our study and analyzed using the random-effects model. Meta-analysis showed the pooled overall CR rate of 70% (95% CI: 63-77%), the pooled ORR rate of 53% (95% CI: 39-67%), and the median overall survival ranged from 7.7 to 16.9 months. A total of 6 studies reported related adverse events, mainly including thrombocytopenia, febrile neutropenia, neutropenia, leukopenia, anemia, and pneumonia. The pooled incidence of overall adverse events was 30% (95% CI: 22-38%), and all adverse events were tolerable and resolved with treatment. CONCLUSIONS: The combination of venetoclax and demethylating drugs has a good therapeutic effect on elderly patients with acute myeloid leukemia, but it also induces some adverse events. Although this therapy has a small impact on the quality of life, further attention is still needed to reduce the occurrence of such adverse events.

The efficacy and safety of triplet regimens based on pomalidomide and dexamethasone for treatment of relapsed/refractory multiple myeloma: a systematic review and meta-analysis.

OBJECTIVE: Triplet regimens based on pomalidomide and dexamethasone have been applied to treat relapsed/refractory multiple myeloma, but the safety and efficacy are not yet very clear. This meta-analysis aimed at comparing the safety and efficacy of different triplet therapies and analyzing the best therapy regimen. MATERIALS AND METHODS: A comprehensive literature search identified a total of 615 studies, and 22 studies assessing 1,889 subjects met the inclusion criteria of this meta: phase II/III trial, over 2 median lines of prior therapy, and detailed efficacy outcomes like overall response rate (ORR), overall survival, and progression-free survival (PFS). All statistical analyses were performed by Revman version 5.3, and the heterogeneity was tested by I2 (25% indicating low heterogeneity, 50% moderate, and 75% high). For those with less heterogeneity, fixed-effect model was used. With a significant high heterogeneity, a random-effect model was used. RESULTS: Pooled analysis showed ORR 66.2% across all triplet regimens based on pomalidomide and dexamethasone. Among all triplet regimens, therapy containing bortezomib showed the highest ORR (90.3%), and the one containing elotuzumab showed the lowest ORR (41.2%). The pooled ORRs for the remaining treatment regimens are as follows: cyclophosphamide (70.1%), isatuximab (66.3%), daratumumab (61.2%), clarithromycin (60.0%), pembrolizumab (47.3%). A total of 21 adverse events appeared in the included studies, with neutropenia being the highest incidence of hematologic adverse events (32.1%) and cough being the highest incidence of non-hematologic adverse events (43.3.%). CONCLUSIONS: Three-drug regimens based on pomalidomide and dexamethasone could yield excellent overall response rate to relapsed/refractory multiple myeloma, but there are still various adverse events; therefore, consequent studies should address these adverse events.

Interplay between the Reorientational Dynamics of the B3H8 - Anion and the Structure in KB3H8.

The structure and reorientational dynamics of KB3H8 were studied by using quasielastic and inelastic neutron scattering, Raman spectroscopy, first-principles calculations, differential scanning calorimetry, and in situ synchrotron radiation powder X-ray diffraction. The results reveal the existence of a previously unknown polymorph in between the α'- and ß-polymorphs. Furthermore, it was found that the [B3H8]- anion undergoes different reorientational motions in the three polymorphs α, α', and ß. In α-KB3H8, the [B3H8]- anion performs 3-fold rotations in the plane created by the three boron atoms, which changes to a 2-fold rotation around the C 2 symmetry axis of the [B3H8]- anion upon transitioning to α'-KB3H8. After transitioning to ß-KB3H8, the [B3H8]- anion performs 4-fold rotations in the plane created by the three boron atoms, which indicates that the local structure of ß-KB3H8 deviates from the global cubic NaCl-type structure. The results also indicate that the high reorientational mobility of the [B3H8]- anion facilitates the K+ cation conductivity, since the 2-orders-of-magnitude increase in the anion reorientational mobility observed between 297 and 311 K coincides with a large increase in K+ conductivity.

MiR-129-2 weakens proliferation and promotes apoptosis of liver cancer cells by suppressing the Wnt signaling pathway.

