The Mind-Body Connection: Exploring the Defining Characteristics of Two Aging Phenotypes

Introduction: Built on the theory of mind-body connection, there has been a growing interest in phenotypes combining physical frailty and cognitive decline. Two examples are motoric cognitive risk syndrome (MCR) and cognitive frailty (CF). MCR, defined by co-presentation of slow gait and subjective cognitive complaint without dementia or mobility disability, is considered a “pre-dementia syndrome.” CF, defined as having both physical frailty and cognitive impairment in the absence of dementia, is posited to be caused by physical frailty. Although both MCR and CF have been associated with dementia risk, the relationship between the two is unknown. We aimed to (1) assess the concordance between the two, and (2) describe the characteristics of those with MCR or CF or both. By doing so, we hope to move beyond risk prediction towards a better understanding of heterogeneity in cognitive decline. Methods: The analysis uses baseline data (year 2011) from the National Health and Aging Trend Study. Frailty was measured by the physical frailty phenotype. Cognitive impairment was based on self/proxy report of dementia and cognitive performance tests. We first estimated the prevalence of 3 groups: having MCR only, having CF only and having both MCR and CF. Next, we examined the associations between group membership and demographic/health characteristics using multinomial logistic regression. Results: Of the 6,212 eligible subjects, 304 had MCR only, 410 were CF only, and 115 had both. While 21.9% of those with CF had MCR, 27.5% of those with MCR had CF. Those who had both were more likely to be Blacks and Hispanics, in a lower socioeconomic status. The CF only group had a stronger association with comorbidity burden than MCR only. Health characteristics were more similar between the CF only group and the both group. The differences between the MCR only and the CF only were mostly due to the exclusion of mobility disability in the case of MCR. Conclusions: There are noteworthy areas of discordance between MCR and CF. The exact etiology of their differences remains undetermined and it is unclear if these syndromes are measuring the same underlying process at different stages of advancement or entirely different pathological processes of cognitive decline

Deficiency of Mkrn2 causes abnormal spermiogenesis and spermiation, and impairs male fertility.

Although recent studies have shed insights on some of the potential causes of male infertility, new underlining molecular mechanisms still remain to be elucidated. Makorin-2 (Mkrn2) is an evolutionarily conserved gene whose biological functions are not fully known. We developed an Mrkn2 knockout mouse model to study the role of this gene, and found that deletion of Mkrn2 in mice led to male infertility. Mkrn2 knockout mice produced abnormal sperms characterized by low number, poor motility, and aberrant morphology. Disruption of Mkrn2 also caused failure of sperm release (spermiation failure) and misarrangement of ectoplasmic specialization (ES) in testes, thus impairing spermiogenesis and spermiation. To understand the molecular mechanism, we found that expression of Odf2, a vital protein in spermatogenesis, was significantly decreased. In addition, we found that expression levels of Odf2 were decreased in Mkrn2 knockout mice. We also found that MKRN2 was prominently expressed in the sperm of normal men, but was significantly reduced in infertile men. This result indicates that our finding is clinically relevant. The results of our study provided insights into a new mechanism of male infertility caused by the MKRN2 downregulation

Toxicities comparison of rotenone and acetone extract of Tephrosiavogelii and Derris trifoliate against Solenopsis invicta

The high rotenone content and the rotenone crude extract of Tephrosia vogelii and Derris trifoliata were evaluated for its efficacy in the control of red imported fire (RIFA), Solenopsis invicta under both laboratory and field conditions. The acetone extracts of D. trifoliata roots and T. vogelii leaves exhibited strong toxicity to macroergate and micrergate of RIFA. When active ingredients of the crude extracts were convert to rotenone, the activity of the acetone extracts were higher than that of rotenone technical material. At the same time, the extracts showed significant inhibitory effect on walking ability and grasping ability of worker ants and stronger than the effect of 98.6% rotenone technical material. Under field conditions, the 0.01% rotenone-bait, formulated with the acetone extract of D. trifoliata roots and T. vogelii leaves, had the same control effect on RIFA as that of 0.01% fipronil-bait when treated after 30 d. The bait formulated with the extract of D. trifoliata exhibited quicker and higher effect on RIFA than that of rotenone technical material. It was showed that the acetone extracts of D. trifoliata roots and T. vogelii leaves are able to control S. invicta under both laboratory and field conditions and can be used as an effective agent against RIFA

Synthesis, Characterization and Antitumor Activity of a Series of Polypyridyl Complexes

A series of polypyridyl complexes have been synthesized. All polypyridyl complexes and some of the soluble ligands have been assayed for antitumor activity in vitro against the HL-60 (the human leucocytoma) cells, BEL-7402 (the human liver carcinoma) cells, KB (the human nasopharyngeal carcinoma) cells and HELA (the human adenocarcinoma of cervix) cells. The results indicate that several complexes have relative activity against different cell lines. Especially, the complexes [Co(bpy)2(pip)]3+, [Co(phen)2(pip)]3+, [Ru(bpy)2(pztp)]2+ and [Ru(pztp)2(bpy)]2+ show relative high activity against four tumor cell lines. Moreover, they are slightly more effective than cisplatin. At the concentration of 100 μg/mL, the complexes show inhibitory rate of 72∼86% for the cancer cells and have no toxicity for MDCK and Vero cells. It is indicated that these complexes can inhibit cancer cells selectively

2-(4-Fluoro­anilino)-3-(2-hydroxy­ethyl)quinazolin-4(3H)-one

The mol­ecular and crystal structures of the title compound, C16H14FN3O2, are stabilized by intra­molecular N—H⋯O and inter­molecular O—H⋯O hydrogen bonds. The existence of non-classical intra­molecular C—H⋯N hydrogen bonds provides a dihedral angle between the fluoro-substituted benzene and pyrimidinone rings of 7.9 (1)°

MiR-143 acts as a tumor suppressor by targeting N-RAS and enhances temozolomide-induced apoptosis in glioma.