OBJECTIVE: To explore the effects of micro ribonucleic acid-129-2 (miR-129-2) on proliferation and migration of liver cancer cells and its possible mechanism. PATIENTS AND METHODS: The expression level of miR-129-2 was measured in liver cancer tissues and adjacent tissues from patients with liver cancer. Its level in liver cancer HepG2 cells and normal liver cells L-02 was also detected via quantitative polymerase chain reaction (qPCR). MiR-192-2 overexpression model was established in the HepG2 cell line. The proliferation and apoptosis levels of cells were determined by methyl thiazolyl tetrazolium (MTT) assay and flow cytometry, respectively. Wound healing assay was performed to detect the migration ability of cells. The expressions level of genes in the Wnt signaling pathway were measured through Western blotting. Xenograft tumor model was conducted in nude mice for exploring the in vivo effects of miR-129-2 on liver cancer growth. RESULTS: The expression level of miR-129-2 was significantly lower in liver cancer tissues than that in adjacent tissues (p<0.01), and it was overtly lower in HepG2 cells than that in L-02 cells (p<0.01). Overexpression of miR-129-2 weakened proliferation and migration abilities of liver cancer cells (p<0.01), and evidently increased apoptosis level (p<0.01). Sex-determining region Y-related HMG-box 4 (Sox4) and matrix metalloproteinase-2 (MMP-2) were downregulated, while phosphorylated glycogen synthase kinase-3ß (p-GSK3ß) was upregulated in liver cancer cells overexpressing miR-129-2. Besides, the weight and volume of tumors in nude mice bearing liver cancer were significantly smaller after overexpression of miR-129-2. CONCLUSIONS: MiR-129-2 weakens proliferation and migration and stimulates apoptosis in liver cancer cells mainly by downregulating Sox4 and inactivating the Wnt signaling pathway.

Epidemiologic and clinical characteristics of 91 hospitalized patients with COVID-19 in Zhejiang, China: a retrospective, multi-centre case series.

BACKGROUND: Recent studies have focused on initial clinical and epidemiological characteristics of the coronavirus disease 2019 (COVID-19), which is the mainly revealing situation in Wuhan, Hubei. AIM: This study aims to reveal more data on the epidemiological and clinical characteristics of COVID-19 patients outside of Wuhan, Zhejiang, China. DESIGN: This study was a retrospective case series. METHODS: Eighty-eight cases of laboratory-confirmed and three cases of clinically confirmed COVID-19 were admitted to five hospitals in Zhejiang province, China. Data were collected from 20 January 2020 to 11 February 2020. RESULTS AND DISCUSSION: Of all 91 patients, 88 (96.70%) were laboratory-confirmed COVID-19 with throat swab samples that tested positive for SARS-Cov-2, three (3.30%) cases were clinically diagnosed. The median age of the patients was 50 (36.5-57) years, and female accounted for 59.34%. In this sample, 40 (43.96%) patients had contracted the disease from local cases, 31 (34.07%) patients had been to Wuhan/Hubei, eight (8.79%) patients had contacted with people from Wuhan, and 11 (12.09%) patients were diagnosed after having flown together in the same flight with no passenger that could later be identified as the source of infection. In particular within the city of Ningbo, 60.52% cases can be traced back to an event held in a temple. The most common symptoms were fever (71.43%), cough (60.44%) and fatigue (43.96%). The median of incubation period was 6 (interquartile range 3-8) days and the median time from the first visit to a doctor to the confirmed diagnosis was 1 (1-2) days. According to the chest computed tomography scans, 67.03% cases had bilateral pneumonia. CONCLUSIONS: Social activity cluster, family cluster and flying alongside with persons already infected with COVID-19 were how people got infected with COVID-19 in Zhejiang.

Effect of the JAK2/STAT3 signaling pathway on nerve cell apoptosis in rats with white matter injury.

OBJECTIVE: The Janus activated kinase 2 (JAK2)/signal transducer and the activator of transcription 3 (STAT3) pathway are involved in many physiological processes, such as cell survival, inflammation, development, proliferation and differentiation. Increasing evidence has shown that this pathway also has neuron-specific functions in the central nervous system. In this study, the functional significance of the JAK2/STAT3 signaling pathway in nerve cell apoptosis in rats with white matter injury was evaluated. MATERIALS AND METHODS: The rat model of white matter injury was established by ligating bilateral common carotid arteries, and the changes of the JAK2 and STAT3 phosphorylation in hippocampal neurons were evaluated using the immunohistochemistry. In addition, the effects of JAK2 inhibitor AG490 and STAT3 small interfering ribonucleic acids (siRNAs) on the expression of phosphorylated-JAK2 (pJAK2), STAT3 messenger RNAs (mRNAs) and pSTAT3 in hippocampal neurons of white matter injury rats were studied. The effects of both on cerebral infarction volume and neuron apoptosis in white matter injury rats were also investigated. RESULTS: The expression of pJAK2 and pSTAT3 were significantly increased after white matter injury in rats (p<0.05). JAK2 inhibitor AG490 markedly decreased the phosphorylation of JAK2 and STAT3 in hippocampal neurons in the model group (p<0.05). STAT3 siRNAs remarkably reduced the expression levels of STAT3 mRNA and protein in hippocampus neurons in the model group (p<0.05), while having no effect on the expression level of pJAK2 protein. AG490 and STAT3 siRNAs notably attenuated the volume of cerebral infarction in the model group, as well as reduced neuron apoptosis after white matter injury. CONCLUSIONS: The inhibition of the JAK2/STAT3 signaling pathway contributed to reducing the volume of cerebral infarction and neuron apoptosis in rats with white matter injury.

Peripheral Blood Leukocyte Telomere Length Is Associated with Age but Not Renal Function: A Cross-Sectional Follow-Up Study.

OBJECTIVES: We aimed to evaluate the relationship between baseline renal function and changes in telomere length in Han Chinese. METHODS: The telomere restriction fragment (TRF) length of leukocytes in the peripheral blood was measured in healthy volunteers recruited in 2014. The estimated glomerular filtration rate (eGFR) was calculated based on serum creatinine (Scr) and serum cystatin C (CysC)-eGFRcys and eGFRScr-cys through the Cockcroft-Gault formula (eGFRC-G) or the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI / eGFRCKD-EPI) equation. The correlation between telomere length changes over time and renal function was analyzed. RESULTS: Leukocyte TRF lengths were negatively correlated to age (r = -0.393, p < 0.001) and serum CysC (r = -0.180, p < 0.01), while positively associated with eGFRCKD-EPI, eGFRC-G, eGFRcys, and eGFRScr-cys (r = 0.182, 0.122, 0.290, and 0.254 respectively, p < 0.01). The 3-year change of telomere length was 46 bp/years. When adjusted for age, the associations between telomere length changes and baseline, subsequent TRF lengths, and serum CysC were no longer present. No association was observed between TRF length changes and renal function. CONCLUSION: The rate of telomere length changes was affected by age and baseline telomere length. The telomere length changes might be important markers for aging.

Regulation of host epithelial responses to Cryptosporidium infection by microRNAs.

Cryptosporidium species infect the gastrointestinal epithelium and other mucosal surfaces of vertebrate hosts. Epithelial cells provide the first line of defence against Cryptosporidium infection and play a critical role in the initiation, regulation and resolution of both innate and adaptive immune reactions. Host miRNAs in mammalian cells have been shown to play crucial roles in cellular responses to infection by diverse pathogens, including viruses, parasites and bacteria. Given the absence of RNAi machinery in Cryptosporidium, lack of miRNA expression in the parasite and minimal invasion nature of infection, Cryptosporidium infection provides an ideal model for exploring miRNA-mediated epithelial cell defence, relevant to infection of mucosal epithelial cells by pathogens in general. Increasing evidence supports that miRNAs may modulate many stages of epithelial responses following Cryptosporidium infection, including activation of the intracellular signalling pathways, production of antimicrobial molecules, expression of cytokines/chemokines, release of epithelial cell-derived exosomes and feedback regulation of immune homeostasis. On the other hand, this parasite may have developed strategies to modulate host miRNA-mediated cellular function for immune evasion. In this review, we will summarize the recent advances on miRNA regulation of epithelial responses to Cryptosporidium infection, with an emphasis on host defence and parasite immune evasion.