Therapeutic applications of microRNAs (miRNAs) in RAS-driven glioma were valuable, but their specific roles and functions have yet to be fully elucidated. Here, we firstly report that miR-143 directly targets the neuroblastoma RAS viral oncogene homolog (N-RAS) and functions as a tumor-suppressor in glioma. Overexpression of miR-143 decreased the expression of N-RAS, inhibited PI3K/AKT, MAPK/ERK signaling, and attenuated the accumulation of p65 in nucleus of glioma cells. In human clinical specimens, miR-143 was downregulated where an adverse with N-RAS expression was observed. Furthermore, overexpression of miR-143 decreased glioma cell migration, invasion, tube formation and slowed tumor growth and angiogenesis in a manner associated with N-RAS downregulation in vitro and in vivo. Finally, miR-143 also sensitizes glioma cells to temozolomide (TMZ),the first-line drug for glioma treatment. Taken together, for the first time, our results demonstrate that miR-143 plays a significant role in inactivating the RAS signaling pathway through the inhibition of N-RAS, which may provide a novel therapeutic strategy for treatment of glioma and other RAS-driven cancers

Estrogen regulates miRNA expression: implication of estrogen receptor and miR-124/AKT2 in tumor growth and angiogenesis.

It is currently known that estrogen plays an important role in breast cancer (BC) development, but the underlying molecular mechanism remains to be elucidated. Accumulating evidence has revealed important roles of microRNAs in various kinds of human cancers, including BC. In this study, we found that among the microRNAs regulated by estrogen, miR-124 was the most prominent downregulated miRNA. miR-124 was downregulated by estradiol (E2) treatment in estrogen receptor (ER) positive BC cells, miR-124 overexpression suppressed cell proliferation, migration and invasion in BC cells; while the suppression of miR-124 using Anti-miR-124 inhibitor had opposite cellular functions. Under the E2 treatment, miR-124 had stronger effect to inhibit cellular functions in MCF7 cells than that in MDA-MB-231 cells. In addition, we identified that ERα, but not ERβ, was required for E2-induced miR-124 downregulation. Furthermore, AKT2, a known oncogene, was a novel direct target of miR-124. AKT2 expression levels were inversely correlated with miR-124 expression levels in human breast cancer specimens. AKT2 was overexpressed in BC specimens, and its expression levels were much higher in ERα positive cancer tissues than those ERα negative cancer tissues. Consistent with miR-124 suppression, E2 treatment increased AKT2 expression levels in MCF7 cells via ERα. Finally, overexpression of miR-124 in MCF7 cells significantly suppressed tumor growth and angiogenesis by targeting AKT2. Our results provide a mechanistic insight into a functional role of new ERα/miR-124/AKT2 signaling pathway in BC development. miR-124 and AKT2 may be used as biomarkers for ERα positive BC and therapeutic effect in the future

Detecting and pyramiding target QTL for plant- and grain-related traits via chromosomal segment substitution line of rice

IntroductionPlant height and grain length are important agronomic traits in rice, exhibiting a strong effect on plant architecture and grain quality of rice varieties.MethodsMethods: A novel rice chromosomal segment substitution line (CSSL), i.e., CSSL-Z1357, with significantly increased plant height (PH) and grain length (GL) was identified from CSSLs constructed by using Nipponbare as a receptor and a restorer line Xihui 18 as a donor. Seven agronomic traits of PH, PL, GL, GW, GPP, SPP, and TGW were phenotyped, and REML implemented in HPMIXED of SAS were used to detect the QTL for these traits. Secondary CSSLs were screened out via marker-assisted selection (MAS) to estimate the additive and epistatic effects of detected QTLs, evaluating the potential utilization of pyramiding the target QTLs for yield and quality improvement of rice varieties.Results and DiscussionResults and Discussion: CSSL-Z1357 carried nine segments from Xihui 18 with an average segment length of 4.13 Mb. The results show that the long grain of CSSL-Z1357 was caused by the increased number of surface cells and the length of the inner glume. Thirteen quantitative trait loci were identified via the F2 population of Nipponbare/CSSL-Z1357, including three each for GL (qGL-3, qGL-6, and qGL-7) and PH (qPH-1, qPH-7, and qPH-12I), among which qGL-3 increased GL by 0.23 mm with synergistic allele from CSSL-Z1357. Additionally, three single (S1 to S3), two double (D1, D2), and one triple segment (T1) substitution lines were developed in F3 via MAS. Results show that pyramiding the segments from Chr.3 (qGL-3 and qPH-3), Chr.6 (qGL-6 and qPH-6), and Chr.7 (Null and qPH-7) tended to result in better phenotype of increased GL and PH and decreased grain width, providing a potential basis for enhancing grain yield and quality in rice breeding