Preclinical study on induction of pluripotent stem cells from urine of dilated cardiomyopathy patients.

OBJECTIVE: Dilated cardiomyopathy (DCM) is featured by left or bilateral ventricular dilation combined with systolic dysfunction. Its clinical manifestations include heart enlargement, cardiac failure, arrhythmia and cardiac arrest. Medication and heart transplantation have but only limited treatment effect on DCM. MATERIALS AND METHODS: Induced pluripotent stem cell (iPSC) treatment provides a new solution for DCM treatment. Human renal epithelial cells were extracted from the urine of patients with DCM and transfected with Sendai virus carrying OCT3/4, Sox2, Klf4 and c-Myc gene to generate iPSCs by reprogramming. RESULTS: The morphology and pluripotency of iPSCs obtained from the renal epithelial cells from patients with DCM were confirmed, as well as the growth characteristics, immunohistochemical features and surface markers of embryonic stem cells. Teratoma was formed in vivo. CONCLUSIONS: We demonstrated that it was feasible to obtain iPSCs from the urine of patients with DCM. This technique lays down the cytological foundation for understanding the pathogenesis and for drug screening and gene therapy for DCM.

Interhemispheric functional and structural alterations and their relationships with alertness in unilateral temporal lobe epilepsy.

OBJECTIVE: Many neuroimaging studies have shown that temporal lobe epilepsy (TLE) is associated with functional and structural abnormalities at specific brain areas. Unfortunately, relatively limited information has been presented about the alterations of interhemispheric functional and anatomic connectivity in patients with unilateral TLE. In the present study, we investigated interhemispheric functional connectivity using a voxel-mirrored homotopic connectivity (VMHC) method. We further revealed fractional anisotropy (FA) changes in the areas with abnormal VMHC values in TLE patients by diffusion tensor imaging (DTI). Moreover, their relationships with alertness in patients with drug-naïve unilateral TLE were also investigated. PATIENTS AND METHODS: Forty-three patients with unilateral TLE (21 left TLE and 22 right TLE) and 20 normal controls (NC) were recruited for case-control study. All of the subjects underwent acquisition of resting-state functional magnetic resonance images, Mini-Mental State Examination (MMSE) and the attention network test. DTI images were collected in 26 patients with unilateral TLE (10 left TLE and 16 right TLE) and 20 NCs. Functional connectivity between bilateral homotopic voxels was calculated. Homotopic regions showing abnormal functional connectivity in patients were adopted as regions of interest for the analysis of DTI. The FA values, MMSE scores, and alertness were compared between groups. Correlation analyses were employed to examine the relationships between each radiographic parameter (VMHC and FA) and each clinical and neuropsychological parameter in patients with drug-naïve unilateral TLE. RESULTS: Compared with NC, patients with left TLE exhibited significantly higher VMHC values in the bilateral angular gyrus, inferior occipital gyrus and superior parietal gyrus and lower VMHC values in the bilateral supplementary motor area, inferior parietal lobule, middle temporal gyrus, and medial superior frontal gyrus. In patients with right TLE, higher VMHC values were found in the bilateral inferior occipital gyrus, parahippocampal gyrus and cerebellum; lower VMHC values were observed in the bilateral middle temporal gyrus and precentral gyrus/inferior frontal gyrus. FA values of the commissural fiber bundles connecting the bilateral parahippocampal gyrus were smaller in the right TLE than those in the NC group. Meanwhile, the alerting effect of patients was determined to be impaired and positively correlated with FA values of the commissural fiber bundles connecting the bilateral parahippocampal gyrus in right TLE patients. CONCLUSIONS: Our findings indicate that the bilateral parahippocampal gyrus may be important to the pathophysiology of patients with drug-naïve unilateral TLE. The significant correlation between the FA values and alertness indicates that structural changes are involved in the alterations in the alertness network in unilateral right TLE patients.

Evaluation of cytotoxicity of some common ophthalmic drugs.

The article "Evaluation of cytotoxicity of some common ophthalmic drugs" by M. Li, X.-M. Chen, J.-J. Liu, D.-M. Wang, L. Gan, X. Lv, Y. Qiao, published in Eur Rev Med Pharmacol Sci 2015; 19 (11): 1945-1950 has been withdrawn.

Evaluation of cytotoxicity of some common ophthalmic drugs.

OBJECTIVE: The study was aimed at evaluating the in vitro cytotoxicity of some commonly used drugs in ophthalmology. Hydrocortisone sodium succinate, Dexamethasone sodium phosphate, 5-Fluorouracil, Tobramycin and Pilocarpine nitrate are frequently used in various indications involving eye care, and the aim was to test the safety of these in cell culture. MATERIALS AND METHODS: The in vitro cytotoxicity was carried out on the NIH 3T3 cell line by the Sulforhodamine B (SRB) assay. RESULTS: With the exception of 5-Fluorouracil, none of the other drugs demonstrated appreciable cytotoxicity up to high concentrations of 200 µg/ml at 48 hours of drug exposure. CONCLUSIONS: Hydrocortisone sodium succinate, Dexamethasone sodium phosphate, Tobramycin and Pilocarpine nitrate were confirmed to be non-cytotoxic while 5-Fluorouracil was highly cytotoxic especially at 48 hours at very low concentrations.

Abdominal injuries involving bicycle handlebars in 219 children: results of 8-year follow-up.

OBJECTIVES: Handlebar injuries are one of the most common causes of abdominal injuries in children. We aim to investigate the epidemiology of bicycle handlebar injuries and to emphasize the severity of the injuries. METHODS: A retrospective analysis of children admitted to our hospital with abdominal injury related to bicycle handlebars was performed. RESULTS: A total of 219 children (187 males and 32 females) younger than 17 years were hospitalized for abdominal handlebar injuries between 2005 and 2013. The age range of the patients was 4-17 (mean 10.93 ± 3.68) years. Most patients had an imprint of the handlebar edge on their abdomen. The most common abdominal organ injury was liver laceration. 33 patients had pancreas injury and 13 patients had hollow organ injury. Most patients were treated conservatively. Surgery was performed in 24 patients. Hospital stay was 4-60 (mean 9.63 ± 13.37) days. CONCLUSIONS: Trend of bicycle handlebar trauma over this time period was related to the local floating population and economy. The most common abdominal organ injury was liver. Hollow organ injury required emergency exploratory laparotomy and the Roux-y anastomosis applied well in cases whose gastrointestinal tract damaged seriously. Pancreatic injury usually led to secondary pseudocyst. The percutaneous ultrasound-guided drainage of pancreatic pseudocyst was really an effective way. The trend in the amylase and lipase levels could reflect the pancreatic injury condition and predict prognosis. Early diagnosis and optimal care without delay may help to reduce the morbidity of injuries to the internal organs. Children with abdominal handlebar injuries should be treated with great care.

A novel FBN1 heterozygous mutation identified in a Chinese family with autosomal dominant Marfan syndrome.

The purpose of this study was to identify the clinical features and mutations in the fibrillin-1 gene (FBN1) in a large Chinese family with autosomal dominant Marfan syndrome (MFS). Seventeen members from a Chinese family of 4 generations were included in the study. All members underwent complete ophthalmic examination. Molecular genetic analysis was performed on all subjects. All exons of FBN1 were amplified by polymerase chain reaction, sequenced, and the sequences were compared with a reference database. Variations were evaluated in family members as well as 100 normal controls. Changes in structure and function of the protein induced by amino acid variation were predicted by bioinformatic analysis. Ectopia lentis, dolichostenomelia, arachnodactyly, and tall stature were present in all patients diagnosed with MFS. The novel heterozygous missense mutation c.2243 T>G (p.C781W) in exon 19 of FBN1 was identified in all 5 patients, but not in other family members or 100 normal controls. This mutation caused an amino acid substitution of cysteine to tryptophan at position 781 (p.C781W) of the FBN1 protein. This mutation occurred in a highly conserved region and may cause structural and functional changes in the protein according to our bioinformatic analysis. Our results suggest that the novel mutation C781W of FBN1 is responsible for the pathogenesis of MFS in this pedigree.

Electroacupuncture inhibits excessive interferon-γ evoked up-regulation of P2X4 receptor in spinal microglia in a CCI rat model for neuropathic pain.

BACKGROUND: Although electroacupuncture (EA) is effective in the relief of neuropathic pain, the underlying mechanisms remain unclear. Previous studies have reported immunomodulatory effects of EA in rats. Since excessive release of interferon-γ (IFN-γ) after nerve injury transforms quiescent spinal microglia into an activated state with more neuropathic pain, associated with purinergic receptor P2X4 expression, it is possible that EA may mediate its analgesic effect by attenuating IFN-γ release and subsequent generation of P2X4R(+) microglia. METHODS: Male rats underwent chronic constriction injury (CCI) or IFN-γ intrathecal injection and von Frey tests were performed to evaluate the effect of EA on pain thresholds. Spinal IFN-γ and P2X4R expression levels were measured by immunohistochemistry, real-time PCR, enzyme immunoassay, and/or western blots. In vitro primary cultures of microglia were used to examine IFN-γ activation of P2X4R(+) cells. RESULTS: In CCI rats, EA treatment significantly increased paw withdrawal threshold relative to control. IFN-γ facilitated P2X4R(+) microglia activation both in vitro and in vivo. EA also down-regulated both P2X4R and IFN-γ expression in the spinal cord after CCI. However, EA did not exert the same analgesic effect after intrathecal IFN-γ injection. CONCLUSIONS: EA ameliorated tactile allodynia after peripheral nerve injury by down-regulating excessive expression of IFN-γ in the spinal cord and subsequently reducing expression of P2X4R.

Early diagnostic and prognostic utility of high-sensitive troponin assays in acute myocardial infarction: a meta-analysis.

BACKGROUND/AIM: To determine the diagnostic and prognostic utility of high-sensitive troponin assays in the very early phase of acute myocardial infarction (AMI) (less than 3 h since symptoms onset) by performing a meta-analysis of prospective studies. METHODS: Relevant studies were identified by searches of MEDLINE and Elsevier Sciencedirect until 31 January 2014 and by reviewing the reference lists from retrieved articles. Prospective studies that reported diagnostic utility in AMI using both high-sensitive troponin assays and conventional cardiac troponin, and reported the estimates of hazard ratio (HR) with 95% confidence intervals (CI) for prognostic utility were included. Data were extracted independently by two authors and summary estimates of association were obtained using a random effects model. RESULTS: Of the seven studies included, four studies reported the diagnostic utility of high-sensitive troponin assays (2863 patients) and three reported the prognostic utility in AMI (2329 patients). Within 12 h of symptoms onset, the pooled sensitivity and specificity of high-sensitive troponin assays were 0.89 (95% CI 0.85-0.91) and 0.89 (95% CI 0.85-0.92), respectively, and within 3 h, the pooled sensitivity and specificity of high-sensitive troponin assays were 0.79 (95% CI 0.71-0.85) and 0.92 (95% CI 0.88-0.96) respectively. Compared with conventional cardiac troponin assays, the high-sensitive troponin assays had higher sensitivity (0.89 vs 0.72) but lower specificity (0.89 vs 0.95) in diagnosing AMI within 12 h of symptoms onset. Within 3 h, the sensitivity of high-sensitive troponin assays was still higher (0.79 vs 0.59), but the specificity was almost the same (0.92 vs 0.95) as that of conventional troponin assays. The elevated high-sensitive troponin assays had an overall pooled HR of 2.66 (95% CI 1.31-5.44) and 2.14 (95% CI 1.15-3.98) for the end-points of death and non-fatal AMI respectively. CONCLUSIONS: These findings provide quantitative data supporting high-sensitive troponin assays having early diagnostic and prognostic utility in AMI.

Association of Klotho and interleukin 6 gene polymorphisms with aging in Han Chinese population.

Certain gene polymorphisms are associated with human aging. This study investigated polymorphisms of a metabolism-related gene, Klotho, and an inflammatory gene, IL6, for association with the aging process in a healthy Han Chinese population. A total of 482 healthy subjects were recruited and divided into aging and young groups according to chronological age and biological age. Snapshots were used to detect a Klotho gene tag SNP (rs571118) and the F-SNPs rs9536314 (F352V) and rs9527025 (C370S), and an interleukin 6 (IL-6) gene tag SNP (rs1524107) and the F-SNPs rs1800795 (-174G/C) and rs1800796 (-572G/C). Klotho F352V and IL-6-174G/C was G homozygous, C370S was T homozygous while IL-6-572G/C MAF less than 5%. There was a statistically significant difference in the Klotho rs571118 SNP between chronological age groups, but not biological age groups. However, other SNPs, including IL-6 gene SNPs, didn't correlate with age in the Han Chinese population. Human aging is a complex process that includes chronological and biological aging. Our current data showed that Klotho gene rs571118 SNP was associated with chronological aging, but not biological aging, in a Han Chinese population. Further study will investigate genetic build up for the difference between chronological and biological aging.

Construction of an integral formula of biological age for a healthy Chinese population using principle component analysis.

BACKGROUND: Whereas chronological age (CA) cannot distinguish functional differences among individuals of the same age, the biological age (BA) may be used to reflect the functional state of the body. The purpose of this study was to construct an integral formula of the BA, by using principle component analysis (PCA). METHODS: The vital organ function of 505 healthy individuals of Han origin (age 35-91 years) was examined. A total of 114 indicators of cardiovascular, pulmonary, and brain functions, and clinical, inflammatory, genetic, psychological, and life habit factors were assessed as candidate indicators of aging. Candidate indicators were submitted with CA to correlation and redundancy analyses. The PCA method was used to build an integral formula of the BA for the population. RESULTS: Seven biomarkers were selected in accordance with a certain load standard. These biomarkers included the trail making test (TMT), pulse pressure (PP), mitral valve annulus ventricular septum of the peak velocity of early filling (MVES), minimum carotid artery intimal-medial thickness (IMTmin), maximum internal diameter of the carotid artery (Dmax), maximal midexpiratory flow rate 75/25 (MMEF75/25), and Cystatin C (CysC). The formula for the BA was: BA = 0.0685 (TMT) + 0.267 (PP) - 1.375 (MVES) + 22.443 (IMTmin) + 2.962 (Dmax) - 2.332 (MMEF75/25) + 16.104 (CysC) + 0.137 (CA) + 0.492. CONCLUSION: Several genetic and lifestyle indicators were considered as candidate markers of aging. However, ultimately, only markers reflecting the function of the vital organs were included in the BA formula. This study represents a useful attempt to employ multiple indicators to build a comprehensive BA evaluation formula of aging populations.

Suppression of SCARA5 by Snail1 is essential for EMT-associated cell migration of A549 cells.

Accumulating evidence indicates that epithelial-to-mesenchymal transition (EMT) might be a key event for cancer progression. The upregulation of Snail1, one of the most extensively studied EMT regulators, has been implicated in cancer metastasis, but the underlying mechanisms remain unclear. This study aims to identify that Snail1 targets regulating EMT-associated cancer cell migration. Human lung carcinoma A549 cells were treated with transforming growth factor beta 1 (TGF-ß1), and EMT-associated phenotypic and functional alterations were monitored. TGF-ß1 induced typical EMT-like morphological changes, 'cadherin switching' and cell migration in A549 cells. TGF-ß1 stimulation induced rapid and persistent upregulation of Snail1. Moreover, Snail1 upregulation was required for EMT-associated cell migration. Several metastasis suppressors with putative Snail1-binding sites in their promoters were dramatically repressed in A549 cells during TGF-ß1-induced EMT. Gain- and loss-of Snail1 function experiments demonstrated that scavenger receptor class A member 5 (SCARA5) was negatively regulated by Snail1. Importantly, SCARA5 downregulation was essential for EMT-induced migration in A549 cells. The chromatin immunoprecipitation assay revealed that Snail1 could bind to the E-box elements in SCARA5 promoter, implying that SCARA5 is a direct Snail1 target modulating cancer cell mobility during EMT. In addition, we showed that DNA methyltransferase 1 was physically associated with Snail1 to silence SCARA5 expression with an unidentified DNA methylation-independent mechanism, suggesting the complexity of Snail1-mediated epigenetic regulation. Collectively, our data demonstrated that EMT-regulator Snail1 suppresses the expression of SCARA5 to promote cancer progression, highlighting the possibility to target Snail1 and SCARA5 for cancer treatment